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ndt

ISSN 1460-2385 (Online)


Volume 36 Supplement 1 May 2021

Volume 36 Supplement 1 May 2021 pages i1–i566


AN INTERNATIONAL BASIC SCIENCE AND CLINICAL RENAL JOURNAL

58th ERA-EDTA Congress, 5–8 June 2021

Congress Abstracts
5

academic.oup.com/ndt

NDT_36_S1_cover.indd 1-3 26-05-2021 14:22:56


58th ERA-EDTA Congress,
5–8 June 2021

Abstract Supplement
CONTENTS

Free Communications (sorted by session)


Stones & brain ...................................................................................................................................................................................................... i1
Cells & immunity................................................................................................................................................................................................. i3
Cysts & cancer...................................................................................................................................................................................................... i5
Genes & kidney .................................................................................................................................................................................................... i7
Pathology meets clinics ...................................................................................................................................................................................... i9
Hypertension & omics...................................................................................................................................................................................... i12
Interventions in CKD ....................................................................................................................................................................................... i16
The virus & the kidney...................................................................................................................................................................................... i19
Basics & clinics in glomerulonephritis........................................................................................................................................................... i21
Beat autoimmunity ........................................................................................................................................................................................... i23
Treatment & outcome of glomerulonephritis .............................................................................................................................................. i26
Basic science in AKI .......................................................................................................................................................................................... i29
AKI: the good, the bad & the ugly................................................................................................................................................................... i32
Prevention of AKI ............................................................................................................................................................................................. i34
Fluid, GFR & co.................................................................................................................................................................................................. i37
Surviving CKD................................................................................................................................................................................................... i41
Pathophysiological pathways in CKD ........................................................................................................................................................... i44
Big data & nephrology ...................................................................................................................................................................................... i47
Anaemia: what else? .......................................................................................................................................................................................... i50
Bones & outcomes in CKD .............................................................................................................................................................................. i53
Plants, coffee & more ........................................................................................................................................................................................ i57
Stop diabetes....................................................................................................................................................................................................... i62
Treat diabetes ..................................................................................................................................................................................................... i65
Dialysis patterns: what’s new? ......................................................................................................................................................................... i67
Protect the membrane ...................................................................................................................................................................................... i70
Outcomes in PD................................................................................................................................................................................................. i73
Dialysis: heart & vessels .................................................................................................................................................................................... i75
Dialysis: quality of life....................................................................................................................................................................................... i77
Dialysis: nutrition & outcomes ....................................................................................................................................................................... i79
Transplantation & new technologies ............................................................................................................................................................. i82
Transplantation: risks & complications ........................................................................................................................................................ i85
Transplantation: short- and long-term outcomes ....................................................................................................................................... i87
Kids & kidney ..................................................................................................................................................................................................... i89
A look in the crystal ball: environment & education................................................................................................................................... i91

Abstract titles marked with an asterisk * denote Moderated Mini-Orals.


Mini Orals (sorted by session)
Acid-base and uric acid .................................................................................................................................................................................... i93
Cell signalling. Cell biology. Hormones ........................................................................................................................................................ i95
Renal development and cystic diseases........................................................................................................................................................ i101
Genetic diseases and molecular genetics ..................................................................................................................................................... i106
Renal pathology. Experimental and clinical ............................................................................................................................................... i120
Hypertension. Experimental ......................................................................................................................................................................... i133
Nephrolithiasis and uric acid......................................................................................................................................................................... i142
Clinical nephrology......................................................................................................................................................................................... i147
Glomerulonephritis ........................................................................................................................................................................................ i198
AKI. Experimental .......................................................................................................................................................................................... i236
AKI. Clinical. Epidemiology and outcome ................................................................................................................................................. i244
AKI. Clinical. Prevention and treatment..................................................................................................................................................... i270
CKD. Lab methods, GFR measurement, urine proteomics ..................................................................................................................... i279
CKD. Pathophysiology, progression and risk factors ............................................................................................................................... i283
CKD. Clinical epidemiology.......................................................................................................................................................................... i300
CKD. Anaemia................................................................................................................................................................................................. i325
CKD. Bone disease .......................................................................................................................................................................................... i337
CKD. Nutrition, inflammation and oxidative stress ................................................................................................................................. i351
CKD. Rehabilitation........................................................................................................................................................................................ i361
Diabetes. Basic research.................................................................................................................................................................................. i365
Diabetes. Clinical studies ............................................................................................................................................................................... i371
Dialysis. Extracorporeal dialysis: techniques and adequacy .................................................................................................................... i381
Dialysis. Peritoneal dialysis............................................................................................................................................................................ i392
Dialysis. Cardiovascular complications....................................................................................................................................................... i409
Dialysis. Vascular access ................................................................................................................................................................................ i430
Dialysis. Anaemia............................................................................................................................................................................................ i442
Dialysis. Bone disease ..................................................................................................................................................................................... i444
Dialysis. Epidemiology and outcome........................................................................................................................................................... i454
Dialysis. Health services research ................................................................................................................................................................. i484
Dialysis. Protein energy wasting, inflammation and oxidative stress .................................................................................................... i494
Renal transplantation. Experimental, immune-tolerance of allogenic and xenogenic transplants.................................................. i502
Renal transplantation. Epidemiology and outcome.................................................................................................................................. i504
Renal transplantation. Treatment and immunosuppression .................................................................................................................. i531
Paediatric nephrology..................................................................................................................................................................................... i544
History of nephrology..................................................................................................................................................................................... i554
Patient education research and training in nephrology............................................................................................................................ i557
Sustainable kidney care .................................................................................................................................................................................. i562
Nephrology Dialysis Transplantation 36 (Supplement 1): i1–i2, 2021
10.1093/ndt/gfab142

STONES & BRAIN


performed for key proteins involved in the renal regulation of acid-base balance.
Additionally, a control group of 6 non-transplanted healthy kidneys was included in
FC001 ACIDOSIS AND ALKALI THERAPY ARE ASSOCIATED WITH the histology analysis.
TRANSCRIPTIONAL CHANGES AND ALTERED ABUNDANCE RESULTS: RNAseq analysis revealed 40 genes differentially expressed between
OF GENES INVOLVED IN CELL METABOLISM AND acidosis and no acidosis groups. While most of the genes tended to be recovered by
BICARBONATE TRANSPORT IN KIDNEY TRANSPLANT alkali therapy, only three fully recovered with bicarbonate supplementation (p-value <
RECIPIENTS 0.05 and log2(fold change) above 0.5). These genes were KCNJ15 (Kir4.2), SHMT1, and
ACADSB. Renal localization of the genes was determined using single-cell RNA
Pedro Henrique Imenez Silva1,2, Anna Wiegand3, Arezoo Daryadel1,2, sequencing data (Ransick et al., Developmental Cell, 2019, doi.org/10.1016/
Ariana Gaspert4, Giancarlo Russo5, Rudolf Peter Wuthrich3, Carsten Wagner1,2, j.devcel.2019.10.005). Most of the genes were expressed in the proximal tubule and
Nilufar Mohebbi3 were organized in the model shown in Figure 1A. Several of these genes participate in
1
University of Zurich, Institute of Physiology, Switzerland, 2National Center of cell metabolism, such as beta-oxidation, and iron, folate, and methionine metabolism.
Competence in Research NCCR Kidney.CH, Switzerland, 3University Hospital of Zurich, Moreover, the Kþ-channel Kir4.2 regulates the activity of the electrogenic sodium
Division of Nephrology, Switzerland, 4University Hospital of Zurich, Institute of bicarbonate cotransporter 1 (NBCe1, SLC4A4) and ammoniagenesis in renal proximal
Pathology and Molecular Pathology, Switzerland and 5University of Zurich, Functional tubules. Immunofluorescence analysis showed that NBCe1 expression in proximal
Genomics Center Zürich, Switzerland tubules was strongly reduced in patients who developed acidosis and was partially
recovered in patients who received alkali therapy (Figure 1B). In type B intercalated
cells, a similar pattern was observed for Pendrin (SLC26A4). No alteration in the
BACKGROUND AND AIMS: Metabolic acidosis is a common event in kidney expression of GDH (GLUD1), AE1 (SLC4A1), AQP2, CA2, RhCG (SLC42A3), and B1
transplant recipients and has been associated to a higher risk of graft loss and subunit of the HþATPase (ATP6V1B1) was observed in kidneys of treated or untreated
mortality. In patients with CKD and acidosis, alkali therapy ameliorating acidosis patients with acidosis.
appears to protect kidney function. However, it is still poorly understood how acidosis CONCLUSION: Kidney transplant recipients suffering from metabolic acidosis show
causes the detrimental effects to kidney graft function and how alkali therapy would distinct expression pattern of genes involved in cell metabolism and acid-base
interact with these mechanisms. Here we aim to identify transcriptomic alterations in transport.
kidney transplant recipients without metabolic acidosis in comparison to patients with
metabolic acidosis with and without alkali therapy. Moreover, we examined
immunolocalization of key proteins involved in acid-base base regulation in biopsies
from these patients.
METHOD: We obtained 22 biopsies of patients 4-6 years after kidney transplantation.
Among these patients, nine were not acidotic (serum [HCO3-]  22 mM), nine had
acidosis ([HCO3-] < 22 mM), and four had acidosis and received sodium bicarbonate FC002 SERUM URIC ACID AND KIDNEY DISEASE MEASURES
(alkali therapy) fully correcting acidosis. Age, immunosuppressive drugs, time after INDEPENDENTLY PREDICT CARDIOVASCULAR AND TOTAL
transplantation, and eGFR were not statistically different between groups. RNA was MORTALITY: THE URIC ACID RIGHT HEART HEALTH (URRAH)
extracted from biopsies and RNAseq was performed. Immunohistochemistry was PROJECT

Francesca Viazzi1, Elisa Russo1, Giovanna Leoncini1, Roberto Pontremoli1,


Claudio Borghi2, on behalf of the Working Group on Uric Acid and Cardiovascular
Risk of the Italian Society of Hypertension (SIIA)3
1
University of Genoa, Department of Internal Medicine, Genova, Italy, 2Alma Mater
Studiorum University of Bologna, Department of Medical and Surgical Science,
Bologna, Italy and 3Italian Society of Hypertension (SIIA), Milano (MI), Milano, Italy

BACKGROUND AND AIMS: Serum uric acid may predict the onset and progression
of kidney disease, and the occurrence of cardiovascular (CVM) and all-cause mortality
(ACM). Nevertheless, it is unclear which is the appropriate definition of hyperuricemia
in presence of chronic kidney disease and whether HU and renal impairment are
independent risk factor for mortality. Our goal was to study the relationship between
uric acid and chronic kidney disease in causing mortality.
METHOD: We retrospectively investigated a total of 21,963 patients from the URRAH
study database for whom data about cardiovascular and all-cause mortality were
available. Hyperuricemia was defined on the basis of the outcome specific cut-off
separately identified by ROC curves according to eGFR strata. The primary endpoints
were ACM and CVM, composite of the occurrence of fatal heart failure and fatal
cerebrovascular and cardiac events. We calculated the hazard ratios for eGFR, serum
uric acid, albuminuria, and their combination.
RESULTS: After a 9.8 -year follow-up, there were 1,582 (7.20%) cardiovascular events
and 3,130 (14.25%) deaths for all causes. The incidence of CVM and ACM increased in
parallel with reduction of eGFR strata and with progressively higher uric acid quartiles.
During 215,618 person-years of follow-up, the incidence rate for CVM, stratified on
the basis of eGFR (>90, between 60 and 90 and <60 ml/min) was significantly higher
in patients with HU and albuminuria (3.8, 22.1 and 19.1, respectively) as compared to
those with only one risk factor or none (0.4, 2.8 and 3.1, respectively, Figure 1). Serum
uric acid and eGFR significantly interact in determining cardiovascular and all-cause
mortality. For each SUA increase of 1 mg/dl the risk for CVM and ACM increased by
10% even after adjustment for potential confounding factors included eGFR and the
presence of albuminuria (Figure 2).
CONCLUSION: Hyperuricemia is a risk factor for cardiovascular and all-cause
mortality additively to eGFR strata and albuminuria, in patients at CV risk.

FC001 Figure 1: A. Model representing how a proximal tubule cell is disturbed in


kidney transplant recipients suffering from metabolic acidosis. Scheme shows genes
differentially expressed in patients with acidosis versus patients that did not display
acidosis. Genes in purple are recovered by alkali therapy. B. Immunofluorescence for
NBCe1 (SLC4A4). Red = NBCe1, Blue = DAPI. PT = proximal tubule, G = glomerulus.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC003 HYPERURICEMIA HAS VASOACTIVE EFFECTS IN


CHOLESTEROL CRYSTAL-INDUCED ACUTE KIDNEY INJURY

Luying Yang1, Elmina Mammadova-Bach1, Attila Braun2, Thomas Gudermann2,


Hans-Joachim Anders1, Stefanie Steiger1
1
Hospital of the Ludwig Maximilian University of Munich, Division of Nephrology,
Department of Medicine IV, Munich, Germany and 2Ludwig Maximilian University of
Munich, Walther-Straub-Institute for Pharmacology and Toxicology, Munich, Germany

BACKGROUND AND AIMS: Numerous observational studies have reported an


association between hyperuricemia (HU) and cardiovascular disease where
atherosclerosis is a leading cause. In advanced atherosclerosis, cholesterol crystal (CC)
embolism is a life-threatening complication with an average mortality of 62.8%.
Clinical manifestations include skin necrosis, intestinal injury and acute kidney injury
(AKI). Autopsies and tissue biopsies reveal CC inside the arterial lumen. In a new
model of CC-induced AKI, we recently found that fibrin clots formed around CC
obstruct peripheral arteries and cause tissue infarction and organ failure. However, the
role of asymptomatic HU in CC-induced AKI is currently unknown. Thus, we
hypothesized that asymptomatic HU improves the outcomes after CC-induced AKI.
METHOD: In vivo, 6 weeks old Alb-creERT2;Glut9lox/lox and Glut9lox/lox control mice
were intraperitoneally injected with tamoxifen to deplete hepatic Glut9 expression.
FC002 Figure 1: Survival without cardiovascular (a) and all-cause mortality (b) on the Both groups of mice were placed on a standard chow diet enriched with inosine for two
basis of eGFR strata and the presence/absence of hyperuricemia weeks. Afterward, a solution of CCs was injected into the left kidney arteries of mice to
induce AKI. Serum and kidneys were collected 24 hours later, and kidney function,
infarct size and kidney injury evaluated using GFR measurement, colorimetric assays,
ELISA and immunohistochemistry of kidney sections. For in vitro studies, we isolated
platelets from healthy mice and cultured them in the presence or absence of soluble
uric acid (sUA) prior to CC activation. After stimulation, platelet aggregation assays
and flow cytometry were performed.
RESULTS: Our in vivo data showed that Alb-creERT2;Glut9lox/lox mice developed
FC002 Figure 2: Cumulative incidence of cardiovascular (a) and all-cause mortality (b) asymptomatic HU without kidney impairment (serum UA levels 9-15 mg/dL), while
on the basis of eGFR strata and presence/absence of hyperuricemia. Glut9lox/lox control mice remained healthy. HU mice displayed a rapid decline in GFR
A-, Normoalbuminuria; Aþ, Albuminuria; HU-, no hyperuricemia; HUþ, of approx. 80% as compared to only 30% in healthy mice after CC-induced AKI, which
hyperuricemia specific for eGFR strata and outcome. was in line with increased serum BUN and IL-6 levels. The rapid GFR decline was due
to vasoconstriction in arteries of the contralateral kidney as determined by aSMA/
fibrin staining and a reduced ratio of lumen versus artery area in mice with HU after
AKI. HU mice also had significantly less kidney infarct size as well as reduced kidney
injury (necrosis and edema) and arterial occlusion. The in vitro data showed that sUA
had no impact on platelet aggregation, activation and degranulation as compared to
medium control in response to CCs.
CONCLUSION: We now show that HU has vasoconstrictive effects in the
contralateral kidney by reducing GFR, while at the same time protects mice from CC-
induced AKI suggesting a compensatory physiological mechanism of autoregulation to
protect nephrons. On the other hand, in patients with chronic kidney disease, HU-
related vasoconstriction might lead to increased arterial blood pressure; thus,
increasing the risk for cardiovascular complications due to platelet activation and
aggregation.

i2 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i3–i4, 2021
10.1093/ndt/gfab124

CELLS & IMMUNITY

FC005 DEPOSITION OF PLATELET-DERIVED MICRO-PARTICLES IN


FC004 PHOSPHATE FACILITATES PHOSPHATURIA BY PIT-2- PODOCYTES CONTRIBUTES TO DIABETIC NEPHROPATHY
MEDIATED ACTIVATION OF ERK1/2 SIGNALLING
INTERNALIZING NAPI-2A FROM THE APICAL BRUSH Sijia Huang1, Jian Lu1, Pei Pei Chen1, Jia Xiu Zhang1, Xue Qi Li1, Bicheng Liu1,
BORDER MEMBRANE INDEPENDENT OF FGF23 Kun Ling Ma1
1
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nephrology,
Stefanie Walter1, Isabel Vogt1, Roland Schmitt2, Dieter Haffner1, Nanjing, P.R. China
Maren Leifheit-Nestler1
1
Hannover Medical School, Department of Paediatric Kidney, Liver and Metabolic BACKGROUND AND AIMS: Diabetic nephropathy (DN) is the leading cause of
Diseases, Hannover, Germany and 2Hannover Medical School, Department of end-stage renal disease in the developed world. Podocyte injury has been shown to be a
Nephrology and Hypertension, Hannover, Germany critical cellular event in the progression of DN. Our previous studies demonstrated that
platelet-derived microparticles (PMPs) mediated endothelial injury in diabetic rats.
BACKGROUND AND AIMS: Increased phosphate load stimulates the secretion of Therefore, this study aimed to investigate whether the PMPs deposit in podocytes and
fibroblast growth factor (FGF) 23 in the bone leading to decreased phosphate its potential effects on podocyte injury in DN.
reabsorption in the kidney. FGF23 activates FGFR1/Klotho/ERK1/2 signalling in METHOD: Deposition of PMPs in podocytes was checked by immunofluorescent
proximal tubule cells to suppress type II sodium phosphate transporters NaPi-2a and staining and electron microscopy. Renal pathological change and ultra-microstructure
NaPi-2c in the apical brush border membrane (BBM) resulting in lower serum were respectively checked by periodic acid-schiff staining and electron microscopy.
phosphate levels. The type III sodium-dependent phosphate transporters PiT-1 and The protein expression of inflammatory cytokines and extracellular matrix was
PiT-2 are expressed in key organs of phosphate regulation and were shown to activate measured by immunohistochemical staining and Western blot.
ERK1/2 in osseous cells in the presence of high extracellular phosphate. Furthermore, RESULTS: The PMPs were found to be widely deposited in podocytes of glomeruli in
PiT-2 was shown to be responsible for the phosphate-dependent FGF23 secretion in diabetic patients and animal models and closely associated with progression of DN.
bone cells. Whether phosphate itself can be sensed by kidney cells and stimulate its Interestingly, aspirin treatment significantly inhibited accumulation of PMPs in
own excretion remains unknown. glomeruli of diabetic rats, accompanied with alleviated mesangial matrix expansion,
The aim of our study was to examine the molecular mechanism regulating renal fusion of foot processes, decreased protein expression of inflammatory cytokines and
phosphate transport in the setting of chronic oral phosphate loading in mice and to extracellular matrix secretion. The in vitro study further confirmed the deposition of
analyse phosphate sensing as well as phosphaturic actions of phosphate itself PMPs in podocytes. Moreover, PMPs stimulation induced phenotype transition of
independent of FGF23. podocytes through decreased protein expression of podocin and increased protein
METHOD: First, eight-week-old male C57BL/6 wildtype mice were fed a 2% high expression of a-SMA and fibronectin, which was correlated with increased production
phosphate diet (HPD) or a 0.8% normal phosphate diet (NPD). Mice were sacrificed of inflammatory cytokines.
after six months and blood and urine were collected to determine parameters of CONCLUSION: Our findings for the first time demonstrated that deposition of PMPs
phosphate homeostasis. Kidneys were isolated to evaluate the HPD-induced regulation in podocytes contributed to the development of DN.
of phosphate transporters by qPCR, immunoblot and histological analyses. Second,
murine proximal tubule (mPT) cells were stimulated with either phosphate or FGF23
in the presence or absence of Foscarnet, as an inhibitor of phosphate transporters, to
verify the molecular mechanism of phosphate sensing. FC006 PP2A PHOSPHATASE INHIBITION IS ANTI-FIBROTIC
RESULTS: Although, HPD caused significantly elevated circulating levels of intact THROUGH SER77 PHOSPHORYLATION-MEDIATED ARNT/
FGF23 which resulted in hyperphosphaturia, serum phosphate levels were still ARNT HOMODIMER FORMATION
enhanced compared to NPD-fed mice. Renal Klotho protein expression was
significantly reduced in HPD mice and histological staining demonstrated lower Gunsmaa Nyamsuren1, Gregor Christof Rapp1, Björn Tampe1, Michael Zeisberg1
1
Klotho accumulation in proximal and distal tubule cells, while FGFR1 was not altered. University of Goettingen Medical Center, Nephrology & Rheumatology, Goettingen,
The FGF23/Klotho/FGFR1 downstream pathway revealed neither a clear activation of Germany
the ERK1/2 signalling pathway nor induction of the transcription factor Egr-1 due to
HPD. Nevertheless, NaPi-2a mRNA expression was significantly reduced in HPD-fed BACKGROUND AND AIMS: Aryl hydrocarbon receptor nuclear translocator
mice compared to NPD group and NaPi-2c was unchanged. The amount of NaPi-2a (ARNT) mediates anti-fibrotic activity in kidney and liver through induction of ALK3-
protein in isolated BBM vesicles of HPD-fed mice was lower compared to NPD and receptor expression and subsequently increased Smad1/5/8 signaling. While expression
immunofluorescent staining confirmed the internalisation of NaPi-2a from the apical of ARNT can be pharmacologically induced by sub-immunosuppressive doses of
BBM. Among the type III sodium-dependent phosphate cotransporters, renal PiT-1 FK506 or by GPI1046, its anti-fibrotic activity is only realized when ARNT-ARNT
mRNA expression was not altered in HPD-fed mice, but PiT-2 was significantly homodimers form, as opposed to formation of ARNT-AHR or ARNT-HIF1a
increased compared to NPD group and immunofluorescent staining revealed an heterodimers. Mechanisms underlying ARNTs dimerization decision to specifically
enhanced localization of PiT-2 on the basolateral membrane of proximal tubule cells. form ARNT-ARNT homodimers and possible cues to specifically induce ARNT
Stimulation of mPTs with phosphate or FGF23 increased the expression of PiT-2, homodimerization have been previously unknown. We here aimed to elucidate the
induced the phosphorylation of ERK1/2 and decreased NaPi-2a in vitro. The pre- molecular mechanisms underlying control of ARNT dimerization decision and to
treatment with Foscarnet blunted the phosphate-mediated activation of ERK1/2 explore its therapeutic potential.
signalling pathway, but not the FGF23-induced effects, suggesting a direct phosphate METHOD: We analyzed dimerization of recombinant and native ARNT by
transporter-regulating mechanism of high phosphate in renal proximal tubule cells. immunoprecipitation, MALDI-TOF mass spectrometry, and LS-MS/MS analysis and
CONCLUSION: A chronic high dietary intake of phosphate results in downregulation proximity ligation assay. Phosphorylation sites were mapped through generation of
of renal Klotho causing hyperphosphatemia, suggesting in part a renal resistance of phosphorylation site mutants and through pharmacological inhibition. For in vivo
FGF23/Klotho signalling pathway. However, HPD-induced internalization NaPi-2a analysis we challenged mice with model of unilateral ureter obstruction and carbon
from the apical BBM pointing to an FGF23-independent mechanism regulating tetrachloride to induce fibrosis in kidney and liver.
phosphate reabsorption. Our data indicate that in the settings of high phosphate- RESULTS: Here we report that inhibition of PP2A phosphatase activity increases
mediated renal resistance of FGF23, phosphate itself may stimulate its urinary intracellular accumulation of ARNT-ARNT homodimers. This effect is dependent on
secretion via PiT-2-mediated activation of ERK1/2 signalling pathway which results in enhanced ARNT-ARNT homodimerization and decreased ARNT proteolytic
NaPi-2a downregulation and hyperphosphaturia independent of FGF23. degradation, but independent of ARNT transcription (which remains unchanged upon
PP2A inhibition). We further identify that Ser77 phosphorylation plays a critical role
in ARNT homodimerization, as ARNT-ARNT homodimers do not form with Ser77/
Asp-mutant ARNT proteins. In light of previous studies which identified anti-fibrotic
activity upon increased ARNT expression, we further demonstrate attenuated fibrosis
upon monotherapy with the PP2A inhibitor LB100, and additive anti-fibrotic activities
upon combination with pharmacological inducers of ARNT expression FK506 or
GPI1046 in murine models of kidney and liver fibrosis.
CONCLUSION: Our study provides additional evidence for the anti-fibrotic activity of
ARNT and reveals Ser77 phosphorylation as a novel pharmacological target to realize
the therapeutic potential of increased ARNT transactivation activity.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC007 CKD DERIVED MUSCLE CELLS RETAIN PHENOTYPIC experimental wells and proliferated for 5 days or until confluent. Once confluent cells
CHARACTERISTICS OF UREIC SARCOPENIA: THE NEXT were differentiated through serum restriction to form mature myotubes (muscle fiber
STEP IN CELLULAR MODELLING FOR THERAPEUTIC like structures) for a minimum of 7 days. Sampling time points were taken throughout
SCREENING to allow for the analysis of markers of proliferation, myogenic capacity, maturation,
inflammation, protein synthesis and protein degradation. Further experiments were
Luke Baker1, Thomas O’Sullivan2, Kathrine Robinson2, Matthew Graham- conducted on mature myotubes, where myotubes from both donor groups were
Brown3,4, Robert Ashford5,6, Alice Smith1,4, Emma Watson3 exposed to either 0.4nM or 100nM of IGF-1 and p-Akt and protein synthesis
1
University of Leicester, Health Sciences, Leicester, United Kingdom, 2University of quantified to investigate the presence of anabolic resistance in CKD derived cells.
Leicester, Respiratory Sicences, Leicester, United Kingdom, 3University of Leicester, RESULTS: We report here that muscle cells derived from CKD patients have
Cardiovascular Sciences, Leicester, United Kingdom, 4University Hospitals Leicester, John significantly higher levels of markers of proliferation (p = 0.041) and myogenic
Walls Renal Unit, Leicester, United Kingdom, 5University of Leicester, Cancer Studies, capacity (p = 0.034). Regarding myotube maturity, lower ratios of mature Myosin
Leicester, United Kingdom and 6University Hospitals Leicester, Leicester Orthopaedics, Heavy Chains were noted in CKD derived cells in comparison with CON derived cells
Leicester, United Kingdom (p = 0.012). On analysis of rates of protein synthesis and degradation in mature
myotubes, no differences were noted in the rate of protein synthesis or the p-Akt in
BACKGROUND AND AIMS: Skeletal muscle wasting and dysfunction is a basal conditions (p > 0.05), however, significant elevations were noted in both protein
debilitating co-morbidity for people who suffer from kidney disease. To date research degradation rates (p = 0.014) and the mRNA gene expression levels of E3-ligases (p =
has sought to understand the mechanisms by which this occurs, in order to inform the 0.016). On analysis of the experimentation investigating anabolic resistance, a degree of
prescription of required interventions in order to counteract such effects. Though anabolic resistance was noted with inhibited p-Akt (p = 0.019) and protein synthesis (p
progress has been made through in-vivo physiology research, the lack of an in-vitro  0.001) noted in cells derived from CKD cells in comparison to CON cells, when
translational model which replicates the phenotype noted in this patient group has exposed to both doses of IGF-1.
hindered progression. The aim of the work presented was to systematically define a CONCLUSION: Here we describe for the first time a human derived, disease specific
human derived skeletal muscle model with cells derived from people with kidney model of uremic sarcopenia with many of the phenotypic traits noted in this
disease, in order to provide a test bed for the future screening of novel therapeutics and population being maintained, such as elevated protein degradation and anabolic
the investigation of the dynamic processes involved in the unwanted characteristics inhibition. This work not only provides a translational mechanistic insight into the
observed in this population. cellular underpinnings of uremic sarcopenia but will allow for the future screening of
METHOD: Skeletal muscle biopsies were taken from the vastus lateralis of non- novel therapeutics, in order manipulate the dynamic processes which lead to the
dialysis dependent CKD patients (CKD; n=12) and Controls (CON; n=12), matched debilitations noted in CKD populations.
for age, sex, ethnicity and physical activity levels. Biopsy samples were subject to an
enzymatic digestion method to enable the isolation of the muscle derived cells required
for cellular experimentation. Once taken through the cell cycle, cells were plated into

i4 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i5–i6, 2021
10.1093/ndt/gfab125

CYSTS & CANCER

FC009 CIRCULATING BIOMARKERS OF COLLAGEN TURNOVER ARE


FC008 INTERDEPENDENT REGULATION OF POLYCYSTIN ASSOCIATED WITH DISEASE SEVERITY IN PATIENTS WITH
EXPRESSION INFLUENCES STARVATION-INDUCED ADPKD
AUTOPHAGY AND CELL DEATH
Nadja Sparding1,2, Federica Genovese1, Morten A. Karsdal1, Judith E. Heida3,
Jean-Paul Decuypere1, Dorien Van Giel2, Peter Janssens3, Ke Dong4, Esther Meijer3, Ronald Gansevoort3, Daniel G. K. Rasmussen1
Stefan Somlo4, Yiqiang Cai4, Djalila Mekahli5, Rudi Vennekens2 1
Nordic Bioscience, Fibrosis, Renal and Cardiovascular Research, Herlev, Denmark,
1 2
KU Leuven, Development and Regeneration, Leuven, Belgium, 2KU Leuven, Cellular Faculty of Health and Medical Science, University of Copenhagen, Biomedical
and Molecular Medicine, Leuven, Belgium, 3University Hospitals Brussels, Nephrology, Sciences, Copenhagen, Denmark and 3University Medical Center Groningen,
Jette, Belgium, 4Yale University, Internal Medicine, New Haven CT, United States of Nephrology Department, Groningen, The Netherlands
America and 5University Hospitals Leuven, Pediatric Nephrology, Leuven, Belgium
BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease
BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited kidney disease characterized by development and growth of
(ADPKD) is mainly caused by mutations in either PKD1 (ca. 78%) or PKD2 (ca. 15%), cysts leading to loss of kidney function. In patients with ADPKD, fibrosis has been
encoding for the proteins polycystin-1 (PC1) or polycystin-2 (PC2), respectively. associated with the expansion of cysts and with an increased rate of progression to end-
Mutations in PKD1 generally lead to a more severe disease progression compared to stage kidney disease (ESKD). Fibrosis is characterized by an imbalanced turnover of
PKD2 patients. The exact function of the polycystins in cyst formation remains extracellular matrix (ECM) components such as collagens. Existing biomarkers of
unclear, but it is clear that the levels of PC1 and PC2 are inversely correlated to cyst ADPKD have limited prognostic ability and the ECM can be a source of novel
formation. Moreover, renal stress has been proposed to enhance cystogenesis. We biomarkers of disease progression. In the current study, we investigated the cross-
therefore aimed to investigate the cellular response towards nutritional stress in mouse sectional association of collagen biomarkers with markers of disease severity in patients
inner medullary collecting duct cells (mIMCDs), either wild-type (WT) or lacking PC1 with ADPKD.
or PC2 (PC1KO or PC2KO), and unique human urine-derived proximal tubular METHOD: Collagen type I, III and VI formation as well as collagen type III
epithelial cells (PTECs) of early-stage ADPKD patients with truncating PKD1 degradation were assessed with the PRO-C1, PRO-C3, PRO-C6 and C3M enzyme-
mutations versus healthy individuals, with a focus on cell survival (autophagy) and cell linked immunosorbent assays (ELISAs). The four biomarkers were measured in serum
death. from 311 patients with ADPKD from the DIPAK-1 (NCT01616927) study at baseline.
METHOD: Cell death was assessed with Cytotox green-based live cell imaging in the Biomarker levels were compared with levels in serum of 38 healthy controls matched
Incucyte, by trypane blue exclusion and by analyzing the levels of cleaved Caspase 3. for sex and age. The difference between the ADPKD and the control group was
Autophagy was measured by LC3 immunoblotting and by counting GFP-LC3 punctae. assessed by Kruskal-Wallis test. The association of the collagen biomarkers with kidney
Autophagy was blocked with Bafilomycin A1. To modulate the levels of PC1 and PC2, function (eGFR) and height adjusted total kidney volume (htTKV) was assessed with
transient overexpression of human PC1 or siRNA-mediated knockdown of PC2 was uni- and multivariate regression analysis. Data was log-transformed if appropriate.
performed. RESULTS: Biomarker levels in the ADPKD patients (age, median (IQR): 49 (43-54)
RESULTS: During chronic starvation, cell death was reduced and autophagy was years; sex: 53% female) were compared with levels in matched healthy controls (age,
increased in mouse PC1- and PC2-deficient mIMCDs. This was validated in human median (IQR): 49 (43-56) years; sex: 53% female). In patients with ADPKD both PRO-
cells from early-stage ADPKD patients. Autophagy inhibition restored cell death C3 and PRO-C6 levels were increased compared to healthy controls (ADPKD vs
resistance in KO cells, implying that decrease in cell death was caused by autophagy controls, PRO-C3 median (IQR): 12.8 (10.5-15.8) vs 8.4 (7.5-10.1) ng/mL; P<0.0001;
upregulation in PC1- and PC2KO cells. Interestingly, PC2 expression was increased in PRO-C6 median (IQR): 11.3 (9.4-13.7) vs 6.8 (5.4-8.8) ng/mL; P<0.0001). PRO-C1
PC1KO cells, while PC2KO displayed a downregulation of PC1. Although PC2 is levels were decreased in patients with ADPKD compared to controls (ADPKD vs
known to regulate autophagy, PC2 knockdown did not reduce autophagy in PC1KO controls, PRO-C1 median (IQR): 47.1 (31.9-65.0) vs 110.9 (83.0-176.4) ng/mL;
cells, while the effect in PC2KO could be reversed by overexpression of PC1. P<0.0001) l, whereas there was no difference in C3M levels between the two groups
CONCLUSION: These findings indicate that PC1 levels determine the transition from (ADPKD vs controls, C3M median (IQR): 11.4 (9.7-13.7) vs 10.3 (8.7-12.5) ng/mL;
renal cell survival to death, leading to enhanced survival of ADPKD cells during P=0.11). None of the investigated biomarkers was associated with TKV, whereas PRO-
nutritional stress. Moreover, PC1 also indirectly influences this process by regulating C3 and PRO-C6 were associated with eGFR in univariate regression analysis (PRO-C3,
PC1 levels during starvation. Our findings imply that in early stage ADPKD, cells with P<0.01; PRO-C6, P<0.001) but not with htTKV (PRO-C3, P=0.49; PRO-C6, P=0.32).
the lowest polycystin levels (which are most prone to form cysts) are more resistant to In a multivariate regression analysis adjusting for sex, age, htTKV and PKD mutation,
stress by autophagy upregulation. This is important, as renal stress is inherent to the both PRO-C3 and PRO-C6 showed a significant negative association with eGFR (both
cystic environment and has been proposed as an additional trigger in cystogenesis. P<0.001).
CONCLUSION: While biomarkers of tubulointerstitial fibrosis (PRO-C3 and PRO-
C6) were elevated in circulation in ADPKD patients, possibly reflecting an elevated
fibrosis activity in the kidneys, levels of collagen type I formation (PRO-C1) were
lower, possibly reflecting a suppressed bone turnover previously observed in patients
with ADPKD. Both PRO-C3 and PRO-C6 showed an independent association with
eGFR, but not with htTKV, when adjusting for known determinants of disease severity.
Such biomarkers deserve further investigation in this patient population, especially
concerning their prognostic abilities, as fibrosis is acknowledged as a driving force in
progression to ESKD.

FC010 4-WEEK ANTIBIOTIC THERAPY PREVENTS RECURRENT


RENAL CYST INFECTIONS IN AUTOSOMAL DOMINANT
POLYCYSTIC KIDNEY DISEASE

Julien Dang1, Bertrand Knebelmann1, Caroline Charlier2


1
Necker-Enfants malades Hospital, Assistance Publique – Hôpitaux de Paris, Nephrology
and Kidney Transplant Department, PARIS, France and 2Necker-Enfants malades
Hospital, Assistance Publique – Hôpitaux de Paris, Infectious Diseases Department,
Paris, France

BACKGROUND AND AIMS: Renal cyst infection (CI) is a major complication of


autosomal dominant polycystic kidney disease (ADPKD), associated with frequent
hospitalization, worsening of kidney function and significant mortality. Data regarding
treatment are scarce and recommendations only expert-based, with low level of
evidence. Prolonged treatment duration and use of lipid-soluble antibiotics may

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

increase antibiotic concentration in infected kidney cysts. However, benefits of this CONCLUSION: Treatment of kidney CI should last 28 days and include when
strategy have never been investigated in clinical practice. possible lipid soluble antibiotics.
METHOD: We undertook a monocentric retrospective study of CI in ADPKD patients
from 2000 to 2018. CI were classified as “definite” (microbiologically proven),
“probable” (clinical/biological and radiological signs) or possible (clinical/biological
signs). Determinants of treatment failure and recurrences were studied.
RESULTS: 139 CI (11 “definite”, 74 “probable”, 54 “possible”) were compiled among
90 patients. Median age was 53 years. 28/90 (31%) were kidney transplant recipients.
Escherichia coli was identified in 89/106 (84%) episodes. Treatment failure was
reported in 22/139 (16%), and found associated with cyst diameter >5cm (80% vs 36%,
P<0.01), cyst wall thickening (53% vs 12%, P<0.001), cyst septations (18% vs 1%,
P<0.01), intracystic gas (18% vs 1%, P<0.01), kidney abscess (35% vs 1%, P<0.001),
higher C-reactive protein level (210 [140-358] vs 145 [99-213] mg/L, P<0.01) or
documentation of Staphylococcus aureus and lugdunensis (P<0.001). Recurrence was
reported in 20/139 (14%) cases within 1-year follow-up. Recurrence rate was lower in
patients treated with lipid soluble antibiotics than with non-lipid soluble antibiotics
(HR=0.34 [0.12-0.97], p=0.045). Most importantly, cases with definite and probable CI
experienced significantly fewer recurrences when treated with longer treatment
duration: 81% for treatment <21 days, 47% for 21-27 days, but only 2% for 28 days
(p<0.0001).

i6 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i7–i8, 2021
10.1093/ndt/gfab131

GENES & KIDNEY mild ADPKD/PCLD, we identified ALG6 as a new candidate gene. ALG6 bears a high
resemblance to other genes implicated in this phenotype in recent years. Through the
100,000 Genomes Project and collaborators we identified three additional patients with
kidney and/or liver cysts carrying a suspected deleterious variant in ALG6.
FC011 KIDNEYNETWORK: USING KIDNEY DERIVED GENE CONCLUSION: We present KidneyNetwork, a kidney specific co-expression network
EXPRESSION DATA TO PREDICT AND PRIORITIZE NOVEL that accurately predicts what genes have kidney-specific functions and may result in
GENES INVOLVED IN KIDNEY DISEASE kidney disease. Gene-phenotype associations of genes unknown for kidney-related
phenotypes can be predicted by KidneyNetwork. We show the added value of
Floranne Boulogne1, Laura Claus2, Henry Wiersma1, Roy Oelen1, Floor Schukking1, KidneyNetwork by applying it to exome sequencing data of kidney disease patients
Niek De Klein1, Shuang Li1, Harm-Jan Westra1, Bert Van der Zwaag2, Franka Van without a molecular diagnosis and consequently we propose ALG6 as a promising
Reekum2, Jan Halbritter3, Nine Knoers1, Genomics England Research candidate gene. KidneyNetwork can be applied to clinically unsolved kidney disease
Consortium4, Patrick Deelen1,2, Lude Franke1, Albertien M. Van Eerde2 cases, but it can also be used by researchers to gain insight into individual genes to
1
University Medical Center Groningen, Genetics, Groningen, The Netherlands, 2University better understand kidney physiology and pathophysiology.
Medical Center Utrecht, Genetics, Utrecht, The Netherlands, 3University Hospital Leipzig, ACKNOWLEDGMENTS: This research was made possible through access to the data and
Internal Medicine, Leipzig, Germany and 4Genomics England, United Kingdom findings generated by the 100,000 Genomes Project; http://www.genomicsengland.co.uk.

BACKGROUND AND AIMS: Genetic testing in patients with suspected hereditary


kidney disease does not always reveal the genetic cause for the patient’s disorder.
Potentially pathogenic variants can reside in genes that are not known to be involved in
kidney disease, which makes it difficult to prioritize and interpret the relevance of these FC012 PRIMARY KIDNEY DISEASE IMPACTS OUTCOME IN CKD
variants. As such, there is a clear need for methods that predict the phenotypic PREGNANCIES: COMPLICATIONS IN COL4A3-5 RELATED
consequences of gene expression in a way that is as unbiased as possible. To help DISEASE (ALPORT SYNDROME) VS OTHER CKD
identify candidate genes we have developed KidneyNetwork, in which tissue-specific PREGNANCIES
expression is utilized to predict kidney-specific gene functions.
METHOD: We combined gene co-expression in 878 publicly available kidney RNA- Rozemarijn Snoek1,2, Margriet Gosselink1,2, Liffert Vogt3, Margriet De Jong4,
sequencing samples with the co-expression of a multi-tissue RNA-sequencing dataset of Agne Cerkauskaite5, Renee Vollenberg2, Nine Knoers4, Titia Lely1, Albertien
31,499 samples to build KidneyNetwork. The expression patterns were used to predict M. Van Eerde2
1
which genes have a kidney-related function, and which (disease) phenotypes might be University Medical Center Utrecht, Department of Obstetrics, The Netherlands,
2
caused when these genes are mutated. By integrating the information from the HPO University Medical Center Utrecht, Department of Clinical Genetics, The Netherlands,
3
database, in which known phenotypic consequences of disease genes are annotated, with the Amsterdam UMC, Department of Nephrology, The Netherlands, 4University Medical
gene co-expression network we obtained prediction scores for each gene per HPO term. As Center Groningen, Department of Clinical Genetics, The Netherlands and 5Vilnius
proof of principle, we applied KidneyNetwork to prioritize variants in exome-sequencing University Hospital, Department of Nephrology, Lithuania
data from 13 kidney disease patients without a genetic diagnosis.
RESULTS: We assessed the prediction performance of KidneyNetwork by comparing BACKGROUND AND AIMS: Chronic kidney disease (CKD) affects approximately
it to GeneNetwork, a multi-tissue co-expression network we previously developed. In 3% of pregnant women. CKD increases the risk of pregnancy complications such as
KidneyNetwork, we observe a significantly improved prediction accuracy of kidney- prematurity, low birthweight and pre-eclampsia. Also, kidney function can deteriorate
related HPO-terms, as well as an increase in the total number of significantly predicted more quickly due to pregnancy. There is limited knowledge on pregnancy outcomes in
kidney-related HPO-terms (figure 1).To examine its clinical utility, we applied specific kidney diseases. The aim of the ALPART network is to study pregnancy
KidneyNetwork to 13 patients with a suspected hereditary kidney disease without a outcomes differentiated by CKD aetiology. We have started with COLA3-5 related
genetic diagnosis. Based on the HPO terms “Renal cyst” and “Hepatic cysts”, combined disease (Alport syndrome), which is one of the most prevalent monogenic kidney
with a list of potentially damaging variants in one of the undiagnosed patients with diseases. Comparing outcomes in COLA3-5 related disease to pregnancies with other

FC011 Figure 1: Kidney Network performs better for kidney-related HPO terms than GeneNetwork. A) 27% of kidney-related phenotypes are predicted significantly better using
KidneyNetwork, as compared to GeneNetwork. B) Density plots of gene prediction scores within two of the most improved phenotypes, hypomagnesemia and tubulointerstitial fib-
rosis, show higher prediction values for genes annotated for the phenotype, while also predicting potential unknown candidate genes. The networks predicted using KidneyNetwork
show more and stronger correlations between the annotated genes than the networks predicted using GeneNetwork.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

CKD aetiologies allows us to investigate whether this specific diagnosis impacts time course and magnitude of reduction was seen in patients <18 years at 64.5% (3.3)
outcome in CKD pregnancies. (N=38), and 18 years old at 59.8% (4.4) (N=16). The oxalate reductions observed in
METHOD: The ALPART network is an international 15-center network, which aims random spot urine samples were comparable to those observed from 24-hour urine
to include 200 COLA3-5 related disease pregnancies. In this intermediary analysis, we collections. The overall mean (SEM) percent reduction in urinary oxalate excretion
present data on 109 pregnancies from 68 women with COLA3-5 related disease. We from 24-hour collections was 63.8% (2.6) across all ages (N=40), 63.2% (3.5) in the
compared outcomes to a cohort of 457 CKD stage 1-2 patients (a similar CKD stage as <18 group (N=23) and 64.8% (3.9) in the 18 group (N=17). The overall mean (SEM)
our cohort) of diverse aetiology from a 2015 Italian study and 159,924 women from the percent reduction in plasma oxalate from baseline to Month 6 was 39.5% (3.7) across
general Dutch population. all ages (N=44), with similar reductions of 39.4% (4.6) and 39.7% (6.5) in patients <18
RESULTS: The main pregnancy and kidney outcomes are presented in Figure 1. Foetal (N=30) and 18 (N=14) years of age, respectively. eGFR was calculated for all patients
outcomes were better in COLA3-5 pregnancies than in pregnancies of women with 12 months of age and remained stable in both age groups during the 6 months of
CKD stage 1-2 of diverse aetiology. We saw less prematurity (17% vs 36% respectively) treatment with lumasiran. The 57 patients had a cumulative exposure of 27.1 patient-
and a higher mean birthweight of 3216 6 663 gram compared to 2768 6 680 in the years and 227 doses were given. Adverse events were reported in 86% of all patients,
Italian cohort. Maternal kidney outcomes should be interpreted with caution (>30% 88% of patients <18, and 82% of patients 18 years of age. All adverse events were
missing data): proteinuria (73%) and hypertension (30%) were more frequent in graded as mild or moderate in severity by the investigator. One patient had a serious
COLA3-5 pregnancies than the Italian cohort. In the ALPART cohort, 10% developed adverse event of viral infection that was not related to lumasiran. In all patients, the
severe hypertension. Median eGFR was not impacted by pregnancy and decline of most common adverse events related to lumasiran were mild, transient, injection site
eGFR before and after pregnancy were not significantly different between groups. reactions, experienced by 30% of all patients, 23% of patients <18 and 47% of patients
18 years of age. No treatment interruptions or discontinuations related to lumasiran
or deaths occurred.
CONCLUSION: Lumasiran reduced urinary and plasma oxalate to a similar degree in
pediatric and adult patients with PH1 enrolled in the Phase 3 studies ILLUMINATE-A
and ILLUMINATE-B. Reductions in urinary oxalate were similar between random
spot urine samples and valid 24-hour urine collections. Overall safety was comparable
between pediatric and adult patients.

FC014 INFLUENCE OF GENETIC VARIATION IN SLC7A13/AGT1 IN


HUMAN CYSTINURIA

Ria Schönauer1, Anna Seidel1, Linda Pöschla1, Elena Hantmann1,


Soumeya Bekri2, Bertrand Knebelmann3, John Sayer4, Ryuichi Ohgaki5,
FC012 Figure 1: Kidney and fetal outcomes in n=109 pregnancies of n=68 women Jan Halbritter1
with COL4A3-5 related disease, compared to the CKD stage 1-2 population (Piccoli et 1
University Hospital Leipzig, Department of Internal Medicine, Division of Nephrology,
al., 2015) and the general Dutch population. The striped bars represent outcomes in
Leipzig, Germany, 2Hospital Center University De Rouen, Institut de Biologie Clinique,
the COL4A3-5 group that have a missing data percentage of >30%. The number of
Rouen, France, 3Hôpital Necker-Enfants Malades, Service de Néphrologie-Dialyse Adulte,
cases the outcome rates are based on in the COL4A3-5 group are noted in the table.
Paris, France, 4University of Newcastle upon Tyne, Institute of Human Genetics,
CKD=chronic kidney disease. SGA=small for gestational age.
Newcastle upon Tyne, United Kingdom and 5Osaka University, Division of Medicine,
Osaka, Japan
CONCLUSION: Fetal outcomes in pregnancies with COLA3-5 related disease seem to
be more favorable than in a cohort with mixed cause of CKD. In this intermediary BACKGROUND AND AIMS: Cystinuria (CU) is an inherited renal disorder based on
analysis, proteinuria levels and frequency of new-onset hypertension in pregnancy are urinary wasting of dibasic amino acids, urinary precipitation, and consecutive cystine
higher. There is no significant eGFR loss during pregnancy or increased eGFR stone formation. It is caused by pathogenic variants in two distinct disease genes,
deterioration in the long-term. The differences between COLA3-5 and general CKD SLC3A1 and SLC7A9, both of which encode subunits of a heterodimeric tubular amino
pregnancies underscore the importance of investigating pregnancy outcomes in acid transporter, rBAT/SLC3A1 and BAT1/SLC7A9, located at the apical membrane of
specific kidney disease phenotypes to ensure adequate (pre-) pregnancy counselling proximal renal tubules. CU is marked by incomplete penetrance and substantial
and care. disease variability. Recently, a novel cystine transporter, consisting of the light chain
AGT1/SLC7A13 and its heterodimeric partner rBAT/SLC3A1 has been identified in
the S3 segment of murine proximal tubules. In this study, we aim at evaluating the role
of AGT1 in cystinuric patients with or without mutations in either SLC3A1 or SLC7A9,
FC013 LUMASIRAN DEMONSTRATED COMPARABLE OXALATE analyzing the role of AGT1/SLC7A13 as novel disease gene or genetic modifier in CU.
REDUCTION AND SAFETY IN CHILDREN AND ADULTS WITH METHOD: A multicenter European CU-cohort comprising 132 individuals was screened
PRIMARY HYPEROXALURIA TYPE 1 for pathogenic variants in SLC3A1, SLC7A9, and SLC7A13 using high-throughput
multiplex PCR-based amplification and next-generation sequencing (MiSeq Illumina)
Hadas Shasha-Lavsky1, Sander Garrelfs2, David Sas3, John Lieske4, Taylor Ngo5, followed by multiplex ligation-dependent probe amplification (MLPA) of SLC3A1 and
Nune Makarova5, John Gansner5, Tracy McGregor5, Yaacov Frishberg6 SLC7A9. For functional in vitro studies, epitope-tagged human and murine rBAT and
1
Galilee Medical Center, Pediatric Nephrology Unit, Nahariya, Israel, 2Emma Children’s AGT1 proteins were transiently expressed in different cell systems. Heterodimer complex
Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands, formation was analyzed by co-immunoprecipitation and western blot studies and
3
Mayo Clinic, Division of Pediatric Nephrology and Hypertension, Rochester, MN, United membrane trafficking was evaluated by immunofluorescence microscopy.
States of America, 4Mayo Clinic, Division of Nephrology and Hypertension, Rochester, RESULTS: Genectic analysis of our CU-cohort did not reveal indiviuals with SLC7A13
MN, United States of America, 5Alnylam Pharmaceuticals, Cambridge, MA, United variation only, however we found three patients harbouring heterozygous missense
States of America and 6Shaare Zedek Medical Center, Division of Pediatric Nephrology, variants in addition to pathogenic or VUS variants in SLC3A1 or SLC7A9. To evaluate
Jerusalem, Israel their influence on the generation of functional cystine transporters in vitro, different
cell models were transiently transfected with plasmids expressing wildtype or mutant
BACKGROUND AND AIMS: Primary hyperoxaluria type 1 (PH1) is a rare genetic proteins. In line with previous reports, co-expression of AGT1 and rBAT wildtype
disorder characterized by hepatic overproduction of oxalate. Excretion of oxalate via allowed efficient complex formation as AGT1-induced maturation of rBAT was
the kidneys leads to recurrent kidney stones, nephrocalcinosis, progressive kidney detected by increased mature N-glycosylation, co-immunoprecipitation and
disease, and multiorgan damage from systemic oxalosis. Lumasiran, a subcutaneously membrane insertion. Whereas AGT1 patient variants p.Met452Thr (SLC7A13
administered RNAi therapeutic indicated for the treatment of PH1 in all age groups, c.1355T>C) and p.Ile174Phe (SLC7A13 c.520A>T) behaved comparable to wildtype
has multiple ongoing phase 3 studies including ILLUMINATE-A, which enrolled 39 AGT1, variants p.Asn45Lys (SLC7A13 c.135C>G) and p.Leu270Phe (SLC7A13
patients 6 years of age with eGFR 30 mL/min/1.73m2, and ILLUMINATE-B, which c.808C>T) led to clearly reduced glycosylation patterns and trafficking deficits of
enrolled 18 patients <6 years of age with eGFR >45 mL/min/1.73m2 if 12 months of rBAT wildtype protein. Next, the mutual influence of pathogenic variation in both,
age or normal serum creatinine if <12 months of age. Here we present a comparison of AGT1 and rBAT, will unravel the consequences of patient-specific molecular
the efficacy and safety of lumasiran in children versus adults with PH1 using pooled interactions on the functional expression of cystine transporter complexes.
data from these two phase 3 studies of lumasiran. CONCLUSION: Here, we report three CU-patients with variants in SLC7A13
METHOD: Efficacy and safety data from ILLUMINATE-A and ILLUMINATE-B, combined with either SLC3A1 or SLC7A9. For two of these variants, in vitro functional
including urinary oxalate, plasma oxalate, eGFR, and adverse events were pooled and analysis revealed pathogenic molecular mechanisms disturbing complex formation,
assessed by age <18 (N=40), or 18 years old (N=17). The analysis included all maturation and trafficking of rBAT. We hypothesize that specific pathogenic variants
available data from 57 patients with PH1, ages 4 months to 60 years, who completed in SLC7A13 interfere with efficient membrane localization of heterodimeric cystine
the initial 6 months of treatment with lumasiran. transporters, which results in modulation of cystine transport in the S3 segment of
RESULTS: During the initial 6 months of treatment with lumasiran, patients with PH1 proximal tubules in CU-patients.
had a rapid and sustained decrease in urinary oxalate. The overall mean (SEM) percent
reduction in urinary oxalate:creatinine ratios as measured in random spot urine
samples from baseline to Month 6 was 63.1% (2.6) across all ages (N=54). A similar

i8 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i9–i11, 2021
10.1093/ndt/gfab138

PATHOLOGY MEETS CLINICS hypercoagulable state and thrombosis, and mice with plasminogen deficiency have
been shown to suffer from developing spontaneous thrombosis. However, the role of
plasminogen in hypercoagulable state and thrombosis in an experimental nephrotic
syndrome has not been investigated before.
FC015 LACK OF PLASMINOGEN RELATES TO A METHOD: We investigated the relationship between plasminogen and a
HYPERCOAGULABLE STATE IN MICE WITH EXPERIMENTAL hypercoagulable state in an inducible nephrotic mouse model with conditional
NEPHROTIC SYNDROME podocyte-specific podocin deletion (Nphs2Dipod * Plgþ/þ, n=12). The Nphs2Dipod mice
with constitutive plasminogen knockout were used as negative plasminogen control
Mengyun Xiao1, Stefanie Hammer2, Wissam A. Khalel2, Lisann Pelzl2, Bernhard (Nphs2Dipod * Plg-/-, n=15). All mice received a daily oral doxycycline administration
N. Bohnert3,4,5, Karina Althaus2, Tamam Bakchoul2, Andreas L. Birkenfeld3,4,5, for 2 weeks for NS induction. The last day of doxycycline treatment was set as day 0.
Ferruh Artunc3,4,5 Spot urine was collected daily for proteinuria and urinary plasmin activity
1
University Hospital Tübingen, Department of Internal Medicine IV, Tübingen, Germany, measurement. Citrate blood was collected from each mouse before induction of NS, 7
2
University Hospital Tuebingen, Center for Clinical Transfusion Medicine, Tübingen, days and 21 days after induction, respectively (Nphs2Dipod * Plgþ/þ mice, n=4/
Germany, 3University Hospital Tübingen, Department of Internal Medicine IV, Division timepoint; Nphs2Dipod * Plg-/- mice, n=5/timepoint). A global assessment of
of Endocrinology, Diabetology and Nephrology, Tübingen, Germany, 4University coagulation (extrinsic coagulation test, EX test) was examined by ClotProV R system.

Tübingen, Institue of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Besides, fibrinolysis was tested by adding tissue plasminogen activator (TPA test).
Center Munich, Tuebingen, Germany and 5University Tübingen, German Center for RESULTS: According to the EX test, uninduced mice with plasminogen deficiency
Diabetes Research (DZD), Tuebingen, Germany showed a significantly reduced clotting time (CT, Plg-/- vs. Plgþ/þ, 42 6 1s vs. 54 6 4s,
p=0.0213), and decreased clot formation time (CFT, Plg-/- vs. Plgþ/þ, 82 6 5s vs. 206 6
28s p<0.0001) with a larger alpha-angle (Plg-/- vs. Plgþ/þ, 75 6 1 vs. 66 6 2 ,
BACKGROUND AND AIMS: Urinary excretion of the fibrinolytic enzyme p=0.0041). The maximum clot firmness (MCF) was significantly increased in
plasminogen has been identified as a characteristic feature of nephrotic syndrome (NS) uninduced plasminogen knockout mice (Plg-/- vs. Plgþ/þ, 45 6 0.5mm vs. 32 6 2.5mm
in both human and experimental mouse models. Lack of plasminogen may lead to a p<0.0001). According to the TPA test, uninduced Nphs2Dipod *Plg-/- mice had a faster

FC015 Figure 1. The parameters and visible results of extrinsic coagulation test (EX test) (a) and (TPA test)(b). The summary of results from EX test (c) and TPA test (d). Data
were presented as Mean 6 SEM. *indicated significance between different genotypes; # indicated significance among different time compared to the baseline values CFT: clot for-
mation time (s); MA: maximum amplitude (mm); ML: maximum lysis (%); LT: lysis time (s).

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

velocity of clot formation (a-angle, 75.6 6 0.2 vs. 66.5 6 1.6 , p=0.0254) and did not
show any clot lysis in contrast to uninduced nphs2Dipod * plgþ/þ mice. After induction
of NS, both Nphs2Dipod * Plg-/- mice and Nphs2Dipod * Plgþ/þ mice developed massive METHOD: Intravital multiphoton microscopy (MPM) of the glomerular vasculature
proteinuria to a comparable extent (Plg-/- vs. Plgþ/þ on day 21, 218 6 46mg/mg crea vs. and filtration barrier structure and function was performed in genetically engineered
203 6 28mg/mg crea), and plasminuria was detectable in nephrotic nphs2Dipod * plgþ/ mice combined with traditional urinalysis and histology-based phenotyping.
þ
mice. With the ongoing loss of plasminogen in the urine, CT and CFT was Glomerular hemodynamic parameters (afferent and efferent arteriole (AA and EA)
significantly reduced in nephrotic Nphs2Dipod * Plgþ/þ mice. MCF was significantly diameters and single nephron glomerular filtration rate (SNGFR)) and podocyte
increased with a faster velocity of clot formation measured by both the EX and TPA calcium entry, as a measure of cell injury, were quantitatively visualized in the FSGS
test. Moreover, clot lysis was significantly reduced. In nephrotic nphs2Dipod *plg-/- mice model Pod-GCaMP5/Tomato TRPC6 transgenic mice (1.5 years of age), in which
at day 21, there was also a tendency towards a decrease in CT, CFT and an increased TRPC6 is overexpressed together with the calcium reporter GCaMP5 in podocytes.
velocity of clot formation. According to both EX and TPA test, there were no Single cell identification and fate tracking of cells of the renin lineage (CoRL) was
significant differences between the genotypes in nephrotic mice any more. performed over time using a second physiologic control mouse model, Ren1d-Confetti
CONCLUSION: The results highlight that loss of plasminogen in the nephrotic state mice that feature a multicolor CFP/GFP/YFP/FP reporter. Three groups of mice in
contributes to a hypercoagulable state with shortened clotting time, clot formation each model received treatment with either vehicle (CTRL), the ARB losartan (Los; 10
time, increased clot firmness, and most strikingly, loss of clot lysis. Changes in mg/kg/day), or sparsentan (120 mg/kg/day) for 6 weeks (FSGS model) or 2 weeks
nephrotic wild-type mice were similar to mice with constitutive plasminogen (control physiology model).
deficiency, indicating that loss of plasminogen plays a role in the hypercoagulable state RESULTS: Both Los and sparsentan treatment attenuated the acute ET þ Ang II-
of nephrotic syndrome. induced elevation of podocyte calcium by 80%, and the development of albuminuria,
and glomerulosclerosis and tissue fibrosis in the FSGS model. Notably, sparsentan
prevented the ET þ Ang II increases in podocyte calcium more than Los and was
significantly more effective in dilating both AA and EA (Fig. 1A, B), increasing SNGFR
FC016 SPARSENTAN IMPROVES GLOMERULAR BLOOD FLOW AND (Fig. 1C), increasing capillary blood flow (2-fold; p<0.0001 vs. CTRL), and decreasing
AUGMENTS PROTECTIVE TISSUE REMODELING IN MOUSE albuminuria (20%; p<0.05 vs. CTRL). Sparsentan also preserved p57þ podocyte
MODELS OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS number by 50% compared to Los (p<0.0001 vs. Los). Similarly, pretreatment with
(FSGS) sparsentan was more effective in preventing glomerular arteriolar vasoconstriction
induced by acute ET þ Ang II iv injection compared to Los (p<0.05 vs. Los). Following
Georgina Gyarmati1, Urvi Shroff1, Audrey Izuhara1, Radko Komers2, a 2-week treatment in control healthy Ren1d-Confetti mice, sparsentan resulted in a
Patricia Bedard2, Janos Peti-Peterdi1 more robust increase compared to Los in the number of Confettiþ cells, clones, and
1
University of Southern California, Los Angeles, United States of America and 2Travere individual cells per clone in the glomeruli and AA (Fig. 1D-F). Renal tubule segments
Therapeutics, San Diego, United States of America also showed active cellular remodeling in response to sparsentan.
CONCLUSION: Serial MPM imaging directly visualized several mechanisms
underlying beneficial antiproteinuric and structural effects of sparsentan in both FSGS
BACKGROUND AND AIMS: Preliminary preclinical and emerging clinical evidence and in the normal mouse kidney and differences between dual ETA/AT1 receptor
indicates strong antiproteinuric actions of dual endothelin type A (ETA) and antagonism of sparsentan and a mono-selective ARB. The sparsentan-induced
angiotensin II type 1 (AT1) receptor antagonism with sparsentan. These glomerular hemodynamic pattern was driven by both AA and EA dilation resulting in
nephroprotective effects have been more pronounced in different experimental and an increase in capillary blood flow. Compared to Los, sparsentan was more effective in
clinical settings compared to current standard of care using an AT1 receptor blocker attenuating ET/Ang II-induced podocyte injury and in activation of resident
(ARB). Considering the broad spectrum of renal actions of endothelin (ET) and progenitor cells and tissue remodeling. These findings suggest multiple layers of renal
angiotensin II (Ang II), inhibition of both pathways using sparsentan is postulated to protective actions by dual ETA and AT1 receptor antagonism.
target multiple renal cell types via a variety of renoprotective mechanisms. The aim of
this study was to determine glomerular action of sparsentan as compared to the ARB
losartan (Los) by direct visualization of effects on renal hemodynamics and tissue
remodeling in the intact living kidney.

FC016 Figure 1: (A) AA diameter, (B) EA diameter, (C) SNGFR, (D-F) Confettiþ
cell and clone numbers in the glomeruli and AA. Statistical significance determined by
ANOVA *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

i10 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: First, we show robust functionality of threeplex smFISH in archived routine
FFPE kidney biopsy samples with single-mRNA resolution. As variations in sample
preparation can negatively influence mRNA-abundance, we established PPIB as an
FC017 DEEP-LEARNING ENABLED QUANTIFICATION OF SINGLE- ideal on-slide reference gene to account for different RNA-integrities present in biopsy
CELL SINGLE-MRNA TRANSCRIPTS AND CORRELATIVE samples. PPIB was chosen for its most stable expression in microarray dataset of
SUPER-RESOLVED PODOCYTE FOOT PROCESS various glomerular diseases determined by the Normfinder algorithm as well as its
MORPHOMETRY IN ROUTINE KIDNEY BIOPSY SPECIMEN smFISH performance.
To segment glomeruli and to label glomerular and tubulointerstitial cell subsets, we
Florian Siegerist1, Eleonora Hay1, Julien Dang2, Nassim Mahtal2, Pierre- established a combination of smFISH and immunofluorescence. As smFISH requires
Louis Tharaux2,3, Uwe Zimmermann4, Silvia Ribback5, Frank Dombrowski5, intense tissue digestion to liberate cross-linked RNAs, immunofluorescence protocols
Karlhans Endlich1, Nicole Endlich1 had to be adapted: For podocin, a small-sized single-step label approach enabled by
1
University Medicine Greifswald, Anatomy and Cell Biology, Greifswald, Germany, small nanobodies and for WT1, tyramide signal amplification was used.
2
Université de Paris, PARCC, INSERM, Paris, France, 3Georges Pompidou European For enhanced segmentation performance, we used deep learning: First, a network was
Hospital, Nephrology Division, Paris, France, 4University Medicine Greifswald, customized to recognize DAPIþ cell nuclei and WT1/DAPIþ podocyte nuclei. Second,
Department of Urology, Greifswald, Germany and 5University Medicine Greifswald, a UNet was trained to segment glomeruli in podocin-stained tissue sections. Using
Institute for Pathology, Greifswald, Germany these segmentation masks, we could annotate PPIB-normalized single mRNA
transcripts to individual cells. We established an ImageJ script to automatize transcript
BACKGROUND AND AIMS: Although high-throughput single-cell transcriptomic quantification.
analysis, super-resolution light microscopy and deep-learning methods are broadly As a proof-of-principle, we demonstrate inverse expression of WT1 and ACE2 in
used, the gold-standard to evaluate kidney biopsies is still the histologic assessment of glomerular vs. tubulointerstitial single cells. Furthermore, in the podocyte subset, WT1
formalin-fixed and paraffin embedded (FFPE) samples with parallel ultrastructural highly clustered whereas no significant ACE2 expression was found under baseline
evaluation. Recently, we and others have shown that super-resolution fluorescence conditions.
microscopy can be used to study glomerular ultrastructure in human biopsy samples. Additionally, when imaged with super-resolution microscopy, podocyte filtration slit
Additionally, in the last years mRNA in situ hybridization techniques have been morphology could be visualized The optical resolution was around 125 nm and
improved to increase specificity and sensitivity to enable transcriptomic analysis with therefore small enough to resolve individual foot processes. The filtration slit density as
single-mRNA resolution (smFISH). a podocyte-integrity marker did not differ significantly from undigested tissue sections
METHOD: For smFISH, we used the fluorescent multiplex RNAscope kit with probes proving the suitability for correlative podocyte foot process morphometry with single-
targeting ACE2, WT1, PPIB, UBC and POLR2A. To find an on-slide reference gene, podocyte transcript analysis.
the normfinder algorithm was used. The smFISH protocol was combined with a single- CONCLUSION: Here we present a modular toolbox which combines algorithms for
step anti-podocin immunofluorescence enabled by VHH nanobodies. Podocytes were multiplexed, normalized single-cell gene expression with single mRNA resolution in
labeled by tyramide-signal amplified immunofluorescence using recombinant anti- cellular subsets (glomerular, tubulointerstitial and podocytes). Additionally, this
WT1 antibodies. Slides were imaged using confocal laser scanning, as well as 3D approach enables correlation with podocyte filtration slit ultrastructure and gross
structured illumination microscopy. Deep-learning networks to segment glomeruli and glomerular morphometry.
cell nuclei (UNet and StarDist) were trained using the ZeroCostDL4Mic approach.
Scripts to automate analysis were developed in the ImageJ1 macro language.

10.1093/ndt/gfab138 | i11
Nephrology Dialysis Transplantation 36 (Supplement 1): i12–i15, 2021
10.1093/ndt/gfab132

HYPERTENSION & OMICS

FC019 PROTEOMIC PROFILING OF GLOMERULI FROM KIDNEYS


FC018 HIGH DIETARY PHOSPHATE INTAKE AND INTRA-CARDIAC WITH HYPERTENSIVE NEPHROPATHY REVEALS SIGNATURE
SYNTHESIS OF FIBROBLAST GROWTH FACTOR 23 OF DISEASE PROGRESSION
SYNERGISTICALLY WORSEN CARDIAC FUNCTION
Håvard Mikkelsen1, Bjørn Egil Vikse1,2, Andreas Scherer3,4, Kenneth Finne1,
Maren Leifheit-Nestler1, Matilda Bariani1, Miriam A. Wagner1, Isabel Vogt1, Hans-Peter Marti1,5
Fiona Eitner1, Andrea Grund1, Thomas Thum2, Oliver J. Müller3, Dieter Haffner1 1
University of Bergen, Department of Clinical Medicine, Bergen, Norway, 2Haugesund
1
Hannover Medical School, Department of Paediatric Kidney, Liver and Metabolic Hospital, Department of Medicine, Haugesund, Norway, 3Spheromics, Kontiolahti,
Diseases, Hannover, Germany, 2Hannover Medical School, Institute of Molecular and Finland, 4University of Helsinki, Institute for Molecular Medicine Finland, Helsinki,
Translational Therapeutic Strategies, Hannover, Germany and 3University Hospital Kiel, Finland and 5Haukeland University Hospital, Department of Medicine, Bergen, Norway
Department of Internal Medicine III, Germany
BACKGROUND AND AIMS: Hypertensive nephropathy (HN) often represents an
BACKGROUND AND AIMS: Left ventricular hypertrophy (LVH) is a major unspecific clinical diagnosis applied to non-diabetic, chronic kidney disease (CKD)
complication of CKD and associates with increased levels of the phosphaturic hormone patients with low-level proteinuria and elevated blood pressure. Kidney biopsy-based
fibroblast growth factor (FGF) 23. FGF23 induces hypertrophic growth of cardiac findings are the diagnostic gold standard, but they are not entirely specific and there is
myocytes in vitro and LVH in rodents, suggesting that FGF23 can directly affect the a need for prognostic markers. We aimed at defining candidate markers that predict
heart. Besides the bone, cardiac myocytes express FGF23, too, and recent studies disease progression based on protein signatures.
demonstrate that its expression is increased in cardiac and kidney injury, suggesting METHOD: We included adult patients (n=17) with an eGFR >30 ml/min/1.73m2 and
that cardiotoxicity of FGF23 may be at least partly due to the paracrine effects of heart- proteinuria <3g/d from the Norwegian Kidney Biopsy Registry (NKBR). Subjects were
derived FGF23. However, it is still questioned whether elevated FGF23 per se is able to divided into two groups: stable patients (n=9) and subjects with HN progression (n=8)
induce pathologic alterations in the heart or whether additional factors in CKD, such as leading to end-stage renal disease (ESRD) within 20 years of follow-up. Glomerular
Klotho deficiency or hyperphosphatemia are required for FGF23 to tackle the heart. cross-sections were microdissected from 10 lm whole archival kidney biopsy sections
By generating a mouse model with cardiac-specific overexpression of FGF23 via and processed for protein extraction. Proteomic analyses were performed at our local
myocardial gene transfer using adeno-associated virus (AAV), we elucidated the facility PROBE in Bergen using a Q-exactive HF mass spectrometer. Abundances of
cardiotoxic properties of elevated FGF23 in (1) unchallenged mice, unbiased of glomerular proteins were compared between the two groups.
alterations usually associated with CKD, and (2) in the presence of high dietary RESULTS: Amongst a total of 1870 quality filtered proteins, we identified 58 proteins
phosphate intake, mimicking the exposure of enhanced serum phosphate. with absolute fold change (FC) 1.5, p0.05, including 17 proteins with absolute FC
METHOD: First, an adeno-associated virus that expresses murine Fgf23 (AAV-Fgf23) 2, indicative of HN progression (highest FC: Cadherin 16 and UDP-glucuronosyl-
under the control of the cardiac troponin T promotor was injected subcutaneously into transferase 2B7). Hierarchical cluster and principal component analysis (PCA) with the
eight-week-old male C57BL/6 wildtype mice. After four months, cardiac function and 17 proteins showed clear separation of samples into these two disease clusters of HN
geometry was assessed by cardiac magnetic resonance imaging (MRI) and progressors and non-progressors. To find proteins as biomarkers for the identification
echocardiography and heart tissue was analysed by qPCR, immunoblot and of progressors, we employed unsupervised K nearest neighbors validation algorithm
histological analyses. The biological activity of AAV-Fgf23-derived cardiac Fgf23 was coupled with leave-one-out internal cross-validation. Thereby, a set of five proteins
determined using isolated neonatal rat ventricular myocytes (NRVM) in vitro. Second, (incl. cadherin 16) performed best and separated the two groups in a PCA, as shown in
AAV-Fgf23 and control mice were fed a 2% high phosphate diet (HPD) or a 0.8% Figure 1. This classifier classified 16 of 17 samples correctly (AUC 0.993),
normal phosphate diet (NPD) and cardiac phenotype was investigated after six misclassifying only one progressor sample. Applying Geneset Enrichment Analysis
months. (GSEA; The Broad Institute, USA), in general metabolic pathways were up-regulated in
RESULTS: AAV-Fgf23 mice showed increased cardiac-specific Fgf23 expression and progressors and structural cell pathways up-regulated in non-progressors. Ingenuity
synthesis of intact Fgf23 (iFgf23) protein in the heart resulting in enhanced circulating Pathway Analysis (IPA; Qiagen, USA) identified Epithelial Adherens Junction
iFgf23 compared to control. Serum of AAV-Fgf23 mice stimulated hypertrophic Signaling as the most affected canonical pathway (p=1.95E-06); five of six member
growth of isolated NRVM and induced pro-hypertrophic gene expression in vitro, proteins were down-regulated in progressors.
indicating that cardiac iFgf23 is biologically active. Likewise, AAV-Fgf23 mice revealed
an activation of renal FGFR1/Klotho/MAPK signalling and subsequent down-
regulation of renal sodium phosphate transporters NaPi-2a and NaPi-2c, causing
reduced tubular phosphate reabsorption. Nevertheless, in unchallenged AAV-Fgf23
mice, impaired cardiac function, LVH and LV fibrosis were lacking.
In contrast, HPD stimulated the bone expression of Fgf23 in both AAV-Fgf23 and Ctrl
mice, while intra-cardiac Fgf23 mRNA levels were only increased in both AAV-Fgf23
groups irrespective of NPD or HPD. However, HPD in AAV-Fgf23 mice promoted O-
glycosylation of cardiac iFgf23, suggesting stabilization of biologically active Fgf23
protein. Echocardiography showed impaired cardiac function in AAV-Fgf23 on HPD
compared to its NPD group, demonstrated by enhanced end-systolic and end-diastolic
volumes, increased systolic and diastolic LV diameters as well as enlarged LV inner
diameters, respectively. Pressure-volume analysis using Millar catheter showed higher
end-systolic and end-diastolic blood pressure (ESP, EDP) in AAV-Fgf23 mice on HPD
compared to NPD. HPD in Ctrl only enhanced EDP, although this did not reach the
level of statistical significance.
CONCLUSION: Chronic exposure to biologically active cardiac iFgf23 per se does not
tackle the heart, while high intra-cardiac Fgf23 synthesis in the presence of high dietary
phosphate promotes cardiotoxicity of Fgf23, which could pose a significant health risk
to the general population.

FC019 Figure 1: Principal component analysis (PCA) with the 5 proteins from the
HN classifier; NP = non-progressors, P = progressors.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Glomerular proteomic profiling can be used to distinct progressors functions were identified. Gene ontology (GO) and the Kyoto Encyclopedia of Genes
from non-progressors in HN. and Genomes (KEGG) pathway enrichment analysis were conducted, and the ligand-
receptor interaction among different cell populations were anlyzed.
RESULTS: 18 distinct cell clusters were identified in kidney from HTN patients.
Endothelial cells overexpressed LRG1, a pleiotropic factor linked to apoptosis and
FC020 SINGLE CELL SEQUENCING REVEALS TRANSCRIPTIONAL
inflammation, which was validated at proteome level in kidney from HTN, providing a
SIGNATURES AND CELL CROSSTALK IN PATIENTS WITH
potential novel molecular target. In HTN patients, mesangial cells highly expressed
HYPERTENSIVE NEPHROPATHY
proliferation related signatures (MGST1, TMSB10, EPS8 and IER2) not detected in
renal diseases before. The upregualted genes in tubules of HTN were mainly
Rong Tang1, Ting Meng1, Wei Lin1, Yong Zhong1
1
participating in inflammatory signatures including IFN-c signature, IL-17 signaling
Xiangya Hospital, Central-south University, Nephrology, Changsha, P.R. China and TLR signaling. Specific gene expression of kidney-resident immune cells including
dendritic cells and CD8þ T cells revealed abnormal regulation associated with cell
BACKGROUND AND AIMS: Hypertensive nephropathy (HTN) is one of the leading adhesion and inflammation. Furthermore, the receptor-ligand interactions analysis
causes of end-stage renal disease (ESRD). HTN is characterized by injury to the indicated cell-cell crosstalks in kidney contribute to recruitment and infiltration of
glomerulus, arterioles and tubulointerstitium, yet the precise mechanisms and cell- inflammatory cells into kidneys, and fibrotic process in hypertensive renal injury.
specific gene expression changes are still unknown. This study used single-cell RNA CONCLUSION: In brief, our data identifies distinct cell-specific gene expression
sequencing (scRNA-seq) to explore novel molecular mechanisms and the gene targets profile, pathogenic signaling pathways and potential cell-cell communication in
for HTN. pathogenesis of HTN. These findings will provide a promising novel landscape for
METHOD: The gene expression profiles of human renal biospsy samples obtained mechanisms and treatment of HTN.
from subjects with HTN and pre-transplant healthy living controls were determined by
scRNA-seq technology. Then the differentially expressed genes (DEGs) and their

FC020 Figure 1: Cell lineage analysis by single-cell RNA-sequencing in HTN and control subjects

10.1093/ndt/gfab132 | i13
Abstracts Nephrology Dialysis Transplantation

FC020 Figure 2: DEGs and intercellular signaling in glomerulus from HTN and control subjects

FC020 Figure 3: DEGs and intercellular signaling in tubules from HTN and control subjects

i14 | Abstracts
Nephrology Dialysis Transplantation Abstracts

FC020 Figure 4: Immune cells subpopulation lineage analysis in HTN and control subjects

FC020 Figure 5: DEGs and intercellular signaling in immune cells from HTN and control subjects

10.1093/ndt/gfab132 | i15
Nephrology Dialysis Transplantation 36 (Supplement 1): i16–i18, 2021
10.1093/ndt/gfab133

INTERVENTIONS IN CKD
and 56 vs 79, with respective annualised rate ratios (95% confidence interval [CI]) of
0.76 (0.50, 1.16), 0.76 (0.48, 1.22) and 0.69 (0.42, 1.12) (Figure). In eGFR tertile 3, the
FC021 EFFICACY OF INTRAVENOUS FERRIC CARBOXYMALTOSE IN total number of CV hospitalisations and CV deaths was significantly lower in the FCM
PATIENTS WITH IRON DEFICIENCY FOLLOWING ACUTE group vs the placebo group (69 vs 107; rate ratio [95% CI] 0.60 [0.39, 0.93]), with a
HEART FAILURE, ACCORDING TO BASELINE EGFR: A nominally lower number of total HF hospitalisations with FCM vs placebo (44 vs 66;
SUBGROUP ANALYSIS OF THE AFFIRM-AHF TRIAL rate ratio [95% CI] 0.62 [0.38, 1.01]). In the time to first event analysis, FCM
significantly reduced HF hospitalisation or CV death vs placebo in eGFR tertile 3
Iain Macdougall1, Ewa A. Jankowska2, Marco Metra3, Gerasimos Filippatos4, (hazard ratio [95% CI] 0.64 [0.42, 0.98]). In eGFR tertiles 1 and 2, differences between
Bridget-Anne Kirwan5, Peter Van der Meer6, Frank Ruschitzka7, Vincent Fabien8, FCM and placebo arms for secondary endpoints did not reach statistical significance.
Sandra Waechter8, Javed Butler9, Stefan D. Anker10, Piotr Ponikowski2 The p-trend for treatment by baseline eGFR subgroup was non-significant for the
1
King’s College Hospital, Department of Renal Medicine, London, United Kingdom, primary outcome (0.941) and also for the secondary outcomes specified here.
2
Wroclaw Medical University, Department of Heart Diseases, Wrocław, Poland, CONCLUSION: In patients with iron deficiency who were stabilised after an episode
3
University and Civil Hospital, Department of Cardiology, Brescia, Italy, 4University of of acute HF, numerically fewer primary and secondary events, endpoints or outcomes
Athens, Department of Cardiology, Athens, Greece, 5SOCAR Research, Department of were consistently observed with FCM vs placebo across the eGFR tertiles. In addition,
Clinical Research, Nyon, Switzerland, 6University Medical Center Groningen, no significant interaction between kidney function and FCM efficacy was noted. Given
Department of Cardiology, Groningen, Netherlands, 7Universit€ atsSpietal Zürich, Klinik that this analysis was limited by small patient numbers following subgroup
für Kardiologie, Zürich, Switzerland, 8Vifor Pharma AG, Glattbrugg, Switzerland, stratification, further studies in larger cohorts with CKD may help to clarify the effect
9
University of Mississippi Medical Center, Jackson, United States of America and of IV FCM in this patient population.
10
Charité, Campus Virchow-Klinikum, Berlin, Germany

BACKGROUND AND AIMS: In the AFFIRM-AHF trial, treatment with intravenous


(IV) ferric carboxymaltose (FCM) reduced the risk of heart failure (HF)
hospitalisations vs placebo in patients with iron deficiency after an episode of acute HF.
Of these patients, 41% had a medical history of chronic kidney disease (CKD). This FC022 AN OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE
prespecified subanalysis of AFFIRM-AHF data was performed to investigate the effect SAFETY AND EFFECTIVENESS OF INTRAVENOUS
of renal function on FCM efficacy. DIFELIKEFALIN IN PATIENTS WITH MODERATE-TO-SEVERE
METHODS: In AFFIRM-AHF, patients stabilised following hospitalisation for acute CKD–ASSOCIATED PRURITUS UNDERGOING HEMODIALYSIS
HF with concomitant iron deficiency (defined as ferritin <100 lg/L, or 100–299 lg/L
with transferrin saturation <20%) were randomised to receive either IV FCM or Daniel Weiner1, Frederique Menzaghi2, Warren Wen2, Jenny Qian2,
placebo before discharge for the index hospitalisation. In this analysis, patients who Catherine Munera2, Sarbani Bhaduri3
had received at least one dose of the study drug, and who had at least one post- 1
Tufts University , Boston, United States of America, 2Cara Therapeutics, Stamford,
randomisation data point and a baseline value for estimated glomerular filtration rate
United States of America and 3Bhaduri Biotech Consulting, El Paso, United States of
(eGFR; calculated using the CKD-EPI formula and baseline creatinine value), were
America
stratified into tertiles according to baseline eGFR. The primary outcome was a
composite of total HF hospitalisations and CV death. Secondary outcomes included
total HF hospitalisations, CV death, time to first HF hospitalisation or CV death, BACKGROUND AND AIMS: Chronic kidney disease–associated pruritus (CKD-aP)
composite of total CV hospitalisations and CV death, and days lost due to HF is a common and highly distressing condition in patients undergoing hemodialysis
hospitalisations or CV death. All outcomes were evaluated up to 52 weeks post- (HD). CKD-aP is associated with sleep disturbances, significant quality-of-life (QoL)
randomisation. impairment, and increased morbidity and mortality. Difelikefalin (DFK) is a selective
RESULTS: Of the 1,108 patients included in primary AFFIRM-AHF analyses, 967 kappa opioid receptor agonist in development for CKD-aP that has minimal central
(FCM: 487; placebo: 480) had a baseline eGFR value and were included in this analysis. nervous system penetration. In placebo-controlled phase 3 trials of patients with
In both groups, 60% of patients had an eGFR <60 mL/min/1.73 m2 following the index moderate to severe CKD-aP undergoing HD, intravenous (IV) DFK had an acceptable
acute HF episode. Patients were divided into eGFR tertiles 1, 2 and 3, with safety profile and demonstrated significant reductions vs placebo in itch intensity. We
corresponding respective baseline eGFR values of <42.96, 42.96 to <64.32, and 64.32 report safety and effectiveness outcomes, including itch-related QoL and sleep
mL/min/1.73 m2. At baseline, the mean age, proportion of females, and proportions of measures, from a phase 3 open-label study of DFK in patients with moderate to severe
patients with ischaemic HF aetiology, a documented history of HF, and a medical CKD-aP.
history of percutaneous coronary intervention, coronary artery bypass graft and/or METHOD: This multicenter, open-label study conducted in the United States and
cardiac resynchronisation therapy, were highest in eGFR tertile 1 and lowest in eGFR Europe enrolled patients with moderate to severe CKD-aP (mean baseline 24-hour
tertile 3. In eGFR tertiles 1, 2 and 3, the number of total HF hospitalisations and CV Worst Itching Intensity Numerical Rating Scale [WI-NRS] score 5) undergoing HD
deaths in the FCM group vs placebo group were, respectively, 115 vs 152, 76 vs 83, for 3 months. Patients received IV DFK 0.5 mcg/kg 3 times/week at the end of each
HD session for up to 12 weeks. Predefined effectiveness endpoints at week 12 included
3-point and 4-point improvement in the weekly mean of the 24-hour WI-NRS
score (range from 0 [no itching] to 10 [worst itching imaginable]). Change from
baseline in QoL at week 12 was assessed using the 5-D itch and Skindex-10,
multidimensional itch-related questionnaires validated in CKD-aP (higher scores
indicate worse QoL). The proportion of patients with no problems (score of 1) on the
skin irritation and self-confidence domains of the EQ-PSO questionnaire was
evaluated. Post hoc endpoints included complete resolution in WI-NRS (75% of
week 12 scores 0 or 1) and Sleep Quality Questionnaire total score assessments (range
of possible scores, 0 [did not interfere] to 10 [completely interfered]), including 3-
point and 4-point improvement in weekly mean score and complete resolution (all
scores of 0) at week 12. Safety assessments and adverse events (AEs) were evaluated.
Data were summarized descriptively.
RESULTS: Among 222 patients who received DFK, 197 (88.7%) completed the study.
At baseline, mean 6SD age was 58.1 612.8 years and 54.5% of patients were male.
Baseline mean 6SD WI-NRS score was 7.6 61.3, Sleep Quality score was 6.6 62.2, 5-
D itch score was 17.1 63.5, and Skindex-10 score was 32.9 614.3. At week 12, the
majority of patients achieved 3-point and 4-point improvement in WI-NRS (73.7%
and 59.3%) and Sleep Quality score (66.0% and 56.7%). Complete resolution of WI-
NRS and Sleep Quality score was observed in 29.4% and 19.1% of patients, respectively
(Figure). DFK was associated with improvements in mean 5-D itch (7.1 64.3) and
Skindex-10 (21.0 615.6) scores at week 12. The proportion of patients reporting no
problems in the skin irritation EQ-PSO domain increased from 1.4% at baseline to
28.9% at week 12, and self-confidence EQ-PSO domain scores increased from 63.5% at

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
baseline to 73.2% at week 12. Overall, 64.4% (143/222) of patients reported 1 was 171.7 6 5.9 cm and 166.3 6 14.9 cm for Bard and placebo patients, respectively.
treatment-emergent AE (TEAE). The most commonly reported TEAEs (4% of Seventeen (74%) pediatric patients were on RAASi treatment.
patients) were diarrhea (5.0% [11/222]), nausea (4.5% [10/222]), and hyperkalemia Treatment of pediatric patients with Bard resulted in a significantly higher mean
(4.1% [9/222]). Serious TEAEs were reported by 20.3% (45/222) of patients; no serious change from baseline in on-treatment eGFR relative to placebo at Week 100 (13.8 mL/
TEAEs were related to study drug. min/1.73 m2; p = 0.017) and higher mean off-treatment eGFR relative to placebo at
Week 104 (14.6 mL/min/1.73 m2; p = 0.0035).
In pediatric patients treated with Bard, UACR remained generally unchanged relative
to baseline at Week 100 (geometric mean 6 SE to baseline ratio: 0.7 6 0.3), while
placebo patients had an increase in UACR (geometric mean 6 SE to baseline ratio: 2.1
6 0.9).
Pediatric patients generally continued along their baseline growth curves for height and
weight in both treatment groups. At Week 100, mean 6 SD changes from baseline in
body weight were 0.5 6 3.9 kg and 3.2 6 3.5 kg and those for height were 1.6 6 1.4 cm
and 4.3 6 5.1 cm for Bard and placebo patients, respectively. Changes in blood
pressure (BP) were similar across treatment groups.
As seen in the adult population, treatment with Bard resulted in transient increases in
mean aminotransferase levels in pediatric patients that remained below 3 x ULN for a
majority (8/11 [73%]) of patients and returned to baseline at Week 104, 4 weeks after
drug withdrawal (mean 6 SD change from baseline in ALT: 0.4 6 3.7 U/L; AST: -0.9
6 5.6 U/L). Increases in ALT did not coincide with increases in total bilirubin and no
Hy’s law cases were reported.
No serious adverse events (AEs) were reported in pediatric patients treated with Bard
and reported AEs were consistent with those observed in previous studies. One
placebo-treated pediatric patient and no Bard patients developed ESKD during the
trial.
CONCLUSION: In CARDINAL, the addition of Bard to RAASi in pediatric patients
with chronic kidney disease due to Alport syndrome appeared to preserve kidney
CONCLUSION: In this phase 3 open-label study in patients with moderate to severe function and very importantly from a safety standpoint, was safe and well-tolerated.
CKD-aP undergoing HD, DFK was generally well tolerated with an acceptable safety
profile. DFK demonstrated effectiveness based on reduction of itch intensity, and
improvements in sleep quality and itch-related QoL at week 12. The majority of
patients reported 3-point or 4-point improvement in WI-NRS and Sleep Quality FC024 SAFETY AND EFFICACY OF PATIROMER FOR
scores, with some reporting complete resolution. Findings from this open-label study HYPERKALAEMIA IN PATIENTS WITH STAGE 1-3A OR STAGE
provide insight into the potential real-world effectiveness of DFK in moderate to severe 3B-5 CHRONIC KIDNEY DISEASE: POOLED ANALYSIS OF
CKD-aP. THE AMETHYST-DN, OPAL-HK AND TOURMALINE TRIALS

Hermann Haller1, Stefano Bianchi2, Kieran McCafferty3, Susan Arthur4, Liliana-


Georgiana Wegmann5, Jeffery Budden6, Matthew Weir7
FC023 SAFETY OF BARDOXOLONE METHYL IN PEDIATRIC 1
Hannover Medical School, Department of Nephrology and Hypertension, Hanover,
PATIENTS WITH ALPORT SYNDROME IN CARDINAL PHASE 3 Germany, 2ASL Toscana Nordovest, Department of Internal Medicine, Italy, 3Barts
TRIAL Health NHS Trust, Department of Nephrology, London, United Kingdom, 4Vifor Pharma
Group, Biostatistics, Redwood City, CA, United States of America, 5Vifor Pharma Group,
Bradley Warady1, Vimal Chadha2, Melanie Chin3, Rasheed A. Gbadagesin4, Medical Affairs, Glattbrugg, Switzerland, 6Vifor Pharma Group, Medical Affairs,
Keisha Gibson5, Debbie Gipson6, Angie Goldsberry3, Kenneth Lieberman7, Redwood City, United States of America and 7University of Maryland School of
Colin Meyer3, Kevin Meyers8, Kandai Nozu9, Megan O’Grady3, Medicine, Department of Medicine, Baltimore, United States of America
Michelle Rheault10, Clifford Kashtan10
1
Children’s Mercy Kansas City, Pediatric Nephrology, Kansas City, United States of BACKGROUND AND AIMS: In patients with CKD and/or heart failure (HF),
America, 2Children’s Mercy Kansas City, Nephrology, Kansas City, United States of hyperkalaemia (HK) is a major problem which limits the use of guideline-
America, 3Reata Pharmaceuticals, Product Development, Plano , United States of recommended renin–angiotensin–aldosterone inhibitors (RAASi). Dose reduction or
America, 4Duke University School of Medicine, Pediatrics, Durham, United States of cessation of RAASi therapy results in increased morbidity and mortality. Improved
America, 5University of North Carolina at Chapel Hill, Medicine and Pediatrics, Chapel strategies to mitigate HK are required to improve clinical outcomes. Patiromer is a
Hill, United States of America, 6University of Michigan, Pediatric Nephrology, Ann Arbor, non-absorbed, sodium-free, Kþ binder that has been shown to reduce serum Kþ in
United States of America, 7Hackensack University Medical Center, Pediatrics, patients with HK, and thereby enable RAASi therapy. We conducted a post-hoc
Hackensack, United States of America, 8CHOP and UPENN, Pediatric Nephrology, analysis to evaluate patiromer’s efficacy and safety in two HK subgroups by CKD
Philadelphia, United States of America, 9Kobe University Graduate School of Medicine, severity: patients with Stage 3b-5 CKD and those with Stage 1-3a.
Pediatrics, Hyogo, United States of America and 10University of Minnesota, Pediatrics, METHOD: Data were combined from the initial 4 weeks of treatment of three studies
Saint Louis Park, United States of America (AMETHYST-DN, OPAL-HK and TOURMALINE). Eligible patients had a diagnosis
of CKD and HK (local laboratory serum Kþ >5.0 mmol/L) and received patiromer 8.4
BACKGROUND AND AIMS: Alport syndrome is a genetic disease accounting for an to 33.6 g/day to start. Subgroups were identified by baseline estimated glomerular
estimated 3% of children with end-stage kidney disease (ESKD) in the US (USRDS, filtration rate (eGFR): stage 3b–5 (severe/end-stage CKD) and stage 1–3a (mild/
2014). Current management recommendations include the use of renin-angiotensin- moderate CKD). The efficacy population comprised randomised patients who received
aldosterone system inhibitors (RAASi) in patients with proteinuria, but no specific 1 dose patiromer and had 1 post-baseline serum Kþ assessment available. Efficacy
therapies have been approved for this disease. A Phase 3 study (CARDINAL; was evaluated as the mean (6 standard error [SE]) change in central laboratory serum
NCT03019185) assessed the safety and efficacy of bardoxolone methyl (Bard) in adult Kþ from baseline to Week 4 (primary endpoint in AMETHYST-DN and OPAL-HK;
and adolescent patients with Alport syndrome. secondary endpoint in TOURMALINE). Safety outcomes, including incidence and
METHOD: CARDINAL was an international, multicenter, double-blind, placebo- severity of adverse events (AEs) with onset during the 4-week evaluation period, were
controlled, randomized trial. Eligible participants were 12 to 70 years old, had assessed in all randomised patients who received 1 dose of patiromer.
confirmed diagnosis of Alport syndrome, baseline eGFR 30-90 mL/min/1.73 m2 and RESULTS: Of the 626 patients evaluable for efficacy, 61.8% were male,
urinary albumin to creatinine ratio (UACR)  3500 mg/g. For pediatric patients (12 to mean6standard deviation (SD) age was 65.669.8 years and 417 (66.6%) had stage 3b-
< 18 years of age), eGFR was calculated using the Bedside Schwartz equation. Patients 5 CKD, including 27 (6.5%) patients with stage 5 CKD. Approximately 34% of patients
were randomized 1:1 to Bard or placebo and were to be followed for up to 104 weeks (2 in both subgroups had HF, predominantly NYHA Class II. Baseline characteristics
treatment periods of 48 weeks and 4 weeks off treatment between Weeks 48 and 52). were similar between the stage 3b–5 and stage 1–3a CKD subgroups, except for serum
The primary efficacy endpoints were changes from baseline in eGFR in patients Kþ (mean6SD: 5.4760.41 and 5.3260.42 mmol/L, respectively), eGFR (mean6SD:
randomized to Bard compared to placebo at Week 48 and Week 100. The key 27.969.0 and 58.0612.8 mL/min/1.73m2), and spot urine albumin:creatinine ratio
secondary endpoints were the off-treatment changes from baseline in eGFR in patients (mean6SD: 126361921 and 60661241 mg/g). In total, 91.8% of patients with stage
randomized to Bard compared to placebo at Week 52 and Week 104, 4 weeks after 3b-5 CKD and 97.6% of patients with stage 1-3a CKD were receiving RAASi therapy at
withdrawal. baseline. Patiromer induced early reductions in serum Kþ, with mean levels decreasing
RESULTS: A total of 23 (15%) pediatric patients were randomized to Bard (n=11) or from baseline to below 5.0 mmol/L by Day 3 or Week 1 in the stage 3b–5 and stage 1–
placebo (n=12). The average age was 15.3 years, mean (6 SD) baseline eGFR was 69.9 3a CKD subgroups, respectively (Figure). The mean change in serum Kþ from baseline
6 15.4 mL/min/1.73 m2 and geometric mean (6 SE) baseline UACR was 230.9 6 95.8 to Week 4 was 0.8460.03 and 0.6060.04 mmol/L in patients with stage 3b–5 and
mg/g. A total of 19 of 23 (83%) pediatric patients were male, and 14 (61%) patients had stage 1–3a CKD, respectively. Overall, 96.4% and 99.0% of patients with stage 3b–5 and
X-linked Alport syndrome, while 6 (26%) patients had autosomal disease. Mean (6 stage 1–3a CKD, respectively, achieved normokalaemia (1 serum Kþ value 3.8–5.0
SD) baseline body weight was 65.5 6 10.2 kg and 57.8 6 16.0 kg and baseline height mEq/L) during the 4 weeks of treatment. In total, 421 patients with CKD stage 3b–5
and 211 with CKD stage 1–3a were evaluable for safety. AEs were reported by 168

10.1093/ndt/gfab133 | i17
Abstracts Nephrology Dialysis Transplantation

(39.9%) and 58 (27.5%) patients with stage 3b–5 and stage 1–3a CKD, respectively. The CONCLUSION: This pooled analysis of three clinical trials clearly demonstrated the
most frequent AEs in stage 3b–5 and stage 1–3a CKD patients, respectively, were efficacy of patiromer to effectively treat HK in patients with CKD, regardless of early or
constipation (7.8% and 2.8%) and diarrhoea (4.0% and 1.9%); all cases were mild or advanced disease, the majority of whom were receiving guideline-recommended
moderate in severity. AEs leading to patiromer discontinuation occurred in 5.7% and RAASi blockade. Patiromer was well tolerated with mild gastrointestinal events in a
2.4% of stage 3b–5 CKD and stage 1–3a CKD patients, respectively. small percentage of patients, and very few discontinuations. Patiromer is an
appropriate choice for the control of HK in patients with CKD stage 3b–5.

i18 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i19–i20, 2021
10.1093/ndt/gfab145

THE VIRUS & THE KIDNEY

FC026 COVID-19 IMPACT ON ELDERLY HEMODIALYSIS


FC025 ACID BASE DISORDERS IN COVID-19 POPULATION: RESULTS FROM THE SPANISH COVID-19 CKD
WORKING GROUP REGISTRY
Gaetano Alfano1, Annachiara Ferrari2, Francesco Fontana1, Giacomo Mori1,
Riccardo Magistroni1, Giovanni Guaraldi3, Gianni Cappelli1 Ander Vergara Arana1,2, Mireia Molina2, Andrés Villegas3, Luis Alberto Sa ~¡nchez
1
Policlinico di Modena Azienda Ospedaliero-Universitaria di Modena, Nefrologia, Ca~¡mara4, Patricia De Sequera Ortiz5, Néstor Toapanta1,2, Joaquın Manrique6,7,
8 4 9 10
Modena, Italy, 2Arcispedale Santa Maria Nuova, Nefrologia, Reggio Emilia, Italy and Amir Shabaka , Ines Aragoncillo , Marıa Carmen Ruız , Silvia Benito ,
3
Policlinico di Modena Azienda Ospedaliero-Universitaria di Modena, Infectious Jose Emilio Sanchez-Alvarez11, Marıa José Soler1,2
1
Disease, Modena, Italy Vall d’Hebron University Hospital, Nephrology, Barcelona, Spain, 2Vall d’Hebron
Research Institute, Nephrology Group, Barcelona, Spain, 3Germans Trias i Pujol
BACKGROUND AND AIMS: Acid-base disorders are common in severely ill patients University Hospital, Nephrology, Badalona, Spain, 4Fundacion para la Investigaci on
and reflect the severity of the underlying pathologic process. The incidence and effects Biomédica Gregorio Mara~ on, Madrid, Spain, 5Infanta Leonor University Hospital,
n
6
of acid-base derangement in COVID-19 patients have been poorly evaluated until now. Nephrology, Madrid, Spain, Complejo Hospitalario de Navarra, Nephrology, Pamplona,
Tropism of the virus for the lungs and kidneys may theoretically lead to frequent acid- Spain, 7Navarra Institute for Health Research, Pamplona, Spain, 8Fundaci on Alcorcon
base alterations due to pneumonia and kidney injury, respectively. To verify the University Hospital, Nephrology, Madrid, Spain, 9Vırgen de las Nieves University
10
derangement of acid-base disorders in COVID-19, we investigated the distribution and Hospital, Nephrology, Granada, Spain, Fundaci o Puigvert, Nephrology, Barcelona,
the impact of acid-base disorders on the survival of symptomatic patients with a Spain and 11Cabue~ nes University Hospital, Nephrology, Gijon, Spain
diagnosis of COVID-19.
METHOD: We retrospectively collected data from electronic charts of all COVID-19 BACKGROUND AND AIMS: Age and chronic kidney disease have been described as
patients hospitalized at the University Hospital of Modena from 4 March to 20 June mortality risk factors for coronavirus disease 2019 (COVID-19). Currently, an
2020. important percentage of patients in hemodialysis are elderly. This study aimed to
Arterial blood gas (ABG) analysis was required to monitor pulmonary gas investigate the impact of COVID-19 in this population and to determine risk factors
exchange and acid-base status. A pH of less than 7.37 was categorized as acidemia and associated with mortality.
a pH of more than 7.42 was categorized as alkalemia. METHOD: Data was obtained from the Spanish COVID-19 CKD Working Group
211 patients were included in the study population. In patients with multiple ABG Registry, that included patients in renal replacement therapy (dialysis and kidney
analyses, we selected only the first measurement. transplantation) infected by COVID-19. From March 18, 2020, to August 27, 2020, 1165
RESULTS: The estimated mean age of the population was 64.7 615,3 years with a high patients on hemodialysis affected by COVID-19 were included in the Registry. A total of
predominance of males (71.6%). Half of the population referred dyspnea and 61.4% at 328 patients were under 65 years-old and 837 were 65 years old or older (elderly group).
physical examination. Most patients (82.6%) were on oxygen therapy when ABG RESULTS: Mortality was 18.6% higher (95% confidence interval (CI): 13.8%-23.4%) in
analysis was performed. Overall, ABG analyses revealed acute respiratory compromise the elderly hemodialysis patients compared to the non-elderly group (see figure). Death
manifesting with a low arterial partial pressure of oxygen (P02, 70.2625.1 mmHg), from COVID-19 infection was increased 5.5-fold in hemodialysis patients compared to
oxygen saturation (SO2, 92%) and a mild reduction of PO2/FiO2 ratio (2316129). mortality in the general population for a similar period, and there was an age-associated
Acid-base disturbance was found in the 79.7% of the patients, and contrary to our mortality increase in both populations (see figure 1). In multivariate Cox regression
expectation, metabolic alkalosis (33.6%) was the main alteration followed by
respiratory alkalosis (30.3%), combined alkalosis (9.4%) respiratory acidosis (3.3%)
metabolic acidosis (2.8%) and other compensated acid-base disturbances (3.6%).
ANOVA with post hoc Tukey, revealed statistically significant differences in age, sex,
serum level of K, Na, bicarbonate, creatinine of PCO2, PO2/FiO2 ratio, CKD,
symptoms (caught, diarrhea) and fatality rate among groups.
Metabolic acidosis was associated with death (HR=8.2; CI 95%, 1,93-32,39; P<0.004),
after adjustment for lung injury (PaO2/FiO2 ratio) tissue hypoperfusion (lactate) and
renal involvement (estimated as GFR< 60 ml/min or development of acute kidney
injury), Pathological pH (alkalosis or acidosis), variations of PCO2 or
hypobicarbonatemia were not associated with mortality in our study population.
Metabolic acidosis occurred in patients with a mean creatinine of 4.564.5 mg/dl.
Notably, 33.3% of patients were on hemodialysis, 33.3% developed COVID-19-
associated acute kidney injury and 33.3% had a GFR <60 ml/min. Patients with
metabolic acidosis had the highest death-fatality rate (100%) after 765.6 days from
admission, 50% died of acute respiratory distress syndrome and 50% of septic shock.
CONCLUSION: In conclusion, all kinds of acid-base alterations were found in
patients with COVID-19. Metabolic and respiratory alkalosis were the most common
acid-base disorders, whereas metabolic acidosis was the only acid-base disturbance
associate with poor outcome in our cohort of patients.

FC026 Figure: Mortality in hemodialysis elderly patients. A: Survival curves in the


hemodialysis population affected by COVID-19 based on age group (elderly and non-
elderly). B: COVID-19 mortality by age range in the hemodialysis population
compared to mortality in the general population for a similar period.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

analysis, age (hazard ratio (HR) 1.58, 95% CI: 1.31-1.92), dyspnea at presentation (HR valuable for clinical triage and optimising hospital capacity utilisation during the
1.61, 95% CI: 1.20-2.16), pneumonia (HR 1.76, 95% CI: 1.12-2.75) and admission to ongoing pandemic.
hospital (HR 4.13, 95% CI: 1.92-8.88) were identified as independent mortality risk
factors in the elderly hemodialysis population. Treatment with glucocorticoids reduced
the risk of death (HR 0.71, 95% CI: 0.51-0.98) in aged patients on hemodialysis.
FC028 COVID-19 RELATED MORTALITY IN KIDNEY TRANSPLANT
CONCLUSION: Mortality is dramatically increased in elderly hemodialysis patients
AND DIALYSIS PATIENTS: A COMPARATIVE, PROSPECTIVE
affected by COVID-19. Age, dyspnea at presentation, pneumonia or hospitalization are
REGISTRY BASED STUDY
factors associated with a worse prognosis, after adjusting dialysis population to other
confounding factors. Treatment with glucocorticoids could be a therapeutic option for
Alexandre Candellier1,2, Eric Jean Goffin1, Priya Vart3,4, Marlies Noordzij3,
this specific population.
Miha Arnol5, Adrian Covic6, Paolo Lentini7, Shafi Malik8, Louis Reichert9,
Mehmet Sukru Sever10, Bruno Watschinger11, Kitty J. Jager12,
Ronald Gansevoort3
FC027 COVID-19 IN PATIENTS ON KIDNEY REPLACEMENT 1
Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research,
THERAPY - CLINICAL CHARACTERISTICS AT TRIAGE Université catholique de Louvain, Department of Nephrology, Brussels, Belgium, 2Centre
ASSOCIATED WITH ADMISSION, READMISSION AND SHORT- Hospitalier Universitaire Amiens-Picardie, Department of Nephrology, Amiens, France,
TERM OUTCOMES 3
University Medical Center Groningen, University of Groningen, Department of Internal
Medicine, Groningen, Netherlands, 4University Medical Center Groningen, University of
Sandip Mitra1, Anu Jayanti1, Priya Vart2, Armando Coca3, Maurizio Gallieni4, Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen,
Marius Altern Øvrehus5, Karsten Midtvedt6, Samar Abd ElHafeez7, Netherlands, 5University Medical Centre Ljubljana, Department of Nephrology,
Ilaria Gandolfini8, Stefan Büttner9, Casper Franssen2, Marc Hemmelder10 Ljubljana, Slovenia, 6University Hospital, ‘Grigore T. Popa’ University of Medicine,
1
Dept. of Renal Medicine, Manchester Foundation Trust, Manchester, United Kingdom, Nephrology Clinic, Dialysis and Renal Transplant Center, ’C.I. PARHON’ , Iasi, Romania,
2 7
Dept. Internal Medicine, University Medical Center Groningen, University of Groningen, San Bassiano Hospital, Bassano del Grappa, Nephrology and Dialysis Unit, Vicenza,
Groningen, the Netherlands., 3Dept. of Nephrology, University Clinical Hospital of Italy, 8University Hospital of Coventry and Warwickshire and University of Leicester.,
Valladolid, Spain, 4Nephrology Unit, Dept. of Biomedical and Clinical Sciences “L. Department of Renal and Transplant, Leicester, United Kingdom, 9Rijnstate Hospital,
Sacco”, Universita di Milano, Italy, 5Dept. of Renal Medicine, St Olavs Hospital, Department of Nephrology, Arnhem, Netherlands, 10Istanbul School of Medicine,
Trondheim University Hospital, Trondheim, Norway, 6Department of Transplantation Istanbul University, Department of Nephrology, Istanbul, Turkey, 11Medical University of
Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway, 7Epidemiology Vienna, Department of Nephrology, Vienna, Austria and 12Amsterdam University
Department- High Institute of Public Health-Alexandria University, Egypt , 8University Medical Center, University of Amsterdam, Amsterdam Public Health research institute,
Hospital Parma, Italy, 9Klinikum Aschaffenburg-Alzenau, Germany and 10Department ERA-EDTA Registry, Department of Medical Informatics, Amsterdam, Netherlands
Internal Medicine, Division of Nephrology, Maastricht University Medical Center,
Maastricht, the Netherlands BACKGROUND AND AIMS: Studies examining kidney failure patients with
COVID-19 reported higher mortality in hemodialysis patients than in kidney
BACKGROUND AND AIMS: Patients on kidney replacement therapy (KRT) are at transplant recipients. However, hemodialysis patients are often older and have more
high risk of developing severe COVID-19 illness and often require high intensity care comorbidities. This study investigated the association of type of kidney replacement
and utilisation of hospital resources. During the ongoing pandemic, the optimal care therapy with COVID-19 severity adjusting for differences in characteristics.
pathway and triage for KRT patients presenting with varying severity of COVID-19 METHOD: Data were retrieved from the European Renal Association COVID-19
illness is unknown. We studied clinical factors and outcomes associated with Database (ERACODA), which includes kidney replacement therapy patients diagnosed
admission, readmission and short-term outcomes. with COVID-19 from all over Europe. We included all kidney transplant recipients and
METHOD: Data from the European Renal Association COVID-19 Database hemodialysis patients who presented between February 1st and December 1st 2020 and
(ERACODA) was analysed. This database includes granular data on dialysis patients had complete information reason for COVID-19 screening and vital status at day 28.
and kidney transplant recipients with COVID-19 from all over Europe. The clinical The diagnosis of COVID-19 was made based on a PCR of a nasal or pharyngeal swab
and laboratory features at first presentation of hospitalized and non-hospitalized specimens and/or COVID-19 compatible findings on a lung CT scan. The association
patients and those who returned for second presentation were studied. In addition, of kidney transplantation or hemodialysis with 28-day mortality was examined using
possible predictors of outcome in those who were not hospitalized at first presentation Cox proportional-hazards regression models adjusted for age, sex, frailty and
were identified. comorbidities. Additionally, this association was investigated in the subsets of patients
RESULTS: Among 1,423 KRT patients (haemodialysis; 1017/kidney transplant; 406) that were screened because of symptoms or have had routine screening.
with COVID-19, 25% (n=355) were not hospitalized at first presentation. Of them, RESULTS: A total of 1,670 patients (496 functional kidney transplant recipients and
only 10% (n=36), presented for a second time in the hospital. The median interval 1,174 hemodialysis patients) were examined. 16.9% of kidney transplant recipients and
between the first and second presentation was 5 days (Interquartile interval: 2-7 days). 23.9% of hemodialysis patients died within 28 days of presentation. In an unadjusted
Patients who re-presented had worsening of pulmonary symptoms, a fall in oxygen model, the risk of 28-day mortality was 33% lower in kidney transplant recipients
saturation (97% to 90%), and an increase in C-reactive protein (26 mg/L to 73 mg/L) compared with hemodialysis patients (hazard ratio (HR): 0.67, 95% CI: 0.52, 0.85).
between their attendances. Patients who re-presented after initial assessment were However, in an age, sex and frailty adjusted model, the risk of 28-day mortality was
older (72 vs. 63 years) and initially more often had pulmonary symptoms and 29% higher in kidney transplant recipients (HR=1.29, 95% CI: 1.00, 1.68), whereas in a
abnormalities on lung imaging compared with those who did not present for a second fully adjusted model the risk was even 43% higher (HR=1.43, 95% CI: 1.06, 1.93). This
time. The 28-day mortality rate of patients admitted at the second presentation was association in patients who were screened because of symptoms (n=1,145) was similar
similar to that of patients admitted at first presentation (26.5% vs. 29.7%, p=0. 61). (fully adjusted model HR=1.46, 95% CI: 1.05, 2.04). Results were similar when other
Among patients who were not hospitalized at first presentation (mortality 6%), age, endpoints were studied (e.g. risk for hospitalization, ICU admission or mortality
prior smoking, clinical frailty scale, and shortness of breath at first presentation were beyond 28 days) as well as across subgroups. Only age was found to interact
identified as predictors of mortality. significantly, suggesting that the increased mortality risk associated with kidney
CONCLUSION: KRT patients with COVID-19 and mild pulmonary abnormalities transplantation was especially present in elderly subjects.
and no signs of pulmonary insufficiency can be safely returned without hospitalization. CONCLUSION: In this study, kidney transplant recipients had a greater risk of a more
These patients should be advised to seek immediate contact when they develop severe course of COVID-19 compared with hemodialysis patients when adjusted for
respiratory distress. Our findings provide support for a risk-stratified clinical approach age, sex and comorbidities.
to admissions of KRT patients presenting with COVID-19. The study findings may be

i20 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i21–i22, 2021
10.1093/ndt/gfab120

BASICS & CLINICS IN GLOMERULONEPHRITIS

RESULTS: We found that endothelial cell-derived miR-192-5p and podocyte-derived miR-


FC029 PODOCYTE AND GLOMERULAR ENDOTHELIAL CELL 378a-3p are upregulated in patients with anti-phospholipase A2 receptor antibody positive
DERIVED MICRORNAS REGULATE PODOCYTE (PLA2R-abþ) iMGN and regulate glomerular NPNT expression (Fig. 1). Overexpression of
NEPHRONECTIN IN MEMBRANOUS GLOMERULONEPHRITIS miR-378a-3p and miR-192-5p as well as morpholino mediated npnt knockdown in
zebrafish induced edema, proteinuria, loss of podocyte markers and podocyte effacement.
Janina Müller-Deile1, Nina Sopel1, Alexandra Ohs1, Ahmed Kotb1, The most prominent phenotype however were structural changes of the glomerular
Groener Marwin1, Christoph Daniel2, Kerstin Amann2, Mario Schiffer1 basement membrane (GBM) with increased lucidity, slicing and lamellation especially of the
1
University of Erlangen, Nephrology, Erlangen, Germany and 2University of Erlangen, lamina rara interna (Fig. 2, Fig. 3). The phenotype was comparable to ultrastructural
Nephropathology, Erlangen, Germany findings seen in iMGN. IgG sized nanoparticles accumulated in lucidity areas of the lamina
rara interna and lamina densa of the GBM in npnt knockdown zebrafish models. Loss of slit
diaphragm proteins and severe structural impairment of the GBM were further confirmed
BACKGROUND AND AIMS: Autoantibodies binding to podocyte antigens cause in podocyte specific Npnt knockout mice (Fig. 4).
idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how CONCLUSION: Podocyte NPNT is important for proper glomerular filter function
autoantibodies reach the subepithelial space because the glomerular filtration barrier is and GBM structure and is regulated by podocyte and glomerular endothelial cell
normally size selective and impermeable for antibodies. derived miRs. We hypothesize that loss of NPNT in the GBM is part of the
METHOD: Kidney biopsies from patients with MGN, cell culture, zebrafish and mice pathophysiology of iMGN and enables subepithelial immune complex deposition in
models were used to investigate the role of nephronectin (NPNT) regulating iMGN.
microRNAs (miRs) for the glomerular filtration barrier.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC030 CONTACTIN-1 IS A NOVEL ANTIGEN IN IDIOPATHIC FC031 LARGE SCALE VALIDATION OF THE NEW INTERNATIONAL
MEMBRANOUS GLOMERULONEPHRITIS AND IN CIDP- PROGNOSTIC SCORE OF IGA NEPHROPATHY ON A FRENCH
ASSOCIATED GLOMERULONEPHRITIS COHORT WITH PROLONGED FOLLOW-UP

Alan Salama1, Janev Fehmi2, Marilina Antonelou1, Jonathan Barratt3, Grégoire Bon1, Perrine Jullien1, Christophe Mariat1, Eric Alamartine1,
Neil Ashman4, Aisling Carr5, Mary Reilly5, Stephen Keddie5, Luis Querol6, Nicolas Maillard1
Sonja Pikkuoeura2, Andrea Cortese5, Emilien Delmont7, Staffan Persson8, 1
CHU Saint Etienne, Néphrologie, Dialyse, Transplantation rénale, France
Aleksandar Radunovic4, Ian Simon David Roberts9, Alexander Davies2,
Simon Rinaldi2
1
BACKGROUND AND AIMS: IgA Nephropathy is the most frequent primary
UCL, Department of Renal Medicine, London, United Kingdom, 2Nuffield Department glomerulonephritis worldwide, with a progression to End Stage Renal Disease in up to
of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom, 3Leicester 30% of cases within 20 years after diagnosis. The severity of this disease is nevertheless
University Hospital, United Kingdom, 4Barts Health NHS Trust, United Kingdom, 5UCL, extremely heterogenous with a majority of slow progression to late stages of Chronic
Neurology, United Kingdom, 6University autonoma de Barcelona, Neurology, Spain, Kidney Disease. The early stratification of risk to progress to ESRD is crucial. In this
7
Hospital La Timone, Marseille, France, 8Lund University, Sweden and 9Oxford aim, International IgA Nephropathy Network recently developped a risk prediction
University, Renal Pathology, United Kingdom tool (IINN tool) to allow an estimation of the probability to progress. The objective of
our study was to validate this prediction tool (i) in our French Caucasien retrospective
BACKGROUND AND AIMS: Recently a number of antigens have been identified as cohort (ii) on long term prognosis.
pathogenic antibody targets in cases of primary membranous METHOD: All biopsy-proven IgA Nephropathy patients from Saint Etienne
glomerulonephritis(MGN), including phospholipase A2 receptor (PLA2R), retrospective cohort for whom proteinuria, mean arterial pressure, CKD-EPI based
thrombospondin type 1 domain containing 7A(THSD7A), and NELL-1, while GFR estimate and adequate Oxford classification at diagnosis were available have been
exostosin is found in secondary (lupus associated) MGN. However, other as yet included for analysis. For each patient the estimate of risk to progress to ESRD and/or
undiscovered antigens are thought to exist. Although rare, there is a recognised 50% GFR decline was computed at 5, 10 and 15 years according to the IINN tool. For
association between chronic inflammatory demyelinating polyneuriopathy (CIDP) and each time of follow-up, risks were grouped and ranked by deciles, and the median
nephrotic syndrome. observed rate of event was compared to the median of predicted risk by decile, at 5, 10
METHOD: We investigated the link between CICP and MGN and the associations and 15 years of follow-up. Correlation between observed and predicted risk was
with Contactin-1(CNTN1), a node of Ranvier neuronal protein, as a potential common expressed as a Pearson correlation coefficient. A R2>0.8 was considered adequate to
autoantigen, by immunohistochemistry, RT-PCR and proteomic analysis of isolated validate the prognosis tool.
glomeruli. We tested sera from 468 patients with suspected immune-mediated RESULTS: A total of 468 patients have been included for analysis, with a median age of
neuropathies, 295 with idiopathic MGN, and 210 disease controls, for CNTN1 38.9 years old, a median proteinuria of 0.5g/day, a mean CKD-EPI of 81,6 mL/min/
antibodies. 1,73m2 and mean arterial pressure of 96.9mmHg at diagnosis. The cumulative number
RESULTS: We describe a series of 16 patients, all presenting with CIDP, nephrotic of events at 5,10, 15 years were respectively of 34, 54, 68. The median follow-up was 12
syndrome due to MGN, and with circulating and deposited anti-contactin-1 (CNTN1) years. The correlations between observed/predicted risks were R2 =0,990 [0,959 ; 0,998]
antibodies (IgG4 predominant in those tested) in the kidney. The onset and resolution at 5 years, R2 = 0,984 [0,930 ;0,996] at 10 years and 0,964 [0,851 ;0,992] at 15 years after
of both disorders had a close temporal relationship, and the majority of cases were diagnosis.
resistant to first-line therapies typically employed for inflammatory neuropathies, but CONCLUSION: In our study we validated the IINN tool to predict the risk to progress
achieved a good outcome with non-standard treatment. Importantly, four (1.4%) to ESRD and/or 50% eGFR decline (i) in a French Caucasian cohort and (ii) even after
further patients with isolated MGN identified from a serum bank of 295 idiopathic 5, 10 and 15 years after diagnosis, allowed by a particularly long follow-up.
MGN patients with no CIDP were also positive for anti-CNTN1 antibodies. CNTN1
protein was detected by mass spectroscopy within glomeruli from patients with
CNTN1 antibodies, but not in healthy kidney or anti-PLA2R associated MGN. CNTN1
mRNA was found in renal cortical tissue.
CONCLUSION: These data provide evidence that CNTN1 antibodies precipitate both
autoimmune neuropathy and MGN. The temporal correlation of these disorders, as
well as the presence of CNTN1 protein and antibodies in both peripheral nerve and
diseased glomeruli, supports a common antibody-mediated pathological process, and
defines a new antigenic target in MGN. CNTN1 antibodies have diagnostic and
therapeutic relevance, and may additionally serve as a means of monitoring disease
activity in both conditions. Other factors may explain presentation with isolated
neurological disease or MGN.

FC030 Figure: From left to right: Contactin 1 staining in patients with CIDP and
MGN at low and high power; and in healthy control kidney; RNA PCR for CTNT1 in
kidney extract, cultured podocytes, PBMC and brain.

i22 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i23–i25, 2021
10.1093/ndt/gfab121

BEAT AUTOIMMUNITY
CONCLUSION: Treatment with avacopan in patients with ANCA-associated
vasculitis with renal disease led to greater recovery in eGFR when compared to
FC032 THE EFFECT OF AVACOPAN, A COMPLEMENT C5A standard prednisone therapy, especially in patients with Stage 4 kidney disease (eGFR
RECEPTOR INHIBITOR, ON KIDNEY FUNCTION IN PATIENTS <30 mL/min/1.73 m2). Avacopan also led to more rapid improvement in the UACR
WITH ANCA-ASSOCIATED VASCULITIS WITH RENAL and urinary MCP-1:creatinine ratio than prednisone. Since albuminuria is an
DISEASE independent risk factor for progression of renal disease (in addition to eGFR decline),
the more rapid improvement in albuminuria with avacopan may also provide long-
David Jayne1, Peter Merkel2, Pirow Bekker3, Jeffrey McMahon3, Thomas term benefit. These findings have important implications for the health of patients with
J. Schall3, On behalf of The ADVOCATE Clinical Trial Investigators3 ANCA-associated vasculitis.
1
University of Cambridge, Department of Medicine, Cambridge, United Kingdom,
2
Hospital of the University of Pennsylvania, Rheumatology Division, Philadelphia,
United States of America and 3ChemoCentryx, Inc., Mountain View, United States of
America

BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic autoantibody (ANCA)- FC033 LONG-TERM FOLLOW-UP OF PATIENTS WITH ANCA-
associated vasculitis is a life- or organ-threatening condition in which patients ASSOCIATED VASCULITIS INCLUDED IN EUROPEAN
experience severe inflammation of small arteries. Renal involvement is common in VASCULITIS SOCIETY RANDOMIZED CLINICAL TRIALS
ANCA-associated vasculitis and is correlated with high morbidity and mortality. SINCE 1995: A SURVIVAL ANALYSIS
Current treatment regimens have limited efficacy for renal disease in patients
presenting with organ- or life-threatening ANCA-associated vasculitis. Beatriz Sanchez Alamo1, Laura Moi2, Mikkel Faurschou3, Thomas Hauser4,
Avacopan, a novel orally-administered antagonist of the complement fragment C5a Ingeborg M. Bajema5, Raashid Luqmani6, Alfred Mahr7, Maria Cid8,
receptor (C5aR), was evaluated through a Phase 3 trial in patients with ANCA Zdenka Hruskova9, Vladimir Tesar9, David Jayne10, Kerstin W.A. Westman1
1
vasculitis. Efficacy and safety results have been previously reported; this abstract Lund University, Nephrology, Lund, Sweden, 2Centre Hospitalier Universitaire Vaudois,
provides details of the effects on renal function in patients with renal involvement. Division of Immunology and Allergy, Department of Medicine, Lausanne, Switzerland,
3
METHOD: The ADVOCATE trial was a randomized, double-blind, active controlled, Copenhagen University Hospital, Rigshospitalet, Department of Rheumatology,
double-dummy, 52-week treatment Phase 3 trial of 331 patients with ANCA-associated København, Denmark, 4IZZ Immunologie-Zentrum, Zürich, Switzerland, 5Leiden
vasculitis. Patients were randomized 1:1 and received either a standard daily prednisone University Medical Center, Department of Pathology, Leiden, Netherlands, 6Nuffield
dosing with taper (i.e., starting at 60 mg / day tapered to 0 mg by Week 21), or daily Orthopaedic Centre, Rheumatology, United Kingdom, 7Centre Hospitalier Universitaire
avacopan. Background therapy included either: a) cyclophosphamide (oral or IV) followed Saint-Louis, Department of Internal Medicine, Paris, France, 8Hospital Clinic, Servicio de
by azathioprine, or, b) rituximab (four IV infusions). Patients with active glomerulonephritis enfermedades autoinmunes, Barcelona, Spain, 9General University Hospital in Prague
at baseline were included in this analysis. Kidney function was analyzed based on the and First Faculty of Medicine, Department of Nephrology, Czech Republic and
10
following parameters, which were assessed at pre-specified time-points: changes in the urine Addenbrooke’s Hospital, Vasculitis and Lupus Service, United Kingdom
albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and
Urinary Monocyte Chemoattractant Protein-1 (MCP-1):Creatinine ratio. BACKGROUND AND AIMS: ANCA-associated vasculitis (AAV) is the most
RESULTS: At the baseline visit, 265 patients had renal disease. eGFR improved more common cause of rapidly progressive glomerulonephritis globally and the most
in the avacopan group (n=131) compared to the prednisone group (n=134). At Week common finding in renal biopsies for those above 75 years of age. Patients with AAV
26, eGFR increased 5.8 mL/min/1.73 m2 (from a baseline of 44.6 mL/min/1.73 m2), have had an improved outcome after the introduction of immunosuppressive therapy.
compared to 2.9 mL/min/1.73 m2 in the prednisone group (from a baseline of 45.6 mL/ However, there is still an increased risk of end stage renal failure, complications to
min/m2), P=0.046. At Week 52, the increases in eGFR were 7.3 mL/min/1.73 m2 and therapy, comorbidities and death. The European Vasculitis Society (EUVAS) has run
4.1 mL/min/1.73 m2, respectively, P=0.029. The improvement was most prominent in several prospective randomized clinical trials (RCT) since late -90’ies as an attempt to
subjects with Stage 4 kidney disease at baseline (eGFR < 30 mL/min/1.73 m2), in improve the outcome for patients with a broad spectrum of AAV. The aim of the
whom eGFR improved 13.7 mL/min/1.73 m2 at Week 52 in the avacopan group (from current study was to analyze results from a 10-year follow-up of patients who have
a baseline of 21.1 mL/min/1.73 m2) compared to 8.2 mL/min/1.73 m2 in the participated in EUVAS’s randomized clinical trials to report on patient outcomes using
prednisone group (from a baseline of 21.6 mL/min/1.73 m2), P=0.005. In addition to current standard of care immunosuppressive treatment.
the differences in eGFR, a more rapid decrease in UACR was observed with avacopan; METHOD: Data on patient outcomes were collected from questionnaires to the
by Week 3 this difference was statistically significant, and at Week 4, a 40% decrease principal investigators of the original RCTS (74 centers from 17 countries in Europe):
from baseline occurred in the avacopan group vs no change from baseline in the MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC.
prednisone group (P<0.0001). By Week 52, both groups showed a similar decrease in All patients were well characterized at inclusion in the trials respectively, as was the
UACR from baseline. The urinary MCP-1:creatinine ratio decreased 59% in the type and duration of induction therapy. Long-term follow-up data regarding
avacopan group by Week 13 vs 52% in the prednisone group, P=0.03, but there was a cumulative duration and type of immunosuppressive therapy, end stage renal failure
similar decrease in the two treatment groups by Week 52. (ESRF), renal transplantation, patient survival and comorbidities as cardiovascular
events, infections were recorded. Efforts have been made to control and validate the
collected data.
RESULTS: The current dataset comprises 858 patients, of whom 708 were eligible to
include in this study. We received questionnaires regarding patient outcomes from
70% of the cohort. The median age was 60 years at time of the diagnosis of AAV; 487
patients had GPA (57%) and 371 MPA (43%). The median follow-up time was 8.0
years (IQR: 2.9-13.6).
During the observation period, there were 305 deaths: 78 patients died within the first
year of follow up, 69 during the following 5 years, and another 158 patients after 5
years. The main causes of death were infections (25%), cardiovascular disease (14%)
and malignancies (13%), followed by pulmonary diseases, vasculitis, others, kidney
disease and gastrointestinal disease. Vasculitis were a major contributor to the causes of
death in 18% of the patients.
Median survival time for the whole cohort was 17.8 years (95%CI: 15.6 – 20.1). Survival
rate at 5 and 10 years was 81.6% and 66.5% respectively.
Advanced age, low estimated glomerular filtration rate and male sex were negative
prognostic factors for patient survival in the Cox model.
When we categorized the deaths according to their initial CKD stage, the highest
number of deaths was found in the group of patients with low eGFR i.e. an initial CKD
stage V (40%). The initial CKD stage, as shown in the Kaplan-Meier curve, was found
to have an important impact on the patient survival (LR: 144.4 p<0.001).
In our cohort, 159 patients (18.5%) reached ESRF, of whom 110 patients died (69%);
the main cause of death in this group was infection.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: In a series of over 800 patients with AAV, ten-year mortality was pts; 92/132 [69.7%] BEL to BEL pts); 49/255 (19.2%) pts had 1 treatment-related AE
predominantly associated with impaired renal function at onset, older age and male (25/123 [20.3%] PBO to BEL pts; 24/132 [18.2% ] BEL to BEL pts); 15/255 (5.9%) pts
gender, rather than subtype of disease. The main strength of this study is that we have had 1 serious AE (5/123 [4.1%] PBO to BEL pts; 10/132 [7.6%] BEL to BEL pts); and
a well-defined cohort of patients with AAV, all with well-defined induction treatments 1 death was reported in the PBO to BEL group.
and a long period of follow-up with the possibility to analyze possible prognostic The proportion of patients achieving PERR and CRR increased from OL baseline to OL
factors regarding outcomes. Further analyses are ongoing regarding comparative Week 28 in both groups (Table). The median (interquartile range [IQR]) for uPCR and
statistics, cumulative incidence of malignancies, renal transplantation and eGFR were maintained from OL baseline through to OL Week 28 (Table).
comorbidities. The data supports efforts to diagnose these patients at an earlier stage, The proportion of SLEDAI score <4 responders in BEL to BEL group tended to
when they have a higher eGFR and to tailor therapy for the individual patient. increase from OL baseline to OL Week 28, and decrease in the PBO to BEL group
Although newer treatment modalities are available, there is still a considerable (Table). SDI worsening (change >0) was experienced by 7 (2.9%) pts (4 [3.3%] PBO to
morbidity and mortality in the long-term. BEL; 3 [2.5%] BEL to BEL) compared with OL baseline.
There was no appreciable change in the number of patients receiving average daily
prednisone-equivalent doses of 5 mg or 7.5 mg from OL baseline to OL Week 28
(Table).
CONCLUSION: BEL was well tolerated as an add-on to ST, with no new safety signals.
Efficacy among pts with LN randomised to BEL during the DB phase was maintained
during the OL phase.
STUDY FUNDING: GSK. Editorial assistance (GSK-funded): Olga Conn, PhD,
Fishawack Indicia Ltd., part of Fishawack Health, UK.

FC033 Figure: Patient survival with respect to CKD stages at entry into RCT

FC034 SAFETY AND EFFICACY OF INTRAVENOUS BELIMUMAB IN


PATIENTS WITH LUPUS NEPHRITIS: A 6-MONTH OPEN-
LABEL EXTENSION

Brad Rovin1, Richard Furie2, Frédéric A. Houssiau3, Gabriel Contreras4,


Y.K.O. Teng5, Paula Curtis6, Anuradha Madan7, Angela Jones-leone7,
Tania Gonzalez-Rivera7, Mohamed Okily6, David Roth7 References
1
The Ohio State University, Division of Nephrology, Columbus, United States of America,
2 1. Almaani S et al. Clin J Am Soc Nephrol 2017;12:82535
Northwell Health, Division of Rheumatology, United States of America, 3Institut de
2. Hanly JG et al. Rheumatol 2016;55:25262
Recherche Expérimentale et Clinique, Université Catholique de Louvain and Service de
3. Hoover PJ et al. Kidney Int 2016;90(3):48792
Rhumatologie, Cliniques Universitaires Saint-Luc, Pôle de Pathologies Rhumatismales
4. Furie R et al. N Engl J Med 2020;383:111728
Inflammatoires et Systémiques, Brussels, Belgium, 4University of Miami Miller School of
Medicine, Division of Nephrology, Division of Hypertension, Department of Medicine,
Miami, United States of America, 5Leiden University Medical Center, Expert Center for
Lupus-, Vasculitis- and Complement-mediated Systemic diseases, Department of
FC035 VOCLOSPORIN INCREASES RENAL RESPONSE AT
Internal Medicine, Leiden, Netherlands, 6GlaxoSmithKline, Brentford, United Kingdom
COMMONLY USED UPCR THRESHOLDS IN PATIENTS WITH
and 7GlaxoSmithKline, Collegeville, United States of America
LUPUS NEPHRITIS

BACKGROUND AND AIMS: Lupus nephritis (LN) is the most common severe Maria Dall’Era1, Paola Mina-Osorio2, Vanessa Birardi2, Simrat Randhawa2
manifestation of systemic lupus erythematosus (SLE), occurring in up to 40% of 1
UCSF Medical Center, Rheumatology, San Francisco, United States of America and
patients (pts) with SLE over their disease course, and resulting in 10–20% of pts 2
Aurinia Pharmaceuticals Inc., Victoria, Canada
progressing to end-stage kidney disease.1-3 The BLISS-LN (GSK Study BEL114054;
NCT01639339) study demonstrated that the addition of intravenous (IV) belimumab
(BEL) to standard therapy (ST) in pts with active LN significantly improved renal BACKGROUND AND AIMS: Voclosporin is a novel calcineurin inhibitor with a
responses over 2 years compared with ST alone.4 Here we present additional safety and favorable metabolic profile and a consistent dose-concentration relationship,
efficacy data from the 6-month open-label (OL) extension phase of BLISS-LN. potentially eliminating the need for therapeutic drug monitoring.
METHOD: In this OL phase, eligible completers of the Phase 3 BLISS-LN study (those We have previously reported the primary endpoint of the Phase 3 AURORA trial
who received BEL or placebo [PBO] through Week 100 and completed Week 104 showing the addition of voclosporin to mycophenolate mofetil (MMF) and a low-dose
assessments) received BEL 10 mg/kg IV plus ST every 28 days for 24 weeks. Endpoints glucocorticoid regimen results in significantly higher renal response (RR) rates at one
at OL Week 28 included: safety; Primary Efficacy Renal Response (PERR; defined as year of treatment compared to MMF and low-dose glucocorticoids alone in patients
urine protein:creatinine ratio [uPCR] 0.7; eGFR no more than 20% below OL with lupus nephritis (LN). For the primary endpoint, RR was defined as 0.5 mg/mg
baseline value or 60 ml/min/1.73m2; no rescue therapy); Complete Renal Response UPCR with stable renal function in the presence of low-dose glucocorticoids and no
(CRR; defined as uPCR <0.5; eGFR no more than 10% below OL baseline value or 90 use of rescue medication.
ml/min/1.73m2; no rescue therapy); uPCR; eGFR; the proportion of pts with Systemic Several studies have demonstrated that proteinuria represents the best single predictor
Lupus Erythematosus Disease Activity Index (SLEDAI) score <4; Systemic Lupus for long-term renal outcomes.1,2 Given the efficacy of voclosporin in terms of
International Collaborating Clinics/American College of Rheumatology Damage Index proteinuria reduction, we conducted a sensitivity analysis evaluating RR with
(SDI); and corticosteroid use. Analyses were based on observed data and summarised additional UPCR targets.
relative to the OL baseline (last available value measured prior to dosing on or before METHOD: A total of 179 participants in the voclosporin (23.7 mg BID) arm and 178
the date of the first OL treatment dose). participants in the control arm from the AURORA trial were included in this analysis.
RESULTS: Of 257 pts (57.4 % of pts in BLISS-LN double-blind [DB] study) screened All participants received MMF (target 1 g BID) and low-dose oral glucocorticoids
and enrolled, 255 pts were treated (safety population: 123 pts switched from PBO to (initiated at 20-25 mg/day and tapered to 2.5 mg/day at 16 weeks).
BEL; 132 pts remained on BEL). In total, 254 pts were included in the efficacy analyses For this post hoc analysis, the UPCR component of RR was revised to include UPCR
(PBO to BEL: 122 pts; BEL to BEL: 132 pts). Mean (standard deviation) age was 35.9 targets at 0.2 mg/mg intervals above and below the original 0.5 target used for the
(10.3) years. primary endpoint in AURORA (i.e., 0.7 mg/mg or 0.3 mg/mg, respectively). Odds
In total, 3.5% of pts withdrew from the OL phase, mainly due to adverse events (AE; ratios for RR at six months and one year of treatment were analyzed using a logistic
2.0%). Overall, 168/255 (65.9%) pts experienced 1 AE (76/123 [61.8%] PBO to BEL regression model with terms for treatment, baseline UPCR, biopsy class, and MMF use

i24 | Abstracts
Nephrology Dialysis Transplantation Abstracts
at baseline and region. iptacopan results in a 49% reduction in proteinuria with no adverse safety findings
RESULTS: RR with UPCR 0.7 mg/mg was achieved by 46.9% of participants in the (ASN 2020 SU-OR39). The aim of this analysis was to determine whether iptacopan
voclosporin arm vs 32.0% of participants in the control arm at one year of treatment treatment altered eGFR slope in this same population.
(OR 2.07, p<0.0014) and 39.1% of participants in the voclosporin arm vs 24.7% of METHOD: Adults with biopsy-proven native C3G received open-label iptacopan for
participants in the control arm at six months of treatment (OR 2.10, p=0.0020). RR 12w (10-100mg bid during w1-3 then 200mg bid w4-12). All had proteinuria >1g/24h,
with UPCR 0.3 mg/mg was achieved by 28.5% of participants in the voclosporin arm low plasma C3, were receiving maximally tolerated stable ACEi/ARB and were
vs 15.7% of participants in the control arm at one year (OR 2.27, p=0.0023 and 22.9% vaccinated against N. meningitidis, H. influenzae and S. pneumoniae. On study
of participants in the voclosporin arm vs 14.0% of participants in the control arm at six completion, all patients received ongoing iptacopan in a long-term extension study
months of treatment (OR 1.90, p=0.0238; Table 1). (NCT03955445). Historical data were collected on eGFR (CKD-EPI) for the two-year
period prior to patients entering the study or since diagnosis where this was less than
two years, and were compared with those obtained in the IA following the
FC035 Table 1. Renal Response at One Year commencement of iptacopan. A generalized linear mixed model, with a common
intercept, a pre-treatment slope and a change in the slope following iptacopan
Control Voclosporin Odds Ratio vs Control treatment was used to predict the pre-post iptacopan change in eGFR over time.
(n=178) (n=179) RESULTS: 12 patients (10 male, 2 female; 11 C3GN, 1 DDD) participated in the IA.
Study baseline mean (SD) age was 26.1 (12.1) yrs, geometric mean (CV%) urine PCR
UPCR Threshold Percent of participants with renal response 397 (56) g/mol and eGFR 57.9 (65.5) ml/min/1.73m2. Complete data sets were
0.7 mg/mg 32.0% 46.9% 2.07 collected for all 12 patients; one patient entered the study immediately following biopsy
diagnosis. During the two years prior to the iptacopan treatment, the mean eGFR slope
0.5 mg/mg 22.5% 40.8% 2.65
was -14.8 ml/min/1.73m2/year (p=0.0016), consistent with the known natural history
0.3 mg/mg 15.7% 28.5% 2.27 of native C3G (Nephron 2020; 144: 272–280). Treatment with iptacopan was
Renal response defined as achievement of UPCR threshold with stable associated with a mean increase in eGFR of 3.1 ml/min/1.73m2 from baseline to 12w,
corresponding to a mean predicted eGFR preservation of 6.4 ml/min/1.73m2 over 12w
renal function (eGFR 60 mL/min or no decline >20% from baseline) in as a result of iptacopan administration (Figure 1, p=0.0459). Data collected in seven
the presence of low-dose glucocorticoids (in the 8 weeks prior to assess- patients who entered the extension study confirmed ongoing eGFR stability until 25
ment) and no use of rescue medication. weeks. There were no deaths or SAEs related to iptacopan and no AEs leading to
iptacopan discontinuation in this patient cohort.

CONCLUSION: Participants treated with voclosporin in addition to MMF and low-


dose glucocorticoids achieved statistically significantly increased renal response rates
regardless of the level of UPCR used, including at an even more stringent 0.3 mg/mg
target. This analysis further supports the efficacy observed with voclosporin in the
Phase 3 AURORA and the prior Phase 2 AURA-LV global trials.
References
1. Fanouriakis A et al. Ann Rheum Dis. 2020;79(1):713–723.
2. Tamirou F et al. Lupus Sci Med. 2015;2(1): e000123.

FC036 Figure: Individual patient eGFR slopes (n=12) for up to 2 years prior to (blue
FC036 IPTACOPAN (LNP023): A NOVEL ORAL COMPLEMENT zone) and following (green zone) commencement of 12w course of iptacopan. Mean
ALTERNATIVE PATHWAY FACTOR B INHIBITOR SAFELY AND eGFR slope and 95% CI indicated by bold blue line and surrounding shadowed area.
EFFECTIVELY STABILISES EGFR IN C3 GLOMERULOPATHY

Edwin Kwan Soon Wong1, Manuel Praga2, Carla Nester3,4, Moglie Le Quintrec5, CONCLUSION: 12 weeks treatment with iptacopan 200mg bid in patients with C3G
Erica Daina6, Giuseppe Remuzzi6, Angelo Trapani7, Yaqin Wang7, Junhao Liu7, resulted in statistically significant and clinically important improvement in eGFR slope
Guido Junge8, Matthias Meier8, Nicholas Webb8 with favourable safety and tolerability in addition to significantly reducing proteinuria.
1
Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom, 2Hospital 12 de Extended iptacopan treatment up to 25 weeks resulted in ongoing stability of eGFR,
Octubre, Madrid, Spain, 3Molecular Otolaryngology and Renal Research Laboratories, suggesting that this may result in clinically relevant prolongation of the time to or even
University of Iowa, Iowa City, IA, United States of America, 4Stead Family Children’s potentially prevention of the development of kidney failure.
Hospital, University of Iowa, Iowa City, IA, United States of America, 5Department of
Nephrology and Renal Transplantation, Lapeyronie Hospital, 34295 Montpellier Cedex
5, France, 6Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy,
7
Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States of America
and 8Novartis Pharma AG, Lichtstrasse 35, 4056 Basel, Switzerland

BACKGROUND AND AIMS: Iptacopan (LNP023) is a highly selective oral low


molecular weight inhibitor of Factor B, a key complement alternative pathway
protease. We have previously reported data from an interim analysis (IA) of a Phase 2
study in patients with native C3G (NCT03832114) showing that a 12-week course of

10.1093/ndt/gfab121 | i25
Nephrology Dialysis Transplantation 36 (Supplement 1): i26–i28, 2021
10.1093/ndt/gfab117

TREATMENT & OUTCOME OF GLOMERULONEPHRITIS CONCLUSION: In a humanized mouse model of IgAN, hematuria bouts following
respiratory tract infections are caused by a neutrophil-mediated alteration of the
glomerular filtration barrier (podocyte damage, complement deposits and loss of
Collagen IV). These findings may help to unveil novel potential therapeutic approaches
FC037 NEUTROPHILS PLAY A KEY ROLE IN THE INITIATION OF to combat one of the key elements in the progression of IgAN and related conditions.
GLOMERULAR HEMATURIA IN A POSTINFECTIOUS IGAN
EXPERIMENTAL MODEL

Carmen Herencia1, Melania Guerrero Hue2, Cristina Vazquez-Carballo1,


Christian De Tymowski3, Julie Bex-Coudret3, Lucas Opazo-Rıos4,
Cristina Garcıa-Caballero5, Jose Luis Morgado Pascual2,5, Sandra Rayego-
Mateos4, Mercedes Vallejo-Mudarra6, Laureline Berthelot7, Angel Sevillano8, FC038 CRESCENTS DERIVE FROM SINGLE PODOCYTE
Manuel Praga9, Santiago Rodriguez de Cordoba10, Jesus Egido4, PROGENITORS AND A DRUG ENHANCING THEIR
Renato Monteiro3, Juan Antonio Moreno6,12 DIFFERENTIATION ATTENUATES RAPIDLY PROGRESSIVE
1 GLOMERULONEPHRITIS
Instituto de Investigaci
on Sanitaria-Fundaci
on Jiménez Dıaz. Universidad Autonoma,
Renal, Vascular and Diabetes Research Laboratory, Madrid, Spain, 2Instituto
Maria Elena Melica1, Giulia Antonelli1, Roberto Semeraro2, Maria Lucia Angelotti1,
Maimonides de Investigaci on Biomédica de C
ordoba (IMIBIC), H.U. Reina Sofıa, GE06
Gianmarco Lugli2, Elena Lazzeri1, Laura Lasagni1, Paola Romagnani1,3
Pathophysiology of renal and vascular damage, Cordoba, Spain, 3Université de Paris, 1
INSERM 1149, CNRS ERL8252, Center for Research on Inflammation (CRI, Paris, France, University of Florence, Department of Experimental and Clinical Biomedical Sciences,
4
Instituto de Investigaci
on Sanitaria-Fundaci
on Jiménez Dıaz. Universidad Autonoma, Firenze, Italy, 2University of Florence, Department of Experimental and Clinical
Renal, Vascular and Diabetes Research Laboratory, madrid, Spain, 5Universidad de Medicine, Firenze, Italy and 3Meyer Children’s University Hospital, Nephrology and
Cordoba, Department of Cell Biology, Physiology and Immunology, Cordoba, Spain, Dialysis Unit, Firenze, Italy
6
Instituto Maim onides de Investigaci
on Biomédica de C
ordoba (IMIBIC), H.U. Reina
Sofıa, GE06 Pathophysiology of renal and vascular damage, cordoba, Spain, 7Université BACKGROUND AND AIMS: Rapidly progressive glomerulonephritis (RPGN)
de Nantes, INSERM, UMR_S 1064, Centre de Recherche en Transplantation et encompasses a group of diverse disorders characterized by the presence of massive
Immunologie (CRTI), Nantes, France, 8Hospital 12 de Octubre, Nephrology, Madrid, hyperplasia of parietal epithelial cells (PEC) as the main histopathological lesion at
Spain, 9Hospital 12 de Octubre, Nephrology, madrid, Spain, 10Center for Biological kidney biopsy. It is associated with a rapid decline in kidney function referred to
Research, Higher Council for Scientific Research and Center for Biomedical Research in altogether as rapidly progressive glomerulonephritis. Typically, crescent formation is
Rare Diseases, Madrid, Spain and 12Universidad de Cordoba, Department of Cell the consequence of diverse upstream pathomechanisms involving the specific
Biology, Physiology and Immunology, cordoba, Spain activation of PEC. PEC normally reside peacefully along Bowman capsule and
represent in part renal progenitor cells (RPC). Previous studies observed RPC markers
BACKGROUND AND AIMS: Hematuria is a common finding in patients with IgA in crescents from patients with different types of glomerulonephritis. Similarities
nephropathy (IgAN), occurring mainly after upper respiratory tract infections. between stem cell niches of bone marrow and kidney, prompted us to hypothesized
Hematuria can lead to acute kidney injury and chronic loss of renal function in IgAN. that crescents result from monoclonal expansion of a single RPC clone conceptually
However, the mechanisms involved in egression of erythrocytes from the glomerular similar to monoclonal diseases originating from hematopoietic stem cells. According to
capillaries into the urinary space are unknown. To answer this question, we developed this analogy, we further hypothesized that drugs known to cure monoclonal disease of
an infection with Streptococcus pneumoniae (SP) in a humanized experimental IgAN the hematopoietic stem cells by enforcing their terminal differentiation could also
model (a1KICD89tg mice) that resembles the pathological and clinical findings of attenuate crescentic glomerulonephritis.
disease (IgA1 and soluble CD89 mesangial deposits, complement activation, METHOD: To address this hypothesis, we established a RPGN disease model in a
proteinuria and hematuria). conditional transgenic mouse based on the mT/mG and the Confetti reporter that
METHOD: a1KICD89tg mice (12 weeks old) received an intranasal instillation of SP allows lineage tracing and clonal analysis of RPCs. Animals were treated with known
(107 bacteria). Blood, urine and renal samples were obtained during 1 month after pharmacological inhibitors of clonal stem cell proliferation in myeloproliferative
induction of respiratory infection. The presence of SP in lungs from these mice was disorders. Crescentic lesions were characterized by super-resolution STED microscopy.
confirmed by microbiological analysis. Hematuria was quantified in the urinary Finally, we employed single cell RNA sequencing of human renal progenitor cultures to
sediment and renal function was determined by biochemical analysis. Renal identify the immature progenitor subset-generating crescent in human to identify
histological characteristics were evaluated by hematoxylin/eosin, masson’s trichrome putative new biomarker(s) of RPNG to validate in biopsy of patients.
and PAS staining. IgA glomerular deposits, activation of complement system and RESULTS: We observed that the crescentic lesions originated from the clonal
infiltration of proinflammatory cells was examined by immunohistochemistry or expansion of single RPC, thus suggesting a clonal stem cell disorder. Therefore, we
immunofluorescence. Circulating leukocyte populations were studied on a administrated a series of drugs known to ameliorates myeloproliferative neoplasms to
hemocytometer. Renal inflammatory cytokines, metalloproteases, as well as markers of our RPGN mouse model as potential therapeutic agents. In particular, treatment with
tubular and glomerular damage were determined in kidneys by RT-PCR and western- one of the compounds induced a reduction in both proteinuria and crescent formation.
blot. To further validate the role of neutrophils in this pathological setting, we selective 3D confocal microscopy and STED super-resolution imaging of glomeruli showed that
depleted these cells through a single injection of anti-Ly6G mAb (200 mg/kg i.p). this compound turned the uncontrolled hyperplasia of a specific immature PEC subset
RESULTS: SP-intranasal instillation in a1KICD89tg mice increased hematuria, into a controlled differentiation into new podocytes thereby restoring the injured
microalbuminuria and proteinuria, peaking at 48h after induction of the respiratory glomerular filtration barrier.
infection. SP instillation caused disruption of the glomerular basement membrane, Single cell RNA sequencing of human renal progenitor cultures identified a new
with decreased expression of the slit diaphragm proteins nephrin and synaptopodin, as marker of the crescent-generating progenitor cells. Expression of this marker in
well as higher glomerular accumulation of IgA and proteins of complement system biopsies of patients with rapidly progressive glomerulonephritis associated with
(C3, MBL). Hematuria intensity was positively correlated with the presence of progression toward end stage kidney disease. Treatment of human PEC with the drug
interstitial F4/80þ macrophages, matrix metalloproteinase 9 (MMP-9), inflammatory that in in vivo experiments showed a therapeutic effect on RPGN reduced proliferation
cytokines and chemokines (IL-1b, IL-6, TNF-a, CCL-2, CCL5 and CX3CL1/CX3CR1) of the immature progenitor subset promoting their differentiation into podocytes.
as well as p65 NF-jB activation. Hematuria was negatively correlated with anti- CONCLUSION: These results demonstrate that glomerular hyperplastic lesions derive
inflammatory IL-10 mRNA expression, Factor H levels and collagen IV content. from clonal amplification of a RPC subset and that shifting proliferation to podocyte
Notably, SP infection induced expression of the tubular injury markers N-GAL and differentiation reverses crescent formation and improves clinical outcome.
KIM-1. Increased peripheral neutrophils levels were observed in the SP-infected
a1KICD89tg mice. Mechanistically, anti-Ly6G-mediated neutrophil depletion reduced
SP-mediated hematuria, proteinuria and albuminuria, prevented loss of synaptopodin
and nephrin, decreased renal inflammation and MMP-9 expression in a1KICD89tg
mice

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
FC039 RENAL OUTCOME AFTER RITUXIMAB IN ADULT-ONSET IGA renal manifestations and is well tolerated. IgAV patients show higher remission rates
VASCULITIS AND CRESCENTIC IGA NEPHROPATHY: A and a longer ESRD-free survival as compared to cIgAN patients.
MULTICENTRE STUDY

Giorgio Trivioli1, Alice Canzian2, Federica Maritati3, Roberta Fenoglio4,


Evangeline Pillebout5, Maria Letizia Urban6, Aladdin Mohammad7,
Estela Nogueira8, Elena Silvestri6, Per Eriksson9, Mårten Segelmark10,
Pavel Novikov11, Helen Harris12, Ilya Smitienko13, Sergey Moiseev11,
Bayram Farisogullari14, Deirdre O’Sullivan15, Cristina Ponte16, Peter Lamprecht17,
Alojzija Hocevar18, Omer Karadag14, Mark Little15, Giacomo Emmi6,
David Jayne19,20, Stephen Mcadoo21, Dario Roccatello4,22, Augusto Vaglio1,23
1
Meyer Children’s Hospital, Nephrology and Dialysis Unit, Florence, Italy, 2Parma
University Hospital, Obstetrics and Gynecologic Unit, Parma, Italy, 3Sant’Orsola
Hospital, Nephrology Unit, Bologna, Italy, 4San Giovanni Bosco Hospital, Centre of
Research of Rheumatologic, Nephrologic and Rare Diseases, Turin, Italy, 5Sant-Louis
Hospital and University Paris Diderot, Department for Nephrology, Paris, France,
6
University of Firenze, Department of Experimental and Clinical Sciences, Florence, Italy,
7
Lund University, Department of Rheumatology, Clinical Science , Lund, Sweden,
8
Centro Hospitalar Universit ario Lisboa Norte, Division of Nephrology and Renal
Transplantation, Lisboa, Portugal, 9Linkoeping University, 10. Department of Medical
and Health Sciences, Linkoping, Sweden, 10Linkoeping University, Department of
Nephrology, Linkoping, Sweden, 11Sechenov First Moschow State Medical University,
Clinic of Nephrology, Internal and Occupational Diseases, Moscow, Russia,
12
Whyteman’s Brae Hospital, Rheumatology Unit, Kirkcaldy, United Kingdom, 13Medical
Center “K + 31”, Moscow, Russia, 14Hacetteppe University, Vasculitis Research Centre,
Ankara, Turkey, 15Tallgath Hospital, Trinity Health Kidney Centre, Dublin, Ireland,
16
Lisbon Academic Medical Centre, Rheumatology, Lisboa, Portugal, 17University of
Lübeck, Department of Rheumatology and Clinical Immunology, Lübeck, Germany,
18
University Medical Centre Ljubljana, Department of Rheumatology, Ljubljana,
Slovenia, 19University of Cambridge, Department of Medicine, Cambridge, United
Kingdom, 20Addenbrooke’s Hospital, Vasculitis and Lupus Clinic, Cambridge, United
Kingdom, 21Imperial College London, Centre for Inflammatory Disease, London, United
Kingdom, 22University of Turin, Centre of Research of Rheumatologic, Nephrologic and
Rare Diseases, Turin, Italy and 23University of Florence, Department of Biomedical
Experimental and Clinical Sciences, Florence, Italy

BACKGROUND AND AIMS: Glucocorticoids (GC) and/or immunosuppressive


agents are the mainstay of therapy for adult-onset IgA Vasculitis (IgAV), but their
efficacy is often partial while their toxicity is relevant. Recently, rituximab (RTX) has
been reported as a safe and effective option but only few data on renal outcome are
available.1 RTX has also been used in a few cases of crescentic IgA Nephropathy
(cIgAN), an IgAN subset with vasculitic lesions and poor response to conventional
immunosuppressive regimens.2 We present the results of a multicentre cohort of
patients with IgAV and cIgAN treated with RTX.
METHOD: The databases of 16 consorted European centres were investigated to
screen for patients with adult-onset, biopsy-proven IgAV and cIgAN (crescents in
25% glomeruli and rapid eGFR worsening at presentation), who received RTX as
induction therapy. We selected patients with active renal manifestations at the time of
RTX. Remission was defined as a Birmingham Vasculitis Activity Score (BVAS)=0 or
<5 if it was due to persistent proteinuria and relapse as an increase in BVAS requiring
change in immunosuppressive therapy.
RESULTS: We identified 38 patients with IgAV and 12 patients with cIgAN who
received RTX and had active renal involvement at the time of treatment. The median
age at onset was 40 years (interquartile range, IQR, 25-53) and more than two-thirds of References
patients were male (Table 1). The median follow-up after RTX was 41 months (IQR
18-60). 1. Maritati F et al. Arthritis & rheumatology 2018; 70(1): 109-14.
Renal outcomes are reported in Table 2. At the time of treatment, 24 patients (48%) 2. Lundberg S et al. Clin Kidney J 2017; 10(1): 20-6.
had eGFR 60 mL/min/1.73 m2. All had IgAV and their median BVAS was 17 (IQR 3. Pillebout E et al. JASN 2002; 13(5): 1271-8.
10-22). Furthermore, all had microhaematuria and proteinuria. Renal histology
showed mesangial or focal endocapillary proliferation in 12/17 (71%) patients who
underwent biopsy (class II-IIIA according to Pillebout3). Twenty patients (83%)
achieved remission; after a median of 12 months (range 9-14), four experienced a
minor relapse and one had a major relapse with significant renal disease progression. FC040 INTERIM RESULTS OF PHASE 1 AND 2 TRIALS TO
Renal function remained stable in all but two patients who developed end-stage renal INVESTIGATE THE SAFETY, TOLERABILITY,
disease (ESRD). Micro-haematuria subsided in 14/24 (58%) and median 24h PHARMACOKINETICS, PHARMACODYNAMICS, AND
proteinuria decreased from 1750 mg (IQR 865-3275) to 175 mg (IQR 100-800) at last CLINICAL ACTIVITY OF BION-1301 IN PATIENTS WITH IGA
follow-up (p=0.029). NEPHROPATHY
Of the 26 patients with eGFR <60 mL/min/1.73 m2, 14 had IgAV and 12 had cIgAN.
All were biopsied and 20 (77%) had diffuse endo/extra-capillary proliferation (classes Jonathan Barratt1, Billy Hour2, Cailin Sibley3, Angelique Mittan3, Suzanne Roy3,
IIIB-IV). Five patients required dialysis but recovered soon after treatment start. Colleen Stromatt3, Aaron Endsley4, Jeannette Lo3, Alan Glicklich3
Remission was achieved by 16/26 (61%); eight (50%) subsequently relapsed and two 1
University of Leicester, Leicester, United Kingdom, 2Amicis Research Center, United
(12%) reached ESRD. At last follow-up, eGFR was 60 mL/min/1.73 m2 in 8/26 (31%),
States of America, 3Chinook Therapeutics, Inc. and 4Certara, Inc
10/26 (48%) had stable renal function as compared to the time of RTX, while 8/26
(31%) had developed ESRD. Median 24h proteinuria decreased from 3400 mg (IQR
2150-6500) to 770 mg (177-1315) (p=0.016). BACKGROUND AND AIMS: IgA nephropathy (IgAN), the leading cause of primary
Remission rate and ESRD-free survival were respectively 86% and 92% in patients with glomerulonephritis, is an autoimmune disease with no approved treatments.1
IgAV, while they were respectively 42% and 42% in cIgAN patients. Furthermore, 21/ Progression to end-stage-renal disease occurs in up to 45% of IgAN patients, requiring
24 (87%) patients who received RTX alone or combined to glucocorticoids but not to dialysis or kidney transplant to manage.2-4 A critical step in IgAN pathogenesis is the
immunosuppressive agents achieved remission and 22/24 (92%) were ESRD-free at last production of galactose-deficient IgA1 (Gd-IgA1) leading to the generation of anti-Gd-
follow-up. Of the 26 patients receiving immunosuppressive agents, 17 (65%) obtained IgA1 autoantibodies and the formation of immune complexes that result in kidney
remission and 18 (69%) were ESRD-free at last assessment. Over the whole follow-up, inflammation and damage.5 A Proliferation-Inducing Ligand (APRIL), a soluble factor
only one patient reported a severe adverse effect related to RTX (pneumonia). that regulates B cell differentiation, proliferation and survival of plasma cells, and IgA
CONCLUSION: Renal involvement in adult-onset IgAV and cIgAN is frequently class-switching is elevated in patients with IgAN6, 7. IgAN patients with high plasma
severe. RTX, combined or not with other immunosuppressive agents, may improve APRIL levels are reported as having higher levels of Gd-IgA1 and proteinuria and

10.1093/ndt/gfab117 | i27
Abstracts Nephrology Dialysis Transplantation

lower estimated glomerular filtration rates compared to those with lower plasma and PD effects of BION-1301, serum levels of BION-1301, free APRIL (fAPRIL), anti-
APRIL levels.7 BION-1301 is a novel humanized blocking antibody targeting APRIL drug antibodies (ADA), neutralizing antibodies (NAbs), and Gd-IgA1 were quantitated
that has been evaluated in a Phase 1 study of healthy volunteers (HV). In Parts 1 and 2 using ELISA-based immunoassays. Serum levels of IgA, IgG, and IgM were measured
of the Phase 1 study in HV, we previously reported that BION-1301 was well-tolerated by immunoturbidimetry. UPCR was assessed from 24-hour urine collections.
with no serious adverse events (SAEs), a pharmacokinetic (PK) half life >30 days and RESULTS: In Part 3 of Phase 1 and the Phase 2 OLE trial to date, BION-1301 has been
demonstrated dose-dependent pharmacodynamic (PD) effects characterized by well tolerated in IgAN patients receiving a 450mg dose every two weeks for 12þ weeks
durable reductions in serum levels of free April (fAPRIL), IgA and Gd-IgA1, IgM, and with no SAEs observed. Consistent with PD responses previously reported in HVs,
to a lesser extent IgG8. Here we present interim results from Part 3 of the Phase 1 and durable reductions in serum levels of fAPRIL and immunoglobulins were also observed
the Phase 2 Open-Label Extension (OLE) trials that characterize the safety, PK and PD in IgAN patients. Clinically meaningful reductions in proteinuria were observed as
profile, and preliminary efficacy of BION-1301 in patients with IgAN. early as 12 weeks and were associated with the reduction in IgA. Additional data from
METHOD: The Phase 1 study (NCT03945318) comprises 3 parts. Parts 1 and 2 patients receiving long-term treatment will be updated.
assessed single- and multiple ascending doses of BION-1301 in HV from 10mg to CONCLUSION: BION-1301 is a novel humanized anti-APRIL monoclonal antibody
1350mg and 50mg to 450mg once every 2 weeks for one month, respectively. Part 3 is being developed as a potential treatment for patients with IgAN. BION-1301 offers
an ongoing, open-label, two cohort design in approximately 20 IgAN patients with disease modifying potential by directly targeting the underlying multi-hit immune
BION-1301 at a starting dose and regimen of 450mg once every 2 weeks for a total of 3 pathogenesis of IgAN, which is not addressed with the current standard of care
months. Key eligibility criteria for Part 3 include: (1) urine protein 0.5 g/24h or treatment. Promising early biomarker and clinical activity responses support the
baseline UPCR 0.5 g/g, (2) stable/optimized dose of ACE-I/ARB or be intolerant to continued development of BION-1301 in IgAN.
ACE-I/ARB, and (3) biopsy-verified diagnosis of IgAN within the past 10 years.
Patients completing Part 3 are eligible to enroll in the Phase 2 OLE study
(NCT04684745) to receive BION-1301 for up to an additional 2 years. To evaluate PK

i28 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i29–i31, 2021
10.1093/ndt/gfab119

BASIC SCIENCE IN AKI

FC042 IRF8 IN CDC1 IS PROTECTIVE IN POST-ISCHEMIC ACUTE


FC041 TUBULAR EPITHELIAL CELL POLYPLOIDY IS ESSENTIAL TO KIDNEY INJURY
SURVIVE AKI BUT IT CONTRIBUTES TO CKD PROGRESSION
Li Na1, Stefanie Steiger1, Lingyan Fei2, Chenyu Li1, Chongxu Shi1, Natallia Salei3,
Letizia De Chiara1, Elena Lazzeri1, Paola Romagnani1,2 Barbara U. Schraml3, Zhihua Zheng2, Hans-Joachim Anders1, Julia Lichtnekert1
1 1
University of Florence, Department of Experimental and Clinical Biomedical Sciences, Ludwig-Maximilian’s-University Hospital, Department of Nephrology, Department of
Firenze, Italy and 2Meyer Children’s University Hospital, Nephrology and Dialysis Unit, Medicine IV, Munich, Germany, 2The Seventh Affiliated Hospital, Sun Yat-sen University,
Firenze, Italy Department of Nephrology, Center of Urology, shenzhen, P.R. China and 3Ludwig-
Maximilian’s-University Hospital, Walter-Brendel-Centre of Experimental Medicine,
BACKGROUND AND AIMS: Acute Kidney Injury (AKI) is a syndrome Munich, Germany
characterized by an acute deterioration of renal function. Due to its high prevalence
and poor short-term outcomes, AKI represents a global healthcare issue. Many BACKGROUND AND AIMS: Post-ischemic acute tubular necrosis is a common
epidemiologic studies have indicated that the development of Chronic Kidney Disease cause of acute kidney disease (AKD) and subsequent chronic kidney disease. In AKD,
(CKD) features prominently among the numerous long-term complications of AKI. mononuclear phagocytes (MPCs) including conventional dendritic cells (cDCs) are
The pathophysiological basis for this phenomenon has remained unclear so far. present during the different phases of kidney injury, repair and regeneration. The
Recently, we found that tubular epithelial cells (TEC) undergo endoreplication- contribution of cDCs to AKD is still poorly understood. Hence, we hypothesized that
mediated hypertrophy after AKI. Endoreplications are incomplete cell cycles that lead transcription factor interferon regulatory factor 8 (IRF8)-specific cDCs regulate the
to the formation of polyploid cells. Physiologically, polyploidy offers several advantages immune response in AKD.
such as rapid adaptation to stress, compensation for cell loss and enhanced cell METHOD: AKD was induced by unilateral ischemia reperfusion injury in IRF8-
function. However, as renal epithelial cells are massively lost after AKI, TEC polyploidy deficient Clec9a-specific DCs (IRF8fl/fl Clec9acre/cre or cre/wt) and wild type C57BL/6
may constitute an effective strategy to sustain a temporary functional recovery of the mice. Immune phenotyping of leukocytes in kidney and spleen and mRNA expression
kidney without restoring tissue integrity potentially leading to CKD. Therefore, we profiling were performed, as well as kidney function evaluated. For in vitro studies,
hypothesized that: 1) polyploid TEC are an adaptive stress response required to IRF8 small interfering RNA transfection technology on bone marrow-derived DCs was
maintain kidney function after AKI; 2) polyploid TEC are involved in the AKI to CKD used.
progression. RESULTS: In the healthy kidney and lymphoid organ (e.g., spleen and kidney draining
METHOD: To address these hypotheses, we employed a series of in vitro and in lymph node), we identified four MPC subsets according to the diverse expression
vivo transgenic models based on the Fluorescence Ubiquitin Cell Cycle Indicator patterns of CD11b and CD11c. Of which, IRF8 was specifically expressed in the
(FUCCI) technology to monitor cell cycle phasing in combination with YAP1 CD11blow CD11chigh R4 subset (containing mainly cDC1). During AKD, IRF8
overexpression or downregulation. In the in vivo models, YAP1 overexpressing mice deficiency in cDCs reduced the number of MHCIIþ DCs accumulating among
and YAP1 knock-out mice were subjected to unilateral ischemia reperfusion injury tubulointerstium space without affecting cDC2 or CD64þ DCs, while completely
(IRI) or glycerol-induced rhabdomyolysis to induce AKI. Polyploid cells have been abolished cDC1 in post-ischemic kidney (See Figure). This was accompanied with a
then characterized by single cell-RNA sequencing analysis, cell sorting, super- decrease in the surface expression of chemokine receptor CCR7 and CCR9, reduction
resolution STED microscopy and transmission electron microscopy in both mouse and in the number of kidney CD4- CD8þ T cells and Tregs, but a moderate increase in
human. TH1-related and pro-inflammatory cytokines and infiltrating neutrophils in the kidney
RESULTS: In vitro, human renal tubular cells undergo polyploidization. The fraction of mice with IRF8-deficient cDCs. This was in line with reduced kidney function,
of polyploid cells significantly decreases when YAP1 nuclear translocation is blocked, marked by aggravated GFR loss, elevated plasma BUN level, kidney atrophy,
indicating a possible involvement of YAP1 in regulating TEC polyploidy. After AKI in pathological tubular injury and living proximal tubule loss. In vitro, bone marrow-
mice, YAP1 expression and nuclear translocation are significantly enhanced. The derived IRF8-deficient DCs showed an impaired ability to repair “artificially injured”
inhibition of YAP1 following AKI, reduces the number of polyploid cells impairing tubular epithelial cells (TECs), accompanied with less phagocytosis capacity and
kidney function and causing a dramatic reduction of mouse survival. In contrast, YAP1 maturation capacity under necrotic TECs soup or histone stimulation.
overexpression leads to an increase in the number of polyploid cells even in the absence CONCLUSION: Our data show that the restricted depletion of IRF8 in cDCs reduces
of kidney damage (healthy mice). Strikingly, these healthy mice, despite having an the number of infiltrating kidney cDC1, which drives tissue inflammation and damage,
increased percentage of polyploid cells, present an unexpected decline of renal function and ultimately aggravates post-ischemic AKD. Thus, cDC1s are having a protective
suggesting an association between increased polyploidy and CKD development. role in AKD.
Indeed, they develop tubulointerstitial fibrosis acquiring a marked senescent
phenotype triggering CKD. Isolation of polyploid cells proved that these cells actively
transcribe and secrete pro-fibrotic factors thus confirming their role in CKD
progression.
CONCLUSION: Collectively, these data suggest that: 1) polyploidization after AKI is
required to maintain kidney function allowing survival; 2) polyploid cells are pro-
fibrotic leading in the long run to CKD progression.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC043 SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR (ODB) has been hypothesized to play a role in this process. However, there is a general
RECEPTOR (SUPAR) DETERMINES OUTCOMES IN CLINICAL lack of research on the long-term effects of acute kidney injury (AKI) on ODB and
AND EXPERIMENTAL SEPTIC ACUTE KIDNEY INJURY their total oxalate-degrading activity (ODA) in fecal microbiota. In this study, we
evaluated whether renal dysfunction could affect intestinal ODB and their total ODA
Christian Nusshag1, Changli Wei 2 , Eunsil Hahm1, Roman Szudarek3, in a rat model of glycerol-induced AKI.
Florian K€alble4, Claudius Speer4, Florian Uhle3, Jesper Eugen-Olsen5, Markus METHOD: The Male Wistar rats (200-300 g, n=20) on oxalate-free diet were
A. Weigand3, Martin Zeier4, Christian Morath4, Thorsten Brenner6, Jochen Reiser1 randomly divided into 2 groups. After 24-h of water deprivation, Group 1 (n=10)
1
Rush University Medical Center, Internal Medicine, RUSH Medical College, Chicago, received an intramuscular injection of 50% glycerol (10 ml/kg of body weight), and
United States of America, 3Heidelberg University Hospital, Anesthesiology, Heidelberg, Group 2 (n=10) served as control. The numbers of ODB (incubated in a highly
Germany, 4Heidelberg University Hospital, Nephrology, Heidelberg, Germany, selective Oxalate Medium and determined using culture method) and total fecal ODA
5
Copenhagen University Hospital Hvidovre, Clinical Research Centre, Hvidovre, were measured after injection on days 7 and 70. The method of redoximetric titration
Denmark and 6University Hospital Essen, Anesthesiology, Essen, Germany with a KMnO4 solution was adopted to evaluate total ODA in fecal microbiota; the
results were expressed as % of oxalate degradation per 0.01 g of feces.
BACKGROUND AND AIMS: Sepsis is the main contributor to the development of Renal injury was assessed by histopathological examination, serum creatinine and daily
acute kidney injury (AKI) in critically ill patients. Plasma soluble urokinase proteinuria levels after removing the animals from the experiment on day 70. Cortical
plasminogen activator receptor (suPAR) is a circulating risk factor for AKI and a new interstitial fibrosis was measured by computerized image analysis on sections stained
prognostic marker for renal outcome prediction. We analyzed the pathophysiological with picrosirius red. The median (Me) and the interquartile ranges (Q25; Q75) were
role and kinetic properties of suPAR in septic AKI in critically ill patients and in a calculated and compared using the nonparametric Mann-Whitney test. The Spearman
murine model of septic AKI. correlation coefficient was used to evaluate association between the examined
METHOD: 200 critically ill patients were enrolled prospectively after meeting Sepsis-3 parameters.
criteria. Serum suPAR levels were measured at 0, 12, 24, 48, 72, 96, 120 and 168-hour RESULTS: The obtained results demonstrated: 1) after glycerol injection on day 7, no
after enrollment (n=1440) and the need for RRT within 7 days (predefined criteria) was differences were found in the numbers of ODB and total fecal ODA between the
assessed as the primary outcome measure. Polybacterial sepsis was induced by cecal experimental and control groups: 5.9 (5.4-6.0) vs 6.0 (5.4-6.4) CFU/g, p=0.65 and 2.0
slurry injection in three mouse strains, respectively wild type (WT, N=16), uPAR- (0.1-5.0) vs 2.5 (2.0-9.0) %/0.01g, p=0.24, respectively; 2) after AKI initiation on day 70,
knockout (KO, N=15), and suPAR transgenic overexpression (OE, N=14). the numbers of ODB and total fecal ODA were significantly lower in Group I
RESULTS: No or mild AKI occurred in 62 patients (31.0%), moderate or severe AKI compared with control Group II (Fig. 1); 3) the higher percentage of renal interstitial
without the need for RRT in 102 patients (51.0%), criteria for RRT were met in 36 fibrosis was, the higher total fecal ODA occurred in the experimental rats (Fig. 2). In
patients (18.0%) and 7 patients (3.5%) died within the 7-day period. Compared to all addition, the number of ODB in feces in Group 1 had an inverse association with
other maximum AKI stages and AKI disease courses within 7 days, patients requiring serum creatinine (r=-0.52, p=0.006) and 24-h proteinuria levels (r=-0.86, p<0.0001).
RRT showed significantly higher suPAR levels at all time-points. Patients with suPAR
levels  12.7 ng/mL (highest quartile) had an unadjusted odds ratio (OR) of 9.73 (95%
confidence interval [CI], 4.31-21.98) and an adjusted odds ratio of 5.22 (95% CI, 2.16-
12.65) for the need for RRT; and 7.47 (95% CI, 3.54-15.74) and 4.44 (95% CI, 1.98-
9.97) for RRT or death within 7 days compared to patients with levels < 12.7 ng/mL.
Compared to KO mice, WT and OE mice showed a significantly greater impairment of
renal function, structure and tubular apoptosis 24 hours after induction of sepsis. The
inflammation levels with respect to Interleukin 6 were comparable between different
strains. Kaplan-Meier analysis revealed a survival benefit of KO mice over OE mice
within 24h (86.7% vs. 50.0%, p=0.033).
CONCLUSION: SuPAR distinguishes between divergent AKI stages/courses and the
need for RRT at any time within 7 days after sepsis diagnosis. Our experimental data
suggest that suPAR is a pathophysiological driver of septic AKI and may serve as a
target for future interventional strategies.

FC044 THE LONG-TERM EFFECTS OF ACUTE KIDNEY INJURY ON


INTESTINAL OXALATE-DEGRADING BACTERIA IN RATS

Natalia Stepanova1, Ganna Tolstanova2, Valentyn Nepomnyashchii1,


Iryna Akulenko2, Svitlana Savchenko1, Mykola Kolesnyk1
1
State Institution “Institute of Nephrology of the National Academy of Medical Science
of Ukraine”, Nephrology & Dialysis, Kyiv, Ukraine and 2Taras Shevchenko National
University of Kyiv, Kyiv, Ukraine FC044 Figure 1: The numbers of ODB and total fecal ODA in the rats of the
experimental (Group I) and the control groups (Group II).
BACKGROUND AND AIMS: Gut microbiota is considered an important factor
affecting oxalate handling in the intestine. It has been demonstrated that intestinal
oxalate secretion provides a complementary route of excretion, and it becomes more
evident when kidney function declines. A diversity of gut oxalate-degrading bacteria

i30 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: AKI had the long-term negative effects on the quantitative and
qualitative characteristics of ODB in fecal microbiota in rats. Moreover, the results of
our study confirmed an increasing trend in total fecal ODA according to the
aggravation of renal interstitial fibrosis in rats.

FC044 Figure 2: Association between renal interstitial fibrosis and total fecal ODA
in the rats with glycerol-induced AKI.

10.1093/ndt/gfab119 | i31
Nephrology Dialysis Transplantation 36 (Supplement 1): i32–i33, 2021
10.1093/ndt/gfab116

FC046 INCIDENCE OF NOSOCOMIAL ACUTE KIDNEY INJURY (AKI)


AKI: THE GOOD, THE BAD & THE UGLY IN A COHORT OF COMMUNITY-DWELLING OLDER ADULTS
OVER 8 YEARS OF OBSERVATION

Natalie Ebert1, Alice Schneider2, Yanina Balabanova3, Gunnar Brobert4,


FC045 URINARY LEVELS OF SARS-COV-2 NUCLEOCAPSID PROTEIN
Dörte Huscher2, Nina Mielke1, Elke Schaeffner1
PREDICT AKI AND FATAL OUTCOME IN COVID-19 1
atsmedizin, Berlin, Germany, 2Charité -
Institute of Public Health, Charite Universit€
Björn Tampe1, Samy Hakroush2 Institut für Biometrie und Klinische Epidemiologie, Berlin, Germany, 3Bayer AG,
1 Epidemiology - Medical Affairs & Pharmacovigilance, Pharmaceuticals, Berlin, Germany
University Medical Center Göttingen, Department of Nephrology and Rheumatology,
and 4Bayer AG, Epidemiology, Stockholm, Sweden
Göttingen, Germany and 2University Medical Center Göttingen, Institute of Pathology,
Göttingen, Germany
BACKGROUND AND AIMS: Acute kidney injury (AKI) is amongst the most
common in-hospital complications especially in old age. Epidemiological data on
BACKGROUND AND AIMS: Acute kidney injury (AKI) is very common in severe
incidence rates (IR) of nosocomial AKI in individuals aged 70þ years, stratified by age,
acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease 2019 (COVID-19),
gender and pre-existing diseases are scarce because older adults are usually
particularlarly among patients requiring intensive care unit (ICU) supportive care and
underrepresented in clinical research.
is considered as an independent risk factor for premature death. SARS-CoV-2 renal
METHOD: We used data from the Berlin Initiative Study (BIS), a longitudinal,
tropism and detection of SARS nucleocapsid protein (SARS-CoV-2 N) in renal tubules
population-based cohort of adults aged 70 with biennial follow-up visits (including
has been described in COVID-19 patients, suggesting that direct viral injury of the
blood and urine tests) in combination with claims data from the AOK Nordost
kidneys may contribute to AKI. SARS-CoV-2 renal tropism has been in part attributed
insurance fund to complement information on diagnoses and in-hospital procedures
to the intrarenal presence of cellular membrane proteins essential for viral entry
(based on ICD-10 and OPS coding). Nosocomial AKI was defined as documented in-
including angiotensin converting enzyme 2 (ACE2) and transmembrane protease
hospital diagnosis (ICD-10: N17.xx) excluding cases with AKI as admission diagnosis.
serine subtype 2 (TMPRSS2). Based on the assumption that renal injury is caused by
Incidence rates (IR) and 95% confidence intervals (CI) of the first nosocomial AKI
direct viral infection of the kidneys, it remains unclear if markers for viral infection
were calculated with the number of incident cases during observation divided by the
(SARS-CoV-2 N) and shedded cellular membrane proteins (ACE2, TMPRSS2) in
total person-years of follow-up, for AKI cases truncated at the first incidence of
urinary samples are useful for early identification of COVID-19 patients at risk for
nosocomial AKI. IR are reported by age strata, sex and preexisting diseases (diabetes,
AKI.
arterial hypertension, atrial fibrillation, heart failure, angina pectoris, peripheral artery
METHOD: A single-center prospective observational study was carried out in adult
disease and impaired kidney function).
cases with confirmed SARS-CoV-2 infection requiring ICU supportive care.
RESULTS: In 2020 individuals (mean age 80.5 years; 52.6% women), 383 developed
Investigators were blinded to clinical data collection and urinary ELISA measurements.
nosocomial AKI over the median [IQR] follow up time of 8.8 [5.9-9.3] years (Fig.1). The
According to the manufacturer’s protocols, urinary levels of SARS-CoV-2 N
IR of nosocomial AKI was 26.8 (95%CI 24.1-29.6) per 1000 person years among all
(KIT40588, Sino Biological), human ACE2 (NBP2-78734, Novus Biologicals) and
patients, with higher IR in men compared to women, and - when stratified by age - lowest
human TMPRSS2 (NBP2-89170, Novus Biologicals) were analyzed. Measurements
IR in age category 70-75 versus the highest IR in age category of  90 years (Fig.1).
were done in triplicates for each urinary sample and compared to the standard curve.
Negative test results were declared as not detectable. Urinary levels of SARS-CoV-2 N,
ACE2 and TMPRSS2 were analyzed at ICU admission and at day 3 and 8 during the
further clinical course of severe COVID-19 for association with AKI and outcome of
COVID-19.
RESULTS: ROC analysis revealed that a cut-off urinary SARS-CoV-2 N level higher
than 512.2 pg/mL at ICU admission effectively identified patients with AKI (AUC 0.81,
p=0.0211). Survival analysis for cumulative incidence of AKI revealed that urinary
SARS-CoV-2 N levels at ICU admission were not only associated with AKI at ICU
admission, but also predicted future development of AKI (HR 5.9, 95% CI 1.4-26,
p=0.0095). Because plasma albumin levels at time of ICU admission have previously
been established as marker to predict AKI and fatal outcome in COVID-19, we next
compared clinical and routine laboratory parameters assessed at ICU admission with
urinary SARS-CoV-2 N measurements to predict AKI with higher accuracy. In line
with aforementioned findings, hypoalbuminemia at time of ICU admission also
predicted AKI among all parameters assessed in our cohort. Confirmed by ROC
analysis, combining urinary SARS-CoV-2 N and plasma albumin measurements for
risk prediction (2-variable model, AUC 0.94, p=0.0009) outperformed urinary SARS- FC046 Figure 1: Age and sex stratified incidence rate (per 1000 person years) of
CoV-2 N alone (AUC 0.81, p=0.0211, comparison of models: p=0.0016) or plasma nosocomial AKI
albumin alone (AUC 0.78, p=0.0343, comparison of models: p=0.0061). Thus,
combined urinary SARS-CoV-2 N and plasma albumin levels assessed at ICU
admission effectively predicted incidence and early onset of AKI during the further IR per 1000 person years were higher in patients with diabetes mellitus (IR: 39.3 vs
clinical course (2-variable model, HR 11.4, 95% CI 2.7-48, p=0.0016). In addition, 22.7), arterial hypertension (IR: 31.1 vs 12.2), chronic heart failure (IR: 41.9 vs 22.3),
combining urinary SARS-CoV-2 N and plasma albumin levels at ICU admission angina pectoris (IR: 37.6 vs 25.7), peripheral artery disease (IR: 55.0 vs 25.1) and
effectively predicted fatal outcome in COVID-19 (2-variable model, HR 7.6, 95% CI impaired kidney function (IR: 43.3 vs 12.4), respectively (Fig.2).
1.3-44, p=0.0240).
CONCLUSION: Urinary SARS-CoV-2 N levels associate with risk for AKI and
correlated with COVID-19 severity. Therefore, we propose that urinary SARS-CoV-2
N could be used as early and easily assessable marker to identify patients at risk for AKI
and premature death in COVID-19.

FC046 Figure 2: Incidence rates (per 1000 person years) stratified by pre-existing
diseases

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Nosocomial AKI is an in-hospital complication common in older CONCLUSION: AKI occurs more frequently and more severely in patients with
adults with IRs rising continuously with age above the age of 70 years. IR of AKI are COVID-19 compared to other respiratory tract infections. It is associated with an
considerably higher in patients with cardiovascular comorbidities. A better increased risk for death, with the highest risk observed in COVID-19 patients. This
understanding of the patient population at risk is of great clinical relevance when underlines the augmented burden of AKI during the COVID-19 pandemic.
aiming to improve prevention strategies.

FC047 COMPARISON OF THE CHARACTERISTICS AND MORTALITY


FC048 IS AKI IN COVID-19 PATIENTS ASSOCIATED WITH
OF ACUTE KIDNEY INJURY IN PATIENTS WITH COVID-19
INCREASED LENGTH OF STAY AND MORTALITY?
AND OTHER RESPIRATORY INFECTIONS: A PROSPECTIVE
COHORT STUDY
Jennifer Ng1, Kristi Sun1, Phoebe Sharratt1, Mark Harber1,
1 2 1 1 Vasantha Muthuppalaniappan1
Matthias Diebold , Tobias Zimmermann , Michael Dickenmann , Stefan Schaub , 1
Stefano Bassetti3, Martin Siegemund2, Tobias Breidthardt3, Raphael Twerenbold4 Whittington Health NHS Trust, Nephrology, United Kingdom
1
University Hospital Basel, Clinic for Transplantation Immunology and Nephrology,
Basel, Switzerland, 2University Hospital Basel, Department of Intensive Care Medicine, BACKGROUND AND AIMS: Acute kidney injury (AKI) affects 22% of hospitalised
Basel, Switzerland, 3University Hospital Basel, Division of Internal Medicine, Basel, patients and is associated with a 21.9% increased risk of mortality in non COVID-19
Switzerland and 4University Hospital Basel, Department of Cardiology, Basel, presentations. Studies of patients hospitalised with COVID-19 have estimated the
Switzerland prevalence of AKI between 5.1-36.6%. The objective of the study was to identify the
prevalence of AKI in COVID-19 patients requiring admissions and associated adverse
outcomes.
BACKGROUND AND AIMS: Previous studies have indicated a coherency between
METHOD: We conducted a retrospective observational cohort study of all patients
coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI), indicating poor
admitted to hospital with a diagnosis of COVID-19 from 10th March to 7th May 2020.
outcomes. However, most studies only included patients with COVID-19 and lacked a
COVID-19 status was defined by a positive COVID-19 PCR nasopharyngeal and
control group. Therefore, the aim of this study was to investigate the prevalence and
oropharyngeal swabs. Patients younger than 18 years of age were excluded from final
prognostic impact of AKI in patients with COVID-19 in comparison with other
analysis. Demographic data, past medical history and blood results were obtained from
respiratory tract infections.
electronic health records. AKI was defined according to KDIGO criteria.
METHOD: The prospective single-center observational case-control COronaVIrus
RESULTS: 382 patients (219 Male) were included in the final analysis. The median age
surviVAl (COVIVA, clinicaltrials.gov NCT04366765) study performed at the
of patients was 69 years (Range 18-99). AKI occurred in 153 (40%) patients (103 Male),
University Hospital Basel Switzerland consecutively enrolled patients presenting to the
with a median age of 74 years. 111 (72.5%) patients had AKI on admission, 42 (27.5%)
emergency department with symptoms suggestive of COVID-19 between March 23
developed AKI while hospitalised. Average clinical frailty score (CFS) in the AKI group
and May 31, 2020. The final diagnosis that led to the inclusion in the study was
was 4. Median creatinine kinase in the AKI group was 213 (IQR 149-1260).
adjudicated by physicians after reviewing all available medical data including
The peak stages of AKI were Stage 1 in 100/153 (65.3%), Stage 2 in 29/153 (19%) and
laboratory test results 30 days after discharge. For this analysis, we compared patients
Stage 3 in 24/153 (15.7%). Of AKI patients 14/153 (9.2%) required renal replacement
tested positive for SARS-CoV-2 with patients tested negative but with an adjudicated
therapy. The mean peak serum creatinine was 246umol/L which was on Day 5 of
diagnosis of upper or lower respiratory tract infection including pneumonia. Primary
admission and Day 11 of symptoms on average. 90/153 (58.8%) patients had recovery
outcome measure was death at 30 days, secondary outcomes were AKI incidence, renal
of kidney function which includes 7 patients (50%) patients becoming dialysis
recovery and need for renal replacement therapy. AKI was defined according to the
independent. 40/76 (53%) patients who required respiratory support with either CPAP
serum creatinine criteria of the 2012 KDIGO clinical practice guideline.
or mechanical ventilation had evidence of AKI compared to 113/304 (37%) of non-
RESULTS: Of the 1086 patients included, 507 had a final adjudicated diagnosis of
ventilated patients.
respiratory tract infection and were eligible for this analysis. Of those, 183 (36%) had a
Amongst patients with AKI, 61/153 (40%) died, 64/153 (42%) were discharged, 20/153
positive PCR swab test for SARS-CoV-2. Baseline characteristics were comparable
(13%) remain in hospital and 8/153 (5%) were transferred to another hospital with 4 of
between patients with and without COVID-19.
the patients still requiring dialysis. In comparison, in patients with no AKI, 43/228
AKI occurred in 95 patients (19%) with a higher incidence (30%, 95%CI 24-37 versus
(19%) died, 174/228 (76%) were discharged, 9/228 (4%) remain in hospital and 2/228
12%, 95%CI 9-17, p<0.001) and a higher severity (KDIGO stage 3, 22% versus 10%,
(1%) were transferred to another hospital.
p=0.003) in patients with COVID-19 as compared to controls, respectively. Need for
Length of stay (LoS) of patients included in the study ranged from 0 to 102 days. The
intensive care (22% versus 6%, p<0.001) and requirement for RRT were higher in
mean LoS in the AKI group was 18.1 6 17.5 days (Range 0-102). The mean LoS in the
patients with COVID-19 (8 patients (4.4%) versus 2 patients (0.62%); p=0.01). Renal
non-AKI group was 10.5 6 13.30 days (Range 0-84). There was a significant difference
recovery at discharge in survivors was similar in patients with (64%) and without
in the LoS between the 2 groups, p<0.01 (95% CI: 4.1, 11.1).
COVID-19 (48%, p=0.175). Survival analysis identified AKI as a predictor of 30-day
Of all 153 AKI patients 61 (40%) deaths occurred, compared to 43/228 (19%) in the
mortality independent of COVID-19 status (adjusted hazard ratio (aHR) 3.44, 95%
non-AKI group, this difference was significant, p<0.01, OR= 2.89 (95% CI: 1.81, 4.58).
confidence interval (CI) 1.55-7.63, p=0.002), but COVID-19 patients with AKI carried
Suggesting that patients with AKI had a 74% chance of increased death.
the highest risk (aHR 4.24, 95%CI 1,82-9.88, p<0.001). (Figure 1)
Univariate analysis showed that age, males, baseline eGFR, albumin, CFS and Charlson
comorbidity index were predictors of AKI. Multivariate analysis showed that
independent predictors of AKI included males, black and Asian race, baseline eGFR
and albumin. An increase in baseline eGFR by 1ml/min in COVID-19 patients was
associated with a 2.4% risk reduction in death, p<0.01, OR= 0.976 (95% CI: 1.02, 1.03).
CONCLUSION: AKI is a poor prognosticator in patients with COVID-19 with
prolonged hospitalisation and increased mortality.

10.1093/ndt/gfab116 | i33
Nephrology Dialysis Transplantation 36 (Supplement 1): i34–i36, 2021
10.1093/ndt/gfab140

PREVENTION OF AKI placebo. However, CRR at Wk 52 based on creatinine-adjusted proteinuria, assessed


using spot urine, showed a better response in the 180 mg group (50%) vs placebo
(42.5%), and the 180 mg dose showed a greater change from baseline over time vs
placebo from Wk 4. Time to CRR was shorter in the 180 mg group (17.3 wks) vs
FC049 A RANDOMISED DOSE RANGING, PLACEBO-CONTROLLED, placebo (20.4 wks). The 180 mg group also showed improvement vs placebo in total
PHASE II STUDY ASSESSING THE EFFICACY AND SAFETY OF SLEDAI (SELENA) and its subscores.
BI 655064, AN ANTAGONISTIC ANTI-CD40 ANTIBODY, IN The unexpected high placebo response prompted a post hoc analysis evaluating
PATIENTS WITH LUPUS NEPHRITIS confirmed CRR (cCRR), whereby confirmation of the endpoint was required at both
Wks 46 (penultimate visit on treatment) and 52. A 15.2% higher cCRR in the 180 mg
David Jayne1, Richard Furie2, Juanita Romero-Diaz3, Hirofumi Amano4, group (44.3%) vs placebo (29.1%) was observed (p=0.26).
Kajohnsak Noppakun5, Harold Michael Gomez6, Rhona Recto7, Valérie Belsack8, While based on a small sample size, there were more reports of infection-related severe
Nora Fagan9, Steven Padula10, Ivette Revollo10, Jing Wu9, Sudha Visvanathan9, and serious adverse events and neutropenia in the 240 mg group compared with
Jürgen Steffgen11 placebo. Of note, in those who experienced neutropenia, a clinical impact (e.g. increase
1
University of Cambridge, Department of Medicine, Cambridge, United Kingdom, in infections) was not established. Aside from these observations, safety data were
2
Northwell Health and Zucker School of Medicine at Hofstra/Northwell, New York, comparable across treatment groups.
United States of America, 3Instituto Nacional de Ciencias Médicas y Nutricion, Salvador Larger decreases from baseline were observed in the percentage of
Zubiran, Mexico City, Mexico, 4Juntendo University Hospital, Tokyo, Japan, 5Chiang Mai CD27IgDCD95þ, CD27IgDþCD95þ, CD27þIgDþCD95þ and
6
University, Chiang Mai, Thailand, Angeles University Foundation Medical Center, CD27þIgDCD95þ B-cell subsets in the 180 and 240 mg groups compared with
Angeles City, Philippines, The, 7Mary Mediatrix Medical Center, Lipa City, Philippines, placebo.
The, 8SCS Boehringer Ingelheim, Brussels, Belgium, 9Boehringer Ingelheim Treatment-emergent anti-drug antibodies (ADAs) were detected in five pts treated
Pharmaceuticals Inc., Ridgefield, United States of America, 10Boehringer Ingelheim with BI 655054, all at low titre, and in one who received placebo; ADAs had no impact
International GmbH, Ingelheim, Germany and 11Boehringer Ingelheim International on pharmacokinetics or safety.
GmbH, Biberach, Germany CONCLUSION: The trial did not meet its primary CRR endpoint. However, when
confirmation of CRR was required at both Wks 46 and 52, the resultant decrease in the
placebo response generated an effect size of 15.2% and 9.1% in favour of 180 mg and
BACKGROUND AND AIMS: In patients (pts) with SLE, activation of the CD40– 240 mg BI 655064, respectively.
CD40L pathway results in stimulation and proliferation of B cells and other
inflammatory cell types. The subsequent generation of autoantibodies and their
deposition in the kidney, as well as activation of myeloid and resident kidney cells,
result in local inflammation and eventually, kidney injury. Thus, CD40 is an appealing
therapeutic target in lupus nephritis (LN). BI 655064 is a humanised anti-CD40
monoclonal antibody that blocks the CD40 pathway in a nanomolar range and
downregulates activated B cells. FC050 THE PREDICTIVE ABILITY OF URINARY BIOMARKERS FOR
This study assessed the efficacy and safety over 52 weeks (wks) of three doses of PROGRESSION OF ACUTE KIDNEY INJURY IN CRITICAL
subcutaneous BI 655064 compared with placebo, as add-on to mycophenolate and ILLNESS
steroids, in pts with active proliferative LN (ClinicalTrials.gov number:
NCT02770170). Stephen Duff1, Ruairi Irwin1, Jean Maxime Cote1, Peter Doran1, Patrick Murray1
METHOD: Overall, 121 pts with LN were randomised, double blind, in a 2:1:1:2 ratio 1
University College Dublin, School of Medicine, Dublin, Ireland
to placebo or BI 655064 120 mg, 180 mg or 240 mg, and received a weekly loading dose
for the first 3 wks, followed by dosing every 2 wks for the 120 and 180 mg doses, and
weekly (120 mg) for the 240 mg group. Key inclusion criteria included an active ISN/ BACKGROUND AND AIMS: Acute Kidney Injury (AKI) is a common hospital
RPS class III or IV (6V) renal biopsy within 3 months prior to screening and a complication associated with high morbidity, mortality and the risk of progression to
screening protein/creatinine ratio of 1 mg/mg. Randomisation was stratified based on CKD. Despite globally increasing rates of AKI and a shortage of critical care beds,
race (Asian vs non-Asian) and screening protein/creatine (UP/UC) ratio (<3 vs 3). clinicians currently lack the tools to predict progression of early AKI. The Dublin
The primary efficacy endpoint was complete renal response (CRR), defined as 24 h Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective multi-center
proteinuria <0.5 g/day and stable eGFR at Wk 52. observational study with a heterogenous cohort of critically ill patients (n= 717). We
hypothesised that a panel of 14 novel urinary biomarkers would predict progression of
AKI.
FC049 Table 1. Efficacy endpoints at Wk 52 METHOD: Biomarker values were measured daily for 7 days from ICU admission,
including on the day of Stage 1-2 AKI diagnoses occurring within 48 hours of ICU
admission. The primary outcome was progression to the composite outcome of
Placebo BI 655064 increased AKI KDIGO Stage, Renal Replacement Therapy (RRT) or Death within 7
120 mg 180 mg 240 mg days of ICU admission. AUC-ROC values and adjusted Odds Ratios were calculated
using multivariate logistic regression, and the additional value of biomarkers over the
(n=40) (n=21) (n=20) (n=40) clinical model (serum creatinine and urine output at time of diagnosis) was assessed. In
Observed CRR, n 20 8 9 18 a secondary analysis,all AKI events within 7 days (including those diagnosed at Stage 3,
Adjusted* CRR, % 48.3 38.3 45 44.6 and/or on days 3-7) were included, with the endpoint of progression to RRT/Death
within 30 days of ICU admission.
Observed cCRR, n 13 5 9 16 RESULTS: AKI developed in 268 patients (37%) within 7 days of ICU admission. 95
Adjusted* cCRR, % 29.1 22.5 44.3 38.2 patients were diagnosed with AKI at Stage 1or2 AKI within 48 hours, of whom 32
(33.7%) progressed to the primary outcome. Adjusted odds ratios for the prediction of
Mean change from baseline in SLEDAI AKI progression were significantly higher for the highest tertile, versus the lowest, of
Total score 6.5 6.1 9.7 8.2 eight biomarkers including uCystatin C (OR 5.2, 95% CI; 1.3-23.6), uAlbumin (OR 4.9,
Non-renal score 1.4 3.0 2.8 3.1 95% CI; 1.5-18.3), uNGAL (OR 4.6, 95% CI; 1.4-17.9) and uIGFBP-7 (OR 4.7, 95% CI;
1.2-21.5). LFABP-1, KIM-1, IL-18 and Alpha-1-M also significantly improved
Renal score 5.1 3.7 6.8 5.0 prediction (Table 1). In ROC analysis of the primary outcome, uCystatin C (AUC 0.75,
Clinical score 5.7 3.9 7.9 6.5 95% CI; 0.63-0.87), uNGAL (AUC 0.72, 95% CI;0.61-0.84), uAlbumin (AUC 0.70, 95%
CRR based on 24 h proteinuria; cCRR based on UP/UC (spot urine) at Wks CI; 0.59-0.82) and IL-18 (AUC 0.70, 95% CI; 0.58-0.82) had moderate accuracy; the
others did not.
46 and 52. *Logistic regression model including treatment and the covari-
ates race and proteinuria at screening.
RESULTS: The placebo response in this trial was higher than expected (48.3%; Table
1); none of the BI 655064 doses increased rates of CRR at Wk 52 compared with

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
METHOD: We compared the predictive value of plasma NGAL, hepcidin-25, and
FC050 Table 1: Biomarkers for the prediction of AKI progression at 7 days NGAL:hepcidin-25 with those of serum creatinine (Cr), and urinary output and
urinary protein for primary endpoint major adverse kidney events (MAKE; acute
kidney injury [AKI] stages 2 and 3, persistent AKI > 48 hrs, acute dialysis, and in-
hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at
intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and
reclassification analyses.
RESULTS: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, and Cr
predicted MAKE (area under the ROC curve [AUC]: 0.77 [95% confidence interval
(CI) 0.60–0.94], 0.79 [0.63–0.95], 0.74 [0.51–0.97]) and AKI (0.73 [0.53–0.93], 0.89
[0.81–0.98], 0.70 [0.48–0.93]). For AKI prediction, NGAL:hepcidin-25 had a higher
discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary
output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial
band, and brain natriuretic peptide did not predict MAKE or AKI (AUC < 0.70). Only
plasma NGAL:hepcidin-25 correctly reclassified patients for MAKE or AKI (category-
free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After
adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25  0.9
independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P =
0.014), whereas Cr did not.
CONCLUSION: NGAL:hepcidin-25 is a promising plasma marker for predicting
postoperative MAKE.

FC051 Figure 1: AUC-ROCs of plasma biomarkers at ICU admission to predict


postoperative MAKE or AKI
Missing values: NGAL (‘MAKE’: n=1/9, ‘no MAKE’: N=2/91; ‘AKI’: n=2/9, ‘no AKI’:
n=0/91), hepcidin-25 (‘MAKE’: n=0/9, ‘no MAKE’: N=1/91; ‘AKI’: n=0/9, ‘no AKI’:
n=1/91), NGAL/hepcidin-25 (‘MAKE’: n=1/9, ‘no MAKE’: N=2/91; ‘AKI’: n=2/9, ‘no
AKI’: n=1/91)
Abbreviations: AUC-ROC, area under the curve of the receiver-operating
characteristics; ICU, intensive care unit; IL, interleukin; NGAL, neutrophil gelatinase-
associated lipocalin; CRP, C-reactive protein; CK, creatine kinase; CKMB, creatine
kinase myocardial band; BNP, B-type natriuretic peptide.
*Indicates biomarker with inverse relationship to outcome.

FC052 ACID-BASE BALANCE DURING IN-SERIES


CONCLUSION: In this cohort study of AKI progression within 7 days of ICU EXTRACORPOREAL CARBON DIOXIDE REMOVAL AND
admission, eight novel urinary biomarkers improved the prediction of AKI progression CONTINUOUS VENOVENOUS HEMOFILTRATION:
after multivariate adjustment. Similarly, ROC analysis found that several biomarkers PREDICTIONS FROM A MATHEMATICAL MODEL
had moderate accuracy for the prediction of AKI progression in the ICU.
John (Ken) Leypoldt1, Joerg Kurz2, Jorge Echeverri3, Markus Storr4,
Kai Harenski2
1
FC051 PREDICTIVE VALUE OF PLASMA NGAL:HEPCIDIN-25 FOR Institute of Biocybernetics and Biomedical Engineering PAS, Warszawa, Poland, 2Baxter
MAJOR ADVERSE KIDNEY EVENTS AFTER CARDIAC Deutschland GmbH, Medical Affairs, Unterschleißheim, Germany, 3Baxter Healthcare
SURGERY WITH CARDIOPULMONARY BYPASS: A PILOT Corporation, Medical Affairs, Deerfield, United States of America and 4Baxter
STUDY International, Hechingen, Germany

Saban Elitok1, Anja Haase-Fielitz2, Martin Ernst3, Michael Haase3,4 BACKGROUND AND AIMS: Critically ill acute kidney injury (AKI) patients may
1 require treatment by extracorporeal carbon dioxide removal (ECCO2R) devices to
Hospital Ernst von Bergmann Potsdam, Department of Nephrology, Potsdam,
Germany, 2Heart Center Brandenburg, Department of Cardiology, Bernau, Germany, allow protective or ultraprotective mechanical ventilation and avoid hypercapnic
3 acidosis. Continuous venovenous hemofiltration (CVVH) and ECCO2R devices can be
Otto-von-Guericke University Magdeburg, Medical Faculty, Magdeburg, Germany and
4 arranged in series to form a single extracorporeal circuit; such a circuit has been
Diaverum, MVZ Am Neuen Garten, Potsdam, Germany
proposed to be optimal, based carbon dioxide removal efficacy, if the ECCO2R device is
BACKGROUND AND AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) and placed proximal to the CVVH device (Allardet-Servent et al, Crit Care Med 43:2570-
hepcidin-25 appear to be involved in catalytic iron-related kidney injury after cardiac 2581, 2015).
surgery with cardiopulmonary bypass. We aimed to explore the predictive value of METHOD: We developed a mathematical model of whole-body, acid-base balance
plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major during extracorporeal therapy using in-series ECCO2R and CVVH devices for
adverse kidney events after cardiac surgery. treatment of mechanically ventilated AKI patients. Equilibrium acid-base chemistry in

10.1093/ndt/gfab140 | i35
Abstracts Nephrology Dialysis Transplantation

blood was assumed as reported previously (Rees and Andreassen, Crit Rev Biomed Eng
33:209-264, 2005). Published clinical data from Allardet-Servent et al of mechanically FC052 Table: Measured and Model Predicted Values of PaCO2 and [HCO3]
ventilated (6 mL/kg predicted body weight or PBW) AKI patients treated by CVVH
without ECCO2R were used to adjust model parameters to fit plasma levels of arterial
partial pressure of carbon dioxide (PaCO2) and arterial plasma bicarbonate PaCO2 (mmHg)/[HCO3] (mEq/L)
concentration ([HCO3]). The effects of applying ECCO2R at an unchanged tidal
volume and a reduced tidal volume (4 mL/kg PBW) on PaCO2 and [HCO3] were then Tidal Volume 6 mL/kg 6 mL/kg 4 mL/kg
simulated assuming carbon dioxide removal rates from the ECCO2R device measured PBW PBW PBW
in the clinical study (91 mL of CO2/min when ECCO2R was proximal and 72 mL of
Without With With
CO2/min when CVVH was proximal).
RESULTS: Agreement of model predictions with the clinical data was good, and model ECCO2R ECCO2R ECCO2R
predictions were relatively independent of the in-series position of the devices (see Clinical Data 47/22 37/22 48/23
Table). Total carbon dioxide removal from the CVVH device via ultrafiltration
predicted by the model was lower after applying ECCO2R at both the unchanged tidal Model (ECCO2R Proximal) 47/22 34/20 49/23
volume (25 mL of CO2/min when ECCO2R was proximal and 39 mL of CO2/min when Model (CVVH Proximal) 47/22 35/20 51/23
CVVH was proximal) and the reduced tidal volume (30 mL of CO2/min when
ECCO2R was proximal and 44 mL of CO2/min when CVVH was proximal). The CONCLUSION: The described mathematical model has quantitative accuracy. It
reduced removal of total carbon dioxide via ultrafiltration when ECCO2R was proximal suggests that overall acid-base balance when using ECCO2R and CVVH devices in a
resulted from the lower total carbon dioxide concentration in blood entering the single, combined extracorporeal circuit will be similar, independent of their in-series
CVVH device. Thus, independent of the in-series position of the devices, the position.
magnitude of this difference in total carbon dioxide removal by the CVVH device (14
mL of CO2/min) approximately cancels out the relative greater efficacy of the ECCO2R
device (19 mL of CO2/min).

i36 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i37–i40, 2021
10.1093/ndt/gfab130

FLUID, GFR & CO UDI was higher for L patients. For patients with eGFR 10-15 ml/min/1.73m2, UDI
occurred in L: 47%, M:27%, H:25%. For patients with eGFR 10-15 ml/min/1.73m2 the
figures were 51, 38 and 12% respectively.
Findings for the subgroup of patients with RBSA measurements were similar.
FC053 RATIO OF MEASURED GFR TO ESTIMATED GFR MAY *:p<0.05; **:p<001;***:p<0.001
PREDICT EARLY DEATH AND REQUIREMENT FOR DIALYSIS CONCLUSION: A low mGFR/eGFR ratio is associated with comorbidity,
malnutrition, inflammation and biochemical uraemia. It a marker of early ESKD, death
James G. Heaf1, Rafal Yahya1, Morten Dahl1,2 and unplanned dialysis initiation, independently of eGFR. Particular attention paid to
1
Zealand University Hospital, Medicine, Roskilde, Denmark and 2Zealand University patients with a low R may lower the incidence of unplanned dialysis requirement.
Hospital, Clinical Biochemistry, Køe, Denmark

BACKGROUND AND AIMS: It has been suggested that, in patients with CKD stage
5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance as
measured by a 24-hour urine collection, is a better measure of renal function than
estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced FC054 FUNCTIONAL SODIUM MAGNETIC RESONANCE IMAGING OF
muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned THE HUMAN KIDNEY
dialysis initiation (UDI) is associated with increased morbidity, mortality, and reduced
modality choice. It is generally considered undesirable. We hypothesized that the ratio Sandrine Lemoine1, Alireza Akbari1, Taylor Marcus1, Christopher McIntyre1
mGFR/eGFR (R) aids prediction of death and end stage kidney disease (ESKD), as 1
London Health Sciences Centre, Kidney Clinical Research unit, London, Canada
defined by permanent dialysis requirement or transplantation.
METHOD: All 24-hour measurements of urea and creatinine excretion were extracted
from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, BACKGROUND AND AIMS: Maintenance of a cortico-medullary concentration
comorbidity, biochemistry, medical treatment, mortality and date of ESKD, were gradient (CMG) required for urine concentration, is one of most important tubular
extracted from patient notes, the National Patient Registry and the Danish Nephrology function. However, we are lacking of functional tubular parameters to explore this
Registry. Patients were included if their eGFR was <30 ml/min/1.73m2. The last function. The only tool available to assess it currently, is urinary osmolarity that is an
available value for each patient was included. indirect and nonspecific maker of CMG.
RESULTS: 1265 patients were included. In 519, body surface area (BSA) was available, In this study, we explore the ability of 23NaMRI in measuring 1) the dynamics of CMG
and the corrected ratio (RBSA) could be calculated. The urea clearance was 49 624% of for the first time compared to urinary osmolarity after a water load 2) the CMG in
creatinine clearance. R was median 0.88 (IQR 0.63-1.15), RBSA 0.87 (0.68-1.06). R was kidney disease.
not related to eGFR. Comorbidity was associated with lower R, e.g. atherosclerosis METHOD: We conducted an exploratory pilot study for 10 healthy controls with
(0.90 60.41 vs. 0.97 60.49*), heart failure (0.80 60.37 vs. 0.95 60.44*), pulmonary water load then 5 cardiorenal patients with kidney disease. 1) Healthy controls were
disease (0.80 60.37 vs. 0.94 60.44***), hepatic disease (0.67 60.41 vs. 0.92 60.43***), asked to be fasting since midnight. Urines sample were collected to measure fasting
but not diabetes mellitus. It was related to albumin (r=0.24***), C-reactive protein (- osmolarity and a first MRIscan were performed to acquire baseline anatomical and
0.22***) and biochemical markers of uraemia, e.g. bicarbonate (-0.19***). Medical sodium images. Once the baseline was completed, healthy participants were asked to
treatment data was available in 137 patients. R was higher in patients treated with ACE ingest water (15 mL/kg) within 15 minutes. Four subsequent sodium pictures were
inhibitors (1.20 60.50 vs. 1.01 60.36*) and diuretics (1.09 60.40 vs. 0.94 60.35*), but acquired an hour after water ingestion. Urine samples were obtained after each sodium
no other treatment groups. acquisition every 15 min during one hours. 2) Cardiorenal patients underwent an MRI
Patients were grouped as high R (H, >1.25), medium (M, 0.75-1.25) or low (L, <0.75). scan, provided a spot urine sample and have blood work collected.
R was not associated with prognosis at one year, but L patients had a significantly All MR experiments were carried out on a GE MR750 3T (GE Healthcare, WI). A
higher ESKD and mortality incidence at 3 months. For patients with eGFR 10-15 ml/ custom-built two-loop (18cm in diameter) butterfly radiofrequency surface coil tuned
min/1.73m2, ESKD incidence was L 22%, M 15%, H 5%, mortality 19, 5, and 2% for 23Na frequency (33.786 MHz) was used to acquire renal 23Na images.
respectively. Similar findings were seen in other groups, e.g. eGFR 15-20 ml/min/ RESULTS: Mean age of the 10 healthy controls was 41.8 6 15.3 years, mean body mass
1.73m2: ESKD 11, 2, and 0%; death 11, 5, and 1%. index (BMI) was 24.3 6 3.8 kg/m2. Mean water intake was 1092 6 233 mL, total water
excreted was 1250 6 301 mL . Mean age of the 5 cardiorenal patients was 76.6 6 12.2

FC053 Figure: Relationship of mGFR/eGFR ratio to ESKD or death in patients with


eGFR 10-15 ml/min/1.73m2, and relationship to unplanned dialysis initiation
incidence.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

years, mean BMI was 28.1 6 6.9 kg/m2. eGFR was 54 6 37 mL/min/1.73m2. Urinary the development database, using quantiles modeled as cubic splines with two linear
osmolarity was 498 6 145 mosm/L and medulla/cortex ratio was 1.35 6 0.11. parts joining at one age-knot of 40 years. The median quantile had a constant first part
Sodium imaging was successfully acquired in all volunteers. In the morning fasting, (slope of zero) and a second part with a negative slope of -0.88235 mL/min/1.73m2 per
medulla/cortex ratio was 1.55 6 0.11 regarding to a urinary osmolarity to 814 6 121 year. To maintain consistency, all quantiles were adjusted to show the same shape as
mosm/L. Mean 6 SD fasting urinary osmolarity dropped significantly to 73 6 14 the medium quantile. Above 65 years, the percentile values were extrapolated using the
mosm/L for maximal dilution, p=0.001. Mean medulla/cortex ratio dropped same mathematical model. We then calculated the percentage of results from the
significantly to 1.31 6 0.09 mosm/L for maximal dilution, p=0.002. Figure 1 displays internal and external validation cohorts that were within the 5th extrapolated
changes of 23NaMRI pictures before (A) then 1h (B), 1H15 (C), 1h30 (D) and 1h45 (E) percentile (P5) and 95th percentile (P95). A sensitivity analysis including the EKD only
after a water load. Urinary osmolarity and medulla/cortex ratio are significantly was performed.
correlated, r=0.54, p=0.0001. RESULTS: Individuals in the development cohort were younger than in the internal or
external validation cohort (47.3610.5 years vs. 68.862.9 years and 71.466.4 years;
respectively, both p<0.001). Individuals in the development cohort had a higher
mGFR than in the internal or external validation cohort (99.9616.4 mL/min/1.73m2
vs. 86.4614 mL/min/1.73m2 and 82.7615.5 mL/min/1.73m2; respectively, both p <
0.001). Among the 147 EKD from the internal validation cohort, none (0%) had mGFR
below the extrapolated P5 and12 (8.1%) had mGFR higher than the extrapolated P95.
Consequently, 135/147 (91.2%) of subjects were between P5-P95. (Figure 1).
Considering the whole external validation cohort (n=329), 5 subjects had mGFR lower
FC054 Figure: 23NaMRI pictures before (A) then 1h (B), 1H15 (C), 1h30 (D) and than extrapolated P5 (1.5%), 25 were above P95, leaving 299 (90.9%) with mGFR
1h45 (E) after a water load between P5 and the extrapolated P95.

We measured corticomedullary gradient in cardiorenal patient with different level of


eGFR to show the ability and feasibility to measure this gradient in pathological
settings. We were able to measure medulla/cortex ratio in patients with CKD with a
mean SNR of 20.45 6 9.45.
CONCLUSION: We explored CMG dynamically every 15 min and we were able to
discriminate significant changes after a water load. We were also able to provide
efficient 23NaMRI pictures in cardiorenal patients with kidney disease.
CMG exploration would provide a relevant assessment of tubular dysfunction
independently of glomerular alteration and thus could be of prognostic value.

FC055 PERCENTILES OF NORMAL MEASURED GLOMERULAR


FILTRATION RATE BASED ON DATA FROM LIVING KIDNEY
DONORS

François Gaillard1,2, Pierre Delanaye3,4, Jessica Van Der Weijden5, Geir Mjøen6,
Ingela Fehrman-Ekholm7, Laurence Dubourg8, Natalie Ebert9, Elke Schaeffner9,
Torbjorn Akerfeldt10, Karolien Goffin11, Lionel Couzi12, Cyril Garrouste13,
Lionel Rostaing14, Marie Courbebaisse15, Christophe Legendre16,
Maryvonne HOURMANT17, Nassim Kamar18, Laurent Weekers3,
Antoine Bouquegneau3, Martin De Borst5, Christophe Mariat19, Hans Pottel20, FC055 Figure 1: mGFR according to age in the development (round dots) and
Marco Van Londen5 external validation cohort (n=329) (triangle dots)
1
Assistance Publique Hopitaux de Paris - Bichat Hospital, Nephrology, Paris, France,
2
Université de Paris, Paris, France, 3Chu De Liège, Liège, Belgium, 4University Hospital of
Nimes, Nephrology, Nı̂mes, France, 5University of Groningen, Groningen, The CONCLUSION: We demonstrate that extrapolated percentiles of mGFR (calculated in
Netherlands, 6Oslo universitetssykehus Rikshospitalet, Nephrology, Oslo, Norway, individuals younger than 65) fits well with the distribution of mGFR in individuals
7
Karolinska University Hospital, Transplantation surgery, Huddinge, Sweden, 8Hospital older than 65. Extrapolation of percentiles to individuals older than 65 is useful to
Edouard Herriot, Physiology, Lyon, France, 9Charité – Universit€ atsmedizin Berlin, Public define age-adapted GFR thresholds for older individuals.
health, Berlin, Germany, 10Uppsala University Hospital, Clinical chemistry, Sweden, 11UZ
12
Gasthuisberg Campus, Nuclear medicine, Leuven, Belgium, Hospital Center University
De Bordeaux, Nephrology, Bordeaux, France, 13CHU Gabriel-Montpied, Nephrology, FC056 ESTIMATING ALBUMIN TO CREATININE RATIO FROM
Clermont-Ferrand, France, 14Chu Grenoble Alpes, Nephrology, La Tronche, France, PROTEIN TO CREATININE RATIO USING SAME DAY
15
European Hospital Georges Pompidou, Physiology, Paris, France, 16Hôpital Necker, MEASUREMENT: VALIDATION OF EQUATION
Nephrology and renal transplantation, Paris, France, 17Chu Nantes-Hotel Dieu,
Nephrology, Nantes, France, 18Hospital Center University De Toulouse, Nephrology and Guillaume Resimont1, Laura Vranken2, Etienne Cavalier2, Pierre Delanaye1,3
renal transplantation, Toulouse, France, 19Chu Nord Saint-Etienne, Nephrology, Saint- 1
Chu De Liège, Nephrology-Dialysis-Transplantation, Liège, Belgium, 2Chu De Liège,
Priest-en-Jarez, France and 20KU Leuven Campus Kulak Kortrijk, Public health, Kortrijk,
Department of Clinical Chemistry, Liège, Belgium and 3University Hospital of Nimes,
Belgium
Department of Nephrology-Dialysis-Apheresis, Nı̂mes, France
BACKGROUND AND AIMS: Studies of healthy individuals or candidates for living
BACKGROUND AND AIMS: According to the KDIGO, severity of chronic kidney
kidney donation, in various geographical areas and ethnic groups, describe a decline of
disease is defined by glomerular filtration rate and albuminuria. Furthermore, these
glomerular filtration rate (GFR) with age. Most data on GFR are obtained from subjects
variables are used for estimating both cardiovascular and end-stage renal disease risk.
in the general population or from candidates for kidney donation who are younger
However, albuminuria is not always available, whereas proteinuria is, notably because
than 65 years. It is currently unknown whether the definition of normal GFR in
of the lower costs of proteinuria. Recently, Weaver & al. developed an equation that
subjects older than 65 years is similar to the definition in those younger than 65 years.
estimates urine albumin/creatinine ratio (ACR) from protein/creatinine ratio (PCR).
Because the age of candidates for living kidney donation is increasing worldwide, lack
For retrospective analyses in clinical research, it might be interesting to be able to
of GFR references for older donors complicates the selection process. Moreover, older
estimate ACR from PCR. The objective of this paper is to assess the performance of
individuals are most likely to have a mildly decreased GFR that may be misinterpreted
Weaver & al. ‘s equation in our population.
as chronic kidney disease. In this study, we calculated percentiles of measured GFR
METHOD: In a University hospital, we retrospectively analysed measurement of ACR
(mGFR) from a large cohort of effective kidney donors (EKD) younger than 65 years,
and PCR obtained on the same day between May 2018 and March 2020. Different
and extrapolated them to subjects older than 65 years. Additionnaly, we collected
assays were considered to measure urine albumin, creatinine and protein (Roche Cobas
mGFR data from different centers within Europe from EKD and/or healthy people
from May 2018 to May 2019 and Abbott Alinity from May 2019 to March 2020). Only
(HP) from the general population older than 65 years. We tested if the distribution of
one (the first available) sample per patient was considered. Patients were then
mGFR of these older subjects fitted with the extrapolated percentiles.
categorized according to the KDIGO classification (A1-A2-A3). We then compared
METHOD: In this retrospective, observational, multi-center study, percentiles of
categorization of patients according to KDIGO between measured and estimated ACR.
mGFR in EKD were calculated from a development cohort of French and Belgian EKD
Sensitivity, specificity, positive predictive value and negative predictive value of
younger than 65 years (n=1983). From the French kidney donor study, 147 EKD older
estimated ACR versus measured ACR were calculated considering two different
than 65 years were considered as the internal validation cohort. In an external
thresholds: A1 versus A2/3 (ACR 30mg/g) or A1/A2 versus A3 (ACR 300mg/g).
validation cohort, data on mGFR of subjects older than 65 years, either EKD or HP
RESULTS: Comparison was done in 2633 and 2386 patients, with Cobas and Alinity,
from the general population (from Germany, Sweden (2), Norway, Netherlands and
respectively. Median age was 63 (IQR 19) and 64 (IQR 19) years old, 43 and 41% were
France, n=2459) were included. Data were fully anonymized and this retrospective
women and 74 and 78% were diabetic (albuminuria measurement is refunded for
study was approved by the respective ethics committees. Percentiles were derived for

i38 | Abstracts
Nephrology Dialysis Transplantation Abstracts
diabetic patients in Belgium) with Cobas and Alinity, respectively. Considering FC057 SALIVARY POTASSIUM FOLLOWS PLASMA POTASSIUM
measured ACR, patients were categorized in A1, A2, A3 in 65,6%, 25,5%, and 8,8%, DYNAMICS IN HEMODIALYSIS PATIENTS
respectively with the Cobas assay. With the Alinity assay, the results were 64,2%,
25,5%; and 10,3%, respectively. Considering estimated ACR, patients were categorized Andras Deak1, Katarina Beli c1, Anna-Maria Meissl1, Katharina Artinger1,
in A1, A2, A3 in 64,7%, 25,7%, and 9,6%, respectively with the Cobas Assay. With the Kathrin Eller1, Bernd Rechberger1, Tobias Niedrist2, Wolfgang Graier3,
Alinity assay, the results were 62,5%, 25,8% and 11,7%, respectively. Regarding A1-A2 Roland Malli3, Helmut Bischof3, Sandra Burgstaller3, Alexander Avian4,
(30mg/g) threshold, sensitivity was 85% and 89%, specificity was 91% and 92%, Claudio Mori5, Alexander Rosenkranz 1, Alexander H. Kirsch1
1
positive predictive value was 83% and 85%, negative predictive value was 92% and 94% Medical University of Graz, Division of Nephrology, Department of Internal Medicine,
for Cobas and Alinity respectively. Regarding A2-A3 (300mg/g) threshold, sensitivity Graz, Austria, 2Medical University of Graz, Clinical Institute of Medical and Chemical
was 93% and 98%, specificity was 98% for both, positive predictive value was 86% and Laboratory Diagnostics, Austria, 3Medical University of Graz, Gottfried Schatz Research
87%, negative predictive value was 99% and 99,8% for Cobas and Alinity respectively. Center (for Cell Signaling, Metabolism and Aging) Division of Molecular Biology and
Values are presented in table 1. Biochemistry, Austria, 4Medical University of Graz, Institute for Medical Informatics,
CONCLUSION: We observed a good concordance between estimated and measured Statistics and Documentation, Graz, Austria and 5Vifor Pharma, Medical Affairs,
ACR. Particularly, no patient in category A3 with measured ACR was categorized A1 Glattbrugg, Switzerland
with the estimating equations. We also observed that concordance was good regardless
of our available assays. Thus, negative predictive value was excellent. BACKGROUND AND AIMS: Hyperkalemia is common in patients on hemodialysis
In conclusion, ACR should be measured when clinically needed, but an estimated ACR (HD) and in cardiorenal patients on RAAS inhibitors. Frequently, hyperkalemia is a
can reasonably be obtained from Weaver’s equation and may provide an accurate leading reason to withdraw potentially lifesaving therapy in cardiorenal patients. Out-
estimation for retrospective clinical research. patient monitoring of plasma Kþ levels due to preanalytical problems has proven
problematic. The present pilot-study examined salivary Kþ levels and kinetics based on
FC056 Table 1: Sensibility, specificity, positive predictive value (PPV), negative plasma Kþ measurements in HD patients employing a novel class of genetically-
predictive value (NPV) for A1-A2 and A2-A3 thresholds for Roche Cobas and Abbott encoded fluorescent potassium-ion indicators, the GEPIIs (Bischof et al. Nat.
Alinity assays. Commun. 2017). HD patients represent a unique population in whom significant Kþ
derangements and rapid Kþ level changes predictably occur and where these
phenomena can be safely investigated.
KDIGO threshold Sensibility Specificity PPV NPV METHOD: Kþ assessments were performed in healthy individuals (n=20) and HD
ACRm/ACRe A1 versus A2/3 84,86% 90,63% 82,58% 91,96% patients (n=30). Study-related procedures were approved by the local Institutional
(Roche Cobas) Review Board. Healthy individuals were recruited on a voluntary basis and provided
only saliva samples. HD patients were recruited from our HD unit. Blood and saliva
ACRm/ACRe A1 versus A2/3 89,46% 91,51% 85,46% 93,97% samples for Kþ assessment were collected simultaneously during three consecutive HD
(Abbott Alinity) sessions (HD1-3) prior to and directly after each session (pre/post HD). Blood was
drawn in a standardized procedure directly from the HD access line and plasma Kþ
ACRm/ACRe A1/A2 versus A3 93,1% 98,5% 85,8% 99,3%
was measured immediately using standardized ion-selective electrodes (ISE). Saliva
(Roche Cobas) samples were gathered in a standardized procedure using a commercially available
ACRm/ACRe A1/A2 versus A3 98,4% 98,3% 86,7% 99,8% collection device (SuperSALTM). Of note, gaining adequate amounts of saliva from
chronic HD patients, who frequently suffer from xerostomia, has proven challenging in
(Abbott Alinity) some cases. The Kþ content of saliva samples was measured by ISE and GEPII-
technique. For the latter, samples were mixed with purified GEPIIs and were inserted
into a fluorescent plate-reader. Probes were illuminated at 430 nm and emission light

10.1093/ndt/gfab130 | i39
Abstracts Nephrology Dialysis Transplantation

were collected at 475 nm and 525 nm, respectively. The ratio of the fluorescent session (HD1-3 pre/post) revealed however no or weak correlation of pre- and post-
intensities (F535/F480) after appropriate calibration is a direct measure of the Kþ dialytic saliva and plasma Kþ values (Figure 1E).
concentration sensed by GEPIIs. CONCLUSION: The GEPII-technique is an easy to use, reliable and suitable method
RESULTS: Kþ determination in saliva samples using the GEPII-technique and ISE for salivary Kþ determination in healthy individuals and in HD patients with accuracy
showed a strong agreement ((Figure 1A), Bias 0,71; 95% limits of agreement from -2.79 and precision comparable to that of ISE. Despite heterogeneous baselines, changes of
to 4.40). Pre-dialytic [Kþ]saliva of HD patients compared to healthy individuals, was [Kþ]saliva represent a sensitive marker of Kþ derangements as well as hyper- and
higher (40,6461,50 vs. 23,1560,76 mmol/l, p<0.05). As expected, each HD session normokalemia in HD patients. Although we observed that [Kþ]saliva dynamically
(HD1-3) led to a significant reduction in [Kþ]plasma, which is followed by a similar, follows [Kþ]plasma , an exact quantification - most likely due to the low number of cases
significant reduction of [Kþ]saliva (Figure 1B). Dynamics of plasma and salivary [Kþ] per HD sessions in this pilot-study – was not possible. Additionally, how closely
showed a very similar pattern: strong reduction during a HD session followed by a [Kþ]saliva tracks [Kþ]plasma in patients with hypokalemia was not addressed in this
marked increase in the dialysis-free period until the next session 48-72h later (Figure study. To confidently answer whether [Kþ]saliva measurement can potentially be used
1C). Although basal [Kþ]saliva shows individual variations, [Kþ]Saliva and [Kþ]plasma in the care of patients at increased risk of hyperkalemia, further studies in a larger
exhibited a tendency of linear association (Figure 1D). Correlation analysis in each HD number of patients need to be conducted.

i40 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i41–i43, 2021
10.1093/ndt/gfab144

SURVIVING CKD micro- and macrovascular disease in a contemporary type 2 diabetes population with
cardiovascular disease or high risk for cardiovascular disease, independent of specific
treatments.
METHOD: Exploratory post-hoc analysis of the two cardiovascular outcome trials in
FC058 THE IMPORTANCE OF ADDRESSING MULTIPLE RISK patients with type 2 diabetes LEADER (NCT01179048; n=8638 with baseline and year
MARKERS IN TYPE 2 DIABETES: RESULTS FROM THE 1 assessment of at least one of the parameters of interest; patients randomised to the
LEADER AND SUSTAIN 6 TRIALS glucagon like peptide-1 receptor agonist [GLP-1 RA] liraglutide or placebo [1:1];
median observation time: 3.8 years) and SUSTAIN 6 (NCT01720446; n=3040 with
Emilie Zobel1, Bernt Johan Von Scholten1,2, Tine Hansen1, Frederik Persson1, baseline and year 1 assessment of at least one of the parameters of interest; patients
Søren Rasmussen2, Benjamin Wolthers2, Peter Rossing1,3 randomised to the GLP-1 RA semaglutide or placebo [1:1]; median observation time:
1
Steno Diabetes Center Copenhagen, Gentofte, Denmark, 2Novo Nordisk A/S, Søborg, 2.1 years). We pooled all participants, including the active (liraglutide/semaglutide)
Denmark and 3University of Copenhagen, Copenhagen, Denmark and placebo-treated groups. We categorised patients according to number of risk
markers with a clinically relevant change 1 year after randomisation and investigated
subsequent risk of major adverse cardiovascular events (MACE: cardiovascular death,
BACKGROUND AND AIMS: The extent to which improvements in multiple risk nonfatal myocardial infarction and nonfatal stroke), expanded MACE (MACE plus
markers affect outcomes in type 2 diabetes is unclear. Our aim was to investigate coronary revascularisation and hospitalisation for heart failure or unstable angina
whether clinically relevant improvement in multiple risk markers confers lower risk of pectoris), cardiovascular death or nephropathy (new onset of macroalbuminuria or

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

doubling of the serum creatinine level and an estimated glomerular filtration rate cystatin C equations compared to those with lowBWz/lowBMI20 phenotype (p=0.044
[eGFR] 45 ml/min/1.73 m2, or the need for continuous renal-replacement therapy, for CAPA, p=0.040 for CKD-EPI_cystatin C). The logistic regression analysis revealed
or death from renal disease). We defined clinically relevant change as: body weight loss that hiBWz/hiBMI20 phenotype was related to lower risk of age and pulse pressure
5%, glycated haemoglobin reduction 1%, systolic blood pressure reduction 5 adjusted albuminuria (OR 0,35 (95%CI[0,12;0,93])
mmHg, low-density lipoprotein cholesterol reduction 0.5 mmol/L, eGFR reduction CONCLUSION: Here we report that lower birth weight in females is associated with
0 ml/min/1.73m2 and urinary albumin-to-creatinine ratio reduction 30% of worse kidney function determined by cystatin C eGFR equations, while in males lower
baseline value. Numbers of risk markers with change were classified as: none (group birth weight z-score is a risk factor for albuminuria in adulthood. Postnatal growth
G0), 1 (G1), 2 (G2), 3 (G3) and 4 (G4). Cox regression analysed risk of each outcome catch-up is not related to worse kidney function. We identified the protective
and tested for trends; models were adjusted for continuous baseline levels of the risk phenotype (hiBWz/hiBMI20) for albuminuria in males and the unfavorable phenotype
markers and treatment group (liraglutide/semaglutide and placebo) and stratified by (hiBWz/lowBMI20) for kidney function in females. This suggests that lower birth
trial. weight and postnatal growth curve have a potential sex specific effect to kidney
RESULTS: The Table contains baseline characteristics of patients in each risk marker function and development of CKD in middle-aged Swedish subjects. Further studies
group. Compared to patients with no risk-marker improvement, patients with 2, 3 or are warranted to address early life factor prognostic accuracy in kidney function and
4 improved risk markers had reduced risk of expanded MACE [hazard ratio (95% outcomes prediction later in the lifetime.
CI): 0.80 (0.67-0.96); 0.80 (0.66-0.97); 0.82 (0.66-1.02)], cardiovascular death [0.66
(0.45-0.96); 0.67 (0.45-0.99); 0.60 (0.38-0.94)] and nephropathy [(0.71 (0.52-0.97); 0.48
(0.34-0.68); 0.43 (0.29-0.65)] (Figure). One improved risk marker conferred no risk
FC060 METABOLIC PROFILING AS A MARKER OF
reduction. The trend of decreased risk for each additional risk marker improvement
CARDIOVASCULAR DISEASE AND ARTERIAL CALCIFICATION
was significant for expanded MACE (p=0.004), cardiovascular death (p=0.005) and
IN THE COPENHAGEN CHRONIC KIDNEY DISEASE COHORT
nephropathy (p<0.0001). We observed a stepwise higher number of patients on GLP-1
RA treatment in the groups with 0, 1, 2, 3 or 4 risk marker improvements as follows:
Ida Maria Hjelm Soerensen1, Line Stattau Bisgaard2,3, Sasha Saurbrey Bjergfelt1,
30.5% in G0, 38.0% in G1, 48.8% in G2, 61.6% in G3 and 75.3% in G4.
Ellen Linnea Freese Ballegaard1, Tor Biering-Sørensen4, Nino Emanuel Landler4,
We observed similar results in separate analyses of the LEADER and SUSTAIN 6 trials. Klaus F. Kofoed5,6, Theis Lange7, Bo Feldt-Rasmussen1, Susanne Bro1,
CONCLUSION: In patients with type 2 diabetes, improvements in two or more risk Christina Christoffersen2,3
markers confer reduced risk of cardiovascular disease and nephropathy as compared 1
Rigshospitalet, Copenhagen University Hospital, Nephrology, Copenhagen, Denmark,
with none or one improved risk marker, most notably for nephropathy. Our findings 2
Rigshospitalet, Copenhagen University Hospital, Clinical Biochemistry, Copenhagen,
stress the importance of multifactorial intervention and underscore the benefit of Denmark, 3University of Copenhagen, Biomedical Sciences, Copenhagen, Denmark,
pleiotropic antidiabetic treatments. 4
Herlev and Gentofte University Hospital, Cardiology, Hellerup, Denmark,
5
Rigshospitalet, Copenhagen University Hospital, Cardiology, Copenhagen, Denmark,
6
Rigshospitalet, Copenhagen University Hospital, Radiology, Copenhagen, Denmark
and 7University of Copenhagen, Public Health, Copenhagen, Denmark

BACKGROUND AND AIMS: The relation between chronic kidney disease and
FC059 EARLY LIFE FACTORS AND ADULT KIDNEY FUNCTION adverse cardiovascular events is well-established. It is also known that traditional risk
ESTIMATED BY CYSTATIN C AND CREATININE factors of cardiovascular disease such as smoking, low-density lipoprotein (LDL)
GLOMERULAR FILTRATION RATE EQUATIONS AND cholesterol and increased blood pressure, cannot fully explain the increased
ALBUMINURIA: A SWEDISH COHORT STUDY cardiovascular burden observed in patients with chronic kidney disease. In addition,
patients with chronic kidney disease do not demonstrate typical clinical symptoms of
Agne Laucyte-Cibulskiene1, Shantanu Sharma1, Peter M. Nilsson1, cardiovascular disease. Thus, good biomarkers for identifying patients at risk and a
Anders Christensson1 better understanding of the pathophysiology leading to cardiovascular disease in
1 patients with chronic kidney disease are needed. The objective of the present study was
Skåne University Hospital, Lund University, Malmö, Department of Clinical Sciences,
to investigate associations between plasma metabolites and prevalent cardiovascular
Malmo, Sweden
disease, as well as subclinical cardiovascular disease measured as coronary artery
calcification score (CACS), in patients with chronic kidney disease.
BACKGROUND AND AIMS: Renal functional capacity is influenced by factors METHOD: More than 200 metabolic biomarkers, including subclasses of lipoproteins
acting early in life, such as intrauterine environment, maturity, birth weight, length at as well as the lipid composition of these, were quantified using nuclear magnetic
birth, placental weight etc. Early life factors are responsible for the number of nephrons resonance spectroscopy in 725 patients and 174 controls from the Copenhagen
a person starts life with, and the consequence of a low nephron number is earlier Chronic Kidney Disease Cohort, a single-centre prospective, observational study of
kidney ageing and chronic kidney disease (CKD). Notably, most reports addressing non-dialysis patients with stage 1-5 chronic kidney disease. Associations between
early life factors in the context of adult kidney function use creatinine-based eGFR metabolites and prevalent cardiovascular disease and between metabolites and CACS
equations and/or albuminuria and lack longer follow-up (<30 years). Therefore, we were determined using multivariable logistic regression and linear regression,
aimed to identify early life factors associated with kidney function, determined by respectively. The statistical models were adjusted for traditional cardiovascular risk
different creatinine and cystatin C equations and urinary albumin-to-creatinine ratio factors and multiple testing. CACS was determined by CT-scannning and calcium
(UACR), more than 40 years later. scores were subsequently divided into categories of 0 (no calcification), 1-100, 101-400
METHOD: 94 women and 494 men, born 1923-50, who participated in The Malmo and > 400.
Diet and Cancer (MDC) study were analyzed. Perinatal data records including birth RESULTS: When comparing metabolite concentrations in patients with controls,
weight (BW), birth length, head circumference, gestational age, placenta weight (PW) patients presented with the expected pattern of dyslipidaemia in CKD. We found that
and mother related risk factors were collected from hospital and regional state archives. they had increased plasma triglyceride concentrations, mainly due to an increase in the
After a follow-up of 46 to 67 years study subjects underwent physical examination, triglyceride concentration in very low-density lipoprotein (VLDL) particles, while the
blood pressure measurements and estimation of glomerular filtration rate (eGFR) concentration of cholesterol in high-density lipoprotein (HDL) particles was decreased.
using 4 different equations: Chronic Kidney Disease Epidemiology Collaboration Overall, 85 metabolites were significantly associated with prevalent cardiovascular
(CKD-EPI) 2012 creatinine and cystatin C formula (CKD-EPI_creatinine, CKD- disease in a model adjusted for eGFR, age and sex (p < 0.001). After further adjusting
EPI_cystatin C), cystatin C eGFR equation based on Caucasian, Asian, pediatric, and for diabetes, body mass index, smoking and cholesterol-lowering medication, the
adult cohorts (CAPA), the Lund-Malmö revised creatinine based eGFR equation significance was lost for all but six metabolites (p < 0.001). The consistent inverse
(LM_rev). Urinary albumin-to-creatinine ratio (UACR) was measured in morning associations with metabolites were primarily involved in HDL metabolism (e.g. ApoA-
urine samples, albuminuria was defined as UACR P3 mg/mmol. Birth weight z-scores 1, HDL-C and HDL-2). This also applied to the concentration of total lipids in large
(gender specific BWz and combined BWz) acquired by using the equation as reported HDL particles, the concentration of phospholipids in large HDL particles and the the
by Marsal et al.(1996). Four growth mismatch phenotypes defined by combining low ratio of phospholipids to total lipids in very small VLDL particles. Of the 84
or high BW z-score (lowBWz or hiBWz respectively) with lower or higher body mass metabolites associated with prevalent cardiovascular disease, 71 were also associated
index at 20 years of age (lowBMI20 ir hiBMI20 respectively). with CACS in a similar pattern. Yet, in the model adjusted for all seven cardiovascular
RESULTS: Linear regression analysis of early life factors indicated that in females birth risk factors, only plasma glucose levels as well as the triglyceride content of larger LDL
weight was positively associated with kidney function measured by both CAPA and particles remained significant.
CKD-EPI_cystatin C. In the whole population, birth weight adjusted for gestational age CONCLUSION: In this study we identified metabolites associated with prevalent
and sex, together with prematurity were independently associated to CKD- cardiovascular disease and subclinical cardiovascular disease (CACS) in patients with
EPI_cystatin C, while BW/PW ratio was related to LM_rev. Logistic regression analysis CKD. For prevalent cardiovascular disease associations were mainly found for HDL
showed that only gender specific BWz and combined BWz shared the same odds ratios associated metabolites, while CACS was associated with an increase in the triglyceride
for age and pulse pressure adjusted albuminuria in males (OR 0,75 (95%CI [0,58; content of LDL particles and glucose. Further work needs to be done to establish
0,96]). While analyzing postnatal growth mismatch we found that females with whether these associations are merely a consequence of the cardiovascular burden or
hiBWz/lowBMI20 phenotype had significantly worse kidney function acquired by both whether there is a causal relation.

i42 | Abstracts
Nephrology Dialysis Transplantation Abstracts
of interest was all-cause mortality. All events were abstracted from hospital discharge
letters and death certificates by trained physicians based on a standardized endpoint
catalogue. Cross-sectional regression models (dependent variables: eGFR, logUACR)
adjusted for confounding variables (Table 1 legend) were fitted. Multi-variable
adjusted Cox proportional hazard regression analyses were conducted. Estimated risks
are expressed as cause-specific hazard ratios (HR) for all-cause mortality and kidney
events, with death of other causes as the competing event. Sensitivity analyses included
evaluation of all models stratified by the three most common causes of kidney disease
in GCKD: hypertensive nephropathy, primary glomerular disease, and diabetic
nephropathy.
RESULTS: Over 6.5 years of follow-up, 473 kidney events and 582 deaths occurred
among 4,950 GCKD patients. Hundred-and-forty-eight deaths and 62 kidney events
occurred in 1,143 hypertensive nephropathy patients, 49 deaths and 118 kidney events
occurred in 935 primary glomerular nephropathy patients, and 170 deaths and 99
kidney events in diabetic nephropathy patients (Table 1). Overall mean age was 60.1
years (612.0), with 60.3% men. Median OPN levels were 29.2 ng/mL (IQR 21.2).
Cross-sectionally a 10% change in OPN was associated with 0.5% lower eGFR on
average (p<0.0001, 95% CI: -6.4 to -4.6) and a 7% change in UACR (p<0.0001, 95%
CI: 0.6 to 0.8) overall. Stratified by leading cause of kidney disease, results for eGFR and
UACR were of similar direction for all groups (Table 1 A). After adjusting for baseline
eGFR and UACR (Table 1 B), higher OPN levels were associated with a higher risk of
kidney events overall (HR 1.4, p<0.001, 95% CI 1.1-1.7). For patients with diabetic
nephropathy this risk was even higher (HR 2.2, p<0.01, 95% CI 1.4-3.6). Higher OPN
levels were also associated with higher risk of all-cause mortality overall (HR 1.5,
p<0.0001, 95% CI 1.3-1.8) as well as for diabetic nephropathy patients (HR 1.7,
p<0.01, 95% CI 1.2-2.4). HRs for the hypertensive nephropathy and primary
glomerular nephropathy groups showed mostly the same effect directions, but did not
reach significance after adjustment.

FC061 OSTEOPONTIN AND ITS ASSOCIATION WITH ADVERSE


EVENTS IN THE GERMAN CHRONIC KIDNEY DISEASE STUDY

Inga Steinbrenner1, Yurong Cheng1, Jennifer Nadal2, Matthias Schmid2, Fruzsina


Kinga Kotsis3, Heike Meiselbach4, Markus Schneider4, Vera Krane5,
Matthias Nauck6, Kai-Uwe Eckardt4,7, Anna Köttgen1, Peggy Sekula1, Ulla
T. Schultheiß3
1
Institute of Genetic Epidemiology, Medical Center - University of Freiburg, Faculty of
Medicine, Freiburg, Germany, 2Institute of Medcial Biometry, Informatics and
Epidemiology, University Hospital Bonn, Bonn, Germany, 3Institute of Genetic
Epidemiology and Medicine IV - Nephrology, Faculty of Medicine and Medical Center -
University of Freiburg, Freiburg, Germany, 4Deparment of Nephrology and
Hypertension, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-
Nuremberg, Erlangen, Germany, 5Department of Internal Medicine I, Nephrology,
University Hospital Würzburg, Germany, 6Institute of Clinical Chemistry and Laboratory
Medicine, University Medicine Greifswald, Greifswald, Germany and 7Deparment of
Nephrology and Medical Intensive Care, Charité, University-MedicineCharité, University-
Medicine, Berlin, Germany

BACKGROUND AND AIMS: Osteopontin (OPN) is synthesized in the thick


ascending limb of Henle’s loop and in the distal tubule. Numerous studies have shown
that OPN mRNA and protein expression is increased in animal models of many
different renal diseases, especially glomerular diseases as well as diabetic nephropathy.
Here, high OPN expression correlated with proteinuria, reduction of creatinine
clearance, fibrosis as well as macrophage and T-cell infiltration. OPN has therefore
been suggested to be a promising biomarker for various kidney diseases. Further
studies are needed to fully understand its role in kidney (patho-)physiology and its
potential as a marker of kidney disease progression and adverse renal events. We CONCLUSION: Higher OPN levels were associated with lower eGFR and higher
therefore evaluated the association of OPN with kidney events and all-cause mortality UACR cross-sectionally and significantly associated with a higher risk of renal events
in a cohort of CKD patients, the German Chronic Kidney Disease (GCKD) study. and all-cause mortality especially for diabetic nephropathy patients even after
METHOD: OPN was measured from baseline serum samples using the Quantikine adjustment for baseline eGFR, UACR and other confounding factors. These results are
Human OPN Immunoassay. Coefficients of variation were <7%. Kidney events supportive of OPN being a potential marker of CKD progression and mortality.
included kidney failure treated with kidney replacement therapy (dialysis,
transplantation), and death due to discontinuation of dialysis treatment. Another event

10.1093/ndt/gfab144 | i43
Nephrology Dialysis Transplantation 36 (Supplement 1): i44–i46, 2021
10.1093/ndt/gfab136

PATHOPHYSIOLOGICAL PATHWAYS IN CKD inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2
diabetes. Whether this effect persist in patients with chronic kidney disease (CKD)
with and without diabetes is unknown. We therefore assessed and compared the effects
of dapagliflozin on albuminuria in patients with CKD with and without type 2 diabetes
FC062 OBESITY AS A CAUSE OF KIDNEY DISEASE - INSIGHTS from the DAPA-CKD trial.
FROM MENDELIAN RANDOMISATION STUDIES METHOD: We randomized 4304 patients with CKD and an eGFR of 25-75 ml/min/
1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g to
Xiaoguang Xu1, James Eales1, Xiao Jiang1, Eleanor Sanderson2, David Scannali1, dapagliflozin (10 mg once daily) or placebo. Change in albuminuria was a pre-specified
Andrew Morris1, Tomasz Guzik3, Fadi Charchar4, Michael Holmes5, exploratory outcome. We used regression in UACR stage, defined as a transition from
Maciej Tomaszewski1 macroalbuminuria (300 mg/g) to micro- or normoalbuminuria (<300 mg/g), and
1
1University of Manchester, United Kingdom, 2University of Bristol, United Kingdom, progression in UACR stage, defined as a transition from non-nephrotic (<3000 mg/g)
3
3University of Glasgow, United Kingdom, 4Federation University Australia and 5John to nephrotic range albuminuria (3000 mg/g), as additional endpoints. Subgroup
Radcliffe Hospital, United Kingdom analyses were performed according to baseline type 2 diabetes status.
RESULTS: Median (25th to 75th Percentile) UACR was 949 (477-1885) mg/g. In
patients with and without type 2 diabetes baseline median UACR was 1017 mg/g and
BACKGROUND AND AIMS: Obesity and kidney diseases are common complex 861 mg/g, respectively. Dapagliflozin, compared to placebo, reduced UACR by 29.3%
disorders with an increasing clinical and economic impact on healthcare around the (95% confidence interval [CI] 25.2, 33.1; p<0.001), with a 35.1% (95%CI 30.6, 39.4)
globe. We aim to examine if modifiable anthropometric indices of obesity exert reduction in patients with type 2 diabetes and 14.8% (95%CI 5.9, 22.9) reduction in
putatively causal effects on different measures of kidney health and disease. patients without type 2 diabetes (p for interaction <0.001). Among 3860 patients with
METHOD: We performed conventional observational and Mendelian randomisation UACR 300 mg/g at baseline, dapagliflozin significantly increased the likelihood of
(MR) study to examine if modifiable anthropometric indices of obesity exert putatively regression in UACR stage (hazard ratio [HR] 1.81; 95%CI 1.60, 2.05). The
causal effects on different kidney health and disease-related phenotypes. These analyses corresponding HRs for patients with and without type 2 diabetes were 2.06 (95%CI
were conducted using approximately 300,000 participants of white-British ancestry 1.78, 2.39) and 1.33 (95%CI 1.07, 1.66), respectively (p for interaction 0.001). Among
from UK Biobank and up to 480,000 participants of predominantly European ancestry 3820 patients with UACR <3000 mg/g at baseline, dapagliflozin significantly decreased
from genome-wide association studies. the risk of nephrotic range albuminuria (HR 0.41; 95%CI 0.32, 0.52). The
RESULTS: The Mendelian randomisation analysis indicated that increasing values of corresponding HRs for patients with and without type 2 diabetes were 0.39 (95%CI
genetically predicted BMI and waist circumference were causally linked to changes in 0.29, 0.51) and 0.50 (95%CI 0.30, 0.82), respectively (p for interaction 0.401).
renal function indices including reduced estimated glomerular filtration CONCLUSION: In patients with CKD with and without type 2 diabetes dapagliflozin
(PeGFRcystatineC=5.96  10-59 for BMI and PeGFRcystatineC=1.72  10-69 for waist significantly reduced albuminuria, with a larger reduction in patients with type 2
circumference) and increased blood urea nitrogen (PBUN=2.01  10-10 for BMI and diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or
PBUN=4.54  10-12 for waist circumference) in UK Biobank individuals. These without type 2 diabetes, but different effects on UACR suggest that part of
associations were replicated using data from CKDGen Consortium individuals dapagliflozin’s protective effect in patients without diabetes is mediated through
(PeGFRcystatineC=1.47  10-5 for BMI and PeGFRcystatineC=7.63  10-5 for waist pathways unrelated to UACR reduction.
circumference; PBUN=1.96  10-4 for BMI and PBUN=3.10  10-3 for waist circumference).
One standard deviation increase in genetically-predicted BMI and waist circumference
decreased the relative odds of kidney health index by 14% and 18% (OR=0.86; 95%CI:
0.82-0.92; P=9.18  10-6 for BMI and OR=0.82; 95%CI: 0.75-0.90; P=2.12  10-5 for waist FC064 A RENAL-CARDIO INFLAMMATORY AXIS MEDIATES
circumference). Approximately 13-16% of the causal effect of obesity indices on kidney CARDIAC DYSFUNCTION IN CKD VIA IL-33-ST2: A NOVEL
health was mediated by blood pressure. Obesity increased the risk of both acute and MECHANISM
chronic kidney disease of several aetiologies including hypertensive renal disease
(OR=1.79; 95%CI: 1.14-2.82; P=1.15  10-2 for BMI and OR=2.41; 95%CI: 1.30-4.45; Alejandro Chade1, Michael Hall2, Deandra Fortenberry3, Drew Bossier3,
P=5.03  10-3 for waist circumference), renal failure (OR=1.51; 95%CI: 1.25-1.83; Gene Bidwell4
P=2.60  10-5 for BMI and OR=1.86; 95%CI: 1.43-2.42; P=4.16  10-6 for waist 1
University of Mississippi Medical Center, Physiology and Biophysics; Medicine; and
circumference) and CKD (OR=1.50; 95%CI: 1.16-1.96; P=2.44  10-3 for BMI and Radiology, Jackson, United States of America, 2University of Mississippi Medical Center,
OR=1.83; 95%CI: 1.28-2.63; P=9.49  10-4 for waist circumference) and diabetic Physiology and Biophysics; Medicine , Jackson, United States of America, 3University of
nephropathy (OR=1.92; 95%CI: 1.44-2.54; P=6.86  10-6 for BMI). Mississippi Medical Center, Physiology and Biophysics, Jackson, United States of
CONCLUSION: These findings indicate that obesity is causally linked to indices of America and 4University of Mississippi Medical Center, Neurology; Cell and Molecular
renal health and the risk of different kidney diseases. This evidence substantiates the Biology, Jackson, United States of America
value of weight loss as a strategy of preventing and/or counteracting a decline in kidney
health as well as decreasing the risk of renal disease. BACKGROUND AND AIMS: We developed a swine model of chronic kidney disease
(CKD) that also display cardiac abnormalities associated with heart failure (HF).
Inflammation contributes to progressive renal dysfunction and increases
cardiovascular mortality of patients with CKD. Interleukin (IL)-33 is a tissue-derived
nuclear cytokine from the IL family. IL-33 constitutively expressed but upregulated and
released after cellular damage or necrotic cell death, acting as a pro-inflammatory
cytokine. We hypothesize that IL-33 plays a prominent mechanistic role in renal-
FC063 DAPAGLIFLOZIN DECREASES ALBUMINURIA IN PATIENTS
cardio pathophysiology in CKD.
WITH CHRONIC KIDNEY DISEASE WITH AND WITHOUT TYPE
METHOD: We induced CKD in 10 pigs via bilateral renovascular disease and
2 DIABETES: INSIGHTS FROM THE DAPA-CKD TRIAL
dyslipidemia. We developed a renally-targeted biopolymer-fused peptide inhibitor of
nuclear-factor kappa (NF-k)B (ELP-p50i) and show it blocks NFkB activity in vitro and
Niels Jong1, Glenn Chertow2, Fan Fan Hou3, John McMurray4, Ricardo Correa-
in vivo. NF-kB is a key pro-inflammatory transcription factor upregulated in CKD and
Rotter5, Peter Rossing6,7, David Sjöström8, Bergur Stefansson8, Robert Toto9,
closely interacts with IL-33. Pigs were observed for 6 weeks, renal (multi-detector CT)
Anna Maria Langkilde8, David C. Wheeler10,11, Hiddo Lambers Heerspink1,11
1
and cardiac structure and function (echo) were quantified, then randomized to single
University Medical Center Groningen, Groningen, The Netherlands, 2Stanford intra-renal ELP-p50i or placebo (n=5 each), and studies repeated 8 weeks later. Blood
University, Stanford, United States of America, 3Division of Nephrology, Nanfang was collected to measure circulating TNF-a, IL-33 and its specific decoy receptor
Hospital, Southern Medical University, National Clinical Research Center for Kidney soluble (s) ST2 (ELISA). Heart weights were measured after euthanasia, and renal and
Disease, Guangzhou, China, 4University of Glasgow, United Kingdom, 5National cardiac expression of ST2 and morphometric analyses were performed.
Medical Science and Nutrition Institute Salvador Zubir an, Mexico City, Mexico, 6Steno RESULTS: Loss of renal function in CKD was accompanied by increased heart weight,
Diabetes Center, Copenhagen, Gentofte, Denmark, 7Copenhagen University, left ventricular (LV) hypertrophy, diastolic dysfunction, abnormal LV strain, renal/
København, Denmark, 8Late-stage Development, Cardiovascular, Renal and cardiac fibrosis, circulating TNF-a, IL-33 but unchanged sST2, and increased renal/
Metabolism (CVRM), Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 9UT cardiac ST2 expression. Most of these changes were improved after intra-renal ELP-
Southwestern Medical Center, Dallas, United States of America, 10University College p50i and accompanied by augmented sST2, suggesting that inhibition of renal
London, United Kingdom and 11The George Institute for Global Health, Newtown, inflammation can attenuate cardiac abnormalities via augmented clearance of IL-33
Australia (Figure).

BACKGROUND AND AIMS: Reductions in albuminuria are consistently associated


with a subsequent lower risk of kidney failure. The sodium glucose co-transporter 2

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
RESULTS: Two-hundred and forty-six patients with biopsy proven ANCA vasculitis
were identified. Fifty percent (n=123), 46% (n=112) and 5% (n=11) were stratified as
low, medium and high risk respectively. Fifty-two percent (n=129) were male and
mean age at biopsy was 66.7612.2 years. This was similar across the risk categories.
Mean eGFR was lower in the high-risk category (High risk 8.666.1 ‘v’ Low risk
45.7626.0 ml/min/1.73m2, p<0.001) and proteinuria was higher (High risk 405 (IQR
170-767) ‘v’ Low risk 81 (IQR 41-155) mg/mmol, p<0.001). Thirty-seven percent
(n=91) were PR3 antigen positive, 2% (n=5) had dual positivity. In the high risk
category, 8 (73%) were PR3 or dual positive. Eighteen (n=7%) patients experienced
pulmonary haemorrhage; representation similar across all risk categories.
Those categorised as medium or high risk were more likely to receive plasma exchange
and/or haemodialysis at presentation (p<0.001) compared with the low risk category.
Overall, 16% (n=40) of patients relapsed with a trend to higher risk of relapse in the
low risk group (27% of these patients, p=0.05). Thirty seven (15%) patients developed
ESKD. Cox proportional hazard model for development of ESKD (Figure 1) shows that
those in high risk ‘v’ low risk category were more likely to reach ESKD (HR 124.8, 95%
CI 26.4-590.3, p<0.001). Patient survival was similar between risk categories.

FC065 Figure 1: Development of ESKD in renal biopsy proven ANCA associated


vasculitis, stratified by renal risk score category

CONCLUSION: A simple RRS, using routinely reported data, in patients with renal
biopsy proven ANCA vasculitis can help to predict development of ESKD. It may also
be predictive of future relapse in those with a lower RRS, most likely explained by
CONCLUSION: Our study supports a prominent role for renal inflammation as a reduced irreversible damage in this group. The RRS could inform monitoring and
driving force for precursors of HF in CKD, proposing a renal-cardio inflammatory axis treatment decisions.
possibly mediated by NF-kB-TNF-a-IL-33/ST2 interactions. TNF-a can stimulate IL- Whilst the numbers are small, a unique strength of this data is that it is based on a
33 as IL33 can activate NF-kB and TNF-a, extending this inflammatory loop in both complete national dataset making it less susceptible to bias from regional variations in
the kidney and heart. We show that a translational renal anti-inflammatory strategy via diagnostic and therapeutic practice.
targeted inhibition of renal NFkB inhibits this axis and improves renal and cardiac
function, which may guide to new treatments targeting renal inflammation in CKD. References
1. Brix SR et al. Development and validation of a renal risk score in ANCA-associated
glomerulonephritis. Kidney Int. 2018 Dec;94(6):1177–1188. doi: 10.1016/
FC065 PREDICTING OUTCOMES IN ANCA ASSOCIATED j.kint.2018.07.020
VASCULITIS: THE COMPLETE SCOTTISH EXPERIENCE

Dominic McGovern1, Jennifer Lees1, Dana Kidder2, James Smith2,


Jamie Traynor1, Neeraj Dhaun3, Robert Hunter3, Nicola Joss4, Michael Kelly5,
Malcolm MacKinnon6, Zoe Cousland7, Kate Shiell8, Michelle Lim9, Colin FC066 DICKKOPF-3 (DKK3) LINKS RECIPROCAL LUNG AND KIDNEY
C. Geddes1, Emily McQuarrie1, Kate Stevens1 INJURY IN MICE AND HUMANS
1
The Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital,
Glasgow, United Kingdom, 2Renal Unit, Aberdeen Royal Infirmary, Aberdeen, United Stefan Schunk1, Christoph Beisswenger1, Triem Sarah1, Gregor Hütter1,
Kingdom, 3Renal Unit, Edinburgh Royal Infirmary, Edinburgh, United Kingdom, 4Renal Tamim Sarakpi1, Peter Boor2, Rudolf Jörres3, Henrik Watz3, Tobias Welte4,
Unit, Raigmore Hospital, Inverness, United Kingdom, 5Renal Unit, Dumfries and Claus Vogelmeier5, Hermann Gröne5, Danilo Fliser1, Robert Bals1,
Galloway Royal Infirmary, Dumfries, , 6Renal Unit, John Hunter Hospital, New Lambton, Thimoteus Speer1
Australia, 7Renal Unit, University Hospital Monklands, Airdrie, United Kingdom, 8Renal 1
Saarland University, Saarbrücken, Germany, 2RWTH Aachen University, Aachen,
Unit, Victoria Hospital, Kirkcaldy, United Kingdom and 9Renal Unit, Ninewells Hospital, Germany, 3Klinikum Großhadern, München, Germany, 4Medizinische Hochschule
Dundee, United Kingdom Hannover, Hannover, Germany and 5Uniklinik Marburg Baldingerstrasse, Marburg,
Germany
BACKGROUND AND AIMS: Outcomes in ANCA vasculitis remain difficult to
predict and therapeutic decision-making can be challenging. We aimed to establish if a BACKGROUND AND AIMS: Chronic kidney disease (CKD) and chronic obstructive
renal risk score (RRS) could predict outcomes in this population. pulmonary disease (COPD) represent global public health problems with high disease-
METHOD: The Scottish Renal Biopsy Registry is a complete national dataset of all related morbidity and mortality. However, the interaction between both diseases
renal biopsies performed in Scotland. Those who had a first renal biopsy between 01/ remains unclear.
01/2014 and 31/12/2017 with evidence of ANCA vasculitis were included. METHOD: In a novel murine model, cigarette smoke (CS)-induced lung injury was
Demographic data, treatment regimens, episodes of relapse and patient and kidney combined with a CKD model (CS-CKD model). In 2,314 patients of the prospective
survival were recorded, retrospectively. The RRS was calculated using the system multi-center COSYCONET study, urinary Dickkopf-3 (DKK3), a renal tubular stress
proposed by Brix et al (1). Each patient was categorised according to % of normal marker, was quantified. The association between urinary DKK3 and trajectories of
glomeruli (N0 >25%, N1 10 to 25%, N2 <10%), % of tubular atrophy/interstitial FEV1 and estimated glomerular filtration rate (eGFR), exercise capacity, risk of
fibrosis (T0 25%, T1 >25%) and eGFR (CKD-EPI) at time of biopsy (eGFR: G0 >15 exacerbation, and mortality was determined (follow-up 37.1 months).
mL/min/1.73 m2, G1 15 mL/min/1.73 m2). Individual scores were summated and RESULTS: In the CS-CKD model, CKD was associated with higher systemic and
patients defined as low, medium or high risk. Cox proportional hazard models were pulmonary inflammation, and the combination of CKD and CS significantly
created for survival to ESKD, relapse and death, stratified by risk category. Analyses aggravated kidney inflammation as well as fibrosis and increased renal expression of
were conducted using R statistical software. DKK3. Abrogation of Dkk3 attenuated kidney injury and pulmonary inflammation

10.1093/ndt/gfab136 | i45
Abstracts Nephrology Dialysis Transplantation

alike. In COPD patients, higher urinary DKK3 was associated with rapidly declining CONCLUSION: In summary, the present study identified a strong pathophysiological
FEV1 (OR 3.36, P<0.0001), higher risk for exacerbation, lower 6-minute walking link between lung and kidney dysfunction, which is at least partially mediated by
distance, and higher all-cause mortality (HR 1.49, P=0.015). Importantly, higher DKK3. Urinary DKK3 allows identification of COPD patients at increased risk for
urinary DKK3 was also associated with declining eGFR during follow-up (OR 2.23, deteriorating pulmonary and kidney function as well as adverse outcomes. These
P=0.0005). Neither eGFR nor proteinuria were associated with lung or kidney patients might particularly benefit from preventive therapeutic strategies as a
dysfunction during follow-up. personalized-medicine approach.

i46 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i47–i49, 2021
10.1093/ndt/gfab122

BIG DATA & NEPHROLOGY METHOD: Nationwide observational cohort study using data from the Swedish Renal
Registry between January 1, 2007 and December 31, 2016, with follow-up until June 1,
2017. Included individuals were receiving nephrologist care and had an eGFR between
10-20 ml/min/1.73m2. A randomized trial was emulated using the cloning, censoring
FC067 WHEN TO INITIATE DIALYSIS TO REDUCE MORTALITY AND and weighting method. Our primary analysis compared late (at an eGFR 5-7 ml/min/
CARDIOVASCULAR EVENTS IN ADVANCED CKD: A 1.73m2 [eGFR5-7]), intermediate (eGFR7-10) and early (eGFR10-14) dialysis initiation to
NATIONWIDE COHORT STUDY validate our analytical methods by comparison with IDEAL. Our secondary analysis
compared fifteen dialysis initiation strategies with eGFR values ranging between 4 and
Edouard Fu1, Marie Evans2, Juan Jesus Carrero3, Hein Putter4, 19 ml/min/1.73m2 in increments of 1 ml/min/1.73m2. Study outcomes were 5-year all-
Catherine M. Clase5, Fergus Caskey6, Maciej Szymczak7, Claudia Torino8, cause mortality and major adverse cardiovascular events (MACE; composite of
Nicholas Chesnaye9, Kitty J. Jager9, Christoph Wanner10, Friedo W. Dekker1, cardiovascular death, non-fatal myocardial infarction and stroke). Adjusted hazard
Merel Van Diepen1 ratios [HR] and cumulative survival proportions were estimated using a dynamic
1
Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The marginal structural model.
Netherlands, 2Karolinska Institute, Department of Clinical Science, Intervention and RESULTS: Among 10,290 individuals with advanced CKD (median age 73 years; 36%
Technology, Stockholm, Sweden, 3Karolinska Institute, Department of Medical women; median eGFR 16.8 ml/min/1.73m2), 3725 individuals initiated dialysis, 4160
Epidemiology and Biostatistics, Sweden, 4Leiden University Medical Center, Department died and 2446 experienced MACE. In trial emulation, the 5-year mortality risk was
of Biomedical Data Sciences, Leiden, The Netherlands, 5McMaster University, 53.0% for eGFR5-7, 50.3% for eGFR7-10 and 49.7% for eGFR10-14. Compared with
Department of Medicine and Health Research Methods, Evidence and Impact, eGFR5-7, the 5-year absolute mortality risk difference was -2.7% (95% CI, -4.6% to -
Hamilton, Canada, 6University of Bristol Medical School, Population Health Sciences, 0.7%) for eGFR7-10 and -3.3% (95% CI, -5.2% to -1.3%) for eGFR10-14, with a HR of
Bristol, United Kingdom, 7Wroclaw Medical University, Department of Nephrology and 0.97 (0.94-0.99) and 0.96 (0.94-0.99), respectively. The 5-year absolute MACE risk
Transplantation Medicine, Wroclaw, Poland, 8Ospedali Riuniti, IFC-SNR, Clinical differences were -1.1% (95% CI, -3.8% to 2.1%) for eGFR7-10 and -3.6% (95% CI, -6.0%
Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio to -1.0%) for eGFR10-14 compared with eGFR5-7, with a HR of 1.00 (0.97-1.04) and 0.96
Calabria, Italy, 9Academic University Medical Center, University of Amsterdam, (0.97-1.00), respectively. When analysing fifteen eGFR thresholds, initiation at eGFR15-
Amsterdam Public Health research institute, ERA-EDTA Registry, Department of Medical 16 was associated with the largest reduction in mortality (absolute difference, -5.9%

Informatics, Amsterdam, The Netherlands and 10University Hospital of Würzburg, [95% CI, -8.0% to -3.1%]; HR, 0.88 [95% CI, 0.85-0.92]) and MACE (absolute
Division of Nephrology, Würzburg, Germany difference, -4.5% [95% CI, -7.6% to -1.4%]; HR, 0.92 [95% CI, 0.89-0.97]), compared
with eGFR4-5. This -5.9% absolute risk difference translates to a mean postponement of
death of 1.8 months over 5-years of follow-up. However, dialysis would need to be
BACKGROUND AND AIMS: There is currently no direct evidence to inform a initiated on average 14 months earlier.
specific glomerular filtration rate (GFR) to initiate maintenance dialysis. Previous CONCLUSION: Early dialysis initiation was associated with a modest reduction in
studies are limited by the number of kidney function thresholds compared, immortal mortality and cardiovascular events. Such a reduction may not outweigh the burden of
time or lead time biases, or small sample sizes. The only randomised trial (IDEAL) longer dialysis treatment duration for the patient.
found no difference between early versus late start, but confidence intervals were wide.

FC067 Figure: Weighted, standardized cumulative incidence curves for mortality


(A, C) and MACE (B, D) stratified by different dialysis initiation strategies.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC068 QUALITY OF LIFE OVER TIME IN OLDER MEN AND WOMEN RESULTS: We included 5151 QoL measurements in 1416 patients over a total of 1986
WITH ADVANCED CKD - RESULTS FROM THE EQUAL STUDY person years of follow-up. Overall, the physical component summary (PCS) declined
with 2.0 (95% CI 1.4-2.6) points and the mental component summary (MCS) by 2.4
Nicholas Chesnaye1, Yvette Meuleman2, Esther De Rooij2, Friedo W. Dekker2, (95% CI 1.8-3.0) points per year. Although women had overall lower QoL scores, figure
Marie Evans3, Fergus Caskey4, Claudia Torino5, Maciej Szymczak6, 1 demonstrates that PCS and MCS declined more than twice as fast in men (PCS: 2.4
Christiane Drechsler7, Christoph Wanner7, Kitty J. Jager1 per year, 95% CI 1.7 – 3.1, MCS: 2.9 per year, 95% CI 2.2 – 3.6) compared with women
1
ERA-EDTA Registry, Dept of Medical Informatics, Academic Medical Center, (PCS: 1.1 per year, 95% CI -0.2 – 2.0, MCS: 1.5 per year, 95% CI 0.5 – 2.4). We
Amsterdam, The Netherlands, 2Leiden University Medical Center (LUMC), Department of identified a non-linear interaction effect between sex and eGFR levels on QoL,
Clinical Epidemiology, Leiden, The Netherlands, 3Karolinska Institutet and Karolinska demonstrating a stronger negative effect of decreased eGFR on both PCS (p=0.02) and
University hospital, Clinical Intervention and technology, Stockholm, Sweden, MCS (p=0.04) in men compared with women. Subsequent adjustment for renal decline
4
University of Bristol, Population Health Sciences, Bristol, United Kingdom, 5CNR-IFC, attenuated the difference in rate of QoL decline between men and women (difference
Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension & after adjustment; PCS: 1.1, 95% CI -0.1 – 2.2, MCS: 1.2, 95% 0.0 – 2.3). In univariable
G.O.M., Reggio Calabria, Italy, 6Wroclaw Medical University, Dept of Nephrology and analyses, higher serum haemoglobin was more beneficial to QoL in men compared to
Transplantation Medicine, Wroclaw, Poland and 7University Hospital Würzburg, women (p-value for interaction; PCS: p=0.03, MCS: p=0.01). Higher serum phosphate
Division of Nephrology, Würzburg, Germany had a strong harmful effect on both PCS and MCS in men, but not in women (PCS &
MCS: p<0.001). The presence of pre-existing diabetes had a negative effect on PCS and
BACKGROUND AND AIMS: Differences between the sexes are apparent in the MCS in men, but to a lesser extent in women (PCS: p=0.02, MCS: p=0.01).
epidemiology of CKD. Cross-sectional studies show that women consistently report a CONCLUSION: Despite the higher overall QoL reported by men, both their physical
poorer health-related quality of life (QoL) than men, however, longitudinal studies are and mental QoL declined approximately twice as fast compared with women. The
lacking. Here we investigate the sex-specific evolution of QoL over time in advanced faster decline in men was mediated in part by their lower levels of renal function, which
CKD. As a secondary aim, we explore the sex-specific determinants of QoL. had a stronger impact on their QoL as compared with women. Furthermore, in
METHOD: EQUAL is an observational prospective cohort study in stages 4 and 5 exploratory analyses we identified that high levels of phosphate, low levels of
CKD patients 65 years not on dialysis with an incident estimated glomerular haemoglobin, and pre-existing diabetes were more detrimental to QoL in men than in
filtration rate (eGFR) < 20 ml/min/1.73m2. Data on QoL (measured using the RAND- women.
36), clinical and demographic patient characteristics were collected between April 2012
and September 2020. QoL trajectories were modelled by sex using linear mixed models,
and joint models were applied to deal with informative censoring. We followed FC069 CHRONIC KIDNEY DISEASE AND ATRIAL FIBRILLATION: A
patients until death or dialysis initiation. DANGEROUS COMBINATION

Gurbey Ocak1,2, Meriem Khairoun2, Othman Khairoun2, Willem Jan Bos1,3,


Edouard Fu4, Maarten J. Cramer5, Jan Westerink6, Marianne Verhaar2, Frank L.
J. Visseren6
1
Sint Antonius Hospital, Department of Internal Medicine, Nieuwegein, The
Netherlands, 2University Medical Center Utrecht, Department of Nephrology and
Hypertension, Utrecht, The Netherlands, 3Leiden University Medical Center, Department
of Internal Medicine, Leiden, The Netherlands, 4Leiden University Medical Center,
Department of Clinical Epidemiology, Leiden, The Netherlands, 5University Medical
Center Utrecht, Department of Cardiology, Utrecht, The Netherlands and 6University
Medical Center Utrecht, Department of Vascular Medicine, Utrecht, The Netherlands

BACKGROUND AND AIMS: Chronic kidney disease (CKD) and atrial fibrillation
(AF) are both risk factors for bleeding, stroke and mortality. Whether the combination
of CKD and AF leads to higher risks of bleeding, stroke and mortality than CKD or AF
alone is not known. The aim of our study was to investigate the interaction between
CKD and AF and outcomes.
METHOD: We included 12,394 subjects referred to the University Medical Center
Utrecht (the Netherlands) from September 1996 to February 2018f for an out-patient
visit with classical risk factors for arterial disease or with symptomatic arterial disease
(Utrecht Cardiovascular Cohort Second Manifestation of Arterial disease (UCC-
SMART) cohort). Hazard ratios (HRs) with 95% confidence intervals (CIs) for
bleeding, ischemic stroke or mortality were calculated with Cox proportional hazards
analyses. Presence of additive interaction between AF and CKD was examined by
calculating the relative excess risk due to interaction (RERI), the attributable
proportion (AP) due to interaction and the synergy index (S).
RESULTS: Of the 12,394 patients, 699 patients had AF, 2,752 patients had CKD and
325 patients had both AF and CKD. Overall, 382 patients developed a first bleeding
event, 421 patients had a first ischemic stroke and 2203 patients died. Patients with
both CKD and AF had a 3.0-fold (95% CI 2.0-4.4) increased risk for bleeding, a 4.2-fold
(95% CI 3.0-6.0) increased ischemic stroke risk and a 2.2-fold (95% CI 1.9-2.6)
increased mortality risk after adjustment as compared with subjects without AF and
CKD (Table 1). Although bleeding and mortality risks were highest for the
combination of AF and CKD, we did not find interaction between AF and CKD.
However, we found an interaction between AF and CKD for ischemic stroke risk (RERI
1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and S 2.40 (95% CI 1.08-5.32))
(Table 1).

i48 | Abstracts
Nephrology Dialysis Transplantation Abstracts
FC070 USE OF POTENTIALLY NEPHROTOXIC MEDICATIONS IN
FC069 Table 1: Interaction between atrial fibrillation and chronic kidney disease PERSONS WITH CHRONIC KIDNEY DISEASE: PARALLEL
COHORT STUDIES IN SWEDISH AND U.S ROUTINE CARE
Atrial Chronic Incidence rate Crude *Adjusted Alessandro Bosi1, Juan Jesus Carrero1, Jung-Im Shin2, Yunwen Xu1,
fibrillation kidney Morgan Grams2, Alexander Chang3, Bjorn Wettermark4, Franz Peter Barany5,
disease Alessandro Gasparini1
1
Karolinska Institute, Department of Medical Epidemiology and Biostatistics, Solna,
per 1000 py HR (95%CI) HR (95%CI) Sweden, 2Johns Hopkins Bloomberg School of Public Health, Cardiovascular and
BLEEDING Clinical Epidemiology, Baltimore, United States of America, 3Johns Hopkins University,
No No 2.6 1 (ref) 1 (ref) School of Medicine, Baltimore, United States of America, 4Uppsala University,
Department of Pharmacy, Social Pharmacy, Uppsala, Sweden and 5Karolinska Institute,
Yes No 7.7 2.7 (1.7-4.4) 1.9 (1.1-3.2) Department of Clinical Science, Intervention and Technology, Solna, Sweden
No Yes 5.7 2.1 (1.7-2.7) 1.5 (1.2-1.9)
Yes Yes 17.2 6.1 (4.3-8.7) 3.0 (2.0-4.4) BACKGROUND AND AIMS: Many adverse drug events are preventable, such as
those potentially resulting from the prescription of nephrotoxic drugs to persons with
INTERACTION: RERI 0.62 (95% CI -0.75-1.99), AP 0.21 (95% CI -0.21-0.62) chronic kidney disease (CKD). We here quantify the extent of contemporary
and S 1.45 (95% CI 0.62-3.43) nephrotoxic medication use in patients with CKD.
ISCHEMIC STROKE METHOD: In two observational cohorts of Swedish (Stockholm CREAtinine
Measurements [SCREAM] project, Stockholm, Sweden) and U.S. (Geisinger Health
No No 2.9 1 (ref) 1 (ref) System, Pennsylvania) adults with confirmed CKD stages G3-G5 undergoing routine
Yes No 8.0 2.7 (1.7-4.4) 1.8 (1.1-3.1) care during 2016-2018, we explored the prescription (in U.S.) and dispensation (in
No Yes 6.1 2.1 (1.7-2.6) 1.5 (1.2-1.9) Sweden) of 115 different ambulatory drugs with proven or purported nephrotoxicity
during the 12 months following study inclusion. We evaluated the proportion of
Yes Yes 21.3 7.3 (5.3-10.0) 4.2 (3.0-6.0) participants receiving nephrotoxic drugs, ranked main contributors and identified
INTERACTION: RERI 1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and clinical predictors.
RESULTS: In the Swedish cohort, there were 57880 patients (54.6% women) with
S 2.40 (95% CI 1.08-5.32) median age of 80.00 (inter-quartile range [IQR]: 73.0-86.0) years and eGFR 48.9
MORTALITY ([IQR]: 39.9-55.0) mL/min/1.73 m2. In the U.S. cohort, there were 16255 patients (59%
No No 14.5 1 (ref) 1 (ref) women) with median age of 76 years and eGFR 44 mL/min/1.73 m2. During
observation, 20% (Sweden) and 17% (U.S.) of patients received at least one nephrotoxic
Yes No 30.7 2.5 (2.0-3.1) 1.4 (1.1-1.8) drug. The top 3 potentially inappropriate nephrotoxic drugs identified were NSAIDs
No Yes 35.8 2.6 (2.4-2.8) 1.5 (1.3-1.6) (9% and 11% of participants in U.S. and Sweden received it), antivirals (2.0% and 2.5%)
Yes Yes 81.7 6.5 (5.6-7.6) 2.2 (1.9-2.6) and immunosuppressants (1.5% and 2.7%). Bisphosphonate use was common in
Sweden (3.3% of participants), but not in U.S. (0.5%). Conversely, fenofibrates were
INTERACTION: RERI 0.34 (95% CI -0.12-0.81), AP 0.15 (95% CI -0.04-0.35) common in U.S. (3.6%), but not in Sweden (0.13%). In adjusted analyses, patients with
and S 1.39 (95% CI 0.86-2.25) young age (<65 years old), women, or with CKD G3 were at higher risk of receiving
nephrotoxic medications in both cohorts (P>0.05 for all). Notably, patients aware of
*Adjusted for age, sex, body mass index, hypertension, stroke, myocar- their CKD (identified either by issued diagnosis or recent visit to a nephrologist), were
dial infarction, peripheral arterial disease, heart failure, diabetes mellitus, at lower risk of nephrotoxic drug use (OR 0.87, 95% CI 0.82-0.92 in Sweden and 0.89,
95% CI 0.81-1.01 in U.S.).
use of anticoagulant drugs (vitamin K antagonists and direct oral anti- CONCLUSION: In two geographically distinct health systems, one in five patients
coagulants), antiplatelet agents and hemoglobin levels with CKD received potentially inappropriate nephrotoxic medications, mainly
NSAIDs. Strategies to increase CKD awareness and physician’s knowledge of drug
nephrotoxicity may reduce inappropriate ambulatory prescriptions and prevent
CONCLUSION: The combination of CKD and AF is associated with high risks for iatrogenic kidney injury.
bleeding, ischemic stroke and mortality. There is a positive interaction between AF and
CKD for ischemic stroke risk, but not for bleeding or mortality.

10.1093/ndt/gfab122 | i49
Nephrology Dialysis Transplantation 36 (Supplement 1): i50–i52, 2021
10.1093/ndt/gfab118

ANAEMIA: WHAT ELSE?


RESULTS: In patients with NDD-CKD, there was a 17.2% reduction in LDL-C
averaged over weeks 12–28 in the roxadustat group (n=1994) vs. a 1.4% increase in the
FC071 ENHANCED DEGRADATION OF 3-HYDROXY-3- placebo group (n=1430) (least-squares mean [LSM] [SE] treatment difference = -19.83
METHYLGLUTARYL COENZYME A REDUCTASE (HMGCR) mg/dL [1.186], p<0.0001) (Table). In patients with DD-CKD, LDL-C was reduced by
MAY CONTRIBUTE TO THE LOWERING OF LDL 18.5% in the roxadustat group (n=1650) vs. 1.7% in the epoetin alfa group (n=1741)
CHOLESTEROL SEEN WITH ROXADUSTAT IN CHRONIC (LSM treatment difference = -15.80 mg/dL, p<0.0001) (Table). In the ID-DD patients,
KIDNEY DISEASE PATIENTS WITH ANEMIA LDL-C dropped by 21.5% in the roxadustat group (n=680) vs. 4.6% in the epoetin alfa
group (n=691) (LSM treatment difference = -17.50 mg/dL, p<0.0001) (Table). After
Aisha Chow1, Simon Roger2, Carol Pollock3, David Gervasi1, Lynda Szczech1, confirming that roxadustat does not directly inhibit HMGCR enzyme activity, we
Gail Walkenshaw1 found that the increase in HMGCR protein levels caused by cholesterol depletion in
1
FibroGen, Inc., San Francisco, United States of America, 2Renal Research, Gosford, cells was suppressed by roxadustat. However, roxadustat had no effect on HMGCR
Australia and 3University of Sydney, Sydney, Australia mRNA expression, indicating that the suppression of HMGCR protein levels by
roxadustat was the result of an effect on protein turnover. Subsequent siRNA studies
revealed that the regulation of HMGCR protein levels by roxadustat was HIF
BACKGROUND AND AIMS: Roxadustat is an oral hypoxia-inducible factor prolyl dependent and mediated via upregulation of INSIG2.
hydroxylase (HIF-PH) inhibitor approved in China and Japan for the treatment of CONCLUSION: These data show that treatment with roxadustat vs. placebo or
anemia in patients with chronic kidney disease (CKD). In Phase 3 clinical studies, epoetin alfa lowered LDL-C in patients with NDD-CKD and DD-CKD, respectively,
roxadustat was shown to increase hemoglobin levels in both dialysis-dependent (DD) and highlight a potential HIF-dependent mechanism for this cholesterol-lowering
and non-dialysis-dependent (NDD) CKD patients with anemia. This increase in effect.
hemoglobin and the accompanying decrease in hepcidin, a hormone that sequesters
iron in intracellular stores, is consistent with the known role that HIF plays in the
regulation of erythropoiesis. The HIF pathway may also influence cholesterol
metabolism; at high altitude, total and low-density lipoprotein cholesterol (LDL-C)
decrease in healthy individuals. The cholesterol biosynthesis pathway is well
characterized and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) has
long been recognized as the rate-limiting enzyme. Multiple feedback mechanisms are FC073 REGIONAL EFFICACY AND SAFETY RESULTS OF
known to regulate HMGCR activity, one of which involves degradation of HMGCR via ROXADUSTAT COMPARED WITH PLACEBO OR
interaction with insulin-induced genes 1 and 2 (INSIG1 and INSIG2), two closely DARBEPOETIN ALFA IN NON-DIALYSIS-DEPENDENT (NDD)
related endoplasmic reticulum membrane proteins. Here, we report clinical trial data CHRONIC KIDNEY DISEASE (CKD) PATIENTS WITH ANAEMIA
showing a reduction in LDL-C in patients with anemia of CKD who were treated with
roxadustat, and describe the results of investigation into the mechanism of this Nada Dimkovic1, Ciro Esposito2, Jonathan Barratt3, Christophe Mariat4,
cholesterol-lowering effect. Evgeny Shutov5, Michael Reusch6, James Young7, Wladyslaw Sulowicz8
METHOD: We studied the effect of roxadustat on LDL-C levels in human subjects and 1
School of Medicine, University of Belgrade, Clinical Department for Renal Diseases,
examined the potential underlying mechanisms via cell culture experiments. Clinical
Zvezdara University Medical Center, 2University of Pavia, Unit of Nephrology and
data were pooled from six pivotal phase 3 studies, three in patients with NDD-CKD
Dialysis, ICS Maugeri, Italy, 3University of Leicester, United Kingdom, 4Service
and three in patients with DD-CKD, including those with incident dialysis (ID; on
Nephrologie Dialyse Transplantation, CHU St Etienne, France, 5Russian Medical
dialysis <4 months at randomization). Mean changes from baseline (CFB) in LDL-C
Academy of Continuous Professional Education, Botkin Clinical City Hospital, Russia,
(regardless of statin use) averaged over weeks 12–28 were analyzed using a mixed 6
Astellas Pharma Europe B.V., The Netherlands, 7Astellas Pharma, Inc., United States of
ANCOVA model of repeated measures. We investigated the effect of roxadustat on
America and 8Collegium Medicum, Jagiellonian University, Department of Nephrology,
HMGCR activity in a cell-free enzyme assay and on HMGCR protein levels in cultured
Poland
Hep3B cells. We explored involvement of the HIF pathway in regulation of HMGCR
protein levels in Hep3B cells by means of HIF-1a/HIF-2a small interfering (si)RNA
knockdown. Protein expression levels were assessed by SDS-PAGE and Western blot BACKGROUND AND AIMS: Roxadustat regulates erythropoiesis and iron
analysis or electrochemiluminescent immunoassays. Gene expression levels were metabolism through hypoxia-inducible factor prolyl hydroxylase inhibition. This
evaluated by real-time quantitative reverse-transcriptase polymerase chain reaction regional analysis evaluated efficacy and safety for roxadustat versus placebo/
(RT-PCR). darbepoetin alfa (DA) in NDD CKD patients with anaemia.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
METHOD: Results from three, double-blind phase 3 studies comparing roxadustat to RESULTS: In total, 4886 patients were randomised in placebo-controlled (2386
placebo (ALPS, ANDES, OLYMPUS) in patients with anaemia and stage 3-5 NDD roxadustat, 1884 placebo) and DA-controlled (323 roxadustat, 293 DA) studies.
CKD were pooled and evaluated alongside results of an open-label study comparing Baseline characteristics of patients treated with roxadustat vs placebo and roxadustat vs
roxadustat to DA (DOLOMITES) in the same population. Efficacy outcomes were DA were similar: baseline Hb (placebo, 9.10 vs 9.10 g/dL; DA, 9.55 vs 9.55 g/dL) and
compared in three regions (Europe, US, and other) in placebo-controlled studies (PCS) iron repletion (placebo, 59.9% vs 59.8%; DA, 56.3% vs 51.9%). Roxadustat was superior
and two regions (Western Europe/Israel and Central/Eastern Europe) in the DA- to placebo for Hb response without rescue therapy (80.2% vs 8.7%; difference of
controlled study (DCS). The primary efficacy endpoint in Europe was haemoglobin proportion [DOP], 71.50%; 95% CI, 69.40-73.51) and noninferior to DA (89.5% vs
(Hb) response, defined as Hb 11.0 g/dL that changed from baseline (CFB) by 1.0 g/ 78.0%; DOP, 11.51%; 95% CI, 5.66-17.36). Mean Hb CFB (Weeks 28-36) achieved
dL in patients with Hb >8.0 g/dL or as CFB 2.0 g/dL in patients with Hb 8.0 g/dL. superiority in pooled analysis vs placebo (LS mean, 1.91 vs 0.14; LSMD, 1.77; 95% CI,
The secondary efficacy endpoint was Hb CFB to Weeks 28-36 without rescue therapy 1.69-1.84; P<0.0001) and noninferiority vs DA (LS mean, 1.85 vs 1.84; LSMD, 0.02;
(intravenous iron, red blood cell [RBC] transfusion, or erythropoiesis-stimulating 95% CI, -0.13 to 0.16). Risk for MACE or MACEþ was similar for roxadustat vs
agent [ESA] for PCS; RBC transfusion or ESA [roxadustat only] for DCS). Incidence of placebo (MACE, 480 [20.1%] vs 350 [18.6%]; HR, 1.10; 95% CI, 0.96-1.27; MACEþ,
treatment-emergent adverse events (TEAEs) was summarised descriptively in two 578 [24.2%] vs 432 [22.9%]; HR, 1.07; 95% CI, 0.94-1.21) and vs DA (MACE, 38
regions in PCS (Europe and non-Europe) and two regions in DCS (Western Europe/ [11.8%] vs 41 [14.0%]; HR, 0.81; 95% CI, 0.52-1.25; MACEþ, 54 [16.7%] vs 43 [18.1%];
Israel and Central/Eastern Europe). HR, 0.90; 95% CI, 0.61-1.32).
RESULTS: A total of 4886 patients were randomised (2709 roxadustat; 1884 placebo; CONCLUSION: Roxadustat corrected Hb more effectively than placebo and
293 DA). A significantly greater proportion of patients in all regions who received comparably to DA in patients with anaemia and stage 3-5 NDD CKD. Cardiovascular
roxadustat had a Hb response without rescue therapy vs placebo (Europe: 77.9% vs safety was comparable between roxadustat and DA and placebo.
16.5%, difference of proportion [DOP] 61.4%, 95% CI: 56.5-66.2; US: 75.4% vs 8.3%,
DOP 67.2%, 95% CI: 62.7-71.6; and other: 83.4% vs 5.5%, DOP 78.0%, 95% CI: 75.4-
80.5) and a numerically greater proportion in both regions vs DA (Western Europe/
FC075 POST-MORTEM HEPATIC AND BONE MARROW IRON
Israel: 93.9% vs 83.5%, DOP 10.4%, 95% CI: 1.2-19.6; Central/Eastern Europe: 86.5% vs
CONTENT IN HEMODIALYSIS PATIENTS: A PROSPECTIVE
75.4%, DOP 10.9%, 95% CI: 3.6-18.3). Mean Hb CFB was significantly greater with
COHORT STUDY
roxadustat vs placebo in Europe (2.01 vs 0.37 g/dL, LSMD 1.70, 95% CI: 1.55-1.84), US
(1.80 vs 0.21 g/dL, LSMD 1.67, 95% CI: 1.53-1.82), and other (1.80 vs 0.06 g/dL, LSMD
Patricia Carrilho1, Anna Lima1, Rita Manso2, Lucinda Nobrega3, Alexandra Lima
1.77, 95% CI: 1.64-1.89) (all P<0.0001) and similar vs DA in Western Europe/Israel
Santos3, Elisa Matos Soares4, Lurdes Bastos4, Pedro Fidalgo5,6
(1.64 vs 1.75 g/dL, LSMD -0.03, 95% CI: -0.30 to 0.23, P=0.80) and Central/Eastern 1
Europe (1.94 vs 1.88 g/dL, LSMD 0.03, 95% CI: -0.14 to 0.21, P=0.72). The range in Hospital Professor Doutor Fernando Fonseca, Nephrology, Amadora, Portugal,
2
incidence for select TEAEs (arteriovenous fistula thrombosis, deep vein thrombosis, Hospital Professor Doutor Fernando Fonseca, Pathology, Amadora, Portugal, 3Hospital
nausea, and seizure) was: 0.3-8.4% for roxadustat and 0.2-4.3% for placebo in Europe; Professor Doutor Fernando Fonseca, Hematology, Amadora, Portugal, 4University of
0.8-10.8% for roxadustat and 0.1-7.0% for placebo in non-Europe; 0-12.1% for Porto, Pharmacy’s Faculty, Porto, Portugal, 5Centro Hospitalar Lisboa Ocidental,
roxadustat and 0-11.8% for DA in Western Europe/Israel; 0.4-6.3% for roxadustat and Nephrology, Carnaxide, Portugal and 6Centro Hospitalar Lisboa Ocidental, Intensive
0-3.4% for DA in Central/Eastern Europe. Care, Lisboa, Portugal
CONCLUSION: In patients with anaemia and stage 3-5 NDD CKD, roxadustat was
more effective than placebo for correcting Hb and generating Hb response without BACKGROUND AND AIMS: Studies using T2 MRI liver scans among Hemodialysis
rescue therapy in Europe, the US, and other countries. It was similarly effective as DA (HD) patients raised concern about the presence of iron overload in this population,
for correcting Hb and generating a Hb response without rescue therapy in Western regularly treated with intravenous (IV) iron.
Europe/Israel and Central/Eastern Europe. The incidence of select TEAEs was Histological evidence of tissue iron overload is scarce, since the majority of studies were
comparable and relatively low in all regions. performed in pre-erythropoiesis- stimulating agents (ESA’s) era, when blood
transfusions were common.
Primary objective: to quantify iron in the liver and bone marrow by biochemical and
histological analysis, in adult CKD stage 5-HD. Secondary objectives: To explore
FC074 POOLED EFFICACY AND CARDIOVASCULAR SAFETY
association of clinical, laboratorial parameters, IV iron therapy and iron stores.
RESULTS OF 3 PLACEBO-CONTROLLED AND 1
METHOD: After approval of local Ethical committee and informed consent from
DARBEPOETIN ALFA-CONTROLLED STUDIES OF
families, liver biopsy and bone marrow aspirate were obtained in the first 24h post-
ROXADUSTAT FOR TREATMENT OF ANAEMIA IN PATIENTS
mortem from 21 chronic HD patients with anemia or under anemia treatment who
WITH NON-DIALYSIS-DEPENDENT CHRONIC KIDNEY
died in Hospital Fernando Fonseca.
DISEASE
Exclusion criteria: blood transfusion in the previous 2 weeks, acute or chronic liver
disease, HIV infection, known hematologic or oncologic disease.
Jonathan Barratt1, Nada Dimkovic2, Evgeny Shutov3, Wladyslaw Sulowicz4,
Clinical, laboratorial and anemia therapy data were retrieved from hospital registry and
Ciro Esposito5, Michael Reusch6, James Young7, Christophe Mariat8
1
outpatient HD centers.
University of Leicester, Leicester, Department of Respiratory Sciences, Leicester, United Biochemical liver iron content (LIC) was quantified by atomic absorption
Kingdom, 2KBC Zvezdara, Clinical Department of Renal Diseases, Belgrade, Serbia, 3City spectrophotometry. Histological semi-quantitative grading of iron storage was made in
Clinical Hospital, State Budgetary Healthcare Institution of Moscow, Moscow, Russia, the liver and bone marrow using Scheuer’s and Gale’s criteria of grading Perls’ stain,
4
Collegium Medicum of Jagiellonian University, Department of Nephrology, Krakow, respectively.
Poland, 5 ICS Maugeri, University of Pavia, Unit of Nephrology and Dialysis, Pavia, Italy, RESULTS: Of 21 patients included, 10 (47,6%) were male, median (IQR) age 76.0
6
Astellas Pharma Europe B.V., Leiden, The Netherlands, 7Astellas Pharma, Inc., (67.5-85.5) years old, 18 (85.7%) white, 3 (14.3%) black, dialysis vintage was 47.0 (12.5-
Northbrook, United States of America and 8Université Jean Monnet, Service de 104.0) months. Charlson Comorbidity index was 10.0 (7.5-11.0), 7 (33%) patients had
Néphrologie, Dialyse et Transplantation Rénale, Laboratoire d’Explorations diabetes, and 11 (52.4%) used an arteriovenous fistula as vascular access. The cause of
Fonctionnelles Rénales, Saint-Etienne, France death was infection (n=9, 42.9%), cardiovascular (N=6, 28.6%), HD withdrawal (n=2,
9.5%) and unknown =3 (14.3%).
BACKGROUND AND AIMS: Roxadustat, an oral hypoxia-inducible factor prolyl Median (IQR) hemoglobin was 9.8 (8.5-11.4) g/dl and 11 (52.3%) patients had
hydroxylase inhibitor, induces a coordinated erythropoietic response by increasing hemoglobin <10 g/dl. Ferritin was 494.0 (136.0-850.5) ng/ml and TSAT 19.9 % (13.3-
endogenous erythropoietin levels and improving iron metabolism. This analysis was 26.0). 19 (90.5%) patients were receiving IV iron therapy. Median (IQR) IV iron
performed to examine the consistency of efficacy and cardiovascular safety results for administered in the previous 6 and 12 months before death was 800 (300-1250) mg
roxadustat vs placebo or darbepoetin alfa (DA) in patients with non-dialysis- and 1500 (650-2175) mg, respectively. All patients were on ESA therapy, median (IQR)
dependent (NDD) chronic kidney disease (CKD). dose 5000 (3000-9000) UI/week and erythropoietin resistance index was 9.6 (4.2-16.6).
METHOD: Results from three phase 3, double-blind studies comparing roxadustat Median (IQR) liver iron content determined by atomic absorption was 42.5 (22.9-69.7)
with placebo (ALPS, ANDES, OLYMPUS) with anaemia and stage 3-5 NDD CKD mmol/g.
were pooled and assessed for consistency with results of an open-label study comparing 9 patients (42.9%) had normal LIC (<36 lmol/g), while the remainder had mild to
roxadustat with DA (DOLOMITES) in predominantly European patients. The primary moderate overload.
efficacy endpoint was haemoglobin (Hb) response, defined as (a) Hb 11.0 g/dL that Median (IQR) Scheuer grade was 2 (1-3) and 13 (62%) of liver biopsies had increased
changed from baseline (CFB) by 1.0 g/dL in patients with Hb >8.0 g/dL or (b) Hb (Scheuer grade > 1) iron deposition at histology. Median (IQR) grade of Perls staining
CFB by 2.0 g/dL in patients with Hb 8.0 g/dL irrespective of and without rescue in the bone marrow was 3 (3-4) and 9 (45%) had increased (Gale’s grade >3) iron
therapy for placebo-controlled (assessed for superiority) and DA-controlled (assessed content in the bone marrow. Iron semi-quantitative scores in liver and bone marrow
for non-inferiority) studies, respectively. The secondary efficacy endpoint was Hb CFB had strong positive correlation (r=0.71, p<0.001).
to Weeks 28-36 using least squares mean difference (LSMD) without rescue therapy. There was a strong positive correlation between LIC and ferritin (r=0.86, p < 0.001)
The key safety endpoints of major adverse cardiovascular event (MACE, comprising and also TSAT (r=0.56, n=16, p=0.02).
death, myocardial infarction, and stroke) and MACEþ (MACE plus hospitalization Hemoglobin was negatively associated with LIC (r= -0.46, p=0.04), and with iron
with heart failure or unstable angina) were adjudicated in all studies. MACE and content in the bone marrow (p=0.04).
MACEþ for roxadustat vs placebo or DA were compared in the intention-to-treat LIC did not associate with ESA dose, C-reactive protein, dialysis vintage or other
sample using a Cox proportional hazards model. clinical parameters.

10.1093/ndt/gfab118 | i51
Abstracts Nephrology Dialysis Transplantation

There was no statistically significant association between the dose of IV iron


administered in the previous 6 and 12 months with LIC, ferritin,TSAT or iron scores
in bone marrow and liver.
CONCLUSION: In these HD patients, there was biochemical and histological evidence
of iron accumulation in liver and bone marrow. Ferritin and TSAT showed strong
correlation with iron deposits, but none was found with the dose of IV iron
administered. In this study, anemia severity was associated with higher degree of iron
storage both in the liver and bone marrow, suggesting a multilevel blocking mechanism
of iron’s utilization.

i52 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i53–i56, 2021
10.1093/ndt/gfab123

BONES & OUTCOMES IN CKD TRAP5b (0.79, 0.83, and 0.79, respectively; p < 0.05, all). Calculated optimal diagnostic
cutoffs in the exploration cohort are shown in Table 1. Applying these cutoffs in the
validation cohort revealed high negative predictive values for both high (92 - 96%) and
low (82 - 90%) bone turnover. Positive predictive values were consistently low.
FC076 DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN CONCLUSION: The diagnostic accuracies of BsAP, Intact P1NP and TRAP5b are
RENAL OSTEODYSTROPHY sufficient to rule out both high and low bone turnover in CKD. Biointact PTH shows
inferior performance, particularly in kidney transplant recipients.
Hanne Skou Jørgensen1,2, Geert Behets3, Etienne Cavalier4, Patrick D’Haese3,
Pieter Evenepoel1,5
1
KU Leuven, Microbiology, Immunology and Transplantation; Nephrology and Renal
Transplantation Research Group, Leuven, Belgium, 2Aarhus University, Institute of
Clinical Medicine, Nephrology, Aarhus N, Denmark, 3University of Antwerp, Institute of
Pathophysiology, Biomedical Sciences, Wilrijk, Belgium, 4Université de Liège, Clinical
Chemistry, Liege, Belgium and 5University Hospitals Leuven, Medicine, Division of
Nephrology, Leuven, Belgium

BACKGROUND AND AIMS: A transiliac bone biopsy is the gold standard for
diagnosing renal osteodystrophy, but is not recommended as part of routine clinical
workup due to its invasive nature. Suitable non-invasive alternatives have yet to be
established. The aim of this study was to investigate the diagnostic accuracy novel
biochemical markers of bone remodeling compared to that of biointact parathyroid
hormone (PTH) for bone turnover as evaluated by histomorphometry.
METHOD: Protocolled bone biopsies were performed in end-stage kidney disease
patients (ESKD, n = 80) and kidney transplant recipients (n = 119). Full-length (1-84)
PTH, bone-specific alkaline phosphatase (BsAP), intact N-terminal propeptide of type
I collagen (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were
measured. Diagnostic performance was evaluated by area under the receiver operator
characteristics curve (AUC). Optimal diagnostic cutoffs were established in an
exploration cohort (n=100), and subsequently validated in a separate subset of patients
(n=99).

FC076 Table 1: FC077 LONG-TERM SAFETY OF TENAPANOR FOR THE CONTROL OF


SERUM PHOSPHORUS IN PATIENTS WITH CKD ON DIALYSIS
Exploration cohort Validation cohort
Daniel Weiner1, Steven Fishbane2, Robert Lynn3, Yang Yang4,
(n = 100) (n = 99) David Rosenbaum4
High turnover AUC Cutoff Sensi- Speci- PPV NPV 1
Tufts Medical Center, Nephrology, Boston, United States of America, 2Northwell Health,
tivity ficity Nephrology, Manhasset, United States of America, 3Kidney Medical Associates, Bronx,
United States of America and 4Ardelyx, Inc., Waltham, United States of America
Biointact PTH, 0.83 (0.71, 0.95) >172 80% 67% 32% 95%
pg/mL BACKGROUND AND AIMS: Tenapanor, a first-in-class, phosphate absorption
BsAP, lg/L 0.85 (0.76, 0.94) >40 71% 85% 50% 93% inhibitor blocks the paracellular absorption of phosphate in the GI tract by local
inhibition of the sodium-hydrogen exchanger (NHE3). It therefore provides a novel,
Intact P1NP, 0.88 (0.80, 0.95) >121 82% 85% 54% 96% non-binder approach for managing hyperphosphatemia. Tenapanor is dosed as one
ng/mL small pill twice daily. In three pivotal trials, tenapanor met its primary phosphorus-
TRAP5b, U/L 0.83 (0.74, 0.91) >5.2 82% 71% 38% 95% lowering outcome. This report evaluates long-term safety data from the longest of these
trials.
Low turnover METHOD: This 52-week study consisted of a 26-week, open-label, randomized
Biointact PTH, 0.75 (0.65, 0.85) <91 67% 54% 34% 82% treatment period with a 12-week placebo-controlled randomized withdrawal period,
pg/mL followed by a 14-week open label safety extension period. Maintenance dialysis patients
with serum phosphorus  6.0 mg/dL and a 1.5 mg/dL increase in serum phosphorus
BsAP, lg/L 0.81 (0.72, 0.90) <24 80% 62% 43% 90% following phosphate binder washout were randomized 3:1 to receive tenapanor 30 mg
Intact P1NP, 0.84 (0.75, 0.93) <50 72% 75% 50% 88% twice daily or sevelamer carbonate, dosed per package insert. At end of the randomized
treatment period all patients in the tenapanor arm were re-randomized 1:1 to either
ng/mL tenapanor or placebo for the randomized withdrawal period followed by tenapanor for
TRAP5b, U/L 0.80 (0.71, 0.91) <4.0 72% 65% 42% 87% the safety extension period. Sevelamer was used as a safety control for comparisons of
serious adverse events/hospitalizations to tenapanor.
AUCs with cutoffs by Liu’s method, and corresponding sensitivity, spe- RESULTS: Tenapanor was generally well tolerated, with diarrhea the only adverse
cificity, and negative/positive predictive values event reported by >5% of patients during the randomized treatment period. Diarrhea
was typically mild-to-moderate in severity, transient, and occurred more commonly
ROC analysis in ESKD vs kidney transplant recipients with CKD stages 2-
during the randomized treatment period than the randomized withdrawal or safety
4 (Figure) showed inferior diagnostic accuracy of all biomarkers for the extension periods. Rates of serious adverse events leading to hospitalization were
prediction of low bone turnover in kidney transplant recipients (p < higher in patients treated with sevelamer than tenapanor (35.8% vs 24.6%). The
highest reported percentages of serious adverse events were infections and infestations
0.05), with biointact PTH no longer showing significant discriminatory (16.1% vs 9.3%) cardiac disorders (8.0% vs 5.7%), respiratory, thoracic and mediastinal
power (AUC 0.59, CI 0.47, 0.70). disorders (8.8% vs 5.5%), and metabolism and nutritional disorders (7.3% vs 3.6%) for
sevelamer and tenapanor, respectively. Adverse events leading to death were higher in
patients treated with sevelamer than tenapanor (3.6% vs 2.9%).
RESULTS: Mean age was 55613 years, two-thirds were men (67%), and 23% had
CONCLUSION: Among maintenance dialysis patients with hyperphosphatemia,
diabetes mellitus. Post-transplant eGFR was 49 [IQR 39, 59] ml/min/1.73m2. Bone
tenapanor, a novel, non-binder, phosphate absorption inhibitor that blocks
turnover was low in 47 (24%), normal in 119 (60%), and high in 33 (17%) patients. All
paracellular absorption of phosphorus with a one tablet twice daily dose, has an
biomarkers differed significantly across categories of bone turnover (p < 0.001). The
acceptable safety profile, and, if approved, may offer a new approach to the treatment
AUC of biointact PTH for high turnover was 0.82 (0.73, 0.91), which was not
of hyperphosphatemia.
significantly different from AUC values for BsAP, Intact P1NP, and TRAP5b (0.87,
0.90, and 0.86, respectively). AUC of biointact PTH for low turnover was 0.71 (0.63,
0.78), which was significantly lower than the values for BsAP, Intact P1NP, and

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC078 REAL-WORLD EFFECTIVENESS OF ETELCALCETIDE VS. FC079 HIGH SERUM PHOSPHATE, A NOVEL POTENTIAL RISK
CINACALCET IN US HEMODIALYSIS PATIENTS: A FACILITY FACTOR FOR BONE FRAGILITY FRACTURES IN THE COSMOS
CALCIMIMETIC PREFERENCE APPROACH STUDY

Angelo Karaboyas1, Daniel Muenz1, Yunji Hwang2, William Goodman2, Pedro Barrera Baena1,2, Minerva Rodrıguez Garcıa2, Enrique Rodrıguez Rubio1,
Sunfa Cheng2, Pooja Desai2, Kathleen Fox2, Bruce Robinson1,3, Ronald Pisoni1 Lucıa Gonza lez Llorente1, Francesco Locatelli3, Jurgen Floege4, Markus Ketteler5,
1
Arbor Research Collaborative for Health, Ann Arbor, United States of America, 2Amgen, Gerard Michel London6, Jose Luis Gorriz Teruel7,8, Manuel Anibal A. Ferreira9,10,
Carmine Zoccali11, Alberto Ortiz12, Martine Cohen-Solal13,14, Miguel Angel  Su
arez
Inc., Thousand Oaks, United States of America and 3University of Michigan,
Department of Internal Medicine, Ann Arbor, United States of America Hevia15, Jesu s Marıa Fernandez Go mez15,16, Beatriz Martın-Carro1,
17,18
Carlos Go mez-Alonso , Cristina Alonso-Montes , Jorge B. Cannata-Andia1,18,
1

José Luis Fernandez-Martin1


BACKGROUND AND AIMS: Calcimimetic therapy, including oral cinacalcet and 1
intravenous (IV) etelcalcetide, is often used to control parathyroid hormone (PTH) Bone and Mineral Research Unit. REDinREN del ISCIII. Instituto de Investigaci on
levels in hemodialysis (HD) patients. In a head-to-head clinical trial, etelcalcetide was Sanitaria del Principado de Asturias (ISPA)., Oviedo, Spain, 2Department of Nephrology.
superior to cinacalcet on PTH reduction. Given that oral administration of cinacalcet is REDinREN del ISCIII. Hospital Universitario Central de Asturias., Oviedo, Spain,
3
susceptible to challenges of self-management and adherence, etelcalcetide may be even Alessandro Manzoni Hospital., Department of Nephrology, Dialysis and Renal
more effective in the real-world setting. To limit confounding by indication, we used a Transplant., Lecco, Italy, 4RWTH Aachen University., Department of Nephrology and
facility calcimimetic preference approach to investigate the comparative effectiveness Clinical Immunology., Aachen, Germany, 5Robert-Bosch-Krankenhaus GmbH,
of etelcalcetide vs. cinacalcet by estimating effects on PTH and other mineral and bone Department of General Internal Medicine and Nephrology, Stuttgart, Germany, 6Centre
disorder (MBD) markers in a cohort of US HD patients. Hospitalier FH., Manhes, France, 7Hospital Clinico Universitario., Department of
METHOD: We used data from the US Dialysis Outcomes and Practice Patterns Study Nephrology., Valencia, Spain, 8Health Research Institute INCLIVA, University of Valencia.,
(US-DOPPS), a prospective cohort study of in-center HD patients. During a 6-month Department of Medicine., Valencia, Spain, 9Universidade Nova de Lisboa., Faculdade de
run-in period from March to August 2019, we evaluated facility calcimimetic Ci^encias Médicas., Lisboa, Portugal, 10Hospital Curry Cabral., Nephrology Department.,
preference by calculating the proportion of calcimimetic users in each facility who were Lisboa, Portugal, 11Ospedali Riuniti CNR National Research Council (Italy)., Clinical
prescribed etelcalcetide (vs. cinacalcet). Among patients with any prescription for a Epidemiology and Physiopathology of Renal Disease and Hypertension and Renal and
calcimimetic during the 6-month run-in period, we evaluated MBD marker outcomes Transplantation Unit., Foggia, Italy, 12IIS-Fundacion Jiménez Dıaz., Department of
(PTH, albumin-corrected serum calcium [Ca], serum phosphorus [P]), averaged over Nephrology and Hypertension, REDinREN del ISCIII., Madrid, Spain, 13Hôpital
the subsequent 6 months, from September 2019 to February 2020. We compared HD Lariboisière., Department of Rheumatology., Paris, France, 14INSERM U1132 & USPC
facilities that treated >75% of calcimimetic users with etelcalcetide (“Etel-first”) vs. Paris-Diderot, Paris, France, 15Hospital Universitario Central de Asturias., UGC of
those that treated >75% of calcimimetic users with cinacalcet (“Cina-first”). Linear Urology., Oviedo, Spain, 16Universidad de Oviedo., Oviedo, Spain, 17Hospital
regression was used to model each continuous outcome. Modified Poisson regression Universitario Central de Asturias, Bone and Mineral Research Unit, REDinREN del ISCIII.
was used to estimate the prevalence ratio (PR) of each MBD marker being out of target Instituto de Investigacion Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain and
18
(PTH >600 pg/mL, Ca <8.4 mg/dL, P >5.5 mg/dL). All models were adjusted for Universidad de Oviedo., Department of Medicine., Oviedo, Spain
patient-level and facility-level confounders and accounted for facility clustering using
GEE. BACKGROUND AND AIMS: Bone fragility fractures (bone fractures) are extremely
RESULTS: We excluded 38 HD facilities with little-to-no calcimimetic use (<10% use frequent in haemodialysis (HD) patients. Serum phosphate (P) has been suggested as a
or <5 total users) because calcimimetic preference could not be reliably defined, and 44 risk factor for bone fracture, nonetheless, evidence is poor. The aim of this study was to
HD facilities with no clear calcimimetic preference (25-75% etelcalcetide use among assess the association between incidence of bone fractures and serum phosphate (P),
calcimimetic users). The analysis included 2156 calcimimetic users: 969 patients from calcium (Ca) and parathyroid hormone (PTH) in patients from the COSMOS study.
45 Etel-first facilities and 1187 patients from 67 Cina-first facilities. In Etel-first (vs. METHOD: COSMOS is an observational, prospective, open cohort study with 3 years
Cina-first) HD facilities, the mean difference in PTH levels (primary outcome) was -99 of follow-up including 6797 haemodialysis patients from 227 centres randomly
pg/mL (95% CI: -179, -19) and the prevalence of PTH >600 was lower (PR=0.75; 95% selected from 20 European countries.
CI: 0.60, 0.94) in adjusted models. The adjusted mean levels of serum Ca and serum P At baseline, demographics, comorbidities, treatments, serum biochemical parameters
(secondary outcomes) were slightly lower in Etel-first (vs. Cina-first) facilities [Table of the previous six months and bone fractures of the previous 12 months were
1]. collected. Every 6 months, all these variables, outcomes, and incident bone fractures,
were collected. Patients who had at least one bone fracture during follow-up were
compared with those who had not.
FC078 Table 1. Comparing MBD marker outcomes in Etel-first vs. Cina-first HD Multivariate binary logistic regression and Poisson regression were used to assess the
facilities association between incidence of bone fractures and serum P, Ca and PTH. Time to
fracture (and possible re-fracture) was also evaluated using Cox regression and Cox
regression for recurrent events. All the results were adjusted by 23 variables including
Ca, P, PTH, albumin and haemoglobin (full adjusted model).
RESULTS: Analysis included 6274 patients who had follow-up data and non-missing
information regarding bone fractures at baseline and during follow-up; 252 patients
(4.0%), suffered at least one incident bone fracture. The fractured patients were older
(68.1612.9 vs. 63.8614.5 years, p<0.001), with a higher percentage of women (56.3%
vs. 38.6%, p<0.001) and history of cardiovascular disease (79.4% vs. 71.7%, p=0.010),
longer haemodialysis vintage (55.9664.0 vs. 38.3648.8 months, p<0.001), and higher
serum calcium (9.260.8 vs. 9.160.7 mg/dL, p=0.025) and lower serum albumin
(3.760.5 vs. 3.860.5 g/dL, p=0.004) levels.
Multivariate binary logistic regression showed that “well known risk factors for bone
fracture”, such as a previous bone fracture (OR: 7.78[95%CI:4.83-12.55], p<0.001),
older age (OR: 1.03[95%CI:1.01-1.04], p<0.001, per 1 year), sex female (OR:
1.71[95%CI:1.28-2.30], p<0.001), haemodialysis vintage (OR: 1.00[95%CI: 1.00-1.01],
CONCLUSION: To our knowledge, this is the first large-scale comparison of IV p=0.002, per 1 month), and serum PTH > 800 pg/mL (OR: 1.60[95%CI: 1.01-2.55],
etelcalcetide with oral cinacalcet in the real-world setting. Our unique approach p=0.047), were associated with a higher incidence of follow-up bone fractures. In
resembles a natural experiment by leveraging practice variation across the US and addition to the “well known bone risk factors for fracture”, serum P > 6.1 mg/dL (OR:
isolating HD facilities with a clear preference for one calcimimetic. Thus, the 1.50[95% CI: 1.07-2.11], p=0.02) and serum Ca > 9.7 mg/dL (OR: 1.42[95%CI: 1.01-
prescribed calcimimetic type for included patients was more likely determined by 2.03], p=0.043), were also associated with a higher incidence of bone fractures in the
facility preference than biased by patient indication. Our results indicate better PTH full-adjusted model.
control (mean levels 100 pg/mL lower) in US HD facilities using etelcalcetide (vs. These findings were partly consistent with Poisson regression for serum P >6.1 mg/dL
cinacalcet) as the primary calcimimetic therapy. Further research is needed to (IRR: 1.46[95% CI: 1.00-2.13], p=0.0085) and serum Ca > 9.7 mg/dL (IRR:
investigate the degree to which the greater real-world effectiveness of IV etelcalcetide 1.49[95%CI: 1.06-2.08], p=0.0047), but not for PTH.
(vs. oral cinacalcet) may be driven by adherence to the prescribed therapy, and how In addition, Cox regression analysis showed association between bone fractures and
clinical outcomes may be affected. serum P >6.1 mg/dl (HR: 1.61 [95%CI: 1.16-2.24], p=0.0049) and 1.60 [95%CI: 1.14-
2.24] (p=0.0066) for simple and recurrent events respectively, but no association was
found with serum Ca and PTH in the 2 full-adjusted models for the Cox regression
analyses.
CONCLUSION: In COSMOS, a large haemodialysis patient’s cohort with 3 years
follow up, serum P was the only biochemical parameter that remained as a significant
risk factor for bone fractures after 4 statistic approaches. Thus, for the first time, in a
large scale well controlled study, high serum P has been identified as a new
independent potential risk factor for incident bone fractures in haemodialysis patients.

i54 | Abstracts
Nephrology Dialysis Transplantation Abstracts
FC080 VARIABILITY IN SERUM PHOSPHATE ASSESSED BY inflammation. Various variability markers have been investigated to study the
DIRECTIONAL CHANGE IS ASSOCIATED WITH INCREASED association between P variability and its association with outcomes, however, the
MORTALITY directional trends have not been studied in depth. We aimed to study directional
changes and investigated its association with outcomes.
Xiaoling (Janice) Ye1, Karlien Ter Meulen2,3, Len A. Usvyat4, Frank Van Der METHOD: All adult incident HD patients treated in Fresenius Medical Care North
Sande2, Constantijn Konings3, Jeroen Kooman2, Peter Kotanko1,5, America (FMCNA) clinics between 01/2010 and 10/2018 were included in this retrospective
Frank Maddux4 cohort study. Serum P levels were averaged from month 1 to 6 after the initiation of dialysis
1
Renal Research Institute, Research, New York, United States of America, 2Maastricht (baseline). Baseline absolute and directional range (DR) of serum P were calculated. DR of P
University Medical Center, Maastricht, The Netherlands, 3Catharina Hospital, Eindhoven, was calculated as: P min/max (t2) – P max/min (t1), with P (t1) and P (t2) represents the
The Netherlands, 4Fresenius Medical Care, Global Medical Office, Waltham, United timepoint when either the min P value or max P value was measured, whichever comes first,
States of America and 5Mount Sinai Hospital, New York, United States of America and with t2 happened after t1. It is positive when the minimum antedates the maximum,
otherwise negative. All-cause mortality was recorded between months 7 and 18. Cox
BACKGROUND AND AIMS: Prior studies showed that there is a wide variability proportional hazards models with spline terms were applied to explore the association
between serial pre-dialysis measurements of serum phosphate (P). Serum P vary can be between absolute and DR of P and all-cause mortality. Additionally, tensor product
due to changes in nutritional intake, underlying bone disorders, medication use or smoothing splines were computed to study the interactions of P with absolute P and DR of
P and their joint associations with outcomes, respectably.

FC080 Figure 1: Risk of death across levels of serum phosphate and absolute range.
Top: contour plot of the estimated hazard ratio of death in the next year as a joint
function of serum P and absolute range for patients with serum P and absolute range
fixed at their median values. Estimates of the joint effects are shown in a region with
sufficient data decided by posterior SDs. Bottom: absolute range slices at different
serum P ranges.

10.1093/ndt/gfab123 | i55
Abstracts Nephrology Dialysis Transplantation

RESULTS: We studied 353,142 patients. The average age was 62.7 years, 58% were in general associated with increased mortality, the effects of an increase are most
male, 64% were diabetic. Baseline P was 4.98 mg/dL, median absolute range was 2.40 predominant in patients with higher levels of serum P, whereas a negative directional
mg/dL, median DR was 1.1 mg/dL. Across different levels of P, both higher levels of range are most predominant in patients with low serum P. This could be explained by
absolute range and DR of P were associated with higher risk of mortality (Figure 1, the fact that patients with lower levels of P are generally malnourished or inflamed,
Figure 2). The associations even seemed stronger in patients with lower levels of serum where a further reduction indicates nutritional deterioration.
P and with negative DR (Figure 1).
CONCLUSION: Lower levels of serum P are independently associated with an
increased risk of all-cause mortality. Whereas both a positive and negative DR of P are

FC080 Figure 2: Risk of death across levels of serum phosphate and directional range. Top: contour plot of the estimated hazard ratio of death in the next year as a joint function of
serum p and directional range for patients with serum P and absolute range fixed at their median values. Estimates of the joint effects are shown in a region with sufficient data decided
by posterior SDs. Bottom: absolute range slices at different serum P ranges.

i56 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i57–i61, 2021
10.1093/ndt/gfab139

PLANTS, COFFEE & MORE accelerated kidney disease progression and cardiovascular burden in CKD. Whilst the
effect of specific nutrients on uraemic toxin generation has been explored, few studies
have characterised the impact of diet quality on the gastrointestinal microbiome in the
CKD population. This study aims to explore the associations between dietary quality,
FC081 ULTRA-PROCESSED FOOD CONSUMPTION AND RISK OF protein-bound uraemic toxins and gastrointestinal microbiome in adults with CKD.
INCIDENT CHRONIC KIDNEY DISEASE: THE LIFELINES METHOD: This was a baseline cross-sectional study of adults with stage 3 to 4 CKD
COHORT who were enrolled in a randomised controlled trial of prebiotic and probiotic
supplementation. Habitual dietary intake was measured using a 7-day diet history
Qingqing Cai1, Minjie Duan1, Louise H. Dekker1, Stephan Bakker1, Martin De method by a specialist Dietitian. Diet quality was assessed using food group analysis;
Borst1, Gerjan Navis1 protein intake, fibre intake, dietary protein:fibre ratio and adherence to plant-based
1
UMCG, Nephrology, Groningen, The Netherlands diet index (PDI) (overall PDI, healthy PDI, unhealthy PDI). Serum uraemic toxins
(free and total; IS and PCS) were determined by ultra-performance liquid
chromatography. Metagenomic sequencing was used to determine gastrointestinal
BACKGROUND AND AIMS: Ultra-processed foods (UPF), that are widespread in microbiota richness, diversity, composition and functional capacity.
Western-style diet, are risk factors for the development of cardiovascular disease, RESULTS: There were 68 CKD patients [66% male, median age 70 (IQR 58-75) years]
diabetes, obesity, hypertension, and all-cause mortality. The role of UPF in kidney with a mean estimated glomerular filtration rate of 34 6 11 mL/min/1.73m2. Greater
function decline, however, is still unknown. The aim of this study was to investigate the adherence to a hPDI was associated with lower levels of free PCS [-0.021 mmol/L (95%
associations of UPF consumption with incident CKD and estimated glomerular CI -0.042 to -0.001)], while a higher intake of dietary fibre intake was associated with
filtration rate (eGFR) decline. Additionally, we considered the heterogeneity of UPF by lower levels of free IS [-0.022 mmol/L (95% CI -0.043 to -0.001)]. Compositionally, the
identifying different patterns of UPF consumption. gastrointestinal microbiota of this cohort was dominated by members of the phyla
METHOD: The study was performed in a prospective general population-based cohort Firmicutes and Bacteroidetes. Supervised analysis at the species level demonstrated that
in the Northern Netherlands. A total of 78 346 participants who were free of CKD at 21% of variance in gastrointestinal microbial composition could be attributed to
baseline were included in this study. The dietary information was assessed at baseline protein:fibre ratio (F=1.27, p=0.04). Further, a higher protein:fibre ratio was associated
using a 110-item food frequency questionnaire. The proportion (in weight) of UPF in with an increased relative abundance of unclassified members of order Oscillospirales.
the total diet was calculated and UPF consumption patterns were identified by Subdoligranulum formicile was correlated with dietary intake of vegetables and
principle component analysis (PCA). Multivariable logistic regression analyses were wholegrains while an unclassified Prevotella species was correlated with food items
used to evaluated the associations of the proportion of UPF consumption and UPF considered discretionary including sweet drinks, sweet desserts, animal fats and
patterns, respectively, with risk of incident CKD and a 20% eGFR decline. potatoes.
RESULTS: Average UPF consumption was 37.7% of total food intake in grams. After a CONCLUSION: The study suggests that habitual diets that are higher in fibre and
mean (SD) follow-up of 7.961.1 years, 2 072 participants developed CKD and 7 611 plant-based foods may positively influence uraemic toxin levels and gut microbiota
had a 20% eGFR decline. The consumption of UPF was independently associated diversity and composition in adults with CKD. These findings provide rationale for
with a higher risk of incident CKD (OR for an absolute increment of 10 % of UPF in well-designed dietary intervention studies targeting the production of uraemic toxins
the diet 1.07 [95% CI 1.01-1.13], P=0.026) and with a higher risk of 20% eGFR and exploring the impact on gut microbiome in the CKD population.
decline (OR10% increment 1.07 [95% CI 1.05-1.10], P<0.001). PCA revealed four
habitual UPF consumption patterns. The “warm savory snack” pattern was associated
with both incident CKD (OR 1.13 [1.04-1.23], P=0.003) and a 20% eGFR decline (OR
1.08 [1.05-1.11], P<0.001). The “sweet snack” pattern was associated with eGFR FC083 PROBIOTIC L.CASEI ZHANG SLOWS THE PROGRESSION OF
decline (OR 1.06 [1.03-1.09], P<0.001) only, whereas the “Dutch traditional” and the ACUTE AND CHRONIC KIDNEY DISEASE
“cold snack” were not associated with CKD or eGFR decline.
CONCLUSION: A higher UPF consumption was associated with higher risks of Rui Zeng1
1
incident CKD and eGFR decline in the general population. Different UPF Tongji Hospital, Tongji Medical College, Huazhong University of Science and
consumption patterns were identified, with different impact on renal risk. The “warm Technology, Division of Nephrology, Wuhan, P.R. China
savory snack” pattern and the “sweet snack” pattern were associated with kidney
function decline. Our findings suggest that UPF need to be considered in designing BACKGROUND AND AIMS: The relationship between gut microbial dysbiosis and
future dietary strategies for CKD prevention. acute or chronic kidney disease is currently acknowledged to be a health concern which
is characterized by immune dysregulation and metabolic disorder. However, the
therapeutic strategies remain to be developed. In the present study, we examined the
protective effects and mechanisms of action of probiotic Lactobacillus casei Zhang (L.
casei Zhang) on bilateral renal ischemia-reperfusion (I/R)-induced injury in mice.
METHOD: We orally gavaged male C57BL/6 mice with or without L. casei Zhang and
probiotic Lactobacillus acidophilus (L. acidophilus) for 4 weeks (1  109 CFU per day)
FC082 DIET QUALITY, PROTEIN-BOUND URAEMIC TOXINS AND
prior to being subjected to ischemia-reperfusion (I/R)-induced injury. Serum, colons
GASTROINTESTINAL MICROBIOME IN CHRONIC KIDNEY
and renal samples were collected after 5 days and 28 days. The composition and
DISEASE
abundance of gut microbiota was investigated by using 16S rRNA. LC-MS
metabolomic analysis technology and GC-MS analysis technology were used to
Catherine McFarlane1,2, Rathika Krishnasamy2,3, Tony Stanton2, Emma Savill2,
investigate the metabolic alterations. To define the intra-renal cell subsets that are
Matthew Snelson4, Gabor Mihala5,6, Mark Morrison7, David W. Johnson3,8,
involved in L. casei Zhang-induced renoprotection, we performed single-cell RNA-
Katrina L. Campbell1,3,5
1
sequencing (scRNA-seq) of kidney samples dissected from L. casei Zhang pretreated
University of Queensland, School of Medicine, Brisbane, Australia, 2Sunshine Coast mice at day 5 after I/R along with samples from non-treated controls.
University Hospital, Birtinya, Australia, 3Australasian Kidney Trials Network, University of RESULTS: Compared to L.acidophilus, L. casei Zhang demonstrated superior capacity
Queensland, Brisbane, Australia, 4Monash University, Department of Diabetes, in restoring intestinal flora homeostasis, protecting intestinal mucosal barrier function
Melbourne, Australia, 5Griffith University, Menzies Health Institute Queensland, Nathan, and improving the disrupted metabolomic profile. L. casei Zhang not only elevated the
Australia, 6Griffith University, Centre for Applied Health Economics, Nathan, Australia, short chain fatty acids (SCFAs) in serum and kidney, but also significantly increased
7
University of Queensland, Diamantina Institute, Faculty of Medicine, Woolloongabba, nicotinamide, by which L. casei Zhang inhibited renal inflammatory response and
Australia and 8Princess Alexandra Hospital, Department of Nephrology, Brisbane, alleviated the damage of renal tubular epithelial cells (TECs) via interacting with
Australia SCFAs receptors on macrophages and TECs, and activating NADþ metabolism in
injured kidneys.
BACKGROUND AND AIMS: Individuals with chronic kidney disease (CKD) have CONCLUSION: These results show that oral administration of L. casei Zhang, by
significantly increased risk of cardiovascular mortality which is only partially explained altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney
by Framingham risk factors. There is a growing body of evidence linking the gut- injury and slow the progression of renal decline.
derived uraemic toxins indoxyl sulphate (IS) and p-cresyl sulphate (PCS) with

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

i58 | Abstracts
Nephrology Dialysis Transplantation Abstracts

10.1093/ndt/gfab139 | i59
Abstracts Nephrology Dialysis Transplantation

i60 | Abstracts
Nephrology Dialysis Transplantation Abstracts

10.1093/ndt/gfab139 | i61
Nephrology Dialysis Transplantation 36 (Supplement 1): i62–i64, 2021
10.1093/ndt/gfab143

STOP DIABETES RESULTS: The recruitment period was 18 months and the median follow-up was 36
(IQR: 20-48) months, after which 27 patients (38.6%) reached the primary endpoint.
At baseline mean IL-6 levels in the whole cohort were 4.58 6 2.90, at 4 months 4.61 6
3.10 and at 12 months: 6.14 6 4.97. Patients were further divided into three groups
FC084 LIPOTOXICITY MEDIATED BY GPR43 ACTIVATION according to the tertiles of baseline IL-6 levels (tertile 1: 0.65–2.65 pg/mL; tertile 2:
CONTRIBUTES TO PODOCYTE INJURY IN DIABETIC 2.66–4.83 pg/mL and tertile 3: 4.84–13.30 pg/mL). There were no differences among
NEPHROPATHY THROUGH MODULATING ERK/EGR1 the groups in demographic characteristics, cardiovascular risk factors, serum creatinine
PATHWAY or proteinuria among the groups.
Correlation analyses for IL6 and other inflammatory parameters were carried out for
Jian Lu1, Jia Xiu Zhang1,2, Pei Pei Chen1, Xue Qi Li1, Bicheng Liu1, all subjects. The results showed that inflammatory parameters had a significant
Kun Ling Ma1 correlation between them. IL-6 levels correlated with TNFa (r: 0.29; 95% CI: 0.05 - 0.49
1
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nan Jing City, P.R. p= 0.02), C-reactive protein (r= 0.61; 95%CI: 0.44 - 0.74 p<0.01), and PTH (r: 0.30,
China and 2Institute of Nephrology, Zhong Da Hospital, Southeast University, Nan Jing 95% CI: 0.03-0.54, p=0.03). However, in the univariate analysis only IL-6 tertiles were
City, P.R. China associated with the primary outcome (OR: 2.41; 95% CI 1.25-4.64, p=0.008).
Patients with the highest IL-6 levels (>4.84 pg/ml) experienced a significantly faster
evolution to endpoint (mean survival: 33.2 months, CI 95%: 25.2-41.3) than the other 2
BACKGROUND AND AIMS: The G-protein-coupled receptor 43 (GPR43) is a post- groups.
transcriptional regulator involved in cholesterol metabolism. Our previous studies In the multivariate Cox regression analysis, the highest levels of IL-6 (Tertile 3) were
demonstrated that intracellular cholesterol accumulation contributed to podocyte significantly associated with the primary outcome (HR:3.86; 95%CI: 1.08-13.86) after
injury in diabetic nephropathy (DN). This study aimed to investigate possible roles of being adjusted for baseline serum creatinine and proteinuria.
GPR43 activation in lipid nephrotoxicity in DN and to explore its potential The time-dependent area under the ROC curve at two years of follow-up was 0.88
mechanisms. (95% CI: 0.79 - 0.97). The best cut-off IL-6 level was found at 4.68 pg/ml (sensitivity:
METHOD: The experiments were conducted by using diabetic GPR43 knockout mice 100%, specificity: 78.7%)
and cell culture model of podocytes. Renal pathological changes were checked by Generalized linear mixed model analysis showed no effect on subsequent IL-6 levels
periodic acid schiff staining, immunohistochemical staining and transmission electron either with RAS blockade monotherapy or dual blockade.
microscopy (TEM). The lipid deposition and free cholesterol contents in kidney tissues CONCLUSION: In conclusion, our results show that higher levels of IL-6 are
were detected by Oil Red O staining, BODIPY staining, and cholesterol quantitative independently associated with progression of DKD in patients with type 2 diabetes,
assay. The protein expressions of GPR43, LC3II, p62 and related molecules of LDLR and that treatment with RAS blockade does not influence these levels. Serum IL-6 may
pathway in kidney tissues and podocytes were detected by real-time PCR, be used as a noninvasive biomarker of progression to ESKD. Since our results show
immunofluorescent staining, and Western blotting. that higher IL-6 levels are associated with a worse renal prognosis, anti- inflammatory
RESULTS: There were decreased plasma level of LDL-cholesterol and cholesterol drugs that modulate IL-6 could be promising therapeutic agents to improve outcomes.
accumulation in kidney tissues of diabetic GPR43 knockout mice. In vitro study Further studies focusing on the potential applications of anti-IL6 treatment in DKD are
demonstrated that acetate, a stimulator of GPR43, increased LDLR-mediated warranted.
cholesterol uptake in podocytes, accompanied with reduced cholesterol autophagic
degeneration, characterized by inhibited LC3 maturation, p62 degradation, and
autophagosome formation. These may evoke synergistic effects attributing to cellular
cholesterol accumulation in podocytes. While genetic knockdown or pharmacological
inhibition of GPR43 inhibited this effect in podocytes. Furthermore, the activation of
GPR43 led to the activation of ERK1/2/EGR1 pathway in podocytes, whereas blocking
ERK1/2 activity or reducing EGR1 expression reversed cholesterol influx and the
inhibition of autophagy mediated by GPR43 activation in podocytes. Meanwhile,
deletion of the GPR43 improved autophagy and inhibited the ERK1/2-EGR1 pathway
of podocyte in diabetic mice in vivo.
CONCLUSION: Activation of the GPR43 mediated lipid nephrotoxicity contributes to
podocyte injury in DN, which was mainly through the activation of ERK/EGR1
pathways. These findings suggested that the GPR43 receptor could be a potential
therapeutic target for the prevention of DN progression.

FC085 Figure: Kaplan-Meier curves displaying the time to event (primary composite
FC085 SERUM INTERLEUKIN-6 LEVELS PREDICT RENAL DISEASE endpoint) for patients in different tertiles of baseline IL-6 levels. Note: Tertile 1: 0.65 - 2.65
PROGRESSION IN DIABETIC KIDNEY DISEASE pg/mL; Tertile 2: 2.66 – 4.83 pg/mL and Tertile 3: 4.83- 13.30 pg/mL.

Beatriz Sanchez Alamo1, Amir Shabaka1, Marıa Victoria Cachofeiro Ramos2,


Gema Maria Fernandez Juarez1
1
Hospital Universitario Fundaci
on Alcorc
on, Nephrology, Alcorcon, Spain and
2
Complutense University of Madrid, Phisiology, Madrid, Spain FC086 GLOMERULI PROTEOME ANALYSIS REVEALS EARLY
DIFFERENCES BETWEEN PRE-EXISTING AND DE-NOVO
BACKGROUND AND AIMS: Inflammation is a main mechanism for the TYPE 2 DIABETES IN HUMAN RENAL ALLOGRAFTS
pathogenesis and progression of diabetic kidney disease (DKD). Interleukin-6 (IL-6) is
an important inflammatory mediator and different studies have suggested its Anne Kipp1, Hans-Peter Marti1,2, Janka Babickova1, Sigrid Nakken1,
involvement in the pathogenesis of DKD. The aim of our study was to evaluate the Sabine Leh1,3, Thea A.S. Halden4, Trond Jenssen4,5, Bjørn Egil Vikse1,6,
association between IL-6 levels and progression of DKD in patients with type 2 Anders Åsberg4,7, Jessica Furriol2
diabetes. We also tested whether the use of optimal doses of RAS blockade in 1
University of Bergen, Department of Clinical Medicine, Bergen, Norway, 2Haukeland
monotherapy had an influence on the levels of IL-6 in comparison with dual blockade. University Hospital, Department of Medicine, Bergen, Norway, 3Haukeland University
METHOD: IL-6 levels were measured at baseline and after 4 and 12 months in 70 Hospital, Department of Pathology, Bergen, Norway, 4Oslo universitetssykehus
patients included in the PRONEDI trial (EUDRACT 2004-002470-31), a multicenter, Rikshospitalet, Department of Transplantation Medicine, Oslo, Norway, 5UiT The Arctic
randomized controlled clinical trial. The study included type 2 diabetes patients with University of Norway, Faculty of Health Sciences, Tromsø, Norway, 6Haugesund
a clinical diagnosis of DKD, stage 2 or 3 CKD, and a urinary protein/creatinine ratio Hospital, Department of Medicine, Haugesund, Norway and 7University of Oslo,
(UPCR) >300 mg/g (morning urine spot) on 2 separate opportunities. The primary Department of Pharmacy, Oslo, Norway
composite endpoint was a >50% increase in baseline serum creatinine, end stage
kidney disease (ESKD) or death. Cox regression model was adjusted for potential
BACKGROUND AND AIMS: Diabetes mellitus, either preexisting or developing after
confounders or modifiers including eGFR calculated using the CKD-EPI equation and
kidney transplantation remains a crucial clinical problem. The aim of this study is to
UPCR. Mixed models were adjusted to study longitudinal data.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
compare the proteome of histologically normal glomeruli from normoglycemic (NG), METHOD: In streptozotocin-induced type 1 diabetic aged mice (wild-type and
T2DM, and PTDM patients one year after kidney transplantation to identify novel apolipoprotein E (apoE) knockout) we analyzed the kidney levels of miR-155 and
early biomarkers detectable prior to the development of histologically visible diabetic markers of renal damage, inflammation and oxidative stress. In vitro, the expression of
nephropathy. miR-155, SOCS1 and STAT1 in mesangial, tubuloepithelial and macrophage cell lines
METHOD: We comparatively analyzed the proteome of histologically normal were modulated by silencing/inhibition or overexpression/mimicking experiments to
glomeruli from normoglycemic (NG) recipients, and recipients with pre-existing type 2 further determine the JAK/STAT pathway activation and expression of downstream
diabetes mellitus (T2DM), or post-transplant diabetes mellitus (PTDM), in protocol target genes.
biopsies obtained one year after kidney transplantation. Glomerular cross-sections RESULTS: In vivo, type 1 diabetes significantly upregulated miR-155 expression in
were microdissected in core biopsies from 8 NG, 8 PTDM and 8 T2DM kidney kidneys from both wild-type and apoE knockout mice (1.8- and 4.5-fold vs respective
transplant recipients. Proteome was determined by liquid chromatography-tandem non-diabetic controls). The miR-155 levels directly correlated with parameters of renal
mass spectrometry. Relative differences in protein abundance and significantly damage (serum creatinine, albuminuria, kidney-to-body weight ratio and renal score)
dysregulated pathways were analyzed. and the mRNA expression of chemokines (Ccl2 and Ccl5) and pro-oxidant enzymes
RESULTS: Proteins related to immune response and inflammation, transport (Nox2 and Nox4), but inversely with antioxidant genes (Sod1 and Cat). In vitro, the
regulation and cell organization and communication, including the nephrin family, expression of miR-155 was increased in renal cells and macrophages exposed to
were more abundant in NG, as compared to the combined groups of diabetic patients. hyperglycemia and/or inflammatory conditions. Overexpression of miR-155 reduced
Proteins involved in cell morphogenesis and adhesion were less abundant in PTDM, as SOCS1 expression, enhanced STAT1 and STAT3 activation and pro-inflammatory
compared to T2DM. In contrast, CCT3, CCT4 and CNDP2 diabetic nephropathy cytokines and chemokines (Il6, Tnfa, Ccl2 and Cxcl10) expression. By contrast, miR-
markers, LDHB and tacrolimus binding protein FKBP1A were significantly 155 antagonist upregulated SOCS1 and had a protective effect on renal cells by
overrepresented in glomeruli from PTDM, as compared to T2DM patients. decreasing STAT1/3 phosphorylation and pro-inflammatory gene expression.
CONCLUSION: These data suggest that glomerular proteome profile differentiates Additionally, loss- or gain-of function experiments indicate a direct implication of
PTDM from NG and T2DM, and disruption of cell-cell interactions at molecular level SOCS1 in the regulation of miR-155 expression by STAT transcription factors.
represents an early event in PTDM development. CONCLUSION: Our study indicates a pro-inflammatory role of miR-155 in diabetic
kidney disease by downregulating renal expression of SOCS1. Therefore, antagonism of
miR-155 may have a renoprotective effect in diabetic nephropathy through SOCS1-
mediated feedback inhibition of JAK/STAT overactivation. Ongoing in vivo studies
with miR-155 inhibitor in experimental diabetes will clarify its role in the development
and progression of diabetic nephropathy.

FC088 DUAL BLOCKADE OF ENDOTHELIN A RECEPTOR (ETA) AND


SODIUM-GLUCOSE COTRANSPORTER 2 (SGLT2) TO
PREVENT DIABETIC KIDNEY DISEASE PROGRESSION ON A
TYPE 2 MURINE MODEL

Ander Vergara Arana1,2, Mireia Molina2, Conxita Jacobs Cacha 2,


Pamela Dominguez2, Begon ~a Benito3, Irene Agraz1,2, Daniel Seron Micas1,2,
Marıa José Soler1,2
1
Vall d’Hebron University Hospital, Nephrology, Barcelona, Spain, 2Vall d’Hebron
Research Institute, Nephrology Group, Barcelona, Spain and 3Vall d’Hebron University
Hospital, Cardiology, Barcelona, Spain

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i)


and endothelin A receptor (ETA) antagonist have shown nephroprotective effects in
FC086 Figure: Protein-protein interaction network (http://string-db.org/). diabetic kidney disease (DKD) through blood pressure and urinary albumin loss
reduction. The protective impact and the pathways through which they exert this
protection have not yet been elucidated. This study aimed to investigate the effects of
the add-on therapy of SGLT2i and ETA antagonists on a type 2 diabetes murine model.
METHOD: 12 weeks-old db/db mice were treated for 8 weeks with different
combinations of empagliflozin 10 mg/Kg/day (SGLT2i), atrasentan 7 mg/Kg/day (ETA
FC087 MIR-155/SOCS1 REGULATORY LOOP INFLUENCES
antagonist) or ramipril 8 mg/Kg/day. A group of non-diabetic mice (db/m) was
DIABETIC KIDNEY DISEASE BY JAK/STAT PATHWAY
included as negative control. In vivo variables were recorded during treatment,
MODULATION
including transdermal measured glomerular filtration rate (GFR) and urinary albumin-
to-creatinine ratio (UACR). After treatment kidneys were preserved for
Ignacio Prieto1, Luna Jimenez-Castilla1, Iolanda Lazaro2, Susana Bernal-Uribe1,
 histopathological studies.
Laura Lopez-Sanz1, Mo nica Flores-Mun ~oz3, Jesus Egido1, Oscar Lopez-Franco3,
RESULTS: After 8 weeks of treatment empagliflozin decreased fasting blood glucose
Carmen Gomez-Guerrero1
1
alone or in combination with atrasentan or ramipril (234.2 mg/dL mean reduction in
Instituto de Investigaciones Sanitarias-Fundaci on Jiménez Dıaz (IIS-FJD), Universidad three treated groups when compared to db/db). Ramipril decreased blood pressure
Autonoma de Madrid (UAM) and CIBERDEM, Renal, Vascular and Diabetes Research (BP) in monotherapy or in add-on therapy. Empagliflozin or atrasentan alone did not
Lab., Madrid, Spain, 2Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS) have any effect on blood pressure, but combination of atrasentan and ramipril had a
and CIBEROBN, Barcelona, Spain and 3Instituto de Ciencias de la Salud, Universidad synergistic effect and reduced both systolic (9.0 mmHg, CI 95%: -16.3 to -1.1; P=0.028)
Veracruzana (UV), Xalapa, Mexico and diastolic BP (11.9 mmHg, CI 95%: -17.7 to -3.1; P=0.005) when compared to
ramipril alone. The combination of atrasentan and ramipril significantly reduced
BACKGROUND AND AIMS: Diabetic nephropathy is the leading cause of chronic UACR (1002 ug/mg, CI 95%: -2312.0 to -32.4; P=0.043). Empagliflozin treatment alone
kidney disease worldwide. Hyperglycemia in concert with cytokines activate Janus or in combination also reduced UACR (686.0 ug/mg mean reduction in three treated
kinase/signal transducers and activators of transcription (JAK/STAT) signaling groups), although this reduction was not statistically significant. In the kidney,
pathway and induce gene expression of many inflammatory and oxidative stress empagliflozin in monotherapy or combination reduced glomerular mesangial matrix
mediators, which are critical events at all stages of diabetic kidney disease. Suppressor expansion (4.85% mean mesangial reduction in three treated groups). Treatments with
of cytokine signaling 1 (SOCS1) is a STAT-inducible protein and a negative feedback atrasentan and ramipril also reduced measangial matrix expansion.
regulator of JAK/STAT pathway. The microRNA-155 is an epigenetic modulator of CONCLUSION: Both empagliflozin and atrasentan demonstrated possible beneficial
SOCS1 gene by repressing its translation and, at the same time, is a transcriptional effects in DKD by reducing BP, UACR, and mesangial matrix expansion. The add-on
target of STAT, thus completing another regulatory loop of JAK/STAT pathway. therapy did not show greater protective effects in the analysed variables. Further
Therefore, our aim was to explore the interplay between miR-155 and JAK/STAT/ studies are needed to characterize these protective effects and pathways involved.
SOCS1 axis in experimental diabetic nephropathy.

10.1093/ndt/gfab143 | i63
Abstracts Nephrology Dialysis Transplantation

FC088 Figure: Effects of treatments with empagliflozin and atrasentan. A: fasting


blood glucose, B: systolic blood pressure (BP), C: diastolic blood pressure (BP), D:
urinary albumin-to-creatinine ratio (UACR), E: mesangial area in relation to tuft area
measured by periodic acid-Shiff. db/m: non-diabetic controls, db/db: diabetic mice,
EMP: empagliflozin, RAM: ramipril, ATR: atrasentan.

i64 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i65–i66, 2021
10.1093/ndt/gfab149

TREAT DIABETES

FC090 EFFECTS OF FINERENONE ON CARDIORENAL OUTCOMES IN


FC089 EFFECTS OF CANAGLIFLOZIN ON MAJOR ADVERSE BLOOD PRESSURE SUBGROUPS IN PATIENTS WITH CKD
CARDIOVASCULAR EVENTS BY BASELINE ALBUMINURIA: AND T2D
INTEGRATED ANALYSES FROM THE CANVAS PROGRAM
AND CREDENCE TRIAL Luis Ruilope1,2,3, Rajiv Agarwal4, Stefan D. Anker5, Gerasimos Filippatos6,
Bertram Pitt7, Peter Rossing8,9, Pantelis Sarafidis10, Roland E. Schmieder11,
David C. Wheeler1,2, Matthew Weir3, Jagadish Gogate4, Vlado Perkovic1, Amer Joseph12, Nicole Mentenich13, Christina Nowack14, George Bakris15
Kenneth W. Mahaffey5 1
Institute of Research imas12, Cardiorenal Translational Laboratory and Hypertension
1
The George Institute for Global Health, UNSW Sydney, Sydney, Australia, 2Centre for Unit, Madrid, Spain, 2University Hospital 12 de Octubre, CIBER-CV, Madrid, Spain,
Nephrology, University College London, London, UK, 3University of Maryland School of 3
European University of Madrid, Faculty of Sport Sciences, Madrid, Spain, 4Indiana
Medicine, Baltimore, MD, United States of America, 4Janssen Scientific Affairs, LLC, University, Richard L. Roudebush VA Medical Center, Indianapolis, United States of
Titusville, NJ, United States of America and 5Stanford Center for Clinical Research, America, 5Charité Universit€
atsmedizin, Department of Cardiology (CVK), and Berlin
Department of Medicine, Stanford University School of Medicine, Stanford, CA, United Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular
States of America Research Partner Site Berlin, Berlin, Germany, 6National and Kapodistrian University of
Athens, Attikon University Hospital, School of Medicine, Department of Cardiology,
BACKGROUND AND AIMS: People with type 2 diabetes mellitus (T2DM) have a Athens, Greece, 7University of Michigan School of Medicine, Department of Medicine,
greater risk of cardiovascular (CV) disease and major adverse CV events (MACE) that Ann Arbor, United States of America, 8Steno Diabetes Center, Copenhagen, Gentofte,
is more common as renal function declines. The sodium glucose co-transporter 2 Denmark, 9University of Copenhagen, Department of Clinical Medicine, København,
(SGLT2) inhibitor canagliflozin reduced the risk of MACE (CV death, nonfatal Denmark, 10Hippokration Hospital, Aristotle University of Thessaloniki, Department of
myocardial infarction [MI], and nonfatal stroke) in patients with T2DM and high CV Nephrology, Thessaloniki, Greece, 11University Hospital Erlangen, Department of
risk or nephropathy in the CANVAS Program and CREDENCE trials, respectively. Nephrology and Hypertension, Erlangen, Germany, 12Bayer AG, Cardiology and
METHOD: This post hoc analysis included integrated, pooled data from the CANVAS Nephrology Clinical Development, Berlin, Germany, 13Bayer AG, Data science and ana-
Program and the CREDENCE trial. The effects of canagliflozin compared with placebo lytics, Wuppertal, Germany, 14Bayer AG, Research and Development, Clinical
on MACE were assessed in subgroups defined by baseline urinary albumin:creatinine Development Operations, Wuppertal, Germany and 15University of Chicago Medicine,
ratio (UACR; <30, 30-300, and >300 mg/g). Hazard ratios (HRs) and 95% confidence Department of Medicine, Chicago, United States of America
intervals (CIs) were estimated using stratified (by study) Cox regression models, with
subgroup by treatment interaction terms added to test for heterogeneity. Interaction P BACKGROUND AND AIMS: Finerenone is a novel, selective, nonsteroidal
values were calculated by including the terms of treatment group, baseline UACR, and mineralocorticoid receptor antagonist (MRA) that significantly reduced the risk of
their interaction in the model. adverse kidney and cardiovascular (CV) outcomes in patients with chronic kidney
RESULTS: A total of 14,543 participants from the CANVAS Program (N = 10,142) disease (CKD) and type 2 diabetes (T2D) in the FIDELIO-DKD trial. In phase II
and CREDENCE (N = 4,401) were included, with mean estimated glomerular filtration studies, finerenone had modest effects on office blood pressure (BP) compared with the
rate of 70.3 mL/min/1.73 m2 and median (interquartile range) UACR of 501.0 (8.4- steroidal MRA spironolactone. We report an analysis of the relationship between
523.6) mg/g. Among participants with baseline UACR measurements, 7038 (48.8%), baseline and changes in office systolic BP (SBP) and outcomes with finerenone in the
2762 (19.1%), and 4634 (32.1%) participants had baseline UACR <30, 30-300, and FIDELIO-DKD trial.
>300 mg/g, respectively. Rates of MACE and its components increased as UACR METHOD: In FIDELIO-DKD, 5734 patients were randomised 1:1 to oral finerenone
increased (Figure). Canagliflozin reduced the risk of MACE compared with placebo in or placebo. Patients with T2D, urine albumin-to-creatine ratio (UACR) 30–<300
the overall population (HR, 0.83; 95% CI, 0.75, 0.92), with consistent effects observed mg/g, estimated glomerular filtration rate (eGFR) 25–<60 ml/min/1.73 m2 and a
across UACR subgroups (interaction P value = 0.42). Canagliflozin also reduced the history of diabetic retinopathy, or UACR 300–5000 mg/g and eGFR 25–<75 ml/
risk of the individual components of CV death (HR, 0.84; 95% CI, 0.72, 0.97), nonfatal min/1.73 m2, and treated with optimised renin–angiotensin system blockade were
MI (HR, 0.83; 95% CI, 0.70, 0.99), and nonfatal stroke (HR, 0.84; 95% CI, 0.69, 1.03), eligible. The primary endpoint was time to kidney failure, sustained eGFR decline
independent of baseline UACR (interaction P values = 0.40, 0.88, and 0.69, 40% from baseline, or renal death. The key secondary endpoint was time to CV
respectively). Canagliflozin was generally well tolerated in the CANVAS Program and death, non-fatal myocardial infarction, non-fatal stroke, or hospitalisation for heart
the CREDENCE trial, with consistent results on safety outcomes across UACR failure. A Cox proportional hazards model was used to investigate the relationship
subgroups. between treatments and efficacy outcomes adjusted for baseline SBP and change in SBP
from baseline to month 4.
RESULTS: A total of 5669 patients with available baseline SBP data were analysed. At
baseline, the mean SBP and diastolic BP were 138.0 and 75.8 mmHg, respectively.
Patients treated for hypertension at baseline received an average of 3.3 antihypertensive
therapies. The study population was stratified by quartiles (Q) of SBP at baseline:
128.7 mmHg (Q1); >128.7–138.3 mmHg (Q2); >138.3–148.0 mmHg (Q3); and
>148.0 mmHg (Q4). Patients in higher SBP categories tended to be older, with higher
median UACR, but similar mean eGFR at baseline. Effects of finerenone, estimated as
hazard ratios (HRs), were consistent across the quartiles for the primary endpoint (HR
[95% CI]: Q1, 0.87 [0.66–1.15]; Q2, 0.76 [0.59–0.98]; Q3, 0.81 [0.65–1.02]; Q4, 0.86
[0.70–1.07]; p-value for interaction=0.87) and the key secondary endpoint (HR [95%
CI]: Q1, 0.95 [0.69–1.29]; Q2, 0.81 [0.60–1.10]; Q3, 0.79 [0.60–1.03]; Q4, 0.91 [0.70–
1.18]; p-value for interaction=0.78) (Figure). Finerenone treatment resulted in a
modest reduction in SBP; over the duration of the trial, overall mean difference in SBP
between treatment groups was –2.7 mmHg. Maximum differences in SBP between
finerenone and placebo were observed at month 4; the mean change in SBP from
baseline to month 4 across SBP quartiles were: Q1: 4.99 and 9.01 mmHg; Q2: –0.85 and
2.43 mmHg; Q3: –5.63 and –2.40 mmHg; Q4: –11.76 and –6.44 mmHg, for finerenone
FC089 Figure: Effects of canagliflozin on MACE and its components overall and by
and placebo, respectively. Adjusting for baseline SBP and SBP change to month 4
baseline UACR.
resulted in small changes in treatment effect for the primary endpoint and the key
secondary endpoint, with only slightly increased HRs for treatment compared with the
unadjusted primary analysis (primary endpoint: HR: 0.85 vs 0.82; key secondary
CONCLUSION: Event rates of MACE and its components increased with higher
endpoint: HR: 0.90 vs 0.86) and no strong indication of an interaction between
UACR. Canagliflozin reduced the risk of MACE and its components in participants
treatment and SBP.
with T2DM and high CV risk or CKD in the CANVAS Program and CREDENCE trial,
with consistent benefits observed regardless of baseline UACR.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

GO and KEGG analysis showed that the main function of the gene modules in both
datasets were related to the activation of inflammatory cells and chemokines pathway.
Through the screening of hub genes and the comparison of expression levels, CCL5,
CXCL1, CXCL6 and CXCL12 were finally obtained as candidate genes. Quantitative
PCR showed that the levels of CCL5 and CXCL1 was significantly increased in DN
group, CCL5 was negatively correlated with eGFR and positively correlated with
urinary protein level, while CXCL1 was negatively correlated with eGFR, but had no
significant correlation with urinary protein level. Multivariate Cox regression showed
that eGFR, urinary protein level, degree of renal fibrosis and urinary CCL5 were
independent risk factors of primary end point.
CONCLUSION: The activation of chemokine signal pathway in renal tissue is
involved in the progression of DN. Urinary CCL5 mRNA can independently predict
the prognosis of DN and may be served as a novel biomarker for the progression of
DN.

FC092 EFFECT OF GEMIGLIPTIN ON BIOMARKERS OF KIDNEY


INJURY AND VASCULAR CALCIFICATION IN DIABETIC
NEPHROPATHY: A RANDOMIZED CONTROLLED TRIAL
CONCLUSION: In FIDELIO-DKD, a small proportion of the effect of finerenone on
cardiorenal outcomes can be attributed to BP. However, most of the effect appears to Thananda Trakarnvanich1, Bancha Satirapoj2, Swangjit Suraamornkul3,
be via BP-independent mechanisms. (Funded by Bayer AG; FIDELIO-DKD Thanit Chiranantawat4, Anoma Sanpatchayapong5, Torpong Chaimon5
1
ClinicalTrials.gov number, NCT02540993) Division of Nephrology, Vajira Hospital, Navamindradhiraj University, Medicine,
Bangkok, Thailand, 2Division of Nephrology, Pramongkutklao Hospital and College of
Medicine, Medicine, Bangkok, Thailand, 3Division of Endocrine and Metabolism, Vajira
Hospital, Navamindradhiraj University, Medicine, Bangkok, Thailand, 4Police General
FC091 URINARY CCL5 MRNA, A POTENTIAL BIOMARKER FOR Hospital, Medicine, Bangkok, Thailand and 5Vajira Hospital, Navamindradhiraj
PROGRESSION OF TYPE 2 DIABETIC NEPHROPATHY University, Radiology, Bangkok, Thailand
Songtao Feng1, Yueming Gao1, Jingyuan Cao1, Di Yin1, Linli Lv1, Bicheng Liu1
1 BACKGROUND AND AIMS: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve
Medical College, Southeast University, Department of Nephrology, Nanjing, P.R. China glycemic control and contain pleiotropic actions on kidney injury, albuminuria and
vascular inflammation especially in animal models. We plan to evaluate the efficacy of
BACKGROUND AND AIMS: In recent years, it has been found that targeted mRNA potent DPP4-inhibitors (gemigliptin) in response to these aspects in diabetic
detection of sediment cells in urine can be used as novel biomarkers for the diagnosis nephropathy patients.
of diabetic nephropathy (DN). However, its value in predicting the progression of DN METHOD: This is a multi-center, prospective, randomized, placebo-controlled trial. A
is not clear. The purpose of this study is to seek for urinary mRNA markers that total of 201 participants were enrolled and randomly assigned to gemigliptin 50 mg
evaluate the prognosis of DN through systems biological screening, clinical verification daily and standard care of diabetes mellitus for 6 months. The changes of coronary
and prospective studies. calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular
METHOD: GEO database and “Nephroseq” platform were searched, and the filtration rate (GFR), markers of vascular calcification and markers of tubular renal
transcriptome data of DN glomeruli and tubules and their clinical information were injury were evaluated at baseline and 6 months.
obtained. Weighted gene co-expression network analysis (WGCNA) combined with RESULTS: Overall 182 patients completed the study. Significantly reductions in
gene ontology (GO) annotation and KEGG pathway enrichment analysis were used to hemoglobinA1C level were seen at month 6 with gemigliptin group (-0.67%) vs.
screen the hub genes negatively related to eGFR, and the hub genes were used as control group (-0.15%; P=0.048). Changes of CAC score, CAVI, estimated GFR and
candidate markers for mRNA detection in urine sediment in DN patients. A total of 91 proteinuria did not significantly difference in the both groups during 6 months of
patients with DN diagnosed by renal biopsy were included, and 60 patients with type 2 study. However, biomarkers of vascular calcification including serum bone alkaline
diabetes and 61 healthy people were selected as the control groups. The mRNA phosphatase and biomarkers of kidney injury including urine neutrophil gelatinase-
expression of candidate molecules was detected by Taqman probe quantitative PCR, associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/
and the correlation between mRNA expression and eGFR and urinary protein levels Cr improved significantly after gemigliptin treatment when compared to the control
were analyzed. Patients with DN were followed up for a median time of 21 months, group. No serious adverse event was found during study.
and the primary end point was defied as end stage renal disease or eGFR decreasing by CONCLUSION: Our study shows that gemigliptin has significant benefits on
more than 50%. Multivariate Cox regression was used to evaluate the value of mRNA biomarkers of renal tubular injury and vascular calcification in patients with diabetic
in predicting DN progression. nephropathy, but gemigliptin does not affect on renal function and coronary
RESULTS: GSE30528 and GSE30529 datasets were selected for analysis, including calcification compared with control. The larger and longer follow-up will be essential
mRNA expression data of 9 cases of DN and 13 cases of normal glomeruli; and 10 cases to determine these beneficial effects.
of DN and 12 cases of normal tubules respectively. The clinical data of the patients in
this study, including gender, race, age and eGFR, were searched on the Nephroseq
platform. The gene modules negatively related to eGFR were screened by WGCNA.

i66 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i67–i69, 2021
10.1093/ndt/gfab128

DIALYSIS PATTERNS: WHAT’S NEW?


FC093 Table 2. Laboratory parameters over time in the study population.

FC093 EFFICACY OF EXPANDED HEMODIALYSIS AT DIFFERENT


DIALYSATE FLOWS

Alejandra Molano-Trivin ~o1,2,3,4, Jasmin Vesga2, Eduardo Zun ~iga1,2,4, Juan


Felipe Gutiérrez4, Carolina Ramos2,4, Claudio Ronco3
1
Fundacion Cardioinfantil, Nephrology, Bogota, Colombia, 2Baxter Renal Care Services
(RCS)-Colombia, Bogot a, Colombia, 3San Bortolo Hospital in Vicenza Casualty,
International Renal Research Institute Vicenza, Vicenza, Italy and 4Universidad del
Rosario, Escuela de Medicina, Bogot a, Colombia

BACKGROUND AND AIMS: Expanded hemodialysis (HDx) is based on hollow fibre


dialyzer focused on improving the clearance of middle molecules as a target for uremia
treatment. According to in vitro and in vivo results, High cut off filters have high
enough clearance to allow diminishing of dialysate flow. Our aim is to compare In a sustainability analysis, part of Blue Planet dialysis research group, we calculated
clearance of middle molecules at different dialysate flow (Qd) in HDx with important savings in water waste in Qd 400 mL/min group.
TheranovaMR membranes. CONCLUSION: MCO dialyzers are at least as effective in reaching HD adequacy
Our aim was to Evaluate efficacy of MCO dialyzer in terms of Kt/V and phosphorus parameters (Kt/V, PO4) at Qd 400 as 500 mL/min with interesting savings of potable
levels at different prescribed dialysate flows (Qd) 400 vs 500 ml/min in HD patients water: 24 Liters were saved in each session per patient.
from 10 renal clinics in Colombia.
METHOD: We performed a Prospective, observational, multicenter cohort study.
Prevalent adult HD patients (>90 days), with weight lower or equal to 70 Kg, were
included between September to November 2017 and prospectively followed for one FC094 THREE VERSUS TWICE-WEEKLY HEMODIALYSIS SESSIONS:
year with routine monthly blood tests for HD adequacy and registered at both Qd A COMMUNITY EXPERIENCE
groups at 1, 3, 6, 9 and 12 months. A mixed-model repeated measures analysis
(MMRM) was performed to identify statistical differences over time. Socio- Paavan Bonagiri1, Meagan Owen1, Shreya Mohandas2, Simrun Sharma3,
demographic and clinical characteristics of all patients were summarized descriptively Abutaleb Ejaz3
1
by Qd. University of Virginia, Charlottesville, United States of America, 2Emory University,
RESULTS: 462 patients were included: 127 with Qd 400 mL/min. We did not find College of Arts and Science, Atlanta, United States of America and 3University of
statistically significative differences in serum levels of albumin, hemoglobin, calcium or Florida, Gainesville, United States of America
phosphorus when comparing Qd 400ml/min vs 500 ml/min. We found statistically
higher Kt/V in Qd 400 mL/min patients. (Table 2). BACKGROUND AND AIMS: We investigated the feasibilty of converting stable end
stage renal disease (ESRD) patients from three to twice weekly hemodialysis (HD)
sessions based on published criteria.
METHOD: ESRD patients on three times weekly (3xwkly) HD sessions for at least 3
FC093 Table 1. Baseline characteristics of the study population. months duration were screened for eligibility for conversion to twice weekly (2xwkly)
maintenace HD schedule in a university-affiliated community dialysis program.
Eligibility criteria were: residual renal function > 3ml/min; urine output >500mL/day;
intradialytic weight gain <2.5kg; hemoglobin >8gm/dL; manageable phosphorus and
potasium levels. Clinical parameters on 3xwkly vs. 2xwkly HD sessions were then
performed in the eligible patients.
RESULTS: 7/71 (9.8%) of the patients met criteria for conversion to 2xwkly HD sessions.
Baseline patient characteristics are shown in Table 1. Major indication for HD initiation was
symptomatic progression of disease. Less than 50% of patients had a functioning
arteriovenous fistula at initiation of HD. In the current cohort, residual renal function >
3mL/min was maintainedfor >200 days after initiation of HD. There were no significant
changes in electrolytes, hemoglobin, nutrition staus or adequacy of dialysis. PTH levels were
not significantly different: 3xwkly, 625.7 þ 546.2pg/mL vs. 2xwkly, 399 þ 344.2pg/mL;
p=0.374). Karnofsky Performance Status Scale improved post conversion but did not
achieve statistical significance (3xwkly, 57.1 vs. 2xwkly, 70; p=0.316). There were no hospital
admissions since conversion to 2xwkly schedule during the study period.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

term HD therapy. A feasibility study (ENDURE study – Clinical trials ID:


NCT04268264) is being conducted with the primary objectives of evaluating the
CONCLUSION: In a community-based dialysis program, 10% of total HD patients
acceptability and tolerance of a new incremental HD regime. Its secondary aims are to
qualified for conversion from 3xwkly to 2xwkly maintenance HD without significant
evaluate the impact of this form of incremental HD on indicators of patient safety and
changes to their laboratory or clinical performance measures. These observations
wellbeing. These indicators include blood pressure (BP) control and interdialytic
stimulate discussion regarding increased application of incremental dialysis initiation
weight gains (IDWG) which are independently associated with adverse cardiovascular
strategies to preserve residual renal function, increase dialysis-free days and alleviate
outcomes in patients on long-term HD. We present preliminary findings from the
transportation and care provider-related burden to patients and families.
study related to systolic BP and IDWG.
METHOD: The ENDURE study is being carried out at a tertiary care hospital in the
United Kingdom. Patients aged > 18 years known to renal services for at least 90 days,
FC095 INCREASED VASCULAR REFILLING BY FEEDBACK- referred for start of HD, were eligible for participation. Following approved consenting
CONTROLLED ULTRAFILTRATION PROFILE procedures, they are started on a new regime of incremental HD starting dialysis twice
weekly with progressive increases in the duration and frequency of sessions over 15
Susanne Kron1, Til Leimbach2, Joachim Kron2 weeks. This period is split in to four phases; phase 1 representing the first two days of
1
Charité - Universit€
atsmedizin Berlin, Departement of Nephrology and Internal Intensive dialysis (baseline) whereas phases 2 – 4 representing the pre-specified incremental
Care Medicine, Berlin, Germany and 2KfH Kidney Centre Berlin-Köpenick, Berlin, steps. Propensity scores were calculated to match each participant (incremental HD
Germany group) with two controls from a database of patients who previously started HD at our
centres using the standard protocol of 3 times weekly, 4hr long sessions. The matching
criteria accounted for 14 key demographic, clinical and laboratory characteristics.
BACKGROUND AND AIMS: Refilling volume has not been a measurable parameter
Results were analysed as intention to treat. In comparing BP and IDWG between the
in clinical practice so far, as knowing the absolute blood volume (BV) is a prerequisite.
two groups, only readings taken pre-dialysis at the first session of the week was
Recently, we developed a method to determine absolute BV, thus enabling
considered. This study has been approved by the West of Scotland Research Ethics
quantification and comparison of the refilling volume under various conditions. In this
committee-4 (Ref: 19/WS/0019).
study, we evaluated refilling with a constant UF rate and with a feedback-controlled UF
RESULTS: Baseline characteristics of the first 15 participants (target 20) and their
profile.
matched controls are presented in table 1. The proportion of females and duration of
METHOD: Forty dialysis patients were included and studied during their routine
previous specialist input was higher in the incremental HD group.
dialysis sessions. Absolute BV was determined by indicator dilution. Immediately at
the beginning of the dialysis session (before UF was started), an on-line infusate bolus
of 240 mL was injected into the venous blood line by pressing a button on the keypad FC096 Table 1. baseline characteristics
of the dialysis machine 5008 (FMC). The resulting increase in relative blood volume
before and after bolus administration (RBVpost-RBVpre) was used to calculate
absolute BV: Incremental HD (n=15) Controls
absolute BV (in mL) = bolus volume (240 mL) x 100 / increase in RBV (in %) (n=30)
Absolute BV at the end of dialysis was calculated as:
absolute BVend = absolute BVbeginning x RBVend in % / 100 Age, years 62.8 (15.2) 59.1 (14.8)
Refilling volume was calculated as: Male, % 53.3% 66.7%
refilling volume = UF volume – (absolute BV beginning – absolute BV end)
Previous specialist input, months162.4 (135.2) 128.8 (108.8)
The refilling fraction is given as:
Refilling fraction = refilling volume / UF volume Permanent vascular access, % 93.3% 96.7%
UF was either set as constant UF rate or as UF profile. In contrast to the constant UF Blood pressures (BP), mmHg
rate, the UF program integrated in the dialysis machine 5008 initially starts with twice
the average UF rate. If half of the prescribed UF target is reached, the control program Systolic BP 164.7 (27.7) 161.8 (27.2)
keeps UF and refilling in balance. Diastolic BP 76.4 (11.0) 76.3 (17.6)
RESULTS: Refilling data of 40 dialysis sessions with constant UF were compared to 40 Body mass index, kg/m2 33.8 (13.2) 34.2 (10.4)
sessions with the feedback-controlled UF profile.
Refilling volumes were 1.72 6 0.76 l during the profiled sessions and 1.60 6 0.64 l in Haemoglobin, g/l 100.5 (11.5) 101.2 (14.9)
sessions with constant UF rate (p < 0.001, Wilcoxon test). UF volumes were similar in eGFR, ml/min/1.73m2 8.7 (3.1) 8.2 (1.5)
both treatments (2.20 6 0.90 and 2.26 6 0.81 L, respectively).
Albumin, g/l 32.3 (4.7) 33.9 (5.2)
There was a strong correlation between refilling volume and UF volume in both
treatments (r = 0.98 with profile, and r = 0.92 with constant UF rate, respectively). Parathyroid hormone, pg/ml 34.1 (23.8) 37.5 (21.5)
The refilling fraction was significantly higher (p < 0.001, t-test) with the feedback- Modality, %
controlled UF profile (77.2 6 8.5%) than with a constant UF rate (70.4 6 9.9%). In one
patient there was a higher refilling fraction with constant UF rate (p < 0.0001). Haemodiafiltration 80.0% 83.3%
Symptomatic hypotension occurred in 3 patients, all in sessions with constant UF rate. Haemodialysis 20.0% 16.7%
Refilling was not lower in these 3 cases.
CONCLUSION: Refilling volume predominantly depended on UF volume. The
refilling was improved by a high UF rate at the beginning of dialysis. This confirms Mean systolic BP declined in both groups after the onset of dialysis
previous data that initially high UF rates induce the refilling sooner, and, therefore, the with similar rates of decline seen in both groups (Fig. 1). The proportion
refilling volume is higher with the same UF.
An increased UF rate at the beginning can improve volume management in of patients with systolic BP > 160 mmHg was higher in the incremental
haemodialysis patients. With a UF profile, more volume can be removed while HD group at baseline (60% vs 46% respectively). In the follow-up
maintaining a stable absolute BV which may prevent hypotension in some cases. We period, this proportion declined in both groups. The proportion of
therefore recommend that such UF profiles should be used more often in routine
clinical practice. patients with BP > 160 mmHg remained higher in the incremental HD
However, with every litre of UF volume, BV is reduced by more than 200 ml, at a group in phases 2 and 4 but was lower in phase 3. There were no signif-
constant UF rate even by approximately 300 ml. This must be taken into account when
icant differences in IDWG between the groups (Fig. 2).
prescribing the UF volume.

FC096 THE EFFECT OF INCREMENTAL START OF HAEMODIALYSIS


ON BLOOD PRESSURE AND INTERDIALYTIC WEIGHT GAIN:
PRELIMINARY FINDINGS FROM THE ENDURE STUDY

Adil Hazara1,2, Victoria Allgar3, Maureen Twiddy4, Sunil Bhandari1,2


1
Hull University Teaching Hospitals NHS Trust, Academic Renal Research, Hull, United
Kingdom, 2Hull York Medical School, Hull, United Kingdom, 3University of Plymouth,
Faculty of Health, Peninsula Medical School, Plymouth, United Kingdom and
4
University of Hull, Institute of Clinical and Applied Health Research, Hull, United
Kingdom

BACKGROUND AND AIMS: Mortality rates are high in patients starting


haemodialysis/haemodiafiltration (HD) therapy. Incremental HD may help reduce this
risk by reducing the burden of early treatment whilst patients are still adapting to long- FC096 Figure 1: Mean systolic BP at the first HD session of the week.

i68 | Abstracts
Nephrology Dialysis Transplantation Abstracts
continued with new tubing and filter. More than one change of a system was never
necessary. In the other 71 sessions, dialysis had to be stopped with retransfusion 5
minutes until 1.5 hours before the scheduled end of therapy, and therapy was
considered as clinically sufficient. The frequency of clotting did not correlate with
dialysis time (Fig.1.). Regarding the venous access clotting happened in 14.6% of acute
CVC, in 12.6% of tunneled CVCs and in 9.4 % of AV-fistulas or -grafts, (Fig 2).

FC096 Figure 2: Mean interdialytic weight change at the first HD session of the
week

CONCLUSION: The ENDURE study tests the feasibility of starting patients on a novel
incremental HD regime. Early data suggest that control of systolic BP and IDWG are
comparable to patients who start dialysis at 3 times weekly. Further work is needed to
understand the impact of reducing dialysis frequency on BP control correlating the
findings with changes residual renal function and objective measures of fluid overload.

FC097 INTERMITTENT HEMODIALYSIS WITHOUT


ANTICOAGULATION

Silvius Frimmel1, Michael Hinz1, Steffen Mitzner1,2, Sebastian Koball1


1
University of Rostock Medical School, Department of Nephrology, Rostock, Germany
and 2Fraunhofer Institute for Cell Therapy and Immunology, Extracorporeal
Immunomodulation Unit, Rostock, Germany

BACKGROUND AND AIMS: Dialysis therapy of patients at increased risk of


bleeding is a well-known clinical problem. Systemic anticoagulation with heparin
increases the risk of severe hemorrhage. Alternative strategies include the use of
heparin-coated dialysis membranes, regional citrate anticoagulation, airless dialysis
tubing, flushing the dialyzer with saline and earlier regional heparin anticoagulation
with protamine reversal. However, either special devices (e.g. airless or heparin coated
tubing) are needed, or the procedures are complex and require additional time and
personnel resources for administration and monitoring. Current data on heparin-free
dialysis are rare. After a pilot study from 282 dialysis sessions we reviewed 949 dialysis
protocols from 2.5 years of 480 hospitalized and outpatient dialysis patients who were
treated without systemic anticoagulation due to an increased risk of bleeding or a
manifest hemorrhage. The duration of each dialysis session and the number of dialyses
with or without clotting were evaluated.
METHOD: A total of 949 dialysis sessions of 480 patients were reviewed from October
2017 to January 2021. Dialysis were performed with Fresenius 4008/5008 (FX80,FX50,
KF-210) and Gambro Artis (Poly170H, Theranova). All dialysis sessions were CONCLUSION: Dialysis without anticoagulation can be performed routinely with
performed via AV-fistula with double-needle puncture or via single- or double-lumen modern synthetic filters and dialysis concentrates. Patients at high risk of bleeding,
central venous catheters (CVC). No additional technical devices or procedures were with manifest hemorrhage or before surgery can undergo dialysis treatment for up to
used beside standard hemodialysis or hemodiafiltration. Some of the patients had five hours without complications. In the present study clotting did not correlate with
coagulopathies (sepsis, liver cirrhosis), thrombocytopenia or were on systemic dialysis time. Patient-specific factors, as the venous access seem to play a more
anticoagulant therapy (vitamin K antagonists, DOAKs, heparin independent from important role. In summary additional cost intensive devices, personnel intensive
dialysis therapy). The primary outcome was the need to interrupt the dialysis session procedures and complex treatment protocols are only rarely needed to perform
because of clotting events due to a complete coagulation of the circuit, a partial heparin-free dialysis for patients at risk.
coagulation of the circuit or a significant rise in the venous pressure.
RESULTS: In 81 procedures (8.5%) systemic clotting made a discontinuation of the
dialysis session necessary. In only 10 sessions (1%), the dialysis treatment had to be

10.1093/ndt/gfab128 | i69
Nephrology Dialysis Transplantation 36 (Supplement 1): i70–i72, 2021
10.1093/ndt/gfab141

PROTECT THE MEMBRANE PET dwell and at PET time points 1-hour and 4-hours were collected and immediately
processed. Additional effluent samples were obtained during unscheduled
hospitalization and in the event of an acute peritonitis. Effluent samples were collected
directly from the drainage bags into standard 9 ml additive-free sample tubes. For ex-
FC098 MESENCHYMAL STEM CELL EXOSOMES AMELIORATE MICE vivo stimulation, 100 ng/ml toll-like receptor (TLR) 4 agonist LPS and TLR2 agonist
PERITONEAL FIBROSIS INDUCED BY HUMAN PERITONITIS Pam3Cys were added to the effluent in the 9 ml collection tubes in duplicates and
DIALYSIS EFFLUENT incubated at 37 C for 24h. Unstimulated samples kept in parallel were used as controls.
IL-6 and TNF-a concentrations were measured with ELISA in the supernatants.
Kehong Chen1, Yani He1 RESULTS: Ex-vivo stimulation of peritoneal cells significantly increased the IL-6 and
1
Daping Hospital, Army medical University, Department of Nephrology, Chongqing, P.R. TNF-a release compared to unstimulated controls and resulted in a dwell-time
China dependent increase, with a significant lower cytokine released at the 1h PET time point.
To assess local inflammation IL-6 levels of crude effluent were determined. IL-6
concentrations remained stable over time on PD. Interestingly, we were able to show
BACKGROUND AND AIMS: Peritoneal fibrosis is a severe complication of higher IL-6 levels in CAPD patients in comparison to APD. As chronic exposure to
peritoneal dialysis, but there are few effective therapies for it. The purpose of this study PD-fluids has been shown to dampen the peritoneal immune competence, consecutive
was to investigate the protective effect of exosomes secreted by mouse bone marrow peritoneal effluent bags, obtained from patients were analysed. In this subcohort of 183
mesenchymal stem cells on peritoneal fibrosis and to reveal the mechanism. 4h-PET effluents we found a decline in cytokine secretion with time on PD (IL-6 r=-
METHOD: Forty-two male C57BL/6 mice were randomly divided into a normal 0.27, p=0.00015, TNFa r=-0.25, p=0.00071). In a subgroup the ex-vivo cytokine release
group, a control group (2.5% glucose dialysate), a peritonitis-effluent group (The of effluent samples from patients with an acute peritonitis was assessed. IL-6 levels of
overnight 2.5% glucose dialysate of patients with peritonitis), a high glucose dialysate acute peritonitis effluent samples did not differ from the stimulated IL-6 levels of
group (4.25% glucose concentration), a peritonitis-dialysate þ exosome group, and a effluent samples without acute peritonitis (2.45 pg/mL vs 2.31 pg/mL, p=0.85, t-test)
high glucose dialysate þ exosome group. The mouse model of peritoneal fibrosis was suggesting that the assay seemingly represents the in-vivo host-defence cytokine release
constructed by intraperitoneal injection of human peritonitis effusion continuously for accurately.
42 days. The mice in the exosome treatment group received intraperitoneal injection of CONCLUSION: The study provides evidence of a correlation of declining local host
mesenchymal stem cell (MSC)-exosomes twice. The level of peritoneal structural and defence and duration of PD-therapy. It supports the hypothesis of PD duration-
functional damage, inflammation, fibrosis and mesothelial cell damage of peritoneum dependent progressive impairment of the ability of the peritoneal immune cells to
were detected. Furthermore, the effect of MSC-exosomes was validated in vitro. secrete cytokines in response to a pathogenic stimulus and thereby dampening the
RESULTS: Peritoneal transport was significantly impaired and peritoneal thickness global peritoneal immuno-competence. This suggests the utility of this clinically
was significantly increased in the peritonitis-effluent group and the high glucose feasible ex-vivo induced cytokine-release assay in peritoneal effluent as a surrogate of
dialysate group after 42 days. The degree of peritoneal inflammation and fibrosis in the the functional peritoneal immune competence. Future analyses need to evaluate the
two groups was significantly higher than the control group. The results suggested that assay as a tool to predict common clinical outcomes and define reference values to
human peritonitis dialysis effluent could be used to construct a mouse model of facilitate stratification of patient populations, clinical staging and to guide novel
peritoneal fibrosis. Masson staining results showed that the fibrosis degree of therapeutic interventions.
peritonitis - effluent þ exosome group was significantly less than the peritonitis -
effluent group. Immunohistochemical analysis showed that the expression levels of
mesothelial markers E-cadherin and ZO-1, neutrophil granulocytes (MPO) and
macrophages (F4/80), and fibrosis markers collagen I and a-SMA in the peritonitis - FC100 ASSOCIATION OF SINGLE AND SERIAL MEASURES OF
effluent þ exosome group were significantly lower than those in the peritonitis - SERUM PHOSPHORUS WITH ADVERSE OUTCOMES IN
effluent group. Similarly, the high glucose dialysate þ exosome group mice showed PATIENTS ON PERITONEAL DIALYSIS: RESULTS FROM THE
significantly lower levels of peritoneal inflammation and fibrosis than the high glucose INTERNATIONAL PDOPPS
dialysate group mice. In vitro experiments showed that exosomes could down-regulate
the secretion of IL-1, IL-6 and TGF- by renal tubular cells stimulated by high glucose Marcelo Lopes1, Angelo Karaboyas1, David W Johnson2,
dialysate, maintain the expression of mesenchymal cell marker (E-cadherin), and Talerngsak Kanjanabuch3, Martin Wilkie4, Kosaku Nitta5, Hideki Kawanishi6,
inhibit the mesenchymal marker (-SMA), suggesting that exosomes could inhibit the Bryce S. Foote7, Ronald Pisoni1
1
transdifferentiation of peritoneal mesenchymal cell-mesenchymal cells (MMT). Arbor Research Collaborative for Health, DOPPS, Ann Arbor, United States of America,
2
CONCLUSION: MSC-exosomes can alleviate peritoneal fibrosis by inhibiting University of Queensland, Department of Nephrology j Division of Medicine, Saint
peritoneal mesothelial cell-mesenchymal cell transdifferentiation. Lucia, Australia, 3Chulalongkorn University, Faculty of Medicine, Bangkok, Thailand,
4
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield Kidney Institute, Sheffield,
United Kingdom, 5Tokyo Women’s Medical University Hospital, Department of
Nephrology, Shinjuku City, Japan, 6Tsuchiya General Hospital, Nephrology, Hiroshima,
Japan and 7Keryx Biopharmaceuticals, Inc., Medical affairs, Boston, United States of
America

FC099 DECLINING PERITONEAL HOST DEFENCES REVEALED BY


BACKGROUND AND AIMS: While it has been established that high serum
EX-VIVO CYTOKINE RELEASE ASSAY OF PERITONEAL
phosphorus is associated with mortality in hemodialysis (HD) patients, there is limited
DIALYSIS EFFLUENT CELLS
evidence in the peritoneal dialysis (PD) setting. We evaluated the association of serum
phosphorus with mortality and major adverse cardiovascular events (MACE) in
Rebecca Herzog1, Lisa Daniel-Fischer1, Isabel Sobieszek1, Christoph Aufricht1,
patients on PD, and investigated various parameterizations using single and serial
Klaus Kratochwill1
1
measurements of serum phosphorus.
Medical University of Vienna, Austria METHOD: We utilized data from 7 countries in phase 1 (2014-2017) of the
Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS): Australia,
BACKGROUND AND AIMS: Infectious complications occur in a significant Canada, Japan, New Zealand, Thailand, the UK, and the US. We investigated the
proportion of PD patients, limiting long-term applicability. Reduced peritoneal association of serum phosphorus and 3 outcomes: all-cause mortality, cardiovascular
immune-competence, caused by the continuous exposure to PD-fluids, has been (CV) mortality, and MACE (CV mortality þ non-fatal angina, myocardial infarction,
described as a therapy-related pathomechanisms, prompting the need for a tool to stroke, and heart failure). We parameterized serum phosphorus using 4 different
assess the functional peritoneal immune status. We established an ex-vivo stimulation methods: (1) single measurement of baseline serum phosphorus [most recent
assay to test host defence mechanisms in only 9ml of PD-effluent. The aim of this study measurement during 6-month run-in period]; (2) mean serum phosphorus over a 6-
was to analyse basal inflammation and immune-competence in the general PD month run-in period; (3) number of months (over the past 6 months) with serum
population at routine conditions to evaluate the assay as surrogate parameter of phosphorus above the target range (>4.5 mg/dL); (4) mean area-under-the-curve
immune competence and linking it to PD vintage and clinical outcome parameters. (AUC), calculated as the average amount of time spent with serum phosphorus >4.5
METHOD: 147 of 284 (51.8%) adult and paediatric PD patients treated between April mg/dL multiplied by the extent to which this threshold was exceeded over 6 months.
2013 and September 2020 at the local Department of Nephrology were included in the Cox regression was used to estimate the association between each of these 4 exposures
analysis. The study was approved by the local ethics committee and was conducted in with the time-to-event outcomes, in models thoroughly adjusted for possible
accordance with the Declaration of Helsinki. Patients were exclusively treated with confounders. Follow-up began after the 6-month run-in period and continued until the
neutral pH/multi-chamber PD fluids during the glucose dwells. The majority of the 558 outcome occurred, 7 days after leaving the facility due to transfer or change in kidney
included PD-effluent samples were obtained during standard 4-hours peritoneal replacement therapy modality, loss to follow-up, or end of study phase (whichever
equilibration tests (PET) with 3.86% glucose containing PDF. Samples from the pre- event occurred first).

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
RESULTS: Our sample consisted of 5904 patients who were on PD. Those with higher METHOD: We enrolled 12 paediatric patients on PD. Half of them affected by FSGS
serum phosphorus levels were younger and had lower hemoglobin levels. Compared to and the others affected by other disorders (NO FSGS). Exosomes from mesothelial
patients with serum phosphorus 3.5 to <4.5 mg/dL, we found an all-cause mortality peritoneal cells were isolated by centrifugation and, using a biotinylated antibody and
hazard ratio (HR) of 1.62 (95% CI: 1.19, 2.20) for patients with serum phosphorus  7 streptavidin magnetic beads. Exosome size was determined by dynamic light scattering,
mg/dL. Strong associations were also observed using serial phosphorus measures and antigen profile of exosomes was assayed by western blot. Mass spectrometry data
[Table]. For example, compared to the reference group of AUC=0, the HR (95% CI) of were analyzed by unsupervised hierarchical clustering using multidimensional scaling,
death was 1.49 (1.10, 2.00) for AUC >1 to 2; and 1.67 (1.15, 2.41) for AUC >2. Akaike in order to identify outliers and dissimilarity between samples. The normalized data
Information Criteria (AIC) results showed that, among the 4 exposures, AUC was the were used to construct a co-expression network using the weighted gene co-expression
strongest predictor of all-cause mortality, and the single phosphorus measure was the network analysis (WGCNA). A weighted adjacency matrix was constructed, and
weakest predictor. Associations between serum phosphorus and adverse outcomes transformed into a topological overlap matrix, which measures the network
were generally stronger for CV death and MACE than for all-cause mortality [Table]. connectivity of all proteins. To identify the relationship between each module and each
CONCLUSION: As seen in HD patients, this analysis demonstrates that serum clinical trait, we used module eigengenes (MEs) and calculated the correlation between
phosphorus is a strong predictor of adverse outcomes in patients on PD. When MEs and the clinical traits. To identify the hub proteins of modules that maximize the
considering serial measurements of serum phosphorus, rates of adverse events began to discrimination between FSGS and NO FSGS samples, we applied T-test, and non-
rise at phosphorus levels >4.5 mg/dL. As recommended by KDIGO guidelines, serial linear support vector machine (SVM) learning. Finally, gene set enrichment analysis
measurements that consider a history of serum phosphorus excursions >4.5 mg/dL was done to build a functional proteins network based on their Gene Ontology (GO)
should be considered when assessing risks of adverse outcomes. annotations extracted from the Gene Ontology Consortium.
RESULTS: Our omic study demonstrated that SVM allowed a complete distinction of
the whole proteomic exosome mesothelial content of FSGS versus NO FSGS (100%
accuracy). Out of the 2490 identified proteins, 40% (995) were involved in endothelial
to mesenchymal transition /fibrosis and in the TGF-B pathway. The WGCNA analysis
highlighted a total of 40 proteins were that maximize the discrimination between FSGS
and NO FSGS patients (Figure 1A). Their expression profile is reported in a heatmap
diagram (Figure 1B).

FC101 Figure 1.(A) Volcano plot of univariate statistical analysis to PDE exosome
of FSGS and Non-FSGS samples and (B) heatmap of statistically significant proteins.

Additionally, we performed GO enrichment analysis (Figure 2) and the algorithm


identified that some of the discriminative proteins (TIMP1, CTHRC1, SPARC,
CHMP4B, COL5A2, ANXA13, FNC2 and CENP-E) were also highly correlated to the
FC101 PROTEOMIC PROFILE OF MESOTHELIAL EXOSOMES peritoneal dialysis vintage, fibrosis, EMT and PM disease.
ISOLATED FROM PERITONEAL DIALYSIS EFFLUENT OF
CHILDREN WITH FOCAL SEGMENTAL
GLOMERULOSCLEROSIS

Edoardo La Porta1,2,3, Maurizio Bruschi4, Giovanni Candiano4, Andrea Petretto5,


Martina Bartolucci5, Xhuliana Kajana4, Gianluigi Zaza6, Simona Granata6,
Isabella Panfoli7, Enrico Vidal8, Gian Marco Ghiggeri9, Enrico Eugenio Verrina3
1
Iclas-GVM Group, Cardionephrology, Rapallo (GE), Italy, 2University of Genoa, DIMI,
Genova, Italy, 3IRCCS Istituto Giannina Gaslini, Dialysis Unit, italy, , 4IRCCS Istituto
Giannina Gaslini, Laboratory of Molecular Nephrology, Genova, Italy, 5IRCCS Istituto
Giannina Gaslini, Laboratory of Mass Spectrometry - Core Facilities, Genova, Italy,
6
University Hospital of Verona, Renal Unit, Department of Medicine, 7University of
Genoa, Departement of Pharmacy-DIFAR, 8University-Hospital of Padova, Pediatric
Nephrology, Dialysis and Transplant Unit, Department for Woman‘s and Child’s Health,
Padova, Italy and 9IRCCS Istituto Giannina Gaslini, Division of Nephrology, Dialysis and
Transplantation, Genova, Italy

BACKGROUND AND AIMS: Peritoneal dialysis (PD) is the worldwide preferred


dialysis treatment for children affected by end stage kidney disease. However, due to
the unphysiological composition of PD fluids, the peritoneal mesothelium of these
patients may undergo structural and functional alterations, which may cause fibrosis.
Several factors may accelerate this process and primary kidney disease may have a
causative role. In particular, patients affected by corticosteroid resistant focal segmental
glomerulosclerosis (FSGS), a rare glomerular disease leading to nephrotic syndrome,
seems more prone to develop peritoneal fibrosis. The mechanism causing this FC101 Figure 2.Venn diagram of total proteins identified and the database resulted
predisposition is still unrecognized. To better define this condition, we carried out, for enriched in GO analysis
the first time, a new comprehensive comparative proteomic mass spectrometry analysis
of mesothelial exosomes from peritoneal dialysis effluent (PDE).

10.1093/ndt/gfab141 | i71
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: Our data demonstrated, for the first time, that mesothelial cells of treated with more biocompatible dialysis solution, reduce the length of time on PD and
FSGS are more prone to activate a pro-fibrotic machinery with exosomes having a personalize type and regimens of PD to minimize the risk of rapid loss of peritoneal
primary role in this process. Moreover, they indicated that identified FSGS-associated membrane.
element in mesothelial exosome protein could be employed as potential new
biomarkers of mesothelial integrity. Finally, results highlighted that FSGS should be

i72 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i73–i74, 2021
10.1093/ndt/gfab135

OUTCOMES IN PD directly exposed to PD fluids, demonstrate inhibition of PD induced immune response


and angiogenesis pathways, of glucose metabolism and cytoskeleton regulation to levels
similar as seen in children with CKD5. Arteriolar lipid and fatty acid metabolism is
selectively altered after KTx. Reversal of low GDP PD induced hypervascularization
FC102 PD INDUCED ARTERIOLAR AND PERITONEAL and inflammation of the parietal peritoneum after KTx, mirror molecular changes in
PATHOMECHANISMS ARE PARTIALLY REVERSED AFTER omental arterioles, while profibrotic activity persists after KTx in omental arterioles
KIDNEY TRANSPLANTATION and in the parietal peritoneum.

Conghui Zhang1, Maria Bartosova1, Betti Schaefer1, Rebecca Herzog2,


Rimante Cerkauskiene3, Karel Vondrak4, Jun Oh5, Günter Klaus6,
Ariane Zaloszyc7, Maria Gema Ariceta Iraola8, Bruno Ranchin9, Aysun
Karabay Bayazit10, Sara Testa11, Christina Taylan12, Johan Vande Walle13,
YOKCHIN YAP14, Rainer Büscher15, Dorota Drozd16, Sotirios G. Zarogiannis17,18,
Klaus Kratochwill19, Claus Schmitt1 FC103 PROTEOME WIDE OXIDATIVE STRESS PROFILING IN
1 MESOTHELIAL CELLS INDUCED BY PERITONEAL DIALYSIS
University of Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg,
FLUID
Germany, 2Medical University of Vienna, Department of Pediatrics and Adolescent
Medicine, Vienna, Austria, 3Vilnius University, Pediatric Center, Lithuania, 4University
Rebecca Herzog1, Anja Wagner1, Klaus Kratochwill1
Hospital Motol, Department of Pediatrics, Prague, Czech Republic, 5University Medical 1
Center Hamburg-Eppendorf, Department of Pediatric Nephrology, University Children’s Medical University of Vienna, Austria
Medical Clinic, Germany, 6University Hospital of Giessen and Marburg, KfH Pediatric
Kidney Center, Marburg, Germany, 7 University Hospital of Strasbourg, Department of BACKGROUND AND AIMS: Reactive oxygen species (ROS) in the peritoneal cavity
Pediatrics 1, Strasbourg, France, 8Hospital Universitario Materno-Infantil Vall d’ Hebron, may result both from CKD and the specific composition of peritoneal dialysis fluids
Barcelona, Spain, 9Hôpital Femme Mere Enfant, Service de Néphrologie Pédiatrique, (PDF). Elevated cellular oxidative stress is defined as a cellular oxidant/antioxidant
lyon, France, 10Cukurova University, Department of Pediatric Nephrology Faculty of imbalance which impairs not only peritoneal cell viability but also contributes to
Medicine, Turkey, 11 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, progression of local and systemic PD-related pathomechanisms. So far only single
Pediatric Nephrology and Dialysis Unit, Milano, Italy, 12University Hospital of Cologne, targets or mediators of oxidative stress were investigated in mesothelial cells exposed to
Pediatric Nephrology, Children‘s and Adolescent’s Hospital, Germany, 13Ghent PD fluids. Here, we aim to analyze the broad impact and also identify individual targets
University Hospital, Pediatric Nephrology, Department of Pediatrics, Belgium, 14Hospital of ROS during PD. Using the developed technique the anti-oxidative effect of alanyl-
Kuala Lumpur, Department of Pediatrics, Malaysia, 15 University Childrens Hospital, glutamine (AlaGln) supplementation of PDF was characterized on the proteome level.
Pediatric Nephrology, Essen, Germany, 16Jagiellonian University Medical College, METHOD: To establish a redox-proteomics workflow for studying oxidative stress in
Krakow, Poland, 17University of Heidelberg, Center for Pediatric and Adolescent peritoneal mesothelial cells we used a gold-standard model of redox-stress (100 mm
Medicine, Germany, 18University of Thessaly, Department of Physiology, Faculty of hydrogen peroxide (H2O2)) and PD-fluid induced stress. Levels of oxidative stress
Medicine, Larissa, Greece and 19Medical University of Vienna, Department of Pediatrics were first evaluated by intracellular ROS levels and superoxide dismutase activity.
and Adolescent Medicine, Vienna, Austria Oxidative stress levels induced by PDF were titrated to comparable levels of H2O2
treatment to be able to characterize redox modifications and the effect of addition of 8
BACKGROUND AND AIMS: Due to the unphysiological composition of PD fluids, mM AlaGln. To detect alterations of the redox proteome we adapted and refined an
chronic peritoneal dialysis (PD) induces progressive peritoneal fibrosis, approach combining redox-sensitive isobaric mass tags and high-performance liquid
hypervascularization, and vasculopathy. The evolution of the PD membrane and chromatography coupled to mass spectrometry (LC/MS). We used a sequential
vasculopathy following kidney transplantation (KTx) is largely unknown. combination of direct and indirect labeling of redox-sensitive cysteine residues.
METHOD: Arteriolar and peritoneal tissues were obtained from 107 children with RESULTS: Exposure to PDF increased intracellular ROS production and accumulation
chronic kidney disease (CKD5), 72 children on PD (treated with neutral pH PD fluids, as well as cell damage assessed by LDH-release compared to control cells. Cells exposed
with low glucose degradation product content, GDP) and 21 children, who underwent to AlaGln supplemented PDF showed less cell damage compared to PDF alone.
KTx 4-5 weeks after a median 21 months of PD. Specimen underwent standardized Addition of AlaGln not only reduced the overall redox status (intracellular ROS and
digital quantitative histomorphometry. Molecular mechanisms were studied in superoxide dismutase activity) but also led to different proteins being affected by redox
omental arterioles microdissected from surrounding fat by multi-omics followed by modifications. The carefully optimized highly sensitive LC/MS-based redox proteomics
Gene Set Enrichment Analysis (GSEA); key findings were validated in parietal tissues workflow allowed identification of 5537 proteins of which 2614 contained a labeled
of independent, matched cohorts by quantitative immunohistochemistry (n=15/ cysteine. H2O2 treatment resulted in a shift of median oxidation from 11% under
group). control conditions to 36%. While PDF alone increased the oxidation level to 31%,
RESULTS: Arteriolar transcriptome and proteome GSEA revealed suppression of AlaGln supplemented PDF only led to 15% oxidation. Pathway analysis of proteins
leucocyte migration and T-cell activation / secretory pathways regulation, of sprouting that changed their oxidation level >50% following the treatment were subjected to
angiogenesis biological processes and of epithelial proliferation and cell cycle after KTx molecular pathway analysis revealing distinct differences. PDF exposure leads to
as compared to PD. Lipid / fatty acid metabolism, autophagy and ATP synthesis regulation of general cell processes like regulation of glucokinase, RNA-binding and
pathways were activated. SUMOylation, addition of AlaGln regulated more specific signaling pathways for
Transcriptome analysis including KTx, PD and CKD5 specifically attributed regulation example fibrosis related pathways like TGF-ß and SMAD signaling.
of arteriolar lipid and fatty acid metabolism to transplantation and comprised 140 CONCLUSION: Redox proteomics of peritoneal cells could represent a novel tool for
transcripts; their regulation was confirmed on the proteome level. Hub gene fatty acid the identification of mediators of uraemia and PD-induced pathomechanisms, and also
synthase was identified by protein interaction analysis (string-db.org). 15 arteriolar to evaluate anti-oxidant pharmacological interventions to improve PD outcomes.
genes activated by PD were inactivated after KTx and included glucose metabolisms
and cytoskeleton related transcripts. 24 transcripts and 10 corresponding proteins
induced by PD were still active after KTx and associated with biological processes
related to TGF-ß signaling, fibrosis and mineral absorption.
In line with arteriolar multi-omics findings, peritoneal hypervascularization induced by
chronic PD was reversed after Tx to CKD5 level. CD45 positive tissue infiltrating
leucocytes count was reduced by 40% and was independently associated with
microvessel density in multivariable analysis including PD vintage, daily GDP
exposure and recent KTx. Peritoneal lymphatic vessel density, submesothelial
thickness, activated fibroblast, fibrin deposit, macrophage and EMT cell counts
remained unchanged after KTx compared to PD. Arteriolar lumen to vessel ratios (a
marker of vasculopathy) were similar in both groups.
Vessel-homeostasis-related proteins in independent, matched cohorts demonstrated
increased caspase-3 abundance in peritoneal arterioles after KTx. Arteriolar VEGF-A,
thrombospondin, angiopoietin1/2, and hypoxia-inducible factor-1 (HIF-1a) were
unchanged, while submesothelial HIF-1a and angiopoietin1/2 were decreased after Tx,
favoring vessel maturation. The abundance of the key driver of fibrosis, TGF-ß-effector
pSMAD2/3, was unchanged in the peritoneum and arterioles after Tx.
CONCLUSION: Our multi-omics analyses of fat covered omental arterioles, not

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC104 CARDIAC GEOMETRY, FUNCTION, AND REMODELING


PATTENRS AND LUNG WATER CONTENT IN PATIENTS
UNDER MAINTENANCE HEMODIALYSIS AND PERITONEAL CONCLUSION: Hemodialysis and PD patients present similar volume overload,
DIALYSIS TREATMENT evaluated with lung ultrasound, and no significant differences in echocardiographic
indices reflecting cardiac geometry, but different patterns of abnormal LV remodeling was
Charalampos Loutradis1, Maria Eleni Alexandrou1,2, Vassilios Sachpekidis3, evident in each dialysis modality, with hemodialysis presenting eccentric and PD
Christodoulos Papadopoulos4, Vasileios Kamperidis5, Maria Toumpourleka4, concentric LVH. These results clearly support that PD is no better than HD with regards
Marieta Theodorakopoulou1, Dimitra Bakaloudi1, Danai Faitatzidou1, to cardiovascular stress, despite the fact that they experience a more stable volume status.
Panagiotis Pateinakis2, Aikaterini Papagianni1, Pantelis Sarafidis1
1
Aristotle University of Thessaloniki, Department of Nephrology, Hippokration Hospital,
Thessaloniki, Greece, 2, Department of Nephrology, Papageorgiou General Hospital of
Thessaloniki, Thessaloniki, Greece, 3, Department of Cardiology, Papageorgiou General FC105 LITHIUM PRESERVES PERITONEAL MEMBRANE INTEGRITY
Hospital of Thessaloniki, Thessaloniki, Greece, 4Aristotle University of Thessaloniki, 3rd BY REDUCING MESOTHELIAL CELL AB-CRYSTALLIN
Department of Cardiology, Hippokration Hospital, Thessaloniki, Greece and 5Aristotle
University of Thessaloniki, 1st Department of Cardiology, AHEPA Hospital, Thessaloniki, Rebecca Herzog1, Guadalupe Gonza lez2, Maria Bartosova3, Juan
Greece Manuel Sacnun1,4, Lisa Daniel-Fischer1, Andreas Vychytil1, Claus Schmitt3,
Manuel Lo pez-Cabrera2, Seth Alper5, Christoph Aufricht1, Klaus Kratochwill1
1
BACKGROUND AND AIMS: Cardiovascular disease is the leading cause of mortality Medical University of Vienna, Wien, Austria, 2CSIC-UAM, Molecular Biology Centre
in patients with end-stage kidney disease (ESKD). Evidence on the possible Severo Ochoa, MAdrid, Spain, 3University of Heidelberg, Heidelberg, Germany,
4
echocardiographic differences between patients undergoing different dialysis modalities is Zytoprotec GmbH, Vienna, Austria and 5Harvard Medical School, Department of
scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA) and left Medicine, Boston, United States of America
(LV) and right ventricular (RV) geometry, systolic and diastolic function, as well as lung
water content in hemodialysis and peritoneal dialysis (PD) patients. BACKGROUND AND AIMS: Renal replacement therapy by peritoneal dialysis (PD)
METHOD: A total of 38 hemodialysis and 38 PD patients receiving treatment for 3 is limited in use and duration by progressive impairment of peritoneal membrane
months, matched in a 1:1 ratio for age, sex and dialysis vintage were included in this integrity and homeostasis. Preservation of peritoneal membrane integrity during
study. Lung ultrasound, two-dimensional and tissue-Doppler echocardiography were chronic PD remains an urgent but long-unmet medical need. PD therapy failure results
performed during an interdialytic day in hemodialysis and before a programmed from peritoneal fibrosis and angiogenesis caused by hypertonic PD fluid (PDF)-
follow-up visit in PD patients. To identify factors possible associated with LVH (left induced mesothelial cytotoxicity. The incompletely defined pathophysiological
ventricular hypertrophy), we performed univariate and multivariate linear regression mechanisms involved confound informed selection of therapeutic targets. Addition of
analyses in the total population studied. cytoprotective agents to PDF have been shown to counteract pathophysiological
RESULTS: No significant differences were evidenced in ultrasound B-lines (4.00 [6.00] vs mechanisms induced by current PDF. Lithium is a well described inhibitor of glycogen
3.00 [4.25]; p=0.623) between the two groups. Vena cava diameter (11.0964.53 vs synthase kinase 3b and has recently been shown to also have nephroprotective effects
14.9164.30 mm; P<0.001) was significantly lower in hemodialysis patients. Indices of LA, in low doses. Here, we aim to characterize icodextrin-based, PDF-induced cellular
RA, LV and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs injury with a combined omics approach and to investigate the effects of LiCl on the
122.83 [52.33] g/m2; P=0.767) was similar, but relative wall thickness (RWT) was marginally PD-induced observed molecular perturbations.
(0.40 [0.14] vs 0.45 [0.15] cm; P=0.055) lower in hemodialysis patients. LV hypertrophy METHOD: To investigate mechanisms of acute cellular damage by PDF we chose an
prevalence, defined as LVMi values >95 or >115 g/m2 for female and male patients, was in vitro model of primary omental-derived peritoneal mesothelial cells with direct
similar between groups (73.7% vs 71.1%; p=0.798), but relative wall thickness (RWT) was exposure to icodextrin-based PDF, followed by short-term or extended recovery for
numerically lower (0.40 [0.14] vs 0.45 [0.15] cm; P=0.055) and fractional shortening detection of short-term and long-term changes in transcriptome, proteome, and cell
(29.1267.07% vs 23.3768.84%; P=0.003) was significantly higher in patients under injury. 0, 2.5 or 10 mM LiCl were added to the PDF. In-vitro findings were validated in
hemodialysis compared to those under PD. Hemodialysis patients presented mainly peritoneal biopsies (n=41) from pediatric PD and CDK5 patients or healthy controls
eccentric (normal RWT and increased LVMi), while PD patients presented mainly and peritoneal effluents from adult and pediatric PD patients (n=27) or ascites samples
concentric LVH (increased RWT and increased LVMi). Left atrial (LA), right atrial (RA) (n=4) as control. For in-vivo experiments, healthy and uremic mice (C57/Bl6, female)
and ventricular (RV) echocardiographic indices were again similar between the two study were chronically exposed to PD-fluid without or with the addition of 5 mM LiCl via an
groups. Ventricular systolic function was similar between-groups, except for stroke volume implanted catheter. In-vivo overexpression of CRYAB was induced by i.p. injection of
(78.97 [24.24] vs 64.66 [27.35] ml; P=0.030) and cardiac output (5.75 [2.29] vs 4.93 [2.10] L/ an adenoviral vector. All animal experiments and use of patient samples were approved
min; P=0.036) which were higher in hemodialysis. With regards to RV systolic function by the local ethics committees and performed according to animal protection laws or
indices, RV systolic pressure (RVSP) was significantly lower in the hemodialysis compared the Declaration of Helsinki, respectively.
to the PD group (20.37 [22.54] vs 27.68 [14.32] mmHg; P=0.009). All diastolic function RESULTS: LiCl significantly improved mesothelial cell survival in a dose-dependent
indices were similar between the two groups. Prevalence of mitral valve (MV) regurgitation manner. Combined transcriptomic and proteomic characterization of icodextrin-based
was significantly lower in the hemodialysis group (10.5% vs 39.5%; p=0.004). According to PDF-induced mesothelial cell injury identified aB-crystallin as the mesothelial cell
the results of multivariate linear regression analysis, only male gender (b=20.677, 95%CI: protein most significantly and consistently counter-regulated by LiCl. In-vitro and in-
3.479 to 37.874; P=0.019) and number of US-B lines (b=0.892, 95%CI:0.071 to 1.713; vivo overexpression of aB-crystallin triggered a fibrotic phenotype and PDF-like
P=0.034) were independently associated with LVMi. upregulation of vascular endothelial growth factor (VEGF), CD31-positive cells, and
TGFb-independent activation of TGFb-regulated targets. In contrast, aB-crystallin
knock-down decreased VEGF expression and early mesothelial-to-mesenchymal
transition (MMT). LiCl reduced VEGF release and counteracted fibrosis- and
angiogenesis-associated processes. aB-crystallin in patient-derived mesothelial cells
was specifically upregulated in response to PDF and increased in peritoneal mesothelial
cells from pediatric PD patient biopsies, correlating with markers of angiogenesis and
fibrosis.
CONCLUSION: The cytoprotective effects of LiCl-supplemented PDF may be
explained by counter-regulation of PD-induced angiogenesis via the novel target aB-
crystallin. Reduction of mesothelial cell damage, peritoneal fibrosis and VEGF suggests
therapeutic potential of this intervention. Repurposing LiCl as a cytoprotective PDF
additive may offer a translatable therapeutic strategy to combat peritoneal membrane
deterioration during PD therapy. Further study of LiCl-supplemented PDF is merited
as a realistic approach to improving treatment longevity and patient outcomes during
PD treatment.

FC104 Figure: Prevalence of different types of abnormal LV geometry in patients


under hemodialysis and peritoneal dialysis.

i74 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i75–i76, 2021
10.1093/ndt/gfab126

DIALYSIS: HEART & VESSELS symptoms and adverse outcomes. Although there are medical therapies approved for
PAD, none of them has been specifically approved por PAD-ESKD. For example,
cilostazol is approved for PAD but its use is limited in PAD-ESKD patients. Surgical
interventions are challenging in these patients due to their specific vascular
FC106 HIGHER MAGNESIUM DIALYSATE CONCENTRATION calcification and show worse outcomes. Therefore, the aims of this study were to
SIGNIFICANTLY IMPROVE SURVIVAL AND CEREBRAL evaluate the effects of the investigational drug SNF472, a selective inhibitor of vascular
OUTCOME IN HD-PATIENTS WITH ATRIAL FIBRILLATION: calcification, on blood perfusion and limb functional recovery in a Vitamin D3 (VitD)-
LONG-TERM STUDY ON GERMAN NETWORK DATA induced rat model of arterial calcification and limb ischemia.
METHOD: Three consecutives daily subcutaneous (s.c) doses of VitD were
Karl August Brensing1, Anna Ochsmann1, Heyder Omran2, administered to 66 male Sprague Dawley rats to induce limb ischemia. Rats were
Gerhard Lonnemann3, Helmut Reichel4, Johannes Duttlinger5 randomized into four groups at day 5 after the start of VitD treatment (when all
1
Nierenzentrum Bonn, Dialysis Unit, Bonn, Germany, 2St. Marien Hospital Bonn, parameters were measured in a satellite group) and were treated for nine days with
Department of Cardiology, Bonn, Germany, 3Eickenhof Dialyse, Langenhagen, placebo s.c., placebo peroral (p.o.), SNF472 (40 mg/kg/day, s.c.) or cilostazol (40 mg/
Germany, 4Nephrologisches Zentrum Villingen-Schwenningen, Villingen- kg/day, p.o.). An additional control group did not receive VitD (sham) and was
Schwenningen, Germany and 5Deutsche Nierenzentren eV, WiNe Institute, Düsseldorf, administered with placebo s.c. during these last nine days. Posterior limb blood
Germany perfusion was measured using laser Doppler imaging at baseline (before calcification
induction), day 4 (before treatment start) and day 13 (end of treatment). Walking
ability was evaluated by measuring Maximum Walking Distance (MWD) and
BACKGROUND AND AIMS: Hemodialysis (HD) patients with atrial fibrillation Maximum Walking Time (MWT) using a rat treadmill at baseline, day 4 and day 11.
(AF) are at high risk for cardio-vascular events, severe bleeding and rapid vascular/ Rats were sacrificed at day 13, and heart and femoral arteries were collected for calcium
valvular calcification. Thus, higher than low standard dialysate Mg (d-Mg) may analysis.
improve outcome by less arrhythmic or calcification impact, but clinical data are RESULTS: Administration of VitD induced heart and femoral artery calcification by
missing. Our study evaluated applied d-Mg, risk-factors and antithrombotic therapies day 5. This calcification was associated with decreased limb blood perfusion and
on long-term outcome in a large representative German HD-cohort. impairment of walking ability (both MWT and MWD) compared to sham. Treatment
METHOD: We used pseudonymized benchmarking data (2013-2018) of 16226 adult with SNF472 inhibited calcification progression in femoral arteries by 41% and in heart
chronic HD patients (informed consent) from DNeV dialysis network. Diagnoses were by 56% compared to placebo. The inhibition of calcification progression by SNF472 led
coded by “International Classification of Diseases (ICD)” and drugs via “Anatomical to a 29% increase in limb blood perfusion (p< 0.001) and a significant improvement in
Therapeutical Chemical (ATC)” codes. Risk scores (Carlson Comorbidity Index=CCI, walking ability (49% in MWD and 43% in MWT; p< 0.05) compared to placebo.
CHA2DS2-VASc and HAS-BLED) were tested for de-novo outcome prediction. Calcification inhibition in femoral arteries was positively correlated with both MWD
RESULTS: At baseline, 2752 (17%) HD-patients had coded AF. CHA2DS2-VASc (4.0/ and MWT (p< 0.0001). No effects of cilostazol were observed in tissue calcification,
SD1.5) and HAS-BLED (3.2/0.9) estimated high risk for embolism/bleeding. Standard limb blood perfusion or walking ability.
dialysate-Mg (sd-Mg; 0.5 mmol/L) was used by 1317 (48%), d-Mg 0.75 had 331 (12%), CONCLUSION: SNF472 attenuates the progression of vascular calcification and
d-Mg >1.0 had 134 (5%) and 970 (35%) patients changed from 0.5 to 0.75 during the improves blood perfusion and the functional parameters MWT and MWD in a rat
study period (change group). Median study time was 2.1 yrs (Range=R: 0.01–6 yrs.). model of PAD vascular calcification. These results support investigation of SNF472 as a
Overall 6-yr mortality was high (63%; Kaplan Meier median survival of 2.9 yrs. potential therapy for PAD-ESKD patients who have vascular dysfunction due to a high
Unchanged d-Mg levels were significantly (p<0.02) related to survival: Patients on sd- degree of arterial calcification.
Mg had lower median survival (2.7 yrs.) than on 0.75 (3.1 yrs; p<0.05) or >1.0 (3.4 yrs;
p=0.02). The change group had the same survival (3.1 yrs) as the 0.75 group (p<0.03
vs. 0.5). Cox-Regression (multivariate, sd-Mg=ref.) revealed d-Mg >1.0 (hazard
ratio=HR 0.74), d-Mg 0.75 (HR 0.79), serum albumin (HR 0.93), age (HR 1.04) and FC108 BASELINE AND CORONARY ARTERY CALCIFICATION
CCI (HR 1.06) as independently related to mortality (p=0.002). Sd-Mg had higher PROGRESSION MODULATES THE RISK OF DEATH IN
(p<0.05) cerebral adverse events (5.2%) than 0.75 (1.8%) and >1.0 group (3.7%). INCIDENT TO DIALYSIS PATIENTS
Apart from dialysis-related heparin-supply four main approaches regarding anti-
coagulation were identified: No therapy, VK-OAC, Heparin or only Aspirin/ Antonio Bellasi1, Luca Di Lullo2, Domenico Russo3, Carlo Ratti4, Mario
Clopidogrel (Asp/Clop): VK-OAC and Asp/Clop had same median survival (2.8 yrs) Gennaro Cozzolino5, Biagio Raffaele Di iorio6
1
both better (p<0.001) than no therapy (1.3 yrs) or Heparin (1.6 yrs), but VK-OAC had Bergamo, Bergamo, Italy, 2Rome, Rome, Italy, 3Naples, Naples, Italy, 4Carpi, Carpi, Italy,
5
higher bleeding rates (6.4%; p<0.001) than Asp/Clop (3.5%). Cerebral adverse events Milan, Milan, Italy and 6Avellino, Avellino, Italy
(3,8% in 6 yrs) were much lower than estimated and similar for all four regimes (R: 3.9-
4.4%). BACKGROUND AND AIMS: It is estimated that Chronic Kidney Disease (CKD)
CONCLUSION: Use of higher d-Mg in HD-patients with AF significantly improved accounts for 5 to 10 million deaths annually, mainly due to cardiovascular (CV)
survival and cerebral outcome, is a feasible cost-effective approach and has more diseases. Although traditional CV risk factors are prevalent, other non-traditional CV
relative impact than well established survival risk-factors such as age, comorbidity risk factors such as vascular calcification (VC) are believed to contribute to this
(=CCI) and serum albumin. Our data warrant prospective trials comparing higher d- disproportionate CV risk burden in CKD subjects. We sought to investigate the
Mg levels with anti-thrombotic drugs and/or left atrial appendage occlusion for better association of Coronary Artery Calcification (CAC) progression with all-cause
evidence. So far, therapy of HD patients with AF should base on implementation of mortality in a cohort of patients new to hemodialysis (HD).
higher d-Mg, prefer Asp/Clop as best anti-thrombotic drugs and clearly avoid more METHOD: This is a post hoc analysis of the Independent study (NCT00710788)
harmful VK-OAC. originally designed to test the impact of 2 different phosphate binder regimens on
various hard as well as surrogate endpoint in HD subjects. A total of 412 (88.4% of the
Independent study cohort) underwent repeated CAC quantification according to the
Agatston methods at study inception as well as after 12 months of follow-up. The
square root method was used to assess CAC progression (CACP) and survival analyses
were used to check the association of CACP and all-cause mortality.
RESULTS: 412 middle age (65 years) men and women (51.2%) were considered.
FC107 SNF472 ATTENUATES THE PROGRESSION OF FEMORAL
Detectable CAC was present in about 2 out 3 patients (68.2%) at study inception. At 12
ARTERY CALCIFICATION AND RECOVERS LIMB BLOOD
months of follow-up completion, about 1 out of 3 subjects (33.1%) experience a
PERFUSION AND WALKING ABILITY IN A RAT MODEL OF
significant CACP. CACP was associated with older age and use of calcium-based
PERIPHERAL ARTERY DISEASE
phosphate binders. At study completion (median follow-up: 36 months) 106 patients
expired of all-cause. Age, diabetes mellitus, atherosclerotic CV events, baseline CAC
Firas Bassissi1, Miguel David Ferrer Reynes1,2, M. Mar Pérez1, Marc Blasco1,
extension were predictors of unfavorable outcome. Multivariable adjusted analysis
Joan Perello1,3, Carolina Salcedo1
1
confirmed an independent association of both baseline CAC (Hazard Ratio 1.29; 95%
Sanifit Therapeutics, Palma, Spain, 2University of the Balearic Islands, Grup de Nutrici
o Confidence Interval: 1.17-1.44) and CACP (HR: 5.16; 95%CI: 2.61-10.21) with all-
Comunitaria i Estrès Oxidatiu, Palma, Spain and 3University of the Balearic Islands, cause mortality. However, CACP diminished the risk associated with baseline CAC (p
Laboratori d’Investigacio en Litiasi Renal, Palma, Spain for interaction term 0.002) and use of calcium-free phosphate binders significantly
weakened the link between CACP (HR. 1.95; 95%CI: 0.92-4.16) and mortality
BACKGROUND AND AIMS: Peripheral artery disease (PAD) is a common co- CONCLUSION: Baseline CAC as well as CACP predict mortality in incident to HD
morbidity in end-stage kidney disease (ESKD) patients undergoing dialysis. The individuals. Nevertheless, CACP mitigates the risk associated with baseline CAC and
prominent vascular calcification in these patients is associated with severity of

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

calcium-free phosphate binders attenuates the association of CACP and mortality, vasculopathy during PD, i.e. disruption of endothelial cell junctions and cytoskeleton
suggesting that CACP modulation may impact survival in this population and induction of apoptosis.

FC109 GLUCOSE DERIVATIVE INDUCED VASCULOPATHY IN FC110 PTH INDCUED ENDMT VIA MIR-29A-5P/GSAP/NOTCH1
CHILDREN ON PERITONEAL DIALYSIS PATHWAY CONTRIBUTED TO VALVULAR CALCIFICATION IN
RATS WITH CKD
Maria Bartosova1, Betti Schaefer1, Conghui Zhang1, Rebecca Herzog2,
David Ridinger3, Ivan Damgov1, Eszter Lévai1,4,5, Iva Marinovic1, Liting Wang1, Yuxia Zhang1, Rining Tang1
Christoph Eckert6, Philipp Romero7, Peter Sallay4, Akos Ujszaszi8, 1
Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine
Markus Unterwurzacher2, Anja Wagner2, Georg Hildenbrand3, Bradley Warady9,
Franz Schaefer1, Sotirios G. Zarogiannis1,10, Klaus Kratochwill2, Claus Schmitt1
1
BACKGROUND AND AIMS: Endothelial-to-mesenchymal transition (EndMT) of
University of Heidelberg, Center of Pediatric and Adolescent Medicine, Heidelberg, valvular endothelial cells is the common pathophysiology of valvular calcification (VC)
Germany, 2Medical University of Vienna, Department of Pediatrics and Adolescent among the patients of non-chronic kidney disease (CKD). However, there are few
Medicine, Vienna, Austria, 3Heidelberg University, Kirchhoff Institute for Physics, studies of valvular calcification in CKD. In our previous work, parathyroid hormone
Heidelberg, Germany, 4Semmelweis University, 1st Department of Pediatrics, Budapest, (PTH) was considered as an important player of EndMT in vascular diseases.
Hungary, 5MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary, Meanwhile, the increasing serum level of PTH in CKD patients is closely related to VC,
6
University of Heidelberg, Institute of Pathology, Heidelberg, Germany, 7University of so whether PTH could induce valvular EndMT and the mechanism involved are
Heidelberg, Department of General, Visceral and Transplantation Surgery, Heidelberg, worthy of further study.
Germany, 8University of Heidelberg, Division of Nephrology, Heidelberg, Germany, METHOD: 5/6 nephroectomy (5/6Nx) with high phosphorus diet was used to
9
Childrens Mercy Kansas City, Kansas City, United States of America and 10University of construct a VC model in rats with CKD. miRNA sequencing was used to find the
Thessaly, Department of Physiology, Larissa, Greece changes of miRNA in human umbilical vein endothelial cells (HUVECs) intervened by
PTH. The expression levels of miR-29a-5p, markers of EndMT and Notch1 pathway
BACKGROUND AND AIMS: Patients with chronic kidney disease patients (CKD) were determined by PCR, western blot and immunofluorescence. The activity of c-
have an exceedingly high cardiovascular risk. While vasculopathy is further accelerated secretase was determined by ELISA. VC was observed by VonKossa staining and
during peritoneal dialysis (PD), the pathophysiological role of reactive metabolites scanning electron microscope.
such as glucose degradation products (GDP) is uncertain. RESULTS: Firstly, we found PTH could induce valvular EndMT in VC among the rat
METHOD: Omental and parietal peritoneal tissues from 100 non-CKD individuals, with CKD, and VC could be alleviated by cinacalcet. As for the contribution of PTH on
107 children with CKD5, 60 children treated with neutral pH, low GDP, and 30 EndMT, in vitro, global microRNA(miRNA) expression profiling of HUVECs was
children treated with acidic pH, high GDP PD fluids underwent standardized digital examined in PTH versus control and miR-29a-5p was identified as the miRNA that
histomorphometry. Omental arterioles localized within the fat tissue, protected from was most notably decreased under PTH stimulation, which could be resumed by
direct PD fluid exposure were microdissected for multi-omics analysis. Key regulated PTHrP(7-34) (PTHR1 inhibitor). Overexpressing miR-29a-5p could inhibit PTH-
pathways were validated by quantitative immunostaining, with localization microscopy induced EndMT in vitro and valvular EndMT in vivo. The dual luciferase assay was
in peritoneal tissues of matched cohorts and in vitro in human umbilical vein verified that c-secretase activating protein (GASP) is the target of miR-29a-5p. miR-
endothelial cells. 29a-5p-mimics, si-GSAP and DAPT (c-secretase inhibitor) could inhibit PTH-induced
RESULTS: Arterioles from children with CKD5 exhibited reduced lumen to vessel c-secretase activation thus blocking Notch1 pathway activation to inhibit PTH-
ratio (L/V) and reduced endothelial telomere length compared to non-CKD induced EndMT in vitro. In vivo, Notch1 pathway activation was observed in VC
individuals; gene ontology analysis identified enrichment of arteriolar genes associated among the rats with CKD. Blocking Notch1 pathway activation by AAV-miR-29a and
with nuclear telomere cap complex and focal adhesion. Pathway analysis of arteriolar DAPT could inhibit vavular EndMT in rats with CKD. In addition, blocking Notch1
cross-omics identified top canonical pathways including telomere extension by pathway activation could also alleviate VC among the rats with CKD.
telomerase, actin cytoskeleton, integrin and tight junction signalling. CONCLUSION: PTH could activate valvular EndMT via miR-29a-5p/GSAP./Notch1
Peritoneal vasculopathy progressed with PD vintage and was more pronounced with pathway, and that could contributed to VC in rats with CKD.
high versus low GDP exposure (p<0.001). Compared to CKD5, low GDP-PD
upregulated 145/110 and downregulated 38/34 arteriolar genes/proteins, high GDP-PD
upregulated 684/137 and supressed 1560/55 genes/proteins (p<0.01). High GDP
milieu induced upregulation of arteriolar genes involved in cell death/apoptosis and
suppressed genes related to cell viability/survival, cytoskeleton organization and
immune response biofunctions. Vasculopathy associated canonical pathways
concordantly regulated on arteriolar gene and protein level with high GDP exposure
included cell death/proliferation, apoptosis, cytoskeleton organization, metabolism and
detoxification, cell junction signalling, and immune response.
Quantitative validation in PD cohorts with similar PD vintage, dialytic glucose
exposure and age (n=15 / group) verified increased proapoptotic activity and
cytoskeleton disintegration with high-GDP exposure; single-molecule-localization
microscopy demonstrated arteriolar endothelial zonula occludens-1 (ZO-1) disruption.
Absolute and relative to endoluminal surface length, arteriolar endothelial cell counts
were inversely correlated with GDP exposure, with apoptosis marker caspase-3, TGF-ß
induced pSMAD2/3, interleukin-6, ZO-1 protein abundance and the degree of
vasculopathy. In vitro, exposure to GDP 3,4-dideoxyglucosone-3-ene dose-
dependently reduced nuclear endothelial lamin-A/C and membrane ZO-1 assembly.
Transendothelial electrical resistance was decreased. ZO-1 and sealing tight junction
claudin-5 protein abundance were decreased in cells after incubation with high GDP
compared to low GDP PD fluid and culture media. On nanoscale level GDP reduced
junction cluster formation in the membrane area.
CONCLUSION: Multi-omics analysis of omental arterioles from children without pre-
existing vasculopathy and life-style related confounders identified key mechanisms of
vascular aging in CKD5 and the major contribution of GDP to accelerated

i76 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i77–i78, 2021
10.1093/ndt/gfab129

DIALYSIS: QUALITY OF LIFE

FC112 HEALTH-RELATED QUALITY OF LIFE (HRQOL) AND


FC111 THE SOCIETAL IMPACT OF DELAYED DIALYSIS INITIATION SYMPTOM BURDEN BEFORE AND AFTER START OF
ASSOCIATED WITH DAPAGLIFLOZIN BASED ON THE DIALYSIS IN OLDER PATIENTS
RESULTS OF DAPA-CKD
Esther De Rooij1,2, Yvette Meuleman1, Johan W. De Fijter2, Kitty J. Jager3,
Phil McEwan1, Oliver Darlington1, Rebecca Boyce1, Hiddo Lambers Heerspink2,3, Nicholas Chesnaye3, Marie Evans4, Fergus Caskey5, Claudia Torino6,
David C. Wheeler2,4, Juan Jose Garcia Sanchez5 Maciej Szymczak7, Christiane Drechsler8, Christoph Wanner8, Friedo W. Dekker1,
1
Health Economics and Outcomes Research Ltd, Cardiff, United Kingdom, 2George Ellen Hoogeveen1,2,9
Institute for Global Health, George Institute, Camperdown, Sydney, Australia, , 1
Leiden University Medical Center (LUMC), Clinical Epidemiology, Leiden, The
3
University of Groningen, Department of Clinical Pharmacy and Pharmacology, Netherlands, 2Leiden University Medical Center (LUMC), Nephrology, Leiden, The
University Medical Center Groningen, Groningen, The Netherlands, 4University College Netherlands, 3Amsterdam UMC, locatie AMC, Medical Informatics, Amsterdam, The
London, Department of Renal Medicine, London, United Kingdom and 5AstraZeneca, Netherlands, 4Karolinska Institutet, Clinical Science, Intervention and Technology,
Milton, United Kingdom Huddinge, Sweden, 5Bristol Medical School, Population Health Sciences, Bristol, United
Kingdom, 6CNR-IFC, Clinical Epidemiology and Pathophysiology of Renal Diseases and
BACKGROUND AND AIMS: Chronic kidney disease (CKD) continues to be a Hypertension & G.O.M., Reggio Calabria, , 7Wroclaw Medical University, Nephrology and
growing health concern worldwide, with an estimated global prevalence of 9.1% in Transplantation Medicine, Wrocław, Poland, 8University Hospital Würzburg,
2017. End-stage kidney disease (ESKD) is commonly treated with dialysis and is Nephrology, Würzburg, Germany and 9Jeroen Bosch Ziekenhuis, Nephrology, ’s-
associated with a significant societal and economic impact. Approximately 34 – 45% of Hertogenbosch, The Netherlands
employed CKD patients will leave employment by the time of dialysis initiation. As
such, there could be significant benefits associated with delaying onset of dialysis. BACKGROUND AND AIMS: The number of older (65y) people with ESKD
Current treatment for CKD consists of ACE-inhibitors and Angiotensin Receptor starting chronic dialysis increased substantially the past decade because of ageing of the
Blockers, which delay kidney replacement therapy by approximately 6 months. DAPA- population due to improved health care. In addition, older age is no longer a
CKD is a randomised, double-blind, placebo-controlled trial in which patients with contraindication for dialysis. Finally, older individuals are more often ineligible for
estimated glomerular filtration rate (eGFR) between 25-75mL/min/1.73m2 and kidney transplantation. Many older people with stage 5 CKD non-dialysis have a low
elevated urinary albumin excretion were assigned to dapagliflozin or placebo in health-related quality of life (HRQOL) and high symptom burden. In this group,
addition to standard of care. The trial ended prematurely due to overwhelming efficacy improving HRQOL and lowering symptom burden may be deemed more important
and showed a 36% reduction in the incidence of ESKD for patients treated with than solely the prolongation of life. Little is known about the effect of dialysis treatment
dapagliflozin. This analysis of the DAPA-CKD study data aimed to look at the societal on HRQOL and symptom burden. Therefore, we investigated the evolution of HRQOL
benefit of delaying initiation of dialysis based on outcomes observed in DAPA-CKD. and symptoms before and after the start of dialysis in older ESKD patients.
METHOD: The incidence of ESKD was predicted for patients treated with METHOD: The European Quality (EQUAL) study is an ongoing European
dapagliflozin compared to placebo over a 10-year time horizon using data from DAPA- prospective multi-center follow-up study in late stage 4/5 CKD patients aged 65
CKD. Parametric survival models were derived from trial results and extrapolated, with years. For the present analyses, we included all patients who started dialysis. HRQOL
Weibull distributions fitted for the incidence of ESKD and mortality. The mean time to was assessed every 3-6 months using the RAND-36 questionnaire, resulting in a
ESKD was estimated for patients treated with dapagliflozin in addition to standard of physical component summary (PCS) and a mental component summary (MCS) score.
care or standard of care alone, and 62% of patients reaching ESKD were assumed to be Component scores ranged from 0-100 with higher scores indicating a better HRQOL.
treated with dialysis, based on results of the DAPA-CKD clinical trial. The benefit of Kidney disease-related symptom burden was assessed every 3-6 months using the
delaying dialysis initiation from a societal perspective was calculated using the average dialysis symptom index (DSI). The sum score for symptom number ranged from 0 to
annual salary in the US and the proportion of working time lost due to dialysis. Inputs 30 and for symptom severity from 0 to 150, with higher scores indicating a higher
were derived based on published US data, and costs were discounted at 3% per annum. symptom burden. We used linear mixed models (LMM) to explore the evolution of
RESULTS: Treatment with dapagliflozin was estimated to delay the mean time to mental and physical HRQOL, symptom number and symptom severity during the year
ESKD by approximately 2 years when compared to placebo. Patients in the placebo preceding and following dialysis initiation.
arm progressed to ESKD at a mean time of 7.8 years, compared to a mean time of 9.9 RESULTS: In total, 571 older dialysis patients were included. At baseline (dialysis
years in the dapagliflozin arm, without adjustment for patient survival. Over a 10-year initiation), mean (SD) age was 76 (6) years, 74% were men, 47% had diabetes, 9% were
time horizon, a cohort of 5,000 patients treated with dapagliflozin in addition to current smokers, 34% had cardiovascular disease and the mean (SD) residual kidney
standard of care were estimated to experience 2,508 ESKD events, a reduction of 519 function was 8.6 (4.4) ml/min/1.73m2. Mean (SD) MSC was 55 (23), PSC was 43 (21),
events in comparison with standard of care alone. Additionally, treatment with and the number of symptoms was 15 (7) with a symptom severity of 88 (18). Overall,
dapagliflozin in addition to standard of care was estimated to prevent 198 renal deaths
compared to treatment with standard of care alone. Delays in dialysis initiation
associated with dapagliflozin treatment was estimated to translate to 10-year reduction
in societal costs of $29.2 million per 5,000 treated patients in a cohort of CKD patients
eligible for treatment with dapagliflozin.
CONCLUSION: Dapagliflozin is associated with a significant reduction in the mean
time to ESKD, therefore delaying the onset of dialysis initiation. In addition to
improving patient outcomes, this delay in progression to ESKD could have notable
economic benefits from a societal perspective.

FC111 Figure: Cumulative incidence and societal costs associated with dialysis

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

LMM showed that in the year preceding dialysis MCS decreased by 15.7 (95% CI: 11.9
to 19.5), PCS decreased by 12.0 (8.2 to 15.7), symptom number increased by 3.5 (2.5 to
4.6) and symptom severity increased by 5.3 (1.8 to 8.8). In the year following dialysis,
MCS increased by 1.9 (-2.7 to 6.5), PCS decreased by 2.1 (-6.9 to 2.8), symptom num-
ber decreased by 0.9 (-0.3 to 2.1) and symptom severity decreased by 7.6 (2.8 to 12.4).
CONCLUSION: Both mental and physical HRQOL, as well as symptom number and
severity, worsened considerably during the year preceding dialysis, but stabilized after
dialysis initiation. These results could aid nephrologists in informing older ESKD
patients who consider starting dialysis and improve the shared decision making
process.

FC113 UTILITY OF A SINGLE ITCH-RELATED QUESTION AND THE


SKINDEX-10 QUESTIONNAIRE FOR ASSESSING PRURITUS
AND PREDICTING HEALTH RELATED QUALITY OF LIFE IN
HEMODIALYSIS PATIENTS

Marcelo Lopes1, Angelo Karaboyas1, Kazuhiko Tsuruya2, Issa Al Salmi3,


Nidhi Sukul4, Elham Asgari5, Anas Alyousef6, Schaufler Thilo7,
Sebastian Walpen7, Frederique Menzaghi8, Ronald Pisoni1
1
Arbor Research Collaborative for Health, Ann Arbor, United States of America, 2Kyushu
University Hospital, Department of Integrated Therapy for Chronic Kidney Disease,
Fukuoka, Japan, 3The Royal Hospital, Muscat, Oman, 4University of Michigan,
Department of Internal Medicine, Division of Nephrology, Ann Arbor, United States of
America, 5Guy’s and St Thomas, Department of Nephrology, London, United Kingdom,
6
Farwaniya Hospital, Division of Nephrology, Kuwait, Kuwait, 7Vifor Pharma, Meyrin,
Switzerland and 8Cara Therapeutics Inc, Stamford, United States of America

BACKGROUND AND AIMS: Chronic kidney disease-associated pruritus (CKD-aP) FC114 LUNG ULTRASOUND-GUIDED ULTRAFILTRATION IN
has been linked with comorbid conditions, and poorer mental and physical health-related HAEMODIALYSIS PATIENTS REDUCES THE RISK OF
quality-of-life (HR-QOL) in hemodialysis (HD) patients. The Skindex-10 questionnaire DIALYSIS HYPOTENSION
and a single itch-related question from the KDQOL-36 have been used to evaluate the
impact of pruritus in HD patients. In this analysis, we investigated the performance of the Claudia Torino1, Rocco Tripepi1, Giovanni Luigi Tripepi1, Francesca Mallamaci1,2,
single question and the Skindex-10 as predictors of HR-QOL in HD patients. Carmine Zoccali3, on behalf of the LUST Working Group4
METHOD: We analyzed data from 4940 HD patients from 17 countries enrolled 1
National Research Council, Institute of Clinical Physiology, Reggio Calabria, Italy,
during year 2 of phase 5 of the Dialysis Outcomes and Practice Patterns Study 2
GOM Bianchi-Melacrino-Morelli, Nephrology Unit, Reggio Calabria, Italy, 3Associazione
(DOPPS, 2013): Belgium, Canada, Germany, the Gulf Cooperation Council (GCC)
Ipertensione Nefrologia e Trapianto Renale (IPNET), Reggio Calabria, Italy and 4LUST
(Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates), Italy, Japan,
Working Group
Russia, Spain, Sweden, Turkey, the UK, and the US. The Skindex-10 scores were
calculated as per Mathur et al. (2010): responses to each of the 10 questions (0-6 scale),
pertaining to how often patients were bothered by itchy skin in the past week, were BACKGROUND AND AIMS: Lung ultrasound (US) is a reliable method for the
summed to create a total summary score (range 0-60, with 0 indicating not at all identification of patients with lung congestion in the hemodialysis population (JACC
bothered) and 3 subdomain scores [i.e., itching (disease) and its impact on mood/ Cardiovascular Imaging 2010;3:586-94) and a high number of US-B lines (an
emotional and social functioning]. The itch-related single question from the KDQOL- equivalent of B lines in the chest X-ray) is a powerful predictor of death and
36 asked: “During the past 4 weeks, to what extent were you bothered by itchy skin?” cardiovascular events in this population (JASN 24:639–646, 2013.) .US-B lines are
with response options including “not at all, somewhat, moderately, very much, strongly related with the Left Ventricular filling pressure (capillary wedge pressure)
extremely”. Itch-related measures were collected concurrently with HR-QOL and may also be potentially useful for the identification of patients with low blood
measures: Physical (PCS) and Mental (MCS) Component Summary scores, derived volume at risk for dialysis hypotension. With this background in mind, in the frame of
from the SF-12. We calculated the Spearman correlation coefficient between the the “LUng water by Ultra-Sound Guided Treatment (LUST) to Prevent Death and
Skindex-10 (total score and for each of its 3 domains) and the single question. We Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy
used separate linear regression models to evaluate the predictive power of 1) the Trial” (NCT02310061) we investigated, as a secondary study end-point, whether the
Skindex-10 score, 2) the single itch question, and 3) both, on PCS and MCS outcomes, systematic use of lung US may mitigate the risk of dialysis hypotension.
based on R-squared values. METHOD: We included in this analysis 377 HD patients. In patients in the active arm
RESULTS: Skindex-10 scores varied across countries; the proportion of patients with a of the trial (n=197) dialysis ultrafiltration prescription was guided by lung US while in
very high Skindex-10 score (50) ranged from 12% in the GCC to only 2% in Italy, the control arm (n=180) ultrafiltration was prescribed on the basis of standard clinical
Russia and Sweden. Across all countries, 55% had a Skindex-10 score=0. For the single criteria. The duration of the trial was 2 years. Hypotensive episodes during dialysis
pruritus question, 37% answered that they were not at all bothered while 16% were very were pre-defined as a reduction in mean arterial pressure of >20%, associated with
much or extremely bothered by itchy skin. The correlation between the single question typical symptoms (light-headedness, sweating, nausea and/or vomiting). Incident rate
and Skindex-10 was 0.71 overall, 0.72 for the disease domain, 0.62 for the social domain, was expressed as number of hypotensive episodes/patient/year. Negative binomial
and 0.70 for the emotional domain. Patient characteristics were similar across categories regression (Biometrics. 2014;70:920-31) was applied to analyse the association between
of both pruritus measures. Regression analyses showed that every 10 points higher in the US-B lines and the incidence rate of dialysis hypotension. Since a high degree of lung
Skindex-10 score was associated with 1.2 point lower PCS (95% CI: -1.4, -0.9) and 1.5 congestion and/or a high variability in lung congestion over time may predispose to
point lower MCS (95% CI: -1.7, -1.3) scores. Similarly, the single question showed dialysis hypotension, in the active arm we also tested the relationship between the
increasingly poorer PCS and MCS scores with a greater degree of being bothered by average number of US-B lines and the standard deviation (SD) of the same parameter
pruritus: compared with patients not at all bothered by itchy skin, patients who were across the trial (2733 pre-dialysis lung US recordings) and the risk of dialysis
moderately bothered had 4.8 point lower PCS (-5.7, -3.9) and 4.3 point lower MCS (-5.3, - hypotension.
3.3) scores. The R-squared for PCS was 0.065 when using the single question and only RESULTS: During the trial, 890 hypotensive episodes occurred in the active arm and
0.033 when using the Skindex-10 as the predictor. R-squared was also higher for MCS 1292 in the control arm. The corresponding incidence rates were 3.15/patient/yr and
when using the single question (0.056) vs. Skindex-10 (0.052). When including both 4.73/patient/yr, respectively, with an Incident Risk Ratio of 0.66 (95% CI: 0.61-0.72,
pruritus measures, the predictive power for PCS did not improve compared to the single P<0.001) underlying a 34% reduction in the risk of this outcome. In the active arm, the
question (R2=0.065), while increasing only slightly (R2=0.063) for MCS. degree of lung congestion across the trial (average number of US-B lines) was positively
CONCLUSION: The single KDQOL-36 question about the extent bothered by itchy associated with a higher risk of dialysis hypotension because for each US-B line there
skin over the past 4 weeks was highly correlated with the Skindex-10 score and at least was a 6% excess (95%CI: 1%-12%, P=0.02) risk of the same outcome. The variability of
as predictive – if not more – of key HR-QOL measures as the Skindex-10. In daily US-B lines (SD) did not significantly associate with the risk of dialysis hypotension
clinical practice, utilizing 1 simple question about the extent patients are bothered by (P=0.09).
itchy skin can be a feasible and efficient way for routine assessment of pruritus to better CONCLUSION: Findings in this study show that lung US is a safe method to guide the
identify HD patients with not only CKD-aP but also poorer HR-QoL. prescription of dialysis ultrafiltration. Indeed, the systematic application of this
technique reduced the risk of dialysis hypotension by the 34%. The finding in the active
arm of the trial that a higher number of US-B lines underlies an excess risk of dialysis
hypotension suggests that special care should be applied to tailor ultrafiltration in
patients with lung congestion to minimize the risk of this outcome.

i78 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i79–i81, 2021
10.1093/ndt/gfab127

DIALYSIS: NUTRITION & OUTCOMES

RESULTS: We enrolled 353,142 patients. The average age was 62.7 years, 58% were
FC115 HIGHER VARIABILITY OF SERUM PHOSPHATE IS male, 64% were diabetic. Baseline P was 4.98 mg/dL, median serum P CV was 0.19.
ASSOCIATED WITH INCREASED MORTALITY RISK ONLY Baseline Alb was 3.61 g/dL. While we studied the joint effect of P variability with Alb
WHEN ASSOCIATED WITH HYPOALBUMINEMIA on outcome, the association between P variability and outcomes appeared to be
predominant in patients with low serum Alb levels (Fig. 1).
Karlien Ter Meulen1,2, Xiaoling (Janice) Ye3, Len A. Usvyat4, CONCLUSION: Higher P variability is associated with adverse outcomes but
Frank Van Der Sande2, Constantijn Konings1, Peter Kotanko3,5, Jeroen Kooman2, predominantly in patients with hypoalbuminemia. This suggests a major role for
Frank Maddux4 malnutrition and/or inflammation as explanatory factors for the association between P
1
Catharina Ziekenhuis, Department of Internal Medicine, Division of Nephrology, variability in outcome. A high P variability in this patient group can be interpreted as
Eindhoven, The Netherlands, 2Maastricht University Medical Center, Department of an additional risk factor. When studying the relation between the variability of a single
Internal Medicine, Division of Nephrology, Maastricht, The Netherlands, 3Renal parameter with outcome, the possible underlying role of “third factors” should be
Research Institute, New york, United States of America, 4Global Medical Office, Fresenius explored, for which the methodology used in this abstract might provide an example.
Medical Care, Waltham, United States of America and 5Icahn School of Medicine at
Mount Sinai Hospital, New York, United States of America

BACKGROUND AND AIMS: Both hypophosphatemia and hypoalbuminemia are


established risk factors for mortality in hemodialysis (HD) patients. Evidence indicates FC116 WEIGHT CHANGE AS A PREDICTOR OF MORTALITY IN
that higher variability of serum phosphate (P) is associated with higher risk of CHRONIC HEMODIALYSIS PATIENTS
mortality. However, little is known about to what extent of this association is
influenced by other risk factors, most importantly nutritional or inflammatory state. Takuhiro Moromizato1,2, Kunitoshi Iseki3,4
1
The aim of this study was to analyze the variability of serum P with all-cause mortality Okinawa Prefectural Nanbu Medical Center & Children’s Medical Center, Renal and
taking into account the interaction with the levels of albumin (Alb) Rheumatology Division, Internal Medicine Department, Shimajiri-gun, Okinawa
METHOD: All adult incident HD patients treated in Fresenius Medical Care North Prefecture, Japan, 2Osaka University, Public Health Graduate School of Medicine, Suita,
America (FMCNA) clinics between 01/2010 and 10/2018 were included. Serum P and Osaka, Japan, 3Nakamura Clinic, Clinical Research Support Center, Urasoe, Okinawa,
Alb levels were averaged from month 1 to 6 after the start of dialysis (baseline). Japan and 4Okinawa Heart and Renal Association, Naha, Japan
Baseline variability of P was described by coefficient of variation (CV). All-cause
mortality was recorded between months 7 and 18. Cox proportional hazards models BACKGROUND AND AIMS: Serial decrease in body weight can be a prognostic
with spline terms were applied to explore the association between variability of P and marker reflecting Protein Energy Wasting (PEW) condition in haemodialysis patients.
Alb and all-cause mortality. Additionally, tensor product smoothing splines were However, the impact of longitudinal body weight changes on mortality have rarely
computed to study the interactions of Alb and P variability and their associations with been evaluated. Therefore, we applied landmark analysis and time-scale mixed
outcomes respectively. regression analyses to clarify the impact of long-term changes in body weight on all-
cause mortality.
METHOD: This study is a post-hoc analysis of the participants in the Olmesartan
Clinical Trial in Okinawan Patients Under OKIDS (OCTOPUS) conducted between
June 2006 and June 2011. We additionally followed up with the participants until 31
July, 2018. During the OCTOPUS trial, the body weight of surviving participants was
repeatedly measured every 6 months. The primary aim of the study was to clarify the
association of serial change in body weights and all-cause mortality. The participants
were categorized into 4 groups based on weight change slope during the first 2 years
(bottom to highest group correspond with the first quartile to the fourth quartile
group). We conducted a landmark analysis to evaluate the influence of weight change
slope on the subsequent survival with Cox-proportional hazard regression. We also
conducted time-scale multilevel regression analyses to draw marginal plots of body
weight with a backward time scale to describe the difference in trajectories of body
weight between deceased and surviving patients.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC116 Figure 1a: Landmark analysis with Kaplan Meier plots showing the adjusted time-scale multilevel regression model, which included all 461 participants,
association of weight change slope and all-cause mortality with a backward time-scale, showed that body weight constantly decreased in deceased
patients, while body weight was longitudinally stable in surviving patients (Fig 1b).
These trends of weight change have been soundly observed in sensitivity analyses.
CONCLUSION: In chronic haemodialysis patients, the higher rate of body weight loss,
such as a decrease in body weight by 1 kg (1.7%) per 6 months, was significantly
associated with higher mortality. Persistent loss of body weight is a significant
predictor of death among chronic dialysis patients.

FC117 TIME TRENDS IN PROBABILITY OF STARTING HOME


DIALYSIS OVER A 20 YEAR PERIOD: A DUTCH REGISTRY
STUDY

Anna Bonenkamp1, Tiny Hoekstra1,2, Marc Hemmelder2,3, Anita Van Eck van der
Sluijs4, Alferso C. Abrahams4, Frans J. Van Ittersum1, Brigit Van Jaarsveld1
1
Amsterdam UMC, locatie VUmc, Nephrology, Amsterdam, The Netherlands, 2Dutch
Renal Registry (RENINE), Nefrovisie Foundation, The Netherlands, 3Mumc+, Nephrology,
Maastricht, The Netherlands and 4UMC Utrecht, Nephrology, Utrecht, The Netherlands

BACKGROUND AND AIMS: A growing number of patients suffers from End Stage
Kidney Disease(ESKD), causing a logistical and economic burden to the healthcare
FC116 Figure 1b: Marginal plots of time-scale mixed regression estimates of body system. Utilization of home dialysis is low in many countries worldwide, although
weight with a backward time scale for deceased and non-deceased patients home dialysis has several advantages including higher quality of life and possibly lower
costs. The aim of this study is to explore time trends in the use of home dialysis in the
Netherlands.
RESULTS: Out of 461 patients in the cohort, 404 participants were analysed in the METHOD: Anonymized registry data from the Dutch Renal Registry (RENINE) were
landmark analysis. Of the participants, 168 (41.6%) were deceased, and 236 used for this study. All dialysis episodes of adult patients who started dialysis treatment
participants (58.4%) survived. Although baseline body weights and indices about body between 1997 through 2016 in the Netherlands were included, including those who
components such as a creatinine index were similar among the 4 groups, multivariate previously underwent kidney transplantation. Dialysis episodes shorter than 90 days
Cox-proportional hazard regression showed that the higher rate of body weight loss were excluded. The probability of starting home dialysis between 1997 through 2016
was associated with higher mortality. Hazard ratios were 2.02 (1.28–3.20), 1.77 (1.10– was evaluated in time periods of 5 years, using logistic regression analysis. Home
2.85), 1.00 (Reference), and 1.11 (0.67–1.83) for first quartile, second quartile, third dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer
quartile (Reference), and fourth quartile group, respectively (P for trend was <0.001). to either within 2 years after dialysis start. A logistic multilevel model was used to
The association was also described using Kaplan-Meier plots, with the P-value of adjust for clustering at patient level. The cumulative incidence function of start of
general Log-rank test being 0.015 (Fig 1a). Marginal plots drawn with a multivariate home dialysis in incident patients was estimated with a competing risk model with
recovery of kidney function, kidney transplantations, and all-cause mortality as

i80 | Abstracts
Nephrology Dialysis Transplantation Abstracts
competing events. All analyses were stratified for age categories at dialysis start: 20-44 analysis. Dialysis withdrawal was an increasingly common cause of death, increasing
years, 45-64 years, 65-74 years and 75 years. from 13.5% in 2000 to 31.2% in 2019 (22.1% overall). In multivariable analysis,
RESULTS: A total of 33,340 dialysis episodes in 31,569 patients were evaluated. increasing age, female sex, increasing dialysis vintage, haemodialysis as treatment
Between 1997 and 2016, mean age at start of dialysis treatment increased from modality, and year of death were independent factors associated with death by dialysis
62.5614.0 to 65.5614.5 years in in-centre haemodialysis patients, whereas it increased withdrawal. Centre variation was large, even after correction for confounding factors
from 51.9615.1 to 62.5614.6 years in home dialysis patients. In patients < 65 years, (36.6% outside 95% control limits).
the probability of starting home dialysis was significantly lower during each 5-year CONCLUSION: Treatment withdrawal has become the main cause of death in the
period compared to the previous period, and kidney transplantation occurred more Netherlands among dialysis-dependent patients during 2000-2020. Large practice
often. In patients  65 years, incidence of home dialysis remained constant, whereas variations were observed between centres, even after correction for confounding
mortality decreased. factors. These findings emphasize the need for timely advance care planning and urge
CONCLUSION: In patients < 65 years, the overall probability of starting home treating health care professionals to better inform their patients when choosing to start
dialysis declined consistently over the past 20 years. The age of home dialysis patients dialysis or not.
increased more rapidly than that of in-centre dialysis patients, implying that pre-
dialysis education and organization of home dialysis must be adapted to the needs of
the elderly patient. These developments have a significant impact on the organisation
of home dialysis for patients with ESKD.

FC118 DIALYSIS WITHDRAWAL IN THE NETHERLANDS BETWEEN


2000-2020: TIME TRENDS AND CENTRE VARIATION

Mathijs Van Oevelen1, Alferso C. Abrahams2, Willem Jan W. Bos1,3,


Tiny Hoekstra4,5, Marjolijn Van Buren1,6
1
Leiden University Medical Center (LUMC), Internal Medicine, Leiden, The Netherlands,
2
University Medical Center Utrecht, Department of Nephrology and Hypertension,
Utrecht, The Netherlands, 3St. Antonius Hospital, Department of Internal Medicine,
Nieuwegein, The Netherlands, 4Stichting Nefrovisie, Utrecht, The Netherlands,
5
Amsterdam UMC, locatie VUmc, Department of Nephrology, Amsterdam, The
Netherlands and 6Haga Hospital, Department of Nephrology, Den Haag, The FC118 Figure 1: Causes of death (grouped) per calendar year of death
Netherlands Proportion of each cause of death per calendar year, unadjusted data.

BACKGROUND AND AIMS: Treatment withdrawal is an important cause of death


among dialysis-dependent patients. Widely variable withdrawal rates were reported in
studies using varying designs and definitions in culturally different regions of the
world, limiting comparability of individual studies. Cessation of life-prolonging
treatment is a well-accepted option in the Netherlands, however it is unclear if these
premises result in higher dialysis withdrawal rates and if this effect is generalisable.
This study aims to describe dialysis withdrawal practice in the Netherlands, focussing
on time trends and practice variation between centres.
METHOD: Patient data was retrieved from RENINE, the Dutch national registration
which includes nearly all patients requiring dialysis for at least 28 days. All patients
who initiated maintenance dialysis from January 1, 2000, to December 31, 2020, and
died within this period were included for analysis. Since the primary aim of this study
concerned cause of death on dialysis, data of patients in whom dialysis was stopped due
to kidney transplantation or recovery of kidney function, were excluded. Main
outcome was death by dialysis withdrawal, as registered by the treating physician using
ERA-EDTA codes. Other causes of death were used as comparison. Time trends for
dialysis withdrawal were first analysed as unadjusted data (proportion per year).
Univariable logistic regression analyses were then used to identify factors associated
with dialysis withdrawal, including year of death in five-year strata. A multivariable
model was subsequently used to determine risks, adjusting for factors associated with
dialysis withdrawal. Centre variation was compared visually by using funnel plots. FC118 Figure 2: Funnel plots for dialysis withdrawal variance between centres
RESULTS: A total of 34.692 patients commenced maintenance dialysis of which Each dot represents one participating centre. Data shown is dialysis withdrawal as a
20.389 died. After applying exclusion criteria, a cohort of 18.412 patients was used for percentage of total causes of death, adjusted for age, sex, dialysis vintage, modality, and
year of death. The horizontal solid line represents the mean (22.1%), dotted lines
represent 95% control limits.

10.1093/ndt/gfab127 | i81
Nephrology Dialysis Transplantation 36 (Supplement 1): i82–i84, 2021
10.1093/ndt/gfab146

TRANSPLANTATION & NEW TECHNOLOGIES

FC120 MAGNETIC RESONANCE IMAGING TEXTURE ANALYSIS


FC119 SURVIVAL BENEFIT OF KIDNEY TRANSPLANTATION PREDICTS INTERSTITIAL FIBROSIS / TUBULAR ATROPHY IN
COMPARED TO REMAINING ON WAITLIST ACROSS TRANSPLANTED KIDNEYS: A SINGLE CENTER CROSS-
DIFFERENT AGES OF TRANSPLANT CANDIDATES: A SECTIONAL STUDY
RETROSPECTIVE COHORT STUDY USING TARGET TRIAL
EMULATION Francesco Fontana1, Filippo Monelli2, Alessia Piccinini3, Giulia Besutti4,
Valeria Trojani5, Guido Ligabue6, Gaetano Alfano1,3, Gianni Cappelli1,3
Christine Wallisch1, Susanne Strohmaier1,2, Michael Kammer1,3, Georg Heinze1, 1
Azienda Ospedaliero-Universitaria di Modena, Nephrology and Dialysis Unit, Modena,
Rainer Oberbauer3, Maria C. Haller1,4 Italy, 2University of Modena and Reggio Emilia, Clinical and experimental medicine
1
Medical University of Vienna, Center for Medical Statistics, Informatics and Intelligent PhD program, Italy, 3University of Modena and Reggio Emilia, Surgical, Medical and
Systems, Section for Clinical Biometrics, Wien, Austria, 2Medical University of Vienna, Dental department of Morphological Sciences, Italy, 4AUSL-IRCCS di Reggio Emilia,
Center for Public Health, Department of Epidemiology, Wien, Austria, 3Medical Department of Radiology, Italy, 5AUSL-IRCCS di Reggio Emilia, Medical Physics
University of Vienna, Department of Medicine III, Division of Nephrology and Dialysis, Deparment, Reggio Emilia, Italy and 6University of Modena and Reggio Emilia,
Wien, Austria and 4Ordensklinikum Linz Elisabethinen, Department of Medicine III, Department of Medicine, Surgery, Mother-infant and Adult, Modena, Italy
Nephrology, Hypertension, Transplantation, Rheumatology, Geriatrics, Linz, Austria
BACKGROUND AND AIMS: Interstitial fibrosis / tubular atrophy (IFTA) is a
BACKGROUND AND AIMS: Kidney transplantation is considered to be the optimal common, irreversible and progressive form of chronic allograft injury, and it is
treatment strategy for eligible end stage renal disease patients. However, the body of considered a critical predictor of kidney allograft outcomes. Inflammation, both
evidence to underpin the anticipated survival advantage for kidney transplant microvascular and interstitial, is on the contrary regarded as a reversible form of graft
recipients is weak, as random treatment allocation to either kidney transplantation or injury. Since treatments for rejection and other causes of graft dysfunction bear
remaining on dialysis is not feasible and previously reported results obtained from substantial toxicity and could have limited efficacy, the extent of irreversible graft
observational studies did not allow for causal interpretation. scarring is a crucial information for the clinician, to evaluate risks and benefits of
The aim of this study is to investigate survival differences of kidney transplantation specific therapies. The diagnosis of kidney graft pathology is acquired through graft
compared to remaining waitlisted on dialysis across different transplant candidate ages biopsy, which is an invasive procedure and can be subjected to sampling bias. Magnetic
applying causal inference methodology. resonance imaging (MRI), especially with functional techniques, has emerged as a
METHOD: We conducted a retrospective cohort study using the Austrian Dialysis and possibility for non-invasive estimation of tissue fibrosis; nevertheless, functional MRI is
Transplant Registry. We included all maintenance dialysis patients who were waitlisted not widely available. Texture analysis MRI (TA-MRI) is a radiomic technique that
for their first kidney transplant between January 2000 and December 2018 and utilized provides a quantitative assessment of tissue heterogeneity from standard MRI images,
repeated updates on waitlisting status and relevant covariates. generating features that can be fitted into a machine-learning model to assess their
To estimate the causal effect of kidney transplantation compared to remaining ability to predict clinical or histological parameters.
waitlisted on all-cause survival we applied a sequential Cox approach mimicking a METHOD: Single-center cross-sectional observational cohort study enrolling kidney
series of target trials, where each trial started at the time of a transplantation. In each of transplant recipients who underwent graft biopsy and graft MRI imaging within 6
these emulated trials transplanted patients were classified as treated and patients with months from biopsy, both on clinical indication, at the “Azienda Ospedaliero-
current active waitlisting status as controls, and the groups were balanced for covariates Universitaria di Modena”, Italy. The study was approved by the local Ethical
by inverse probability weighting. Controls who were transplanted at later times were Committee (AOU0010167/20). The primary outcome was to identify the best TA-MRI
censored but assigned to the treated group in a later target trial of the series. All trials features subset for estimation of IFTA > 50% in graft biopsy. Secondary outcomes
were combined into a single data set and analyzed by a Cox proportional hazards were estimation of: IFTA > 25%, presence of total inflammation (ti) and microvascular
model using inverse probability weighting also to adjust for artificial censoring. inflammation (glomerulitis þ peritubular capillaritis [gþptc]). Graft biopsy was
Additionally, we evaluated potential effect modifications by age at trial initiation reported according to Banff 2017 system. Radiomic analysis was performed on axial T2
(continuous) and stratified our analyses by time on waitlist before trial initiation (up to pre-contrast and T1 fat-suppressed post-contrast sequences. The whole renal
1 year, between 1 and 2 years, and more than 2 years). Results are reported as hazard
ratios (HRs), 5-year survival probabilities and restricted mean survival time together
with respective bootstrap confidence intervals (CIs).
RESULTS: The study cohort consisted of 4206 patients, of whom one third were
women and the mean age was 52 years. In total, 3399 patients (81%) received a
transplant and 1256 patients died. The median time from waitlisting to transplantation
was 1.8 years.
Overall, patients who received a kidney transplant had a significant survival benefit
compared to patients who remained waitlisted (HR 0.36, 95% CI 0.29 to 0.43).
Assessing survival across different ages showed a significant benefit for kidney
transplantation for patients between 32 and 77 years of age at time of transplantation
(e.g. HR at age of 70: 0.43, 95% CI 0.33 to 0.54). For older and younger patients our
analysis did not provide definitive conclusions due to limited sample sizes.
Transplanted patients had higher predicted survival and longer restricted mean
survival time compared to patients remaining waitlisted. For example, within 5 years
after engraftment, a transplanted patient 70 years of age at trial initiation had a 0.28
higher survival probability (95% CI 0.20-0.37) and was expected to gain 0.75 years of
survival time. Our stratified analyses showed a survival benefit for kidney
transplantation regardless of time on waitlist before trial initiation across all ages.
CONCLUSION: Our study provides robust evidence based on state-of-the-art causal
inference methodology for increased survival after kidney transplantation across
different transplant candidate ages and irrespective of time on waiting list.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts

parenchyma (PAR) was segmented and labelled on T2 and T1, renal cortex (COR)
only on T2. After imaging preprocessing, PyRadiomics was used to extract radiomic
features. After removal of shape features, 93 features were included and reduced using
LASSO regression to produce radiomic signatures. These were introduced in Machine
Learning (ML) models to test the association with outcomes. Results are reported as
AUC and a value of sensitivity and specificity.
RESULTS: Sixty patients were included in the study, and 67 graft biopsy – graft MRI
pairs were available for analysis. Demographic and clinical characteristics of enrolled
patients are depicted in table 1; histological diagnosis and main Banff histological
parameters from graft biopsies in table 2. Among ML models, three showed an
acceptable performance. T2 COR “firstorder_minimum/firstorder_range/
glrlm_run_entropy” for IFTA>50% (AUC=0.77, sensitivity=73%, specificity=71%), T1
PAR “firstorder_energy” for IFTA>25% (AUC=0.71, sensitivity=74%,
specificity=51%), T1 PAR “firstorder_energy/
gldm_small_dependence_low_gray_level_emphasis” for gþptc >0 (AUC=0.74,
sensitivity= 78%, specificity=68%); see figures 1–3. No acceptable prediction was
detected for ti >0.

CONCLUSION: Our study shows that TA-MRI feature signatures can predict the
degree of IFTA in graft biopsies, with an acceptable diagnostic performance. These
results suggest to further investigating TA-MRI from standard MRI sequences as
potential tool to assess graft chronic parenchymal injury. Moreover, since graft biopsy
results can be jeopardized by limited sample size, we hypothesize that evaluation of
IFTA through TA-MRI could provide more comprehensive information regarding the

10.1093/ndt/gfab146 | i83
Abstracts Nephrology Dialysis Transplantation

whole parenchyma. To test this hypothesis, we are currently evaluating the association METHOD: From January 2013 to December 2019, we prospectively performed 114
of TA-MRI radiomic features and baseline eGFR and eGFR variation over time. 18FDG-PET/CT in 105 adult KTR who underwent per cause transplant biopsy for
suspected TCMR. Biopsy-proven polyoma-BK nephropathies (n=7) and
uninterpretable PET images (n=2) were excluded. PET/CT was performed 194619
minutes after administration of 243635 MBq of 18FDG, before any
FC121 THE UPTAKE OF PET RADIOTRACER 18 F-
immunosuppression change. The mSUVs were measured in both upper and lower
FLUORODEOXYGLUCOSE BY THE RENAL ALLOGRAFT
poles of the renal allograft. The acute Banff score was conventionally defined as the
SIGNIFICANTLY CORRELATES WITH THE ACUTE BANFF
sum (from 0 to 15) of g (glomerulitis), ptc (peritubular capillaritis), t (tubulitis), i
SCORES OF CORTEX INFLAMMATION
(inflammation in non-scarred cortex) and v (endarteritis). The Banff “total i” score
(from 0 to 3) corresponds to the total cortical inflammation, including scarred and
Laurent Weekers1, Pierre Lovinfosse2, Hans Pottel3, Antoine Bouquegneau1,
non-scarred cortex. Regression of mSUV against the acute Banff score was performed,
Catherine Bonvoisin1, Christophe Bovy4, Stéphanie Grosch4, Roland Hustinx2,
and Pearson correlation coefficients were calculated. The distribution of mSUV
François Jouret1
1
between “total i” groups was assessed by the non-parametric Kruskal-Wallis test
ULiège Academic Hospital (ULiège CHU), Division of Nephrology-Dialysis- followed by Dunn’s post hoc test.
Transplantation, Liege, Belgium, 2ULiège Academic Hospital (ULiège CHU), Department RESULTS: The mean age of the cohort was 51.5614.3 years, with M/F ratio of 67/38.
of Nuclear Medecine, Liege, Belgium, 3KU Leuven Campus Kulak Kortrijk, Department of The prevalence of biopsy-proven TCMR and borderline was 20.9% and 16.2%,
Public Health and Primary Care, Kortrijk, Belgium and 4ULiège Academic Hospital respectively. The mean mSUV of the 105-case cohort was 1.8260.45. The highest value
(ULiège CHU), Department of Pathology, Liege, Belgium of acute Banff score was 12, while 55.2% of biopsies were scored as 0. The distribution
of “Total i” score was: 0 (58.8%); 1 (20.6%); 2 (8.8%); 3 (11.8%). Regression showed a
BACKGROUND AND AIMS: Acute T-cell mediated rejection (TCMR) is associated significant correlation between mSUV and acute Banff score (p<0.0001), with adjusted
with the recruitment of mononuclear leukocytes into the renal transplant, which R2 of 0.38. The mSUV value was significantly different between subgroups of “Total i”
corresponds to the core of the conventional Banff classification. The boosted (p, 0.0047), with 2.3360.76 in score 3 versus 1.6860.24 in score 1.
metabolism of these inflammatory cells can be assessed by positron emission CONCLUSION: 18FDG-PET/CT may help noninvasively assess the degree of allograft
tomography (PET) quantifying the renal uptake of 18F-fluorodeoxyglucose (18FDG). inflammation in KTR with suspected TCMR.
The correlation of biopsy-based Banff versus PET-based scores of acute inflammation
in the renal transplant is unknown.

i84 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i85–i86, 2021
10.1093/ndt/gfab147

TRANSPLANTATION: RISKS & COMPLICATIONS

Bone densitometry
FC122 BONE DENSITOMETRY IN RENAL TRANSPLANTED PATIENTS
Lumbar spine
Bone Mineral Density 1.1 (1 – 1.2)
Ana Carina Ferreira1,2, Marco Mendes1, Cecılia Silva1, Patrıcia Cotovio1, T-score -1.1 (-1.9 to -0.1)
^s Aires1,2, David Navarro1, Fernando Caeiro1, Rute Salvador3, Bruna Correia3,
Ine
Guadalupe Cabral3, Fernando Nolasco1,2, Manuel Anibal A. Ferreira1,2 Z-score -0.8 (-1.8 to 0.4)
1
Hospital Curry Cabral, Nephrology, Lisboa, Portugal, 2Nova Medical School, Femural neck
Nephrology, Lisboa, Portugal and 3CEDOC, Tissue Repair and Inflammation Lab, Lisboa, Bone Mineral Density 0.86 (0.77 to 0.96)
Portugal
T-score -1.4 (-2.2 to -0.6)
BACKGROUND AND AIMS: Renal transplant and associated immunosuppression Z-score -0.7 (-1.5 to 0)
can influence bone volume. The aim of this study was to analyze the relations between Total femur
bone biopsy data and levels of bone-related molecules [phosphorus (Pi), Calcium (Ca), Bone Mineral Density 0.9 (0.8 to 1)
Magnesium (Mg), parathyroid hormone (PTH), bone alkaline phosphatase (bAP),
calcitonin, vitamin D (vitD), alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin], T-score -1 (-2.1 to -0.4)
obtained 1-year after transplantation with bone densitometry findings in the same time Z-score -1 (-1.45 to 0.2)
point in renal transplanted patients.
METHOD: We performed a prospective cohort study of a consecutive sample of de
FRAX risk
novo single renal transplanted patients in our unit. At inclusion, demographic, clinical Osteoporotic fracture j hip fracture 3.5% (2.2 – 6.2)j 0.8% (0.2 – 2.7)
and transplant-related data were collected, X-ray of the pelvis and hands (Adrag~ao
score) and echocardiographic findings were recorded. All patients were submitted to a
laboratorial evaluation and a bone biopsy at baseline. Patients were followed for 12
months, after which performed laboratorial evaluation, 2nd bone biopsy,
echocardiogram, X-ray of pelvis and hands, bone densitometry (DXA) and non-
contrast cardiac CT. For this report we use the information of the 2nd analysis:
laboratorial information, bone histology information, as well the densitometry
evaluation. Continuous variables were presented as medians and categorical variables FC123 RENAL TRANSPLANTATION MITIGATES INCREASED
as frequencies. Associations between variables were performed using Wilcoxon rank- BIOLOGICAL (EPIGENETIC) AGE IN CHRONIC KIDNEY
sum test, Fisher exact test, Kruskal Wallis rank test or Spearman correlation test. DISEASE
Multivariate analysis was performed using linear regression models. STATA software
was used and p < 0.05 was considered statistically significant. Ognian Neytchev1, Anna Witasp2, Louise Nordfors2, Abdul Rashid Tony Qureshi2,
RESULTS: We recruited 84 patients and, at the end of 12 months, we performed a 2nd Lars Wennberg3, Helen Erlandsson3, Thomas Ebert2, Colin Selman4, Paul Shiels1,
evaluation in 69 patients. Median age 53 years, 48 men, 53 caucasian (78.8%), median Peter Stenvinkel2
BMI 24.6, median dialysis vintage 55 months. Patients had a median cumulative 1
University of Glasgow, United Kingdom, College of Medical, Veterinary & Life Sciences
steroid dose of 5692.5 mg. Analyzing bone biopsies, we found that 28 patients had Institute of Cancer Sciences, Glasgow, United Kingdom, 2Karolinska Institutet, Renal
adynamic bone disease; 6 had hyperparathyroid bone disease; 2 had osteomalacia and 3 Medicine M99, Stockholm, Sweden, 3Karolinska Institutet, Transplantation, Stockholm,
other abnormal mineralization; 8 patients presented only with osteoporosis. There was Sweden and 4 Institute of Biodiversity, Animal Health and Comparative Medicine,
no significant difference between bone volume / total volume pre transplant (18%) and College of Medical, Veterinary & Life Sciences Institute of Cancer Sciences, Glasgow,
1 year after transplantation (19%). Using DXA technique, 14 patients were classified United Kingdom
has having osteoporosis, and all those had low volume at the bone biopsy. Nevertheless,
in 4 patients low bone turnover was also present. The positive predictive value dropped BACKGROUND AND AIMS: Chronic kidney disease (CKD) shares important
from 100% to 57%, if we add the other abnormalities of bone, in addiction to the features of a dysregulated ageing process with other common “burden of lifestyle”
volume. DXA exam wasn’t a good tool to detect a normal bone volume, as the negative diseases, which aggregates into the diseasome of ageing. Typically, this is hallmarked by
predicted value dropped from 78% (normal volume, irrespective of turnover and an acceleration of epigenetic (DNA methylation-based) clocks. It remains to be
mineralization) to 37% (normal bone biopsy). Nevertheless, overall bone volume determined if current therapeutic interventions, such as renal transplantation or
assessed by a bone biopsy correlated well with densitometry findings. dialysis, can slow this clock, and thus the rate of biological ageing, in CKD. We
CONCLUSION: DXA exam isn’t a good tool to identify the bone quality. Nevertheless, therefore assessed the rate of biological ageing in CKD patients and whether these
once osteoporosis is detected the probability of the patient having low bone volume is therapies impact on it, by measuring epigenetic age before and 1 year after treatment.
high, but we still need a bone biopsy in order to exclude mineralization or turnover METHODS: Whole blood samples were taken from CKD 5 patients at baseline and 1 year
deviations. after renal transplantation (n=12) or dialysis (n=11; peritoneal dialysis n=7, haemodialysis
n=4) as well as from age and sex-matched population-based controls (n=24). DNA
methylation was measured using the Illumina Infinium Human Methylation 450K
BeadChip and epigenetic age was calculated using three independent DNA methylation
clocks: the Horvath, Hannum, and PhenoAge clocks. Additionally, a novel composite clock
incorporating these three clocks was evaluated. We then calculated the age acceleration
(difference between epigenetic and chronological age) for each clock and compared average
age acceleration between groups and across time points.
RESULTS: Incident dialysis patients displayed accelerated ageing versus
chronologically age-matched controls (p<0.001). We observed a PhenoAge age
acceleration difference in both the transplant (8.5 years, p=0.001) and dialysis (9.7
years, p<0.001) groups at baseline compared to control. After 1 year, we also observed
a decrease of the age acceleration in the transplant group (mean reduced by 4.4 years,
p=0.016), but not in the dialysis group (mean reduced by 0.7 years, p=0.668).
CONCLUSION: CKD 5 patients display an increased biological (i.e. epigenetic) age.
This age acceleration is mitigated one year after renal transplantation, but not in
patients undergoing dialysis. Neither therapy reverses high biological age.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

p=0.001) and cumulative steroid dose (b=0.18, p=0.004), and determinants of BAr
were age (b=-0.15, p=0.002), and BMI (b=0.33, p=0.002).
CONCLUSION: Bone turnover is normal in the majority of kidney transplant
recipients at 1 year post-transplant, despite a high prevalence of hyperparathyroidism.
Low levels of bicarbonate, phosphate, and calcidiol may contribute to delayed bone
mineralization in kidney transplant recipients.

FC125 DIURETIC USE IS ASSOCIATED WITH INCREASED RISK FOR


POSTTRANSPLANTATION DIABETES MELLITUS IN RENAL
TRANSPLANT RECIPIENTS

Sara Sokooti Oskooei1, Sok Cin Tye2, Rianne M. Douwes1, Hiddo Lambers
Heerspink2, Stephan Bakker1
1
University Medical Center Groningen, Internal Medicine, Groningen, The Netherlands
and 2University Medical Center Groningen, Clinical Pharmacology, Groningen, The
Netherlands

BACKGROUND AND AIMS: Posttransplantation diabetes Mellitus (PTDM) is one


of the major medical problems in renal transplant recipients (RTRs). Diuretic-induced
hyperglycemia and diabetes have been described in the general population. We aimed
to investigate whether diuretics also increase PTDM risk in RTRs.
METHOD: We included 486 stable outpatient RTRs (with a functioning graft 1 year)
FC124 PATTERNS OF RENAL OSTEODYSTROPHY ONE YEAR AFTER without diabetes from a prospective longitudinal study (the Transplantlines Food and
KIDNEY TRANSPLANTATION Nutrition Study [NCT02811835]). Participants were classified as diuretic users and
non-diuretic users based on their medication use recording at baseline. PTDM was
Hanne Skou Jørgensen1,2, Geert Behets3, Patrick D’Haese3, Pieter Evenepoel1,4 defined according the American Diabetes Association’s diagnostic criteria for diabetes.
1
KU Leuven, Microbiology, Immunology and Transplantation; Nephrology and Renal Multivariable Cox proportional-hazards regression analyses were performed to assess
Transplantation Research Group, Leuven, Belgium, 2Aarhus University, Institute of the prospective association between diuretic use and the risk of PTDM development.
Clinical Medicine, Nephrology, Aarhus N, Denmark, 3University of Antwerp, Institute of RESULTS: Median time since transplantation was 5.4 (2.0-12.2) years and 168 (35%)
Pathophysiology, Biomedical Sciences, Wilrijk, Belgium and 4University Hospitals RTRs were taking diuretics. After 5.2 (IQR, 4.0 5.9) years of follow up, 54 (11%) RTRs
Leuven, Medicine, Division of Nephrology, Leuven, Belgium developed PTDM. In Kaplan-Meier (log-rank test, p<0.001) and Cox regression
analyses, diuretic use was found to be associated with incident PTDM after adjustment
BACKGROUND AND AIMS: Bone disease after kidney transplantation is an issue of for age, sex, fasting plasma glucose (FPG), and HbA1c (hazard ratio[HR] 3.28, 95% CI
growing concern, as prolonged graft survival and older age of recipients necessitate 1.84-5.83; p<0.001). The association remained independent of further adjustment for
focus on long-term health burdens such as osteoporosis and fractures. Pre-existing type potential confounders, including lifestyle, use of other medication, kidney function,
of renal osteodystrophy, post-transplant immunosuppressive treatment, and de novo transplantation-specific parameters, BMI, lipids, and blood pressure. Exploratory
disturbances of mineral metabolism all contribute to bone disease in kidney transplant analyses further indicates that, in Cox regression analyses, both thiazide (n=74) and
recipients. The current pattern of renal osteodystrophy after kidney transplantation is loop diuretics (n=76) as two main types of diuretics used among RTRs appeared to be
not well characterized. This study reports histomorphometric findings of protocolled associated with the development of PTDM, independent of age, sex, FPG, and HbA1c
bone biopsies in a large cohort of kidney transplant recipients 1 year post-transplant. ([HR 2.70, 95% CI 1.24-5.29; p=0.012], and [HR 5.08, 95% CI 2.49-10.34; p<0.001],
METHOD: Histomorphometric analysis of transiliac bone biopsies with prior respectively).
tetracycline labelling was performed in 141 kidney transplant recipients. Biochemical CONCLUSION: This study demonstrates that diuretics overall, associated with the
measurements included bioactive parathyroid hormone (PTH), total calcium, risk of developing PTDM in RTRs, independent of established risk factors for PTDM
phosphate, calcidiol, bicarbonate, and sclerostin. Kruskal-Wallis and Wilcoxon signed development. The association was consistent for thiazide and loop diuretics.
rank tests were used to evaluate differences across categories and between groups,
respectively. Stepwise multivariate linear regression was performed to identify key
demographic and biochemical determinants of bone turnover (bone formation rate,
BFR), mineralization (mineralization lag time, Mlt), and volume (Bone area, BAr).
RESULTS: Mean age was 57611 years, 71% were men, and all were Caucasian. Mean
eGFR was 49616 (range 19 to 106) ml/min/1.73 m2. Hyperparathyroidism (PTH >
1.5xUNL) was seen in 48%, hypercalcemia (>10.3 mg/dL) in 18%, hypophosphatemia
(<2.3 mg/dl) in 12%, and vitamin D deficiency (<15 ng/mL) in 4% of patients.
Categorization of bone turnover, mineralization, and volume is shown in Figure 1.
Bone turnover was normal in the vast majority (71%). Patients with low turnover
(26%) had received a higher cumulative steroid dose (2.78 vs 2.34g in low vs non-low
turnover; p=0.02).
Patients with delayed mineralization (16%) were younger (52 vs 58 yrs, p=0.02) and
had received a higher cumulative steroid dose (2.85 vs 2.36g, p=0.003). They had
higher levels of PTH (124 vs 53 ng/L, p<0.001), and lower levels of phosphate (2.68 vs
3.18 mg/dL, p<0.001), calcidiol (29 vs 37ug/L, p=0.02), bicarbonate (21.3 vs 23.3
mmol/L, p=0.004), and sclerostin (493 vs 594 pg/mL, p=0.03) compared to patients
with normal mineralization. Patients with low bone volume tended to be older (61 vs FC125 Figure 1: Kaplan-Meier curves depicting PTDM incident according to
56 years, p=0.07). diuretic usage in diuretic users (n=186) and non-diuretic users (n=318).
Independent determinants of BFR were PTH (b=0.68, p<0.001) and cumulative
steroid dose (b = -0.22, p=0.02). Determinants of Mlt were phosphate (b=-0.48,

i86 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i87–i88, 2021
10.1093/ndt/gfab148

TRANSPLANTATION: SHORT- AND LONG-TERM


OUTCOMES

FC126 IMPACT OF POLYCLONAL ANTI-T-LYMPHOCYTE


IMMUNOGLOBULINS ON THE RECURRENCE OF IGA
NEPHROPATHY AFTER KIDNEY TRANSPLANTATION: THE
PIRAT STUDY

Nicolas Maillard1, Nassim Kamar2, Maryvonne Hourmant3, Emmanuel Morelon4,


Moglie Le Quintrec5, Claire Pouteil-Noble4, Luc Frimat6, Sophie Caillard7,
Didier Ducloux8, Pierre Merville9, Matthias Buchler10, Laetitia Albano11,
Benoit Barrou12, Christophe Mariat1
1
CHU Saint Etienne, Nephrology, Dialysis, Transplantation, SAINT ETIENNE, France,
2
CHU Toulouse, Néphrologie et transplantation d’organes, 3CHU Nantes, Néphrologie
Immunologie Clinique, 4Hospices Civils de Lyon, Transplantation, Néphrologie et
Immunologie Clinique, 5CHU Montpellier, Néphrologie, Dialyse, Transplantation, 6CHRU
Nancy, Néphrologie, 7CHRU Strasbourg, Néphrologie et Transplantation, 8CHU
Besançon, Néphrologie Transplantation, 9CHU Bordeaux, Néphrologie, Transplantation,
10
CHRU Tours, Néphrologie - hypertension artérielle, dialyses, transplantation rénale,
11
CHU Nice, Néphrologie Dialyse Transplantation rénale and 12Assistance Publique
Hopitaux de Paris, Urologie, Néphrologie, Transplantation

BACKGROUND AND AIMS: IgA Nephropathy (IgAN) often recurs on kidney


transplants, accounting for a significant specific kidney failure occurrence after ten
years of transplantation vintage. Polyclonal anti-T-lymphocyte antibodies (PATLA)
immunosuppressive induction has been shown to be associated with a lower rate of
IgAN recurrence compared to basiliximab and no induction in a retrospective study.
The aim of the PIRAT study was to compare an induction by PATLA versus
basiliximab by the mean of a randomized controlled trial. FC127 SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS
METHOD: Adults with biopsy-proven primary IgAN as primary cause of end stage of (SGLT2I) SHORT-TERM OUTCOME IN DIABETIC KIDNEY
renal disease, first transplantation, panel reactive antibody <50% could be included in TRANSPLANT RECIPIENTS
the study. Patients were randomized 1:1 prior to transplantation to receive either
PATLA (Grafalon, 4mg/kg for 3 days, then two days 3mg/kg) or basiliximab (20mg at Jude Yagan1, Tarek S.H. Mahmoud2, Osama Geith2
1
transplantation and 4 days after). Both groups received methylprednisolone followed Organ transplant centre, nephrology, Kuwait, Kuwait and 2Kuwait City, organ trans-
by oral corticoids for at least one year, tacrolimus and mycophenolic acid. Primary plant centre, Kuwait City, Kuwait
outcome was the clinico-histological recurrence defined by both IgA deposition on
transplant biopsy and albuminuria>300mg/d during 5 years post-transplantation. BACKGROUND AND AIMS: The emergence of positive data on the use of sodium
Protocol biopsy at 5 years was highly recommended. glucose co-transporter inhibitors (SGLT2i) in the last several years, begged the
RESULTS: A total of 117 patients were finally included in 13 French transplant question of whether their positive outcomes can be seen in kidney transplant
centers, with 60 patients in the PATLA group and 57 in the basiliximab control group. recipients, as they have the same and even more pronounced cardiovascular risk
Both groups were similar (median, PATLA vs. basiliximab, p>0.05 wilcoxon test) in factors than the general population and in addition, we got better in improving graft
term of sex ratio (4.45 vs 4.57), recipient age (47.9 vs. 47.7 years old), dialysis vintage and patients survival in the short term , but we lack the tools to improve long term
(26.2 vs. 24.6 months), age at IgAN diagnosis (35.0 vs. 42.2 years old), cold ischemia patients and graft survival where so many patients die from cardiovascular disease with
(780 min vs 682 min), warm ischemia (34 vs. 36.1min), proportion of living donors a functioning graft or lose their graft from chronic changes and chronic antibody
(33% vs. 25%). The 5-year protocol biopsy was performed on 48% vs. 45% of patients, mediated rejection with difficult to control blood pressure and proteinuria
with overall proportion of patients evaluated by at least one biopsy of 63% vs. 66%. For these reasons we need more powerful tools , like the SGLT2i bearing in mind the
A trend in favor to the protection by PATLA from the occurrence of a clinico- unique side effects that might be amplified in kidney transplant recipients receiving
histological recurrence was found (hazard ratio, univariate Cox model 0,35 [0.11-1.1], immunosuppression like urinary tract infection, and the dip in serum creatinine.
p=0.082). METHOD: We collected data retrospectively from transplant records of patients with
Biopsy proven histological recurrence was significantly lower after PATLA induction type II diabetes mellitus (T2D) or post-transplant diabetes mellitus (PTDM) (n=79)
(HR 0.34 [0.16-0.76], p=0.0079). PATLA group experienced more infections (40 vs. 28 who were receiving SGLT2i agents plus standard of care [SOC] management and
p=0.06), a lower number of graft losses (3 vs 9, p=0.07), a lower number of biopsy- compared them to (n=56) similar diabetic patients who were only on SOC
proven acute rejections (5 vs 10, p=0.17). Similar rates of cytomegalovirus and BK virus management.
infections were found. RESULTS: The two groups were comparable regarding age, sex, type of donor, type of
CONCLUSION: PATLA for immunosuppressive induction was found protective from diabetes (T2D PTDM), post-transplant period, induction immunosuppression and use
the recurrence of IgA deposition during the first 5 years after transplantation, of CNI. Though improvement of HbA1c was not significantly different between the
compared to basiliximab. A similar trend, although not significant, was found about two groups, patients on SGLT2i showed better drop in HbA1c compared to the SOC
the clinico-histological recurrence which was the predefined primary outcome. group (0.7% versus 0.5% respectively). Reduction of BMI was equal between the two
groups (-1.1%) and there was no significant difference in the number of blood pressure
medications (average 2 drugs per patient). Kidney function was assessed by the eGFR
using CKD-EPI equation and by urine albumin/creatinine ratio (ACR). The eGFR was
calculated at start then at 1,3,6 and 12 months. In SGLT2i group, eGFR showed a dip at
3 months (from 66 to 63.35 ml/min) then started to improve gradually toward the end
of the year and maintained at a level close to baseline (65.44 ml/min). The SOC group
showed gradual drop in eGFR over the year from 65.76 to 63.19 ml/min. Urine ACR
reduced in the SGLT2i group from 48.79 to 23.79 mg/mmol creatinine and increased
from 42.84 to 63.16 mg/mmol creatinine in the SOC group. The incidences of graft
rejection, urinary tract infection, genital infection, myocardial infarction, heart failure
or cerebrovascular stroke were not different between the groups.
CONCLUSION: Use of SGLT2i in managing diabetic patients post kidney
transplantation is safe and has better short-term outcomes on renal function with
comparable safety compared to standard of care therapy.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

FC128 NON-HLA ANTIBODIES AND EPLET MISMATCHES IN KIDNEY


TRANSPLANT RECIPIENTS WITH A HISTOLOGICAL PICTURE
OF ANTIBODY-MEDIATED REJECTION WITH AND WITHOUT CONCLUSION: Despite highly prevalent HLA-DSA before and after transplantation
HLA DONOR-SPECIFIC ANTIBODIES in KT with histological ABMR, 27% of cases did not show circulating HLA-DSA. Pre-
KT AT1R-Ab associated with ABMR-DSAþ, but not MICA-Ab, ETAR-Ab or EC-
Marta Crespo1, Laura Llinas1, Dolores Redondo Pachon1, Carrie L. Butler2,3, XMþ. Any of them associated significantly with ABMR-DSA-. Epitope mismatch
Javier Gimeno4, Maria Jose Perez-Saez1, Anna Buxeda1, Carlos Arias-Cabrales1, predicted both postransplant DRB-DSA and ABMR-DSAþ. Detection of pre-KT
Montserrat Folgueiras1, Sara Sanz1, Nicole M. Valenzuela2,3, Elaine F. Reed2,3, HLA-DSA and/or AT1R-Ab, together with HLA epitope mismatch assessment, are
Julio Pascual Santos1 valuable tools for better DSA and ABMR prediction in KT patients.
1
Hospital del Mar and Hospital del Mar Medical Research Institute, Department of
Nephrology, Barcelona, Spain, 2UCLA Immunogenetics Center, University of California,
Los Angeles, CA, United States of America, 3David Geffen School of Medicine, University FC129 CHANGES IN PERIPHERAL NK CELLS IN KIDNEY
of California, Department of Pathology and Laboratory Medicine, Los Angeles, CA, TRANSPLANT RECIPIENTS WITH AND WITHOUT HLA DSA
United States of America and 4Hospital del Mar and Hospital del Mar Medical Research
Institute, Department of Pathology, Barcelona, Spain Laura Llinas1, Dolores Redondo Pachon1, Da lia Raı̈ch Regué1, Maria Jose Perez-
Saez1, Sara Sanz1, Carlos Arias-Cabrales1, Anna Buxeda1, Carla Burballa1, José
BACKGROUND AND AIMS: Correlation between antibody-mediated rejection Miguel Lopez-Botet2,3, Julio Pascual Santos1, Marta Crespo1
1
(ABMR) and HLA donor-specific antibodies (DSA) is strong but imperfect in kidney Hospital del Mar and Hospital del Mar Medical Research Institute, Department of
transplant (KT) recipients, raising the possibility of other detrimental antibodies Nephrology, Barcelona, Spain, 2Hospital del Mar and Hospital del Mar Medical
contributing to ABMR. The role of non-HLA antibodies on outcomes is not well Research Institute, Department of Immunology, Barcelona, Spain and 3University
known. Pompeu Fabra, Barcelona, Spain
METHOD: We retrospectively assessed KT biopsies scored according to Banff’15
classification. Pre- and post-KT serum samples were checked for HLA and non-HLA BACKGROUND AND AIMS: Antibody-mediated rejection (ABMR) is a frequent
antibodies (MICA-Ab, angiotensin II type 1 receptor (AT1R)-Ab, endothelin-1 type A cause of renal allograft loss. There is increasing evidence of the role of Natural Killer
receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC- (NK) cells in the establishment of ABMR damage. Our group described that patients
XM)). We also analyzed HLA epitope mismatches between donors and recipients. with donor-specific antibodies (DSA) and ABMR present higher proportions of
RESULTS: One-hundred eighteen patients with normal (n=19), ABMR histology NKG2Aþ NK cell subset in peripheral blood than those without HLA DSA or HLA
(n=52) or IFTA (n=47) in their biopsy were studied. Graft survival was worse in ABMR antibodies.
patients (p=0.003). Pre-KT HLA-DSA were more frequent in ABMR cases (p=0.006). METHOD: We selected 177 kidney transplant recipients (KT) with renal biopsies
At biopsy, 73% ABMR patients had HLA-DSA (p<0.001). Pre-KT AT1R-Ab were 2011-2017: 77 with ABMR (DSAþ: 53, DSA-: 24) and 100 without ABMR (DSAþ: 15,
more frequent in ABMR compared with IFTA and normal cases (p=0.003), without DSA-: 85). We assessed graft survival with a median time of follow-up since the renal
differences in other non-HLA antibodies. Fourteen patients with histological ABMR biopsy of 53 months. In 138 KT we evaluated the peripheral blood NK cell
(27%) had no detectable HLA-DSA post-KT and only 3 had non-HLA Ab. However, immunophenotyping and its value as a prognostic biomarker.
these ABMR-DSA- cases showed similar biopsy changes and graft survival compared RESULTS: Graft survival was worse in ABMR-KT at the end of follow-up (p<0.001)
with ABMR-DSAþ. Pre- or post-KT non-HLA antibodies other than AT1R-Ab were independently of DSA detection (p=0.63). Regarding NK cell immunophenotyping, we
detected similarly in ABMR and in normal or IFTA cases. Both total class II and DRB1 observed a lower proportion and absolute NK cell count in ABMRþDSAþ-KT and
epitope mismatches were associated with postransplant DSA and ABMR-DSAþ. ABMRþDSA–KT compared with ABMR-DSA–KT (p=0.027, p=0.017).
Multivariate analysis showed that both pre-KT HLA-DSA and AT1R-Ab (DSA: OR: ABMRþDSAþ-KT showed higher proportion of NKG2Aþ NK cells compared with
3.39 [1.20-9.59], p=0.021; AT1R-Ab: OR: 5.31 [1.75-16.10], p=0.003) were strong ABMR-DSA–KT (p=0.007). All ABMRþ patients, independently of DSA detection,
independent predictors of postransplant ABMR-DSAþ (Table 1). presented lower absolute NKG2A- NK cell count in comparison with ABMR-DSA–KT
(p=0.001, p=0.017). Finally, a proportion of NKG2A- <30% was associated with lower
FC128 Table 1. Logistic regression analysis of ABMR-DSAþ risk factors. graft survival 36 months after graft biopsy with ABMR (p=0.067) (Figure).

Univariate Multivariate
Risk factor OR (95% CI) p-value OR (95% CI) p-
value
HLA-DSA pre-KT 5.26 (2.03-13.62) 0.001 3.39 (1.20-9.59) 0.021
AT1R-Ab pre-KT 7.86 (2.75-22.41) <0.001 5.31 (1.75-16.10) 0.003
ETAR-Ab pre-KT 1.56 (0.60-4.05) 0.36
MICA-Ab pre-KT 0.97 (0.23-4.14) 0.96
Positive EC-XM 0.81 (0.08-8.23) 0.86
pre-KT
Class I antibody- 0.97 (0.88-1.07) 0.53
verified epitope
mismatches FC129 Figure: Graft survival in patients with and without ABMR grouped
Class II antibody- 1.12 (1.01-1.25) 0.029 1.07 (0.95-1.21) 0.26 according to NKG2A- > or <30% at biopsy.
verified epitope
mismatches CONCLUSION: Graft survival is worse in ABMRþ compared with ABMR- KT
independently of DSA detection. Kidney transplant recipients with ABMR show
reduced peripheral absolute numbers of NK cells and NKG2A- NK cells regardless of
undetectable DSA. This NK cell phenotype associated with a worse medium-term graft
survival in cases with ABMR.

i88 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i89–i90, 2021
10.1093/ndt/gfab134

KIDS & KIDNEY

FC130 RANDOMIZED, PLACEBO-CONTROLLED, PHASE 3B TRIAL


OF TOLVAPTAN IN THE TREATMENT OF CHILDREN AND
ADOLESCENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC
KIDNEY DISEASE (ADPKD): 1-YEAR DATA

Djalila Mekahli1,2, Lisa Guay-Woodford3, Melissa Cadnaparphornchai4,


Laurence A. Greenbaum5, Mieczysław Litwin6, Tomas Seeman7,
Ann Dandurand8, Lily Shi9, Kimberley Sikes9, Susan Shoaf8, Franz Schaefer10
1
University Hospitals Leuven, Department of Paediatric Nephrology, Leuven, Belgium,
2
PKD Research Group, Department of Development and Regeneration, Leuven,
3
Children’s National Health System, Center for Translational Science, Washington, DC,
United States of America, 4Rocky Mountain Hospital for Children at Presbyterian/St.
Luke’s Medical Center, Rocky Mountain Pediatric Kidney Center, Denver, CO, United
States of America, 5Emory University School of Medicine and Children’s Healthcare of
Atlanta, Department of Pediatrics, Division of Pediatric Nephrology, Atlanta, GA, United
States of America, 6Children’s Memorial Health Institute, Department of Nephrology,
Kidney Transplantation and Arterial Hypertension, Warsaw, Poland, 7Charles University
and Motol University Hospital, Department of Paediatrics, 2nd Faculty of Medicine, FC130 Figure 1: Mean percent change in total kidney volume by MRI from baseline
Prague, Czech Republic, 8Otsuka Pharmaceutical Development & Commercialization, to Month 12 in subjects ages 12–17 years
Princeton, NJ, United States of America, 9Otsuka Pharmaceutical Development &
Commercialization, Rockville, MD, United States of America and 10Center for Pediatrics
and Adolescent Medicine, Division of Pediatrics Nephrology, Heidelberg, Germany

BACKGROUND AND AIMS: Tolvaptan (TOL) is a vasopressin V2 receptor


antagonist that inhibits total kidney volume (TKV) growth and kidney function decline
in adults with rapidly progressing ADPKD. The therapeutic potential of TOL in
pediatric patients at risk of early disease progression has not been previously reported.
We conducted a clinical trial of TOL in children and adolescents with early manifesting
ADPKD to evaluate pharmacodynamic properties and preliminary efficacy and safety
information in this age group.
METHOD: This was a Phase 3b, 2-part trial (EudraCT: 2016-000187-42;
ClinicalTrials.gov: NCT02964273). Phase A (reported here) was a 1-year, randomized,
double-blind, placebo (PBO)-controlled, multicenter trial; Phase B is an ongoing, 2-
year, open-label extension. Subjects had to be diagnosed with ADPKD (presence of
renal cysts with family history and/or genetic diagnosis), with estimated glomerular
filtration rate (eGFR) 60 mL/min/1.73 m2 and body weight 20 kg. The target
population was aged 12-17 years; subjects aged 4-11 years were also allowed to enter if
eligibility criteria were met. Starting and maintenance TOL/PBO doses were based on
body weight. The co-primary endpoints were changes from baseline in spot urine
osmolality (Uosm) and specific gravity at Week 1; additional endpoints were the 12-
month changes in TKV and eGFR. Safety and tolerability were monitored. In this FC130 Figure 2: Mean change in estimated glomerular filtration rate from Day 7 in
exploratory trial, outcomes were summarized descriptively, with no statistical subjects ages 12–17 years
comparisons planned between groups.
RESULTS: Of 91 subjects enrolled (66 aged 12–17 years and 25 aged <12 years), 48
were randomized to TOL and 43 to PBO. Among enrolled subjects, there was a history CONCLUSION: TOL demonstrated activity indicative of effective V2 receptor
of hypertension in 23.1%, proteinuria 15.4%, kidney pain 12.1%, and hepatic cysts antagonism in children and adolescents with ADPKD. In addition, our trial yielded
6.6%. Mean changes (6SD) from baseline in spot Uosm and specific gravity at Week 1 preliminary results suggestive of efficacy in slowing TKV growth and eGFR decline
were greater with TOL vs PBO: -386 (284) vs -93 (332) mOsm/kg and -0.009 (0.007) vs with acceptable tolerability, warranting further investigation in pediatric patients with
-0.002 (0.008), respectively. In subjects aged 12–17 years (1 subject with tuberous ADPKD. The 2-year, Phase B extension to this trial is ongoing. Sponsored by OPDC,
sclerosis and ADPKD excluded as an outlier), the mean % TKV change (6SD) from Inc.
baseline to Month 12 was 4.6% (9.1) for TOL and 7.7% (9.3) for PBO (Figure 1). Mean
change (6SD) in eGFR from Day 7 to Month 12 in subjects ages 12–17 years was 0.4
(10.3) mL/min/1.73 m2 for TOL and -3.5 (10.9) mL/min/1.73 m2 for PBO (Figure 2).
The most frequent treatment-emergent adverse events during Phase A were (TOL vs
PBO): polyuria (25.0% vs 2.3%), blood creatinine increased (18.8% vs 4.7%),
pollakiuria (18.8% vs 0.0%), cough (14.6% vs 11.6%), nocturia (14.6% vs 4. 7%), thirst
(14.6% vs 2.3%), abdominal pain (12.5% vs 7.0%), constipation (10.4% vs 2.3%), and FC131 OFATUMUMAB OR RITUXIMAB FOR CHILDREN WITH
orthostatic hypotension (10.4% vs 0.0%). Potentially clinically significant increases in STEROID-DEPENDENT NEPHROTIC SYNDROME. A
creatinine (>1.5 x baseline) occurred in 4 TOL subjects and no PBO subject. No RANDOMIZED CONTROLLED TRIAL
subject had elevated transaminases or drug-induced liver injury. Serious adverse events
were reported in 1 TOL subject (viral pericarditis) and 6 PBO, none considered related Pietro Ravani1, Manuela Colucci2, Maurizio Bruschi3, Marina Vivarelli2,
to treatment. One subject discontinued due to pollakiuria (TOL) and 1 due to dizziness Michela Cioni3, Armando Di Donato3, Paolo Cravedi4, Francesca Lugani3,
(PBO). Francesco Emma2, Andrea Angeletti3, Gian Marco Ghiggeri 5
1
Cumming School of Medicine U C, Calgary, Canada, 2Bambino Ges u Children’s
Hospital, Roma, Italy, 3Istituto Giannina Gaslini, Genova, Italy and 4Icahn School of
Medicine at Mount Sinai, New York, United States of America

BACKGROUND AND AIMS: The chimeric anti-CD20 monoclonal antibody


rituximab has been successfully used in steroid-dependent forms of nephrotic
syndrome (SDNS) to maintain oral-drug-free remission, but relapses at one year occur
in almost half of the patients. Ofatumumab, a fully human anti-CD20 monoclonal
antibody, may be superior to rituximab in maintaining remission of SDNS. We

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

compared the efficacy and safety of ofatumumab vs. rituximab in children and young February 2013 and January 2019, 365 children with relapsing SSNS (mean age: 7.6 6
adults with SDNS (NCT02394119) and evaluated the risk of relapse following steroid 3.5 y) were recruited from 91 sites and randomised (1:1) according to a minimisation
and calcineurin-inhibitor tapering and withdrawal. algorithm based on background treatment (no background treatment; low-dose
METHOD: We randomly assigned 140 children and younger adults (age 2-24 years) prednisolone only; low-dose prednisolone and other immunosuppression; other
with SDNS maintained in remission with steroids and calcineurin-inhibitors to receive immunosuppression only). At the start of an URTI, children received 6 days of
intravenous ofatumumab (1.500 mg/1.73 m2; intervention) or rituximab (375 mg/m2; prednisolone 15 mg/m2 or matching preparation of placebo. Those already taking
control). Following infusions, oral drugs were tapered and withdrawn. Participants alternate day prednisolone rounded their daily dose using trial medication to the
were followed for 24 months. The primary outcome was relapse at one year, defined by equivalent of 15 mg/m2 or their alternate-day dose, whichever was the greater. The
protein-creatinine ratio 2000 mg/g or >3þ protein on urine dipstick for 3 primary outcome was the incidence of first URTI-related relapse (URR) following any
consecutive days. Cellular and safety data were also assessed. URTI over 12 months. Secondary outcomes were the overall rate of relapse, changes in
RESULTS: At 12 months, 36 patients (51.4%) relapsed in the rituximab arm and 37 background treatment, cumulative dose of prednisolone, rates of serious adverse
(52.8%) in the ofatumumab arm (Odds Ratio [OR] 1.06; 95% confidence interval [CI] events, incidence of corticosteroid adverse effects, change in Achenbach Child
0.55 to 2.06). At 24 months, 46 children relapsed in the rituximab arm (65.7%) and 53 Behaviour Checklist score and quality of life. Analysis was by intention to treat. The
in the ofatumumab arm (75.7%). In both arms, circulating B cell levels declined economic evaluation used trial data and a decision-analytic model to estimate Quality-
following treatment and recovered between 3 and 9 months. Higher pretreatment Adjusted-Life-Years (QALYs) and costs at 1-year, which were then extrapolated over
levels and faster recovery after decline of memory B cells predicted relapse. 16 years.
CONCLUSION: In children and younger adults with SDNS, ofatumumab is not RESULTS: 80 children completed 12 m follow-up without an URTI. Consent was
superior to the chimeric anti-CD20 antibody rituximab. Immune phenotyping data withdrawn for 32 children, 14 prior to an URTI, leaving a modified intention to treat
indicate that anti-CD20 therapies alter the course of the disease by interfering with analysis population of 271 children (134 and 137 in prednisolone and placebo arms
memory B cell populations and can be used to predict response to anti-CD20 respectively). There were 384 URTIs and 82 URRs in the prednisolone arm, and 407
treatment. URTIs and 82 URRs in the placebo arm. The number of patients experiencing a URR
was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms respectively
(adjusted risk difference: -0.024, 95% CI: -0.14 to 0.095; P=0.7). There was no evidence
that the treatment effect differed when data were analysed according to background
treatment. There were no significant differences in secondary outcomes between
treatment arms. A post-hoc subgroup analysis assessing primary outcome in 58
children of South Asian ethnicity (RR 0.66, 95% CI: 0.396 to 1.105) versus 213 of other
ethnicity (RR 1.11, 95% CI: 0.806 to 1.535) showed possible efficacy of intervention in
those of South Asian ethnicity (test for interaction P=0.09). Giving daily prednisolone
at the time of an URTI was found to increase QALYs and decrease overall costs, when
compared to standard care, a finding that was robust to sensitivity analysis.
CONCLUSION: In a large and methodologically-robust study, PREDNOS 2 has
shown that giving 6 days of daily low-dose prednisolone at the time of an URTI does
not reduce the risk of relapse of nephrotic syndrome in UK children, but could offer a
cost-effective use of health care resources. Further work is needed to investigate inter-
ethnic differences in treatment response, and the pathogenesis of individual viral
infections and their effect on nephrotic syndrome.

FC133 HEMODIAFILTRATION IS ASSOCIATED WITH REDUCED


INFLAMMATION AND INCREASED BONE TURNOVER
FC131 Figure: Relapse-free survival by treatment arm: rituximab (control; grey line) COMPARED TO CONVENTIONAL HEMODIALYSIS IN
and ofatumumab (intervention; dark line). (Odds Ratio [OR] 1.06; 95% confidence CHILDREN - THE HDF, HEART AND HEIGHT (3H) STUDY
interval [CI] 0.55 to 2.06).
Dagmar-Christiane Fischer1, Colette Smith2, Francesca De Zan3, Varvara Askiti4,
Aysun Karabay Bayazit5, Nur Canpolat6, Mieczyslaw Litwin7, Fabio Paglialonga8,
Franz Schaefer9, Claus Schmitt9, Rukshana Shroff3
1
Rostock University Medical Centre, Department of Pediatrics, Rostock, Germany,
2
FC132 SHORT COURSE DAILY LOW-DOSE PREDNISOLONE AT THE Institute of Global Health, University College London, London, United Kingdom,
3
TIME OF UPPER RESPIRATORY TRACT INFECTION (URTI) IN University College London Great Ormond Street Hospital for Children and Institute of
NON-SELECTED CHILDREN WITH RELAPSING STEROID Child Health, London, United Kingdom, 4A & P Kyriakou Children’s Hospital, Athens,
SENSITIVE NEPHROTIC SYNDROME DOES NOT PREVENT Greece, 5Cukurova University, Adana, Turkey, 6Cerrahpasa School of Medicine, Istanbul,
URTI-RELATED RELAPSE: THE PREDNOS 2 TRIAL. Turkey, 7Children’s Memorial Health Institute, Warsaw, Poland, 8Fondazione IRCCS Ca’
Granda Ospedale Maggiore Policlinico, Milan, Italy and 9Center for Pediatrics and
Martin Christian1, Nicholas Webb2, Samir Mehta3, Afentou Nafsika4, Adolescent Medicine, Heidelberg, Germany
Rebecca Woolley3, Emma Frew4, Elizabeth Brettell3, Adam Khan3, David Milford5,
Detlef Bockenhauer6, Moin A. Saleem7, Angela Hall8, Ania Koziell9, BACKGROUND AND AIMS: Children on dialysis have a high burden of bone related
Heather Maxwell10, Shivaram Hegde11, Hitesh Prajapati12, Rodney Gilbert13, comorbidities and fractures. We report a post-hoc analysis of the HDF-Hearts-Height
Caroline Jones14, Karl McKeever15, Wendy Cook16, Natalie Ives3 study to determine the prevalence and risk factors for mineral bone disease in children
1
Nottingham Children’s Hospital, Paediatric Nephrology, Nottingham, United Kingdom, on hemodiafiltration (HDF) and conventional hemodialysis (HD).
2
Manchester Children’s Hospital, Manchester, United Kingdom, 3Birmingham Clinical METHOD: 144 children were included in baseline cross-sectional analysis, of which
Trials Unit, Birmingham, United Kingdom, 4University of Birmingham, Birmingham, 103 (61 HD, 42 HDF) completed 12-month follow-up. Biomarkers of bone formation
United Kingdom, 5Birmingham Children’s Hospital, Birmingham, United Kingdom, and resorption, inflammatory markers, fibroblast growth factor-23 (FGF23) and klotho
6
Great Ormond Street Hospital for Children, London, United Kingdom, 7Bristol were measured.
Children’s Hospital, Bristol, United Kingdom, 8Leicester Children’s Hospital, Leicester, RESULTS: Inflammatory markers interleukin-6 [IL-6], tumor necrosis factor-alfa
United Kingdom, 9Evelina Children’s Hospital, London, United Kingdom, 10Royal [TNF-a], and high-sensitivity CRP [hsCRP] were lower in the HDF compared to HD
Hospital for Sick Children, Glasgow, United Kingdom, 11University Hospital of Wales, cohorts at baseline and 12 months (p<0.001). Concentrations of bone formation
Cardiff, United Kingdom, 12Leeds Children’s Hospital, Leeds, United Kingdom, (bone-specific alkaline phosphatase, BAP) and resorption (tartrate-resistant acid
13
Southampton Children’s Hospital, Southampton, United Kingdom, 14Alder Hey phosphatase 5b [TRAP5b]) markers were comparable between cohorts at baseline, but
Children’s Hospital, Liverpool, United Kingdom, 15Royal Hospital for Sick Children, after 12-months the BAP/TRAP5b ratio increased in HDF (p=0.004) and was
Belfast, United Kingdom and 16Nephrotic Syndrome Trust (NeST), Taunton, United unchanged in HD (p=0.44). On adjusted analysis the BAP/TRAP5b ratio was 2.66-fold
Kingdom lower (95%CI -3.91, -1.41; p<0.0001) in HD compared to HDF. FGF23 was
comparable between groups at baseline (p=0.52) but increased in HD (p<0.0001) and
BACKGROUND AND AIMS: At least 80% of children with steroid sensitive nephrotic remained static in HDF (p=0.34) at 12-months. Klotho levels were similar between
syndrome (SSNS) have relapses and many are triggered by upper respiratory tract groups and unchanged during follow-up. The FGF23/klotho ratio was 3.86-fold higher
infections (URTIs). Previous small studies (4 studies, 232 patients in total), mostly in (95% CI 2.15, 6.93; p<0.0001) in HD compared to HDF.
children already taking maintenance corticosteroid in countries where URTI CONCLUSION: We conclude that children on HDF have increased bone turnover, an
epidemiology is different to Europe, showed that giving daily low-dose prednisolone for attenuated inflammatory profile and lower FGF23/klotho ratios compared to those on
5-7 days during an URTI reduces the risk of relapse. The objective of the PREDNOS 2 HD. Long-term studies are required to determine the effect, if any, of an improved
trial was to determine if these findings were replicated in a large UK population of bone biomarker profile on fracture risk and growth.
children with relapsing SSNS on different background medication or none.
METHOD: A randomised, double-blind, placebo-controlled trial, including a model-
based economic evaluation was carried out in 122 UK paediatric departments. Between

i90 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i91–i92, 2021
10.1093/ndt/gfab137

A LOOK IN THE CRYSTAL BALL: ENVIRONMENT &


EDUCATION
RESULTS: 462 patients with weight lower than 70 Kg were analysed, 127 patients
received Qd 400 mL/min.
When diminishing Qd from 500 to 400 mL/min, 24 litres were saved per session per
FC134 WATER SAVING COMPARISON AT DIFFERENT DIALYSATE patient without detriment of middle molecule clearance. There were no differences in
FLOWS IN EXPANDED HEMODIALYSIS adequacy HD parameters between Qd prescriptions (Table 1 and 2).
CONCLUSION: HDX allows lowering of Qd to 400 mL/min without harm for
Alejandra Molano-Trivin ~o1,2,3,3, Jasmin Vesga3, Gregorio Romero1, patients and with remarkable savings of potable water: 24 Litres were saved in each
Claudio Ronco1 session per patient that can be translated in almost 3500 Litres of water each year by
1
San Bortolo Hospital in Vicenza Casualty, International Renal Research Institute patient which is enough for one year for 47 adults. (Based on the WHO minimum for
Vicenza, Vicenza, Italy, 2Fundacion Cardioinfantil, Nephrology, Bogot
a, Colombia and basic health protection of at least 20 L per person/day) (2).
3
Baxter Renal Care Services (RCS)-Colombia, Bogot a, Colombia We consider our results especially relevant since the World Health Organization
estimates that within the next 5 years, over 50% of world population could reside in
geographies lacking sufficient access to water.
BACKGROUND AND AIMS: Expanded hemodialysis (HDx) improves clearance of
We hope that our results from the Blue Planet dialysis research group, alongside with
middle molecules as a target for uremia treatment. According to previously published
Dr. Agars and Dr. Barracloughs green nephrology initiatives, can help educate the
results, high cut off filters have high enough clearance to allow diminishing of dialysate
nephrology community on the ecological impact of dialysis and can present an
flow (Qd) without detrimental in HD adequacy outcomes with less water waste.
innovative solution to offer HD therapy even in countries suffering from limited access
According to World Health Organization (WHO), globally, almost 800 million people
to potable water.
lack access to safe water and 2.5 billion lack access to optimal sanitation. Is our duty to
search for ways to avoid water waste.
Our aim is to describe the differences in water use between HDX patients receiving Qd
400 mL/min (Group 1) vs 500 ml/min (group 2) in HD patients from 10 renal clinics in
Colombia as an alternative to reduce water waste in chronic HD as a strategy from Blue
Planet Dialysis initiatives.
METHOD: We performed a Sub-analysis of CORHEX Study: We calculated water use
at different Qd from our database: prospective, multicentre, observational cohort study
of 992 adult patients undergoing chronic HD from 12 renal clinics in Colombia who
were switched from high-flux HD to MCO therapy and observed for 12 months. All
patients were prescribed with HDX three times a week for a minimum of 4 hours.
We analysed patients with weight lower than 70 Kg at different Qd prescriptions to
calculate water use at different Qd prescriptions and performed a prediction analysis,
adjusting to Qd 400 mL/min, the whole potential population with weight lower than 70
Kg.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

energy-efficient facilities may be an important prerequisite for improving the


environmental impact of dialysis. The Passive House concept is an internationally
recognised, performance-based energy standard in construction which so far has been
rarely applied to medical facilities and never to dialysis centres. We report our
experience with the first passive-house certified dialysis facility in Europe.
METHOD: The Passive House concept is a sustainable construction standard for
nearly zero energy buildings (the Resolution of the European Parliament of 31/01/2008
has called for its implementation by all member states by 2021). Principles and design
tools of the Passive House concept are freely available for all architects. The concept
combines a particularly high level of insulation with a specific system of ventilation.
Geothermal energy and energy from inside the building such as the body heat from the
residents or solar heat entering the building are the main energy sources. Passive House
buildings allow for heating and cooling related energy savings of up to 90% compared
with typical building stock and over 75% compared with average new buildings.
RESULTS: The François Berthoux Center (www.artic42.fr) is a 4 400 m2 dialysis
facility operated by 40 health care agents and providing care to 135 patients. It was
designed following the Passive-House standard, applied for the first time to such a
medical building. Several adjustments specific to the dialysis activity were necessary.
The most unexpected aspect was the importance of hemodialysis machines as an
energy source. Thorough thermal evaluation showed that the heat provided by
different type of hemodialysis machines was systematically superior to the energy
mandatory during the coldest day of the year (>10 W/m2). In practice, the center
turned out to be fully operational with no external source of heating. The downside was
that the geothermal pump system was not sufficient to fully regulate temperatures
during the warmest period of the year. Optimal cooling was achieved by the addition of
conventional AC systems in the hemodialysis rooms. Overall, as compared to a similar
FC135 A STEP TOWARD GREEN NEPHROLOGY: APPLYING THE
center, energy savings provided by the The François Berthoux Center were
PASSIVE HOUSE CONCEPT TO THE CONSTRUCTION OF
substantially less than what is expected from a conventional Passive House building
DIALYSIS FACILITIES
but were over 50%. The extra-cost of the construction was estimated to 3 to 5%.
CONCLUSION: In conclusion, the concept of eco-friendly building should extend to
Christophe Mariat1, Jocelyne Rey2, Annie Olivier2, Perrine Jullien2
1
dialysis facilities. Application of the Passive House Standard in the context of
University Jean Monnet - CHU de SAINT-ETIENNE - ARTIC 42, Nephrology, SAINT- hemodialysis requires to take into account some specificities that can impact the global
ETIENNE, France and 2ARTIC 42, Dialysis Center, SAINT-ETIENNE, France environmental performance of the building. However, the net result is clearly in favor
of such a construction, which is both affordable and sustainable.
BACKGROUND AND AIMS: The environmental impact of dialysis is now being
largely recognized. It requires from the nephrology community to actively explore
novel environmentally responsible health-care practices. Among them, conception of

i92 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i93–i94, 2021
10.1093/ndt/gfab077

ACID-BASE AND URIC ACID

MO002 THE EXPRESSION OF AQUAPORINS IN A MOUSE CEREBRAL


MO001 THE EUROPEAN DRTA REGISTRY: AN INITIAL DATA ISCHEMIC MODEL WITH MANNITOL EFFECTS
ANALYSIS*
Yasuko Tanaka1, Shin Koike2, Kaho Kashima1, Asuka Kaseda1, Kenichi Ishibashi1
Detlef Bockenhauer1, Francesco Emma2, Amina Talhi3, Svetlana Papizh4, 1
Meiji Pharmaceutical University, Pathophysiology, Kiyose, Tokyo, Japan and 2Meiji
Bahriye Atmis5, Nakisa Homan6, Bagdagul Aksu7, Fernando Santos8, Pharmaceutical University, Analytical Chemistry, Kiyose, Tokyo, Japan
Olivia Boyer9, Marc Fila10, Umut Selda Bayrakci11, Loai Akram Ouda Eid12,
Maria VanDyck13, Carlos Moguel14, Selçuk Yüksel15, Nur Canpolat16,
Franz Schaefer17, Jun Oh18, Max Liebau19, Maria Gema Ariceta Iraola14, BACKGROUND AND AIMS: As the brain edema influences the outcomes of many
Rosa Vargas-Poussou9, Elena Levtchenko13, Sergio Camilo Lopez-Garcia1, edematous brain diseases due to the limited intracranial space, the role of aquaporins
Tanja Wlodkowski17, Rezan Topologlu20 (AQPs) in brain edema needs to be clarified to advance its treatment especially in
1 increasing ischemic brain diseases. Although the importance of AQP4 at the Blood
University College London, Renal Medicine, London, United Kingdom, 2Bambino Ges u, Brain Barrier (BBB) has been well characterized, the roles of other AQPs is still
Roma, Italy, 3Hôpital Femme Mère Enfant - Service des Urgences, Bron, France, 4Pirogov unknown, especially a relatively new AQP11. As AQP11 is expressed in the brain
5
Russian National Research Medical University, Moskva, Russia, Çukurova University, capillary (Koike S et al. Int J Mol Sci. 17:861, 2016), AQP11 may also be important for
Medicine, Cukurova, Turkey, 6Iran University of Medical Sciences, Tehran, Iran, 7Istanbul the regulation of brain edema. The aim of the present study is to clarify the role of
University Faculty of Medicine, Turkey, 8University of Oviedo, Oviedo, Spain, 9Hôpital AQP11 in cerebral ischemic model to identify new treatment of cerebral edema.
Necker, Paris, France, 10Hospital Arnaud-De-Villeneuve, Montpellier, France, 11Ankara METHOD: AQP expression in the brain was examined by RT-PCR. Common cervical
Şehir Hastanesi, Turkey, 12Dubai, United Arab Emirates, 13UZ Gasthuisberg Campus, artery was ligated for 15 min to produce ischemic-reperfusion model of brain
Leuven, Belgium, 14Vall d’Hebron University Hospital, Barcelona, Spain, 15Pamukkale infarction to induce brain edema. As the first step to study the involvement of AQPs in
University, Turkey, 16Cerrahpaşa, Turkey, 17University Hospital Heidelberg, Heidelberg, this process, the mRNA expression of AQP1, AQP4, AQP11 and GFAP were
Germany, 18Uni Klink Eppendorf, Hamburg, Germany, 19Uniklinik Köln - Klinik und monitored after reperfusion which are expressed at BBB. As mannitol is often
Poliklinik für P€ €
adiatrie, Köln, Germany and 20Hacettepe Universitesi Tıp Fakültesi, Turkey employed for the treatment of brain edema, the effects of single or twice doses of 1.1M
mannitol 0.1 mL/g body weight i.p. on the expression of AQP1, AQP4 and AQP11
BACKGROUND AND AIMS: Distal renal tubular acidosis (dRTA) is a rare disorder mRNA were examined after 6 h in control mice. Furthermore, hypertonic 2M NaCl
characterised by an inability of the distal tubule to secrete acid, leading to metabolic was also challenged to simulate the osmotic effect: a single or twice doses of 2M NaCl
acidosis. Clinical consequences typically include hypokalaemia, hypercalciuria with 0.16 mL/g body weight were administered intraperitoneally, i.p.
nephrocalcinosis and/or urolithiasis, as well as bone disease. Treatment with adequate RESULTS: The expression of AQP1 mRNA increased by 20% one and two hours after
alkali supplementation corrects the acidosis and hypercalciuria, but there are few data 15-min ligation, while the expression of AQP4 mRNA decreased transiently just after
on long-term outcome. In 2018, a registry for dRTA was established by the European the ligation but increased at 24 h by 10%. On the other hand, the expression of AQP11
Society for Paediatric Nephrology, hosted by the European Rare Kidney Disease mRNA started to decrease from 30 min after the ligation to continue decreasing up to
Reference Network. Here, we present an initial analysis of data in the registry. 24h by 40% in wild mice, while the decrease of AQP11 mRNA only observed at 24h by
METHOD: Analysis of data entered into the registry by the cut-off data of 18/11/2020. 20% in AQP11 heterogenous KO mice. A single mannitol i.p. did not change serum
RESULTS: A total of 135 patients had been entered, of which 106 had additional data osmolality from 320 to 317 mOsm, while twice i.p. in 6 h interval increased serum
from an annual follow-up visit. Median age at last visit was 10 years (range 0-54), osmolality to 328 mOsm. Both procedures similarly decreased the expression of all
including 16 adults (>17y). Genetic testing had been performed in 91 subjects and AQPs: AQP1 by 80%, AQP4 by 40%, and AQP11 by 50%. Similar studies were
causative variants were reported in 74 (81%). Pertinent clinical details according to conducted with 2M NaCl. A single dose of 2M NaCl increased serum Na/Osm from
genetic group are listed in table 1. 151/319 to 154/322 mEq/mOsm, which decreased AQP1 by 50%, AQP11 by 35% and
Treatment was provided with at least 15 different preparations, containing citrate or no change of AQP4. On the other hand, twice doses in 3 h interval increased serum
bicarbonate, given in 1-10 (median 3) daily doses. Na/Osm to 208/435 mEq/Osm, which did not change all AQP expressions.
Adequate treatment at last follow-up, as judged by a plasma bicarbonate level >21 CONCLUSION: As AQP4 KO mice survive longer in brain edema models, decrease of
mmol/l and a urine calcium-creatinine ratio in the age-specific normal range was AQP4 by mannitol will be beneficial as brain infarction increased AQP4 expression in
present in 46% of subjects. our study. However, further decrease of AQP11 by mannitol will be detrimental as
There was a trend for higher eGFR and height SDS in subjects with adequate treatment AQP11 was already decreased in brain infarction. As AQP11 KO mice die within a
compared to those without, but this was not statistically significant. month due to polycystic kidneys, the studies on brain infarction in brain capillary
CONCLUSION: Currently available data demonstrate the difficulties in treating specific AQP11 conditionaly KO mice are currently underway.
dRTA, with less than half of subjects achieving adequate control of their acidosis. By
collecting long-term data, the registry will provide important information on the
prognosis and complications of dRTA and to what degree these can be prevented with
treatment. Enrollment of further, especially adult patients will contribute to our MO003 DISTAL RENAL TUBULAR ACIDOSIS IN PATIENTS WITH
understanding of this rare disorder. AUTOIMMUNE DISEASES

Oana Ion1,2, Valentina-Georgiana Fratila1,2, Andreea Gabriella Andronesi1,2,


Parameter/ ATP6V0A4 ATP6V1B1 SLC4A1 UNKNOWN Camelia Achim1,2, Elena Georgia Micu1, Roxana Jurubita1, Raluca Bobeica1,
genetic group Gener Ismail1,2
1
Subjects (N) 39 32 3 61 Fundeni Clinical Institute, Bucharest, Romania and 2Carol Davila University of
Medicine and Pharmacy, Bucharest, Romania
Age at presentation 1 (0-24) 2 (0-66) 1 (1) 2 (0-117)
(range) [months] BACKGROUND AND AIMS: Distal renal tubular acidosis (DRTA) is characterized
Median height -0.6 (-2.85 -0.9 (-5.32 -0.91 (-0.96 -0.72 (-4.44 by hyperchloremic metabolic acidosis, with normal anion gap and with the inability to
SDS (range) to 2.0) to 0.76 to -0.86) to -1.18) acidify the urine to a pH lower than 5.3. DRTA can evolve without symptoms and
systemic acidosis, this form being defined as incomplete DRTA, that necessitates the
Median eGFR 101 105 95 99 (44-190) use of a urinary acidification test like the Furosemide and Fludrocortisone test for
(range) ml/min/ (45-188) (62-185) establishing the diagnosis. There are several cases of type 1 DRTA reported in patients
with autoimmune diseases, especially Sjögren syndrome and systemic lupus
1.73m2 erythematosus (SLE), most of them being diagnosed due to severe symptoms caused by
the associated hypokalemia. The prevalence of the DRTA in patients with autoimmune
diseases is unknown, especially if we refer to the incomplete form.
METHOD: We conducted an observational prospective study in a selected cohort of
21 patients diagnosed with autoimmune diseases, who presented for evaluation in our
clinic during December, 2020 and January, 2021. We included patients diagnosed with
SLE, Sjögren syndrome, ANCA vasculitis, cryoglobulinemic vasculitis, who were

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

submitted to Furosemide/Fludrocortisone test in our nephrology department. The MO004 PRIMARY BILIARY CHOLANGITIS PRESENTING WITH RENAL
urinary pH was evaluated hourly for 6 hours after the test began. The test was FANCONI SYNDROME: A FORGOTTEN PHENOTYPE
considered positive if the urinary pH did not decrease < 5.3.
RESULTS: The study included 21 patients (16 females, 5 males, mean age 41.52 6 Chaoxui Er1, John Sayer1
1
17.58 years), diagnosed with SLE (13 patients, mean age 30.23 6 10.34 years, eGFR Newcastle Freeman Hospital, Renal Medicine, Newcastle-upon-Tyne, United Kingdom
81.61620.39 ml/min/1.73 m2), pANCA vasculitis (6 patients, mean age 60.83 6 6.14,
eGFR 40 6 12.64 ml/min/1.73 m2), Sjogren syndrome (one 44 year-old patient, eGFR BACKGROUND AND AIMS: Primary biliary cholangitits (PBC) is an autoimmune
39 ml/min/1.73 m2) and cryoglobulinemic vasculitis (one 69 year-old patient, eGFR 31 liver disease, leading to liver fibrosis and cirrhosis. It is a rare disease affecting 1 in 3-
ml/min/1.73 m2). The test was positive for 4 patients out of 21 (3 females, one male; 4000 people and is more common in females. Symptoms may go unnoticed and
one with SLE, one with pANCA vasculitis, one with Sjogren syndrome and one with include itch and fatigue. Most patients have anti-mitochondrial antibodies (AMA) as
cryoglobulinemic vasculitis). Although 2 patients developed hypokalemia defined as a well as raised gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)
level of serum potassium lower than 3.5 mmol/l after the test and 1 patient augmented levels. First line treatment for PBC is ursodeoxycholic acid and is usually continued
previous hypokalemia, there was not a significant change in kalemia (3.93 6 0.32 lifelong. It improves liver biochemistry, histological progression of liver disease and
mmol/l before the test vs 3.95 6 0.49 mmol/l after the test, p=0.835). Although none of liver transplant-free survival. Renal complications of PBC include distal renal tubular
the patients developed metabolic alkalosis after the test, there was a significant increase acidosis (RTA), tubule-interstitial nephritis (TIN) and renal Fanconi syndrome.
in the level of serum bicarbonate (26.6 (2.2) mmol/l before the test vs 28.2 (2.7) mmol/l METHOD: We reviewed a case of PBC presenting with renal Fanconi syndrome.
after the test, p=0.005) and also in the level of serum pH (7.36 6 0.04 before the test vs RESULTS: A 48-year-old female was referred to the renal clinic due to progressive
7.38 6 0.04 after the test, p=0.018). None of the patients reported digestive or allergic decline in renal function since she was diagnosed with type 2 diabetes in 2007. She was
side effects. It was interesting that the patients with vasculitis responded with delay to also known to have AMA (>1:640) and previously had transient transaminitis. She was
the treatment and urinary acidification under the pH of 5.3 occurred after a mean clinically well with no major symptoms but reported that she had had a few episodes of
period of 3.2 hours in comparison to 1.5 hours in patients with SLE (p=0.014). urinary tract infection in the previous year. Her diabetes was managed with lifestyle
Regarding the histological data, both the patients with vasculitis were elders, with an modifications in the past until a few months ago when Metformin was introduced.
altered kidney function (both with a eGFR of 31 ml/min/1.73 m2) and severe tubular However, her HbA1c level had never been greater than 55 mmol/mol. Urine dipstick in
atrophy and interstitial fibrosis on kidney biopsy. The female patient with the clinic showed pH of 6, bloodþ, glucoseþþþ, proteinþþþ and ketone trace. The
cryoglobulinemic vasculitis also had positive titers for antinuclear antibody, anti Ro- severity of glycosuria was inconsistent with her glycaemic control. There was a
antibodies and anti-La antibodies. The patient with Sjögren syndrome was diagnosed disparity between her urine albumin/creatinine ration (ACR) of 18.8g/mol and
with nephrocalcinosis and the kidney biopsy was not effectuated. The youngest patient protein/creatinine ratio (PCR) of 124mg/mmol. Myeloma screen was negative and
with a positive test had preserved renal function, without tubular or interstitial lesions further urine analysis showed generalised aminoaciduria. She also had hypouricaemia,
on kidney biopsy, but with a pattern of membranous lupus nephritis and with intense intermittent hypophosphataemia and non-anion gap metabolic acidosis. These results
immunological activity (ANA, anti ds-DNA antibodies, anti RNP and Sm antibodies, are in keeping with renal Fanconi syndrome. Her eGFR was 48 ml/min/1.72m2 in
antiphospholipid syndrome). 2007 and was 21 ml/min/1.72m at the time of review. A renal biopsy was undertaken,
CONCLUSION: Incomplete DRTA was found in 4 out of 21 patients with and the appearances were suggestive of mild tubulo-interstitial nephritis; the glomeruli
autoimmune diseases, one with Sjogren syndrome and nephrocalcinosis, two with were unremarkable; there was mild chronic tubulo-interstitial damage. She was started
pANCA and cryoglobulinemic vasculitis with decreased eGFR and severe tubular on oral steroid, sodium bicarbonate and ursodeoxycholic acid. The course of steroid
atrophy and interstitial fibrosis and one young female with SLE. had a slight transitory beneficial effect on the renal function.
CONCLUSION: Distal RTA is the usual renal feature of PBC, occurring in 1/3 of cases
with advanced disease. In contrast, proximal RTA associating with renal Fanconi
syndrome occurs rarely. Like our case, the cases that have been previously reported
show that Fanconi syndrome occurred during the early phase of PBC in the absence of
marked hepatic abnormalities, and were associated with CKD.
Fanconi syndrome and TIN are renal features of mitochondrial cytopathies and are
perhaps a forgotten association of PBC. Antimitochondrial antibodies may play a role
in the onset of tubulo-interstitial nephritis and Fanconi syndrome.

i94 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i95–i100, 2021
10.1093/ndt/gfab079

CELL SIGNALLING. CELL BIOLOGY. HORMONES

MO005 GENERATION OF NOVEL 3D CO-CULTURE SYSTEMS TO


STUDY PODOCYTOPATHIES EX VIVO IN A PERSONALIZED
MANNER*

Victoria Rose1, Nina Sopel1, Alexandra Ohs1, Christina Warnecke1,


Mario Schiffer1, Janina Müller-Deile1
1
Universit€atsklinikum Erlangen, Medizinische Klinik 4 – Nephrologie und
Hypertensiologie, Erlangen, Germany

BACKGROUND AND AIMS: The smallest filtration unit of the kidney, the glomerulus, CONCLUSION: We generated a 3D co-culture model that better represents the
is composed of capillaries formed by glomerular endothelial cells (GEC), glomerular complexity of the glomerulus ex vivo. It is indicated that this model provides better
basement membrane and podocytes. Furthermore, glomerular mesangial cells (GMC) physiological conditions. By an insertion of patient-specific hiPSC-derived podocytes
between the capillary loops give structural support. It is known that loss of podocyte foot in the 3D co-culture we will investigate glomerular diseases in a personalized manner
processes is leading to a dysfunctional glomerular filtration barrier and is seen in glomerular in the future.
diseases like focal segmental glomerulosclerosis and other podocytopathies.
Indeed, it is hard to investigate podocytes in culture because podocytes are terminally
end-differentiated cells that do not proliferate, lack foot processes and cell type-specific
markers. Although conditionally immortalized human podocytes regained the capacity
of proliferation, marker expression and behaviour differ between cell lines. The
overarching aims of this study are to generate a 3D glomerular co-culture model that
better reflects the in vivo phenotype of glomerular cell types. We want to investigate MO006 CHANGES IN THE KYNURENINE PATHWAY LEAD TO
cell-cell contact, interaction and communication and extracellular matrix production ALTERATIONS IN NAD BALANCE AND BIOENERGETICS
in 3D glomerular co-cultures. Furthermore, patient-derived hiPSC-podocytes will be PARAMETERS IN GLOMERULAR CELLS IN VITRO AND
used in the glomerular co-cultures to investigate podocyte disease in a personalized CONTRIBUTE TO PROTEINURIA IN A ZEBRAFISH MODEL*
manner and to identify potential therapeutic targets.
METHOD: The hanging droplet method was used to produce 3D glomerular Patricia Bolanos-Palmieri1, Ahmed Kotb1, Heiko Schenk2, Heike Ba €hre3,
spheroids. Therefore, human differentiated immortalized podocytes, human GECs and Patricia Schroder4, Mario Schiffer5
human GMCs were inserted in a medium-droplet hanging from the lid of a petri dish 1
Translational Research Center, Medizinische Klinik 4 – Nephrologie und
and harvested at different time points. Fluorescent cell lines of the different glomerular Hypertensiologie, Erlangen, Germany, 2Medizinische Hochschule Hannover,
cell types were tracked in a time-lapse experiment to study if cell attachment and Nephrologie, Hannover, Germany, 3Medizinische Hochschule Hannover, Research Core
spheroid formation undergoes a specific order and structure. Glomerular spheroids Unit Metabolomics, Hannover, Germany, 4MDI Biological Laboratory, Bar Harbor,
were further characterized regarding the expression of podocyte-specific markers and United States of America and 5Universit€
atsklinikum Erlangen, Medizinische Klinik 4 –
extracellular matrix synthesis by immunohistochemistry, electron microscopy and Nephrologie und Hypertensiologie, Erlangen, Germany
qPCR and were compared to human cells isolated from glomeruli. Furthermore,
scRNA-sequencing analysis was performed in 2D mono-cultures of human GECs, BACKGROUND AND AIMS: Tryptophan catabolism is carried out by the enzymes
GMCs and immortalized podocytes and on 3D co-cultures to see if this change in of the kynurenine pathway leading to the de novo synthesis of NAD and the
culture conditions leads to transcriptomic alterations. For the generation of patient- production of a series of bioactive metabolites. Kynurenine 3-Monooxigenase (KMO)
derived podocytes, skin fibroblast of patients with podocyte mutations (INF2 mutation is a key component of this pathway and it is one of the enzymes responsible for the
and WT1 mutation) and from healthy controls were reprogramed in iPSCs and degradation of kynurenine. The kynurenine metabolites participate in various cellular
differentiated into podocytes that keep the patient’s mutation. processes, so systemic dysregulation of tryptophan metabolism, marked by increased
RESULTS: First time-lapse experiments of glomerular co-cultures showed that human kynurenine in the circulation, has been linked to the onset and severity of a wide range
podocytes and human glomerular endothelial cells attach to each other (Fig. 1a) and of pathologies, such as chronic kidney disease and associated co-morbidities. Since the
histological sections revealed that the glomerular spheroids are encapsulated by a enzymes of the kynurenine pathway are expressed in the kidney and the metabolites
monolayer of cells (Fig. 1b). SEM allowed ultrastructural characterization of the 3D are cleared in the urine, we aim to describe the effects of changes in tryptophan
spheroid-like structures (Fig. 1c). TEM revealed cell protrusions of podocytes that were catabolism on glomerular cells, both in vitro and in vivo.
not seen in monocultures (Fig. 1d, e). We could also demonstrate production of METHOD: Modulation of KMO expression or enzymatic function was performed in a
extracellular matrix by the cells (Fig. 1f). Immunohistochemistry and qPCR showed transgenic zebrafish line that allows for the monitoring of a fluorescently labelled
expression of collagen-IV and laminin. During the reprogramming of patient-derived protein in the circulation as an indicator for proteinuria. Morpholinos targeting three
fibroblasts, size of the generated hiPSC decreased and the nuclei to cell body ratio enzymes of the kynurenine pathway were injected into fish embryos, leading to a
increased. HiPSCs formed colonies with distinct boarders and the proliferation rate knockdown of Afmid, Kmo and Kynu. Additionally, dechorionated larvae were treated
increased. Furthermore, generated hiPSC showed similar gene expression of with a Kmo inhibitor administered via the embryo rearing media, starting at 48hpf. In
pluripotency markers compared to a commercial hiPSC control cell line and podocytes all cases at 96hpf, circulating fluorescent protein levels were determined, larval
derived from these hiPSC expressed synaptopodin (Fig. 2). phenotype was scored based on the severity of the edema, and samples were collected
for metabolite analysis or fixed and prepared for imaging. Since the kynurenine
pathway results in the de novo production of NAD, and the enzyme KMO is located in
the outer mitochondrial membrane, cultured murine parietal epithelial cells as well as
immortalized human and mouse podocytes were incubated with a KMO inhibitor.
Changes in NADþ and NADH, as well as alterations in the mitochondrial membrane
polarization were assessed. Additionally, the oxygen consumption rate was measured
in order to determine if KMO inhibition leads to changes in the bioenergetics
parameters of glomerular cells in vitro.
RESULTS: The modification of Afmid, Kmo and Kynu expression levels by
morpholino mediated knockdown or inhibition of Kmo lead to the accumulation of
upstream kynurenine metabolites in the treated larvae, as was confirmed by mass
spectrometry analysis. Following our previous results, alteration of the kynurenine
pathway led to the development of yolk sac edema, pericardial effusion and loss of
protein from the circulation, accompanied by an enlargement of the Bowman’s space
and changes in nephrin expression in the glomerulus of the treated larvae. Under cell
culture conditions, KMO inhibition in immortalized podocytes led to a reduction in
cell size and focal adhesion proteins (podocalyxin). The NADþ/NADH ratio as well as
mitochondrial membrane polarity were also altered. Additionally, changes in spare
respiratory capacity, coupling efficiency and proton leak suggest that alterations in the

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

kynurenine pathway might impair the cell’s ability to adapt its bioenergetic profile in cells, the subtoxic concentration showed no significant effects in terms of reactive
response to stress. oxygen and nitrogen species (ROS and RNS) production, total glutathione levels
CONCLUSION: Taken together these results suggest that the modulation of (tGSH) or total antioxidant status (TAS). On the other hand, the EC50 showed
tryptophan catabolism through the kynurenine pathway may contribute to significant disruption of the oxidative status of the cell, with over 60 % depletion of
maintaining the structural integrity of glomerular cytoskeleton as well a flexible energy tGSH cell contents (p < 0.01) and a significant decrease of TAS (p < 0.05). However,
metabolism in podocytes. Moreover, the results from our in vivo model also suggest this effect was not accompanied by an increase, but rather by a significant decline in
that imbalances in kynurenine metabolites might ultimately impact the function of the ROS and RNS production of about 50 % below control (p < 0.0001). At the EC50, but
glomerular filtration barrier. not at EC01, it was also observed the disturbance of the mitochondrial and energetic
homeostasis, as showed by the increment of intracellular free calcium levels,
hyperpolarization of the mitochondrial membrane, and decay of the ATP levels (p <
0.0001). Cell death induced by gadolinium was characterized by typical morphological
MO007 ANALYSIS OF CALCIUM SIGNALING IN AUTOSOMAL
changes of late apoptosis and necrosis, with a significant increase in propidium iodide
DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)
uptake and lactate dehydrogenase leakage (p  0.0001) at EC50. The presence of
neutral lipids-containing vesicles was observed in the cytoplasm of cells exposed to
Dorien Van Giel1,2, Jean-Paul Decuypere2, Djalila Mekahli2,3, Rudi Vennekens1
1
gadolinium using the fluorescent dye BODIPY, already noticeable at the subtoxic
VIB Center for Brain and Disease Research, Laboratory of Ion Channel Research, concentration. Cells exposed to gadolinium also showed increased expression of IL6,
Leuven, Belgium, 2KU Leuven, Department of Development and Regeneration - PKD though this effect was only significant at the EC01 (p < 0.05).
Research Group, Leuven, Belgium and 3University Hospitals Leuven, Department of CONCLUSION: Gadolinium showed marked cytotoxic potential at micromolar levels
Pediatric Nephrology, Leuven, Belgium in HK-2 cells. This cytotoxicity was characterized by increased oxidative stress
independent of ROS and RNS production and mitochondrial dysfunction followed by
BACKGROUND AND AIMS: Autosomal Dominant Polycystic Kidney Disease cell death via late apoptosis and necrosis. At a subtoxic concentration, gadolinium was
(ADPKD) is an inheritable kidney disease characterized by the development of fluid- also able to elicit the accumulation of lipidic vesicles within the cells’ cytoplasm, and to
filled cysts in all nephron segments, leading to loss of renal function. Mutations in trigger a pro-inflammatory response. Although it is still unclear which amount of
PKD1 or PKD2, which encode polycystin-1 and polycystin-2, are the most common gadolinium is in fact released from the complexes commonly used as contrast agents,
cause of ADPKD. The molecular mechanisms underlying cystogenesis are poorly this study shows that gadolinium ion has direct nephrotoxic potential, with noteworthy
characterized but it is postulated that disturbed calcium homeostasis is a primary event manifestations at subtoxic concentrations.
in cystogenesis. The precise molecular players that cause this disturbance are still a ACKNOWLEDGMENTS: This work was supported by Applied Molecular Biosciences
poorly explored area, especially in relevant human cell types. We therefore aim to Unit (UCIBIO), financed by national funds from FCT/MCTES (UIDB/04378/2020), by
characterize the profile of calcium-coupled receptors and channels in a human renal North Portugal Regional Coordination and Development Commission (CCDR-N)/
epithelial cell model, to identify which receptors and channels are present and whether NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024).
their function is affected in ADPKD.
METHOD: Human urine-derived conditionally immortalized proximal tubule
epithelial cells (ciPTECs) of ADPKD patients and healthy controls were screened for
MO009 ROLE OF GDF-15, YKL-40, AND MMP-9 IN PATIENTS WITH
calcium-coupled GPCRs, using a GPCR agonist library on Fura-2 loaded cell
ESKD: FOCUS ON SEX SPECIFIC ASSOCIATIONS WITH
populations seeded in 96-well format using the Flexstation3 (Molecular Devices).
VASCULAR OUTCOMES AND ALL-CAUSE MORTALITY
Validation of specific hits was done using single-cell measurements with a fluorescence
microscope and built-in perfusion system. The expression of TRP channels and STIM/
Agne Laucyte-Cibulskiene1,2, Liam Ward1, Thomas Ebert1, Guilia Tosti3,
Orai proteins was determined via qPCR.
Claudia Tucci3, Leah Hernandez1, Peter Stenvinkel1, Valeria Raparelli3,
RESULTS: From a library of 418 GPCR agonists a selective amount of calcium-
Karolina Kublickiene1
coupled GPCRs was found functionally active in ciPTECs. ciPTECs from both healthy 1
controls and ADPKD patients were found to functionally express purinergic -, Karolinska Institutet, Division of Renal Medicine, Department of Clinical Science,
histamine -, serotonin and dopamine receptors. Through qPCR we found expression of Intervention and Technology, , Stokholm, Sweden, 2Lund University, Skåne University
various TRP channels, including TRPML1, TRPC1/3, TRPM3/4/7, TRPV4 and Hospital, Department of Clinical Sciences, Malmo, Sweden and 3Sapienza University of
TRPA1, as well as high expression of STIM1/2 and Orai1/2/3. Rome, Department of Experimental Medicine, Rome, Italy
CONCLUSION: We describe the first thorough characterization of molecular players
involved in calcium signalling mechanisms in human renal epithelial cells, including BACKGROUND AND AIMS: This study was performed on behalf of the GOING-
the profile of calcium-coupled GPCRs and the expression of TRP channels and STIM/ FWD Consortium.
Orai proteins, of further interest to investigate disturbed calcium dynamics in ADPKD. The importance of sex difference in the development of cardiovascular complications is
well appreciated, however, further studies are warranted to assess if sex specific
pathophysiological changes occur under uremic environment. Little is known about
the relationship between the uremic phenotype and novel cardiovascular biomarkers
MO008 NEPHROTOXIC MECHANISMS OF GADOLINIUM:
like growth differentiation factor 15 (GDF-15), cartilage glycoprotein 39 (YKL-40), and
IMPLICATIONS FOR THE USE OF GADOLINIUM-BASED
matrix metalloproteinase 9 (MMP9), and if they have a sex specific effects in relation to
CONSTRAST AGENTS
inflammation, vascular remodelling, cardiovascular outcomes and all-cause mortality.
Therefore, we hypothesise that there is a sex specific relationship between GDF-15,
Nıcia Reis Sousa1,2, Alice Santos-Silva3, Susana Coimbra2,3, Maria Joa ~o Valente3
1
YKL-40, MMP9 and vascular outcomes defined as athero-/arteriosclerosis and vascular
Instituto Superior Politécnico de Benguela, Departamento de Ci^encias e Tecnologia da calcification.
Saude, Benguela, Angola, 2Cooperativa de Ensino Superior Politécnico e Universitario METHOD: ESKD patients (n = 231), males (n = 152) and females (n = 79), not
(CESPU), Instituto de Investigaç~ao e Formaç~
ao Avançada em Ci^encias e Tecnologias da receiving renal replacement therapy were selected from two ongoing prospective CKD
Saude (IINFACTS), Gandra, Paredes, Portugal and 3UCIBIO, REQUIMTE, Laborat orio de cohorts from the Division of Renal Medicine, Karolinska University Hospital, Sweden.
Bioquımica, Departamento de Ci^encias Biol ogicas, Faculdade de Farmacia da Three putative CVD biomarkers, GDF-15, YKL-40 and MMP9 were analysed using
Universidade do Porto, Porto, Portugal enzyme-linked immunosorbent assay (ELISA) kits. Biomarker level/activity was
analysed in the context of gut microbiota derived TMAO, vascular calcification
BACKGROUND AND AIMS: Gadolinium-based contrast agents are widely used for (determined as CAC score on CT scans, aortic valve calcification (AVC) and medial
magnetic resonance imaging, and although they may be considered well tolerated at calcification on epigastric artery biopsies), inflammatory response, oxidative stress and
recommended dosing levels, recent evidences support the deposition of free all-cause mortality.
gadolinium in the tissues, and its slow release into circulation, resulting in long-term RESULTS: The levels of investigated biomarkers have not differed between female and
toxicity, which is aggravated in renal patients. The kidney, as the major excretion organ male patients with ESKD. However, GDF-15 correlated with TMAO in females from
of these agents, and particularly the proximal tubule, as a common location of more severe cohort that are not receiving renal replacement therapy yet, whereas in
xenobiotics’ bioaccumulation, may be key targets of gadolinium’s deleterious effects. males increased GDF-15 level was associated with higher Agatston score on CT-scans,
This study aimed at unveiling the nephrotoxic potential and the underlying inflammatory biomarker (IL-6) and oxidative stress biomarker 8-OHdG. None of
mechanisms of toxicity of gadolinium, using an in vitro model of normal human biomarkers was related to intimal medial calcification assessed in epigastric artery
proximal tubular cells (HK-2 cell line). biopsies. Comorbidity analysis revealed elevated GDF-15 levels in both females and
METHOD: HK-2 cells were exposed for 24 h to a wide concentration range of males, while increased MMP-9 levels were observed only in females with diabetes
gadolinium, in the form of trichloride hexahydrate, and cell viability was assessed to mellitus, but not with CVD. When assessing death of any cause in our cohorts, both
estimate the half maximal effective concentration (EC50) and the subtoxic deceased males and females had higher GDF-15 concentration (p = 0.01 and p < 0.001,
concentration eliciting 1 % of cell death (EC01). These ECs were further used to respectively), meanwhile only YKL-40 level was increased in deceased males (p = 0.02).
determine the effects of gadolinium on the cell’s oxidative status, mitochondrial CONCLUSION: In summary, here we report that in males GDF-15 and YKL-40 were
function, cell death mechanisms and lipid deposition, through variable colorimetric related to vascular calcification, inflammageing and oxidative stress, while in females
and fluorometric assays. Expression of the pro-inflammatory gene IL6 was also the relationship of GDF-15 with TMAO was observed. Higher MMP-9 level was seen
determined through quantitative PCR. in males without diabetes and in females with confirmed diabetes mellitus. YKL-40
RESULTS: Gadolinium induced cell death in a concentration-dependent manner, with increase in males and GDF-15 in both males and females were associated with all-cause
estimated EC01 and EC50 of 3 and 340 mM, respectively. When compared to control mortality. Our findings suggest that sex specific associations exist and those could have

i96 | Abstracts
Nephrology Dialysis Transplantation Abstracts
a potential to affect development of cardiovascular complications in patients with SV40 large T antigen. Ten to 12 days differentiated podocytes were used for
ESKD. experiments. Differentiated cells were either transfected with a miR-192 or control miR
mimic or pre-incubated with different inhibitors for components of both the canonical
and the non-canonical TGFb signaling pathways, followed by culture with or without
additional TGFb. Cell lysates were prepared to be used for Western Blot or qPCR
MO010 COLLAGEN TYPE VI PRODUCTION BY KIDNEY
analyses.
FIBROBLASTS IS DEPENDENT ON THE RIGHT STIMULI AND
RESULTS: Treatment of immortalized human podocytes with TGFb decreased NPNT
MAY SELF-PERPETUATE FIBROSIS
expression on mRNA and protein level. After transfecting immortalized human
podocytes with a miR-192 mimic, a GEC-derived miR up regulated by TGFb
Alexandra Louise Møller1,2, Daniel G. K. Rasmussen1, Morten A. Karsdal1,
stimulation, we observed reduced NPNT expression, compared to control miR
Federica Genovese1
1
transfection.
Nordic Bioscience A/S, Herlev, Denmark and 2University of Copenhagen, Biomedical Blocking TGFb receptor I signaling with the specific inhibitor SD208, caused higher
Sciences, Faculty of Health and Medical Sciences, Copenhagen, Denmark NPNT protein abundance, while NPNT mRNA expression remained unchanged.
Targeting downstream parts of both the canonical and non-canonical TGFb pathways
BACKGROUND AND AIMS: Accumulation of extracellular matrix (ECM) proteins by using inhibitors for single molecules of the respective arms of the intricate TGFb
is a hallmark of kidney fibrosis, which can lead to altered tissue homeostasis, kidney pathway showed ambiguous results. Suppression of either Smad2 and/or Smad3
failure, and ultimately death. Many different cell types are involved in this process, but tended to enhance NPNT protein levels, accompanied by mostly unaltered mRNA
fibroblasts are the main source of ECM proteins such as collagen type I (COL I), III expression. Blockade of different parts of the non-canonical TGFb pathway also up
(COL III), and VI (COL VI). Recently, it was suggested that a fragment of COL VI, regulated protein expression of NPNT. However, NPNT mRNA expression was more
released during collagen maturation, is a bioactive molecule (endotrophin; ETP) with variable. Therefore, regulation of podocyte NPNT might not be due to changes in
signaling potential, indicating that collagens are not just passive structural proteins. In mRNA transcription, but to modifications on posttranscriptional level.
this study, we investigated the effect of different pro-fibrotic stimulants on COL VI CONCLUSION: Treating immortalized human podocytes with TGFb or TGFb-
production and the effect of ETP itself on human kidney fibroblasts in the scar-in-a-jar induced miR-192 reduced NPNT expression on both the mRNA and protein level.
(SiaJ) cell model. More detailed analysis with inhibition of different parts of the canonical and non-
METHOD: Cells were seeded in 48-well plates at 30.000 cells/well and incubated for canonical TGFb pathways hint that both pathways are involved in NPNT expression.
24h in DMEM þ 10% FBS for adherence. Cells were then starved by incubating them Therefore, we suggest that the regulation of podocyte NPNT by TGFb is fine-tuned via
for further 24h in DMEM þ 0.4% FBS. To induce fibrogenesis, fresh medium was both the canonical and non-canonical pathways with additional modulation through
added at day 0 with 225/150 mg/mL Ficoll 70/400 and 1% ascorbic acid, containing TGFb dependent miRs.
either 7-, 0.7-, or 0.07 nM PDGF-AA, 8-, 0.8-, or 0.08 nM PDGF-BB, 4-, 0.4-, or 0.04
nM PDGF-CC, 7-, 0.7-, or 0.07 nM PDGF-DD, 0.9-, or 0.09 nM CTGF, 0.02 nM TGF-
b or 30 nM ETP. Medium was changed and collected on days 3, 6, 10, and 13.
MO012 ACE2 AND SARS-COV-2 INFECTION RISK: INSIGHTS FROM
Biomarkers of COL I (PRO-C1), III (PRO-C3), and VI (PRO-C6) formation were
PATIENTS WITH TWO RARE GENETIC TUBULOPATHIES,
assessed in the medium by enzyme-linked immunosorbent assays developed at Nordic
GITELMAN‘S AND BARTTER’S SYNDROMES
Bioscience.
RESULTS: The stimulation of kidney fibroblasts with PDGF-AA, -BB, -CC, and -DD
Giovanni Bertoldi1, Matteo Rigato1, Luca Sgarabotto1, Lisa Gianesello1,
caused an increase in PRO-C6 compared to the unstimulated cells at every time point
Verdiana Ravarotto1, Paul A Davis2, Lorenzo Calo 1
(P<0.0001). The increase in formation peaked at day 10, and a dose-dependent 1
increase in COL VI levels was observed with PDGF-DD treatment. Interestingly, University of Padova, Department of Medicine, Nephrology, Dialysis and
CTGF treatment did not enhance the synthesis of COL VI at any time point, and TGF- Transplantation Unit, Padova, Italy and 2University of California at Davis, Department
b treatment suppressed PRO-C6 levels compared to the untreated cells (not of Nutrition, Davis, United States of America
significant). The stimulation with 30 nM ETP caused an increase in PRO-C1
(P<0.0001) and PRO-C3 (P<0.0001) compared to the unstimulated cells on days 6, 10, BACKGROUND AND AIMS: COVID-19 is spreading globally with Angiotensin
and 13. The increase in collagen formation peaked at day 10 for both markers, with a Converting Enzyme (ACE)-2 serving as the entry point of SARS-CoV-2 virus. This
7.28-fold increase for COL I and a 4.13-fold increase for COL III. raised concerns how ACE2 and Renin-Angiotensin (Ang)-System (RAS) are to be dealt
CONCLUSION: The production of COL VI, an important mediator of fibrosis and with given their involvement in COVID-19’s morbidity and mortality. Specifically,
inflammation through its bioactive fragment endotrophin, shows a differential expression increased ACE2 expression in response to treatment with ACE inhibitors (ACEi) and
after stimulation of kidney fibroblasts with different pro-fibrotic growth factors. Ang II receptor blockers (ARBs) might theoretically increase COVID-19 risk by
Interestingly, members of the PDGF family induced COL VI production, whereas CTGF increasing SARS-CoV-2 binding sites. However, ACE2 is part of the protective
and TGF-b did not. Moreover, we confirmed that ETP itself could stimulate kidney counter-regulatory ACE2-Ang1-7-MasR axis, which opposes the classical ACE-AngII-
fibroblasts to produce more ECM proteins; hence COL VI may self-perpetuate fibrosis. This AT1R regulatory axis. We used Gitelman’s and Bartter’s syndromes (GS/BS) patients,
SiaJ model, combined with ECM formation biomarkers, could be used to elucidate the rare genetic tubulopathies, who have endogenously increased levels of ACE2, to
mechanisms behind acute and sustained matrix production profiles in vivo. provide more insight on these issues.
METHOD: 128 genetically confirmed GS/BS patients, living in Lombardia, Emilia
Romagna and Veneto, the Northern Italy hot spots for COVID-19, were surveyed via
telephone survey regarding COVID-19.
MO011 PODOCYTE NEPHRONECTIN IS REGULATED BY
RESULTS: The survey found no COVID-19 infection and absence of COVID-19
TRANSFORMING GROWTH FACTOR BETA VIA THE
symptoms in any patient. Comparison analysis with the prevalence of COVID-19 in
CANONICAL AND NON-CANONICAL PATHWAYS
those Regions [8.96% (95% CI 8.96-8.99% vs 0.00% (95% IC 0.00-3.62%)] showed
statistical significance (p<0.01).
Nina Sopel1, Alexandra Ohs1, Mario Schiffer1, Janina Müller-Deile1
1
CONCLUSION: The results of the study contribute to suggest that increased ACE2 does
Universit€atsklinikum Erlangen, Medizinische Klinik 4 – Nephrologie und not increase risk of COVID-19 and that ACEi and ARBs by blocking excessive AT1R-
Hypertensiologie, Erlangen, Germany mediated Ang II activation, might favour the increase of ACE2-derived Ang 1-7. The GS/BS
patients’ increased ACE2 and Ang 1-7 levels and their characteristic chronic metabolic
BACKGROUND AND AIMS: The glomerular basement membrane (GBM), alkalosis might suggest for SARS-COV-2 a mechanism similar to that of chloroquine/
podocytes and glomerular endothelial cells (GEC) are composing the glomerular hydroxychloroquine effect altering ACE2 glycosylation which resulted, in previous studies,
filtration barrier (GFB) within the glomerulus. Both podocytes and GEC are essential in SARS-COV binding inhibition and block/inhibition of viral entry. Studies from our
components for the synthesis of the extracellular matrix (ECM) of the GBM. laboratory are ongoing to explore in GS/BS ACE2 glycosylation.
One ECM protein of the GBM, which is mainly produced by podocytes is
nephronectin (NPNT). An altered expression pattern of NPNT has been observed in
different kidney diseases. While NPNT was shown to be down regulated in
MO013 SENESCENCE-LIKE CHANGES IN B CELL PHENOTYPE IN
membranous glomerulonephropathy, its expression was elevated in diabetic
HEMODIALYSIS PATIENTS
glomerulopathy, compared to healthy controls.
Using a morpholino-induced knockdown of npnt in zebrafish larvae, proteinuria,
Georgios Lioulios1, Asimina Fylaktou2, Aliki Xochelli2, Erasmia Sampani1,
podocyte foot process effacement and thickening of the lamia rara interna of the GBM
Ioannis Tsouchnikas1, Panagiotis Giamalis1, Dimitra Vasileia Daikidou1,
were observed. Mice that were intra peritoneally injected with a microRNA 378a (miR-
Zoi Mitsoglou1, Aikaterini Papagianni1, Maria Stangou1
378a) mimic showed a decrease in NPNT expression in the kidneys on both mRNA 1
and protein level, suggesting a regulatory effect of miR-378a on NPNT. In addition, in Ippokrateio - General Hospital of Thessaloniki, Department of Nephrology, Aristotle
cultured human podocytes treatment with transforming growth factor beta (TGFb), as University of Thessaloniki, Thessaloniki, Greece and 2Ippokrateio - General Hospital of
well as transfection with miR-378a mimic down regulated NPNT mRNA and protein Thessaloniki, Department of Immunology, National Peripheral Histocompatibility
expression. Center, Thessaloniki, Greece
By blocking different parts of the TGFb pathway, we want to further investigate the
mechanisms by which TGFb mediates the regulation of NPNT in podocytes. BACKGROUND AND AIMS: End Stage Renal Disease (ESRD) is characterized by
METHOD: Our main model for this study are immortalized human podocytes, which susceptibility to infections, high prevalence of cancer and cardiovascular disease and
are proliferating at 33 C and differentiating at 37 C due to a temperature sensitive poor response to vaccination. All of the above are potential consequences to

10.1093/ndt/gfab079 | i97
Abstracts Nephrology Dialysis Transplantation

compromised immune function seen in ESRD and demonstrated by profound immune METHOD: The rat MCs treated with different concentrations of DHI (0, 50, 100, 200, 500,
cells phenotype changes, resembling the natural course of senescence; therefore termed 1000, and 2000 uL/L) for 12 h, then incubated with or without 100 ng/ml LPS for another 24
immunosenescence. Whereas alterations of T cells in ESRD have been largely studied, h. Subsequently, cell proliferation was determined by Cell Counting Kit-8 (CCK8).
there are insufficient data regarding B cell immunity. In this study we evaluate the Furthermore, the rat MCs treated with low-dose DHI (250 uL/L), median-dose DHI (500
effects of hemodialysis (HD) on B cells, in terms of untimely expression of uL/L) and high-dose DHI (1000 uL/L) for 12 h or Ammonium pyrrolidine dithiocarbamate
immunosenescent phenotype. (PDTC) for 30 min before 24h treatment of LPS. Then the activation of NF-jB was detected
METHOD: B cells phenotype was analyzed by flow cytometry in 25 ESRD patients on by Western blot and immunofluorescence. The protein levels of ICAM-1, TGF-b1, iNOS
HD (M/F 15/10, Mean Age 59614.7yrs). Patients on HD with systemic diseases, and FN in rat MCs were detected by Western blot.
malignancy or recent (<3 months) episode of infection were excluded. Subpopulations,
including naı̈ve (IgDþCD27-), IgM memory (IgDþCD27þ), switched memory (IgD-
CD27þ) and late memory (IgD-CD27-) B cells were determined. Findings were
compared to 12 healthy controls of similar age.
RESULTS: In HD patients a severe B lymphopenia was observed; a decrease in B cells both
percentage (6.562.7% vs 11.964.5%, p<0.0001) and absolute number [88(53) vs 229(271)
cells/ll, p<0.0001]. Naı̈ve and late memory B cells proportions were similar between
patients and controls, however, absolute number was significantly lower in HD patients for
both subsets [55(54)vs118(216) cells/ll, p=0.006, and 7(7) vs 21(24) cells/ll, respectively,
p=0.001]. Switched memory B cells declined in HD both in terms of percentage [15.7(11.7)%
vs 25.7(18.9)%, p:0.03] and absolute number [13(10) vs 59(64) cells/ll, p=0.00].
CONCLUSION: Chronic hemodialysis results in B cell phenotype alterations similar
to normal aging. Switched memory B cells, the predictors of optimal antibody
responses are significantly reduced, and this may act as an additional factor to relative
immune deficiency of dialysis patients.

MO014 DANHONG INJECTION INHIBITS LIPOPOLYSACCHARIDE-


ENHANCED CELL PROLIFERATION OF RAT RENAL
MESANGIAL CELLS VIA NF-KB SIGNALING PATHWAY

Liu Hua1, Lei Chen2, Limin Wei2, Hongli Jiang1


1
the First Affiliated Hospital of Xi‘an Jiaotong University, Dialysis Department of
Nephrology Hospital, Xi’an, P.R. China and 2the First Affiliated Hospital of Xi‘an
Jiaotong University, Dialysis Department of Nephrology Hospital

BACKGROUND AND AIMS: Mesangioproliferative glomerulonephritis (MsPGN) is


well known as one of the leading causes of end-stage renal failure (ESRD), especially in
the Asian population. The principal characteristic of MsPGN is the over proliferation
of glomerular mesangial cells (MCs) accompanied by expansion of the extracellular
matrix (ECM). Our previous studies demonstrated that Danhong injection (DHI), is a
traditional Chinese medicine injection, could improve the renal function and inhibit
the MCs proliferation and ECM expansion in rats with MsPGN. However, the
molecular mechanisms have not been fully elucidated. To explore the potential
mechanisms of DHI in the treatment of MsPGN, we investigated the effects of DHI on
lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-jB) activation and its
downstream inflammatory mediators, such as intercellular adhesion molecule-1
(ICAM-1), transforming growth factor-beta 1 (TGF-b1), inducible nitric oxide
synthase (iNOS) and fibronectin (FN) protein expression in rat MCs.

i98 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: The results of CCK-8 revealed that DHI significantly suppressed LPS- CD8þ cells. Proportions and absolute numbers of CD4þCD28null and
induced cell proliferation (shown in Fig.1). LPS stimulation resulted in a significant CD8þCD28null cells were estimated, and results were correlated to patients age and
increment of p65 contents in nucleus and a decrement of p65 contents in cytoplasm in time on HD. Patients with malignant or systemic disease were excluded, as those with
rat MCs compared with NC. PDTC and DHI exerted potent inhibitory effect on inadequate HD (KT/V<1,2), or recent (<3months) infection. Results were compared
increasing expression of p65 in nucleus and decreasing in cytoplasm compared with to those of 27 healthy controls, similar age, sex, and race.
LPS treatment group. The inhibitory effect on NF-jB nuclear translocation of DHI was RESULTS: HD patients had significantly reduced lymphocyte count (p<0.001),
in a dose- dependent manner (shown in Fig.2). The Western blot assay showed that the percentage and total count of CD3þ cells (p=0.04, p<0.0001, respectively) and CD4þ
protein level of IjB-a in cytoplasm treated by LPS decreased significantly compared cells (p=0.005, p<0.001, respectively). Percentage of CD4þCD28null and
with that in control (shown in Fig. 3) and this decrement was significantly reversed by CD8þCD28null cells were both increased in patients compared to controls (p=0.009,
PDTC and DHI. In addition, the protein expression of ICAM-1, TGF-b1, iNOS and p=0.01, respectively). However, although changes in CD8CD28null cells were evident
FN was also inhibited by PDTC and DHI (shown in Fig. 4). early, even in <2yrs, similar changes in CD4CD28null cells, appeared only after 2yrs
CONCLUSION: DHI significantly repressed LPS-induced cell proliferation and FN on HD, (p=0.004).
expression in rat MCs through inhibiting the activation of NF-jB signaling pathway Age of the patients had significant correlation with CD8þCD28null cells (r=0.4,
and protein expression of its downstream inflammatory mediators. The ameliorative p=0.001). In the older groups (>40yrs) patients had significantly increased
effects of DHI on MsPGN might be associated with this inhibition effect on NF-B CD3þCD28null, CD4þCD28null and CD8þCD28null cells, compared to older
signaling pathway. controls (p=0.002, p=0.003, p=0.01, respectively).
CONCLUSION: CD28 expression is significantly reduced on CD4þ and CD8þ cells
in HD patients. CD8þCD28null expression is significantly affected early, both by age
and HD, while CD28 expression on CD4þ seems to be more stable, as CD4þCD28null
MO015 ANALYZING THE EFFECT OF MICROPLASTIC PARTICLES
cells increase in older patients, after long time on HD.
ON HUMAN PODOCYTES

Melina Yarbakht1, George Sarau2, Lasse Kling2, Janina Müller-Deile1,


Ahmed Kotb1, Silke Christiansen2, Mario Schiffer1 MO017 THERAPEUTICAL POTENTIAL OF ENZYME REPLACEMENT:
1
Friedrich-Alexander University,Translation Research Center, Department of Nephrology, NEW INSIGHTS AND PERSPECTIVES IN HUMAN
University Hospital, Erlangen, Germany and 2Max Planck Institute for the Science of ENDOTHELIAL CELLS TREATED WITH CHLOROQUINE
Light, Erlangen, Germany
Paulo C. Gregorio1, Regiane Cunha1, Gilson Biagini2, Bruna Bosquetti1,
Julia Budag1, Alberto Ortiz3,4, Maria Dolores Sanchez-Nino4,5, Fellype Barreto2,
BACKGROUND AND AIMS: Despite increasing use of plastic based products and
Andréa E. M. Stinghen1
their potential health risks on the humans, very little is known about their possible 1
accumulation in the food chain and their further long-term effect on the human health. Universidade Federal do Paran a Campus Centro Politécnico, Basic Pathology
Recently, there are increasing reports related to the potential risk of polystyrene Department, Experimental Nephrology Laboratory, Curitiba, Brazil, 2Universidade
microplastics to the human respiratory system and human intestinal epithelia cell line. Federal do Paran a, Internal Medicine Department, Division of Nephrology, Curitiba,
In this study, we assayed the primary effect of microplastic particles on the human Brazil, 3Hospital Universitario Fundacion Jiménez Dıaz, Nephrology and Hypertension
kidney cells. To that aim, we used human podocytes cells and four different types of Division, Madrid, Spain, 4IIS, Fundaci
on Jiménez Diaz, Madrid, Spain and 5Autonomous
plastic particles including; polyvinyl chloride (PVC), polypropylene (PP), polyamide University of Madrid, 6Department of Pharmacology, School of Medicine, Madrid, Spain
(PA) and tyre wear particles to evaluate the effects of microplastics on the viability and
morphology of human podocytes in vitro. BACKGROUND AND AIMS: COVID-19 is a pandemic with no end in sight. There is
METHOD: In this study, we applied different biological methods such as, cell viability only one approved antiviral agent but global stocks are deemed insufficient. Despite in
test and phalloidin staining, to assay the toxicity of particles and their further effects on vitro antiviral activity, clinical trials of chloroquine and hydroxychloroquine were
the actin cytoskeleton organization in human podocytes, respectively. Furthermore, disappointing, and they may even impair outcomes. Chloroquine causes zebroid
Raman imaging is used to track particle attachment on the cells and to evaluate the deposits reminiscent of Fabry disease (a-galactosidase A deficiency) and endothelial
possible changes in the cell compartment following the particle treatment. The particle cells are key targets of COVID-19. The study aims to investigate in vitro the effect of
uptake by the cells and changes in cellular biological features were visualized with the enzyme replacement therapy (ERT) in chloroquine-induced endothelial dysfunction.
use of scanning electron microscopy (SEM). METHOD: We have explored the effect of chloroquine on cultured endothelial cells
RESULTS: As a primary result, the cytotoxicity response of particle treatment was and its modulation by recombinant a-galactosidase A (agalsidase-b). Following dose-
found to be dependent on the polymer type. As an example higher concentration of PP response studies, 0.5 lg/mL chloroquine was added to cultured human endothelial
particle as compared to PVC, PA, and tyre wear caused a similar rate of cell mortality. cells. Neutral red and Lysotracker were used to assess lysosomes. Cytotoxicity was
Furthermore, the degree of particle attachment on the cells depended on their adhesion evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) -
properties, which was higher in PA, PVC and tyre wear in comparison to PP particles. MTT assay and cell stress by assessing reactive oxygen species (ROS) and nitric oxide
These particles remained attached to the cell surface even after two-three times of (NO). In endothelial cells, chloroquine induced dose-dependent cytotoxicity at in vitro
washing with PBS. Based on the phalloidin staining results, particle treatment induced test concentrations for COVID-19 therapy.
cytoskeleton reorganization in podocytes in vitro. With the use of Raman imaging RESULTS: Chloroquine significantly induced the accumulation of acid organelles
particle attachment was confirmed based on the fingerprint spectra related to each (P<0.05), increased ROS levels, and decreased NO production (P<0.05), in vitro.
particle. These adverse effects of chloroquine on endothelial cell biology were decreased by
CONCLUSION: This study suggests that exposure duration and particle agalsidase-b (P<0.05).
concentrations are two of the key factors to evaluate the toxicological effect of particles CONCLUSION: Chloroquine-induced endothelial cell cytotoxicity and stress is
on podocytes as a highly-specialized epithelial cells in the kidney. It is supposed that attenuated by agalsidase-b treatment. This suggests that endothelial cell injury may
two mechanisms can be related to the harmful effects of plastic particles on podocytes. contribute to the failure of chloroquine as therapy for COVID-19 and may be at least
First, particle attachment on the cell surface leading to limitation of nutrient uptake by in part related to causing dysfunction of the lysosomal enzyme a-galactosidase A.
the cells. Second, uptake of smaller size particles into the cells through phagocytosis.
More studies are necessary to determine the direct effect of microplastics on human
kidney cells.

MO016 CD28 AS A MARKER OF T CELL IMMUNOSENESCENCE IN


PATIENTS ON HEMODIALYSIS

Georgios Lioulios1, Erasmia Sampani1, Dimitra Vasileia Daikidou1, Aliki Xochelli2,


Efstratios Kasimatis1, Zoi Mitsoglou1, Maria Stangou1, Asimina Fylaktou2,
Aikaterini Papagianni1
1
Ippokrateio - General Hospital of Thessaloniki, Department of Nephrology, Aristotle
University of Thessaloniki, Thessaloniki, Greece and 2Ippokrateio - General Hospital of
Thessaloniki, Department of Immunology, National Peripheral Histocompatibility
Center, Thessaloniki, Greece

BACKGROUND AND AIMS: Reduced expression of CD28 molecule on CD4þ and


CD8þ cells is a potential marker of senescence and has also been described in end
stage renal disease (ESRD). Aim of the present study was to evaluate changes of CD28
expression on CD4þ and CD8þ cells in ESRD patients, and to assess possible effects of
ageing and HD.
METHOD: Flow cytometric analysis was performed in 96 patients [M/F 54/42 Age
56.6(18-81)yrs] on HD to evaluate the expression of CD28 antigen on CD4þ and

10.1093/ndt/gfab079 | i99
Abstracts Nephrology Dialysis Transplantation

MO018 QUORUM SENSING MOLECULE INDUCES THE RECEPTOR- CONCLUSION: Treatment of 3OC12-HSL reduces endothelial cell viability, and this
INTERACTING PROTEIN KINASE 1-DEPENDENT APOPTOSIS effect is synergistical with LPS. 3OC12-HSL induces apoptotic cell death, through the
SYNERGISTICALLY WITH LIPOPOLYSACCHARIDE IN activation of the RIPK1 pathway, moreover, it is amplified in combination with LPS.
ENDOTHELIAL CELLS

Jungho Shin1, Sun Hee Ahn1, Dong-Jin Oh2


1
Chung-Ang university, Internal Medicine, Seoul, Korea, Rep. of South and 2Hanyang
University, Internal Medicine, Goyang, Korea, Rep. of South

BACKGROUND AND AIMS: Endothelial dysfunction is an initial step for sepsis-


associated organ failure. Bacterial quorum sensing molecules play as pathogen-
associated molecular patterns, however, the impact of quorum sensing molecules on
endothelial cells remains uncertain. This study investigated the molecular mechanism
of quorum sensing molecule-induced cell death and the interaction with
lipopolysaccharide (LPS) in human umbilical vein endothelial cells.
METHOD: Endothelial cells were treated with varying concentrations of N-3-
oxododecanoyl-HSL (3OC12-HSL) and LPS derived from Pseudomonas aeruginosa.
RESULTS: Treatment of 3OC12-HSL reduced cell viability in dose-dependent
manners, and the combination of this molecule and LPS exacerbated cell deaths in
compared to single treatment of LPS. The terminal deoxynucleotidyl transferase dUTP
nick end labeling assay revealed that there were clear increases in apoptotic death
following the 3OC12-HSL treatment. Treatment of 3CO12-HSL activated the receptor-
interacting protein kinase 1 (RIPK1) pathway, resulting in increases in expression of
caspase 8 and caspase 3. Moreover, the combination treatment of LPS and 3OC12-HSL
amplified these expressions.

i100 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i101–i105, 2021
10.1093/ndt/gfab081

RENAL DEVELOPMENT AND CYSTIC DISEASES

MO020 AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE,


MO019 MATERNAL UNDERNUTRITION AMELIORATES CYST CYTOPENIA AND POSTTRANSPLANT OUTCOMES: A
GROWTH IN ADPKD MODEL MICE* RETROSPECTIVE ANALYSIS

Junpei Yoshikawa1, Nishio Saori1, Fumihiko Hattanda1, Daigo Nakazawa1, Pieter Schellekens1,2, Djalila Mekahli2,3, Rudi Vennekens4, Isabelle Meyts5,6,
Tatsuya Atsumi2 Dirk Kuypers1, Bert Bammens1
1 1
Hokkaido University Graduate School of Medicine, The Division of Rheumatology, University Hospitals of Leuven, Department of Nephrology, Dialysis and Renal
Endocrinology and Nephrology, Department of Medicine 2, Sapporo, Japan and 2 Transplantation, Leuven, Belgium, 2KU Leuven, Department of Development and
Regeneration, GPURE, PKD Research Group, Laboratory of Pediatrics, Leuven, Belgium,
3
BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease University Hospitals of Leuven, Department of Pediatric Nephrology, Leuven, Belgium,
4
(ADPKD) is characterized by the progressive development of kidney and liver cysts. KU Leuven, Department of Cellular and Molecular Medicine, VIB Centre for Brain and
The major factors predicting disease progression in ADPKD are total kidney volume, Disease Research, Laboratory of Ion Channel Research, Leuven, Belgium, 5KU Leuven,
genotype, age, sex. Recently, several studies have suggested that dietary intervention Department of Microbiology, Immunology and Transplantation, Inborn errors of
might be a potential treatment to prevent ADPKD progression. On the other hand, it immunity, Leuven, Belgium and 6University Hospitals of Leuven, Department of
has been reported that low-birth weight infants because of maternal global nutrient Pediatrics, Pediatric Immunology, Leuven, Belgium
restriction are at increased risk for hypertension, type 2 diabetes, and metabolic
syndrome and chronic kidney disease. However, little has been reported on BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease
relationship between maternal undernutrition and cyst formation in ADPKD. (ADPKD), the most common monogenetic inherited kidney disease, has been reported
Therefore the purpose of this study is to clarify whether maternal undernutrition is to be associated with distinct cytopenias. The pathophysiological mechanism behind
associated with progression in ADPKD. this association and its clinical implications are unknown. Sparse and conflicting data
METHOD: We used Pkd1 conditional knockout mice (Pkd1flox/floxMx1-Cre mice). have suggested a tendency to greater vulnerability for cancer and infections in ADPKD
The offspring of dams given food ad libitum (control(CON)) and those subjected to renal transplant recipients as compared to their non-ADPKD counterparts.
nutrient restriction throughout pregnancy (food restriction (FR)) were examined. In Furthermore polycystin expression has been demonstrated in lymphocytes in vitro
FR, nutrient-restricted mothers were given about half amount of food by control mice with impact on lymphocyte function. From this background, cytopenia could be
during pregnancy. After delivery, food for children was given ad libitum. Mice were hypothesized to be directly induced by the molecular PKD defects and to impact on
injected with polyinosinic-polycytidylic acid for 6 consecutive days from postnatal day outcome in affected patients. The main interest of the current study is to confirm the
5 (P5) to P10 to inactivate Pkd1. We analyzed the phenotype of cystic kidneys by association between ADPKD and cytopenia in a well-defined clinical cohort of patients
kidney/body weight ratio (2KW/BW), and cystic index (CI) which was defined as the at the time of kidney transplantation. Furthermore, the impact of ADPKD and
percentage of areas occupied by cysts at P20, 35, 56. We carried out a series of analyses cytopenia on posttransplant outcomes is studied.
by kidney/body weight ratio, liver /body weight ratio or cystic index (CI) which was METHOD: Baseline (pre-transplantation) and follow-up data from all patients who
defined as the percentage of areas occupied by cysts. Elastica-Masson staining was underwent a first renal transplantation between 01/04/1964 and 01/09/2019 at the
performed for analyzing tissue fibrosis. The fibrotic index (FI) was expressed as the Leuven University Hospitals were retrieved from the renal transplantation database.
(fibrotic area/ total non-cystic area) 100 (%). For evaluation of glomerular RESULTS: 4103 patients were included: 611 ADPKD and 3492 non-ADPKD.
hypertrophy, glomerular area was measured in PAS-stained kidney sections using Immediately before transplantation, significant differences in total white blood cell
Image J software. The assay of renal function was performed by using UN-ML kit. We (6.33 þ/- 2.59 ADPKD versus 7.17 þ/- 2.21 non-ADPKD; p<0.0001), neutrophil (4.04
also performed western blotting of signaling pathway of proliferation by using whole þ/- 1.59 versus 4.54 þ/- 1.88; p<0.0001), lymphocyte (1.45 þ/- 0.05 versus 1.57 þ/-
kidneys. Data are shown as mean 6 SEM. Two-tailed Student’s t-test was performed 0.68; p<0.0001), basophil (0.041 þ/- 0.084 versus 0.046 þ/- 0.048; p<0.0001),
for comparing two groups. eosinophil (0.23 þ/- 0.24 versus 0.29 þ/- 0.33; p<0.0001) and thrombocyte counts
RESULTS: Food restriction of pregnant dams reduced birth weight. (FR 1.2660.16 g (203.00 þ/- 67.21 versus 230.18 þ/- 76.00; p<0.0001) between ADPKD and non-
vs CON 1.5560.11g). However, FR showed rapid gain weight. There was no significant ADPKD patients were observed. After multiple linear regression analysis, ADPKD
difference after P20. There were no difference between two groups in 2KW/BW, serum remained significantly associated with total white blood cell, neutrophil, monocyte and
blood urea nitrogen (BUN) levels, CI of kidney and liver until P35. At P56, 2KW/BW thrombocyte counts.
was significantly greater in FR (4.5960.52%) than in CON mice (2.9160.98%; In terms of post-transplant outcomes, significant univariate differences between
p<0.01). CI of both kidney and liver was significantly higher in FR than in CON ADPKD and non-ADPKD transplant recipients in favor of the ADPKD patients were
(Kidney : FR58.162.04% vs CON46.363.04%; p<0.05) (Liver : FR11.161.41% vs observed for overall survival, time to first rejection and time to transplant failure. On
CON 4.8960.61%; p<0.001). BUN levels elevated in FR (FR 58.165.76mg/dL vs CON the contrary, a significantly faster onset of the first posttransplant malignancy and
46.365.11mg/dL; p<0.05) .FR showed glomerular sclerosis with PAS staining. Mean infection was observed in ADPKD as compared to non-ADPKD. Furthermore, the
Glomerular volume was significantly increased in FR compared with CON (P35: FR numbers of posttransplant infections and malignancies tended to be higher in the
56256419lm2 vs CON 32556433lm2; p<0.001, P56: FR 578061195lm2 vs CON ADPKD patient cohort, the number of transplant rejections was significantly lower.
37566266lm2; p<0.001) . FR group showed significantly greater fibrosis in kidney While pre-transplantation lymphopenia was univariately associated with lower overall
(P35: FI 15.362.04% vs CON 11.161.41%; p<0.01,P56: FI 42.163.2% vs CON survival, none of the other post-transplant outcomes was associated with lymphopenia,
30.863.89%; p<0.001). In western blotting analysis, MAPK pathway and mTOR nor with any of the other blood cell counts. After multivariate Cox proportional hazard
pathway were suppressed in FR compared with CON at P20. In contrast, MAPK regression analysis, ADPKD remained significantly associated with time to first
pathway and mTOR pathway were upregulated in FR compared with CON at P56. rejection (p=0.0310; HR 0.632) and overall survival (p<0.0001; HR 0.512). None of the
CONCLUSION: Maternal undernutrition accelerates disease progression via kidney blood cell count variables retained significance in the multivariate outcome models.
fibrosis, MAPK and mTOR pathway. CONCLUSION: This large retrospective single center study confirmed the association
between cytopenia and ADPKD immediately before kidney transplantation.
Furthermore, ADPKD was also associated with differences in posttransplant outcomes.
In multivariate survival analysis, the impact of ADPKD on outcomes outweighed that
of other variables, amongst others the blood cell counts. From this, it is tempting to
speculate that ADPKD influences outcome through a disease-related impact on blood
cells, however many more factors are most probably involved. The hypothesis that
cytopenia could be an extra-renal manifestation of ADPKD, directly linked to its
genetic basis, and its impact on outcome warrant further investigation.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

MO021 ENHANCED MCP-1 RELEASE IN EARLY AUTOSOMAL This study aims to evaluate ex vivo through a molecular biology approach the OxSt
DOMINANT POLYCYSTIC KIDNEY DISEASE status of ADPKD patients under treatment with tolvaptan (Jinarc) and compare with
both a group of untreated young ADPKD subjects with preserved renal function
Peter Janssens1, Jean-Paul Decuypere2, Stéphanie De Rechter2, Luc Breysem3, (eGFR> 80 mL/min/1.73m2) and a cohort of healthy subjects as controls.
Dorien Van Giel2, Jaak Billen4, An Hindryckx5, Luc De Catte5, METHODS: In mononuclear cells of 9 ADPKD patients treated with tolvaptan, 9
Marcella Baldewijns6, Kathleen Claes7, Karl Martin Wissing1, untreated ADPKD patients with preserved renal function (eGFR> 80 mL/min/
Koenraad Devriendt8, Bert Bammens9, Isabelle Meyts10, Vicente Torres11, 1.73m2) and 9 healthy subjects we evaluated the state of OxSt in terms of protein
Rudi Vennekens12, Djalila Mekahli2 expression of p22phox, subunit of NADH/NADPH oxidase essential for the
1
UZ Brussel, Nephrology, Jette, Belgium, 2KU Leuven, Development and regeneration, production of superoxide; protein expression of Heme oxygenase (HO)-1, protective
Leuven, Belgium, 3KU Leuven, Radiology, Leuven, Belgium, 4KU Leuven, Laboratory from OxSt and anti-inflammatory and MYPT-1 phosphorylation, marker of Rho
Medicine, Leuven, Belgium, 5KU Leuven, Obstetrics and gynecology, Leuven, Belgium, kinase activation, deeply involved in OxSt signaling for the induction of
6
KU Leuven, Pathology, Leuven, Belgium, 7Ugent, Pathology, Belgium, 8KU Leuven, cardiovascular-renal remodeling;
Genetics, Belgium, 9KU Leuven, Nephrology, Belgium, 10KU Leuven, Pediatrics, Belgium, RESULTS: In patients with tolvaptan treated ADPKD, protein expression of p22phox
11
Mayo Clinic College of Medicine, Nephrology and Hypertension, United States of and phosphorylation state of MYPT-1 were significantly reduced compared to
America and 12KU Leuven, Cellular and molecular medicine, Belgium untreated young ADPKD subjects with normal GFR (p=0.01 and p=0.03, respectively).
Phosphorylation of MYPT-1 was significantly reduced in patients treated with
BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease tolvaptam vs untreated patients and also when compared to healthy controls (p=0.01
(ADPKD) is caused by mutations in either the PKD1 or PKD2 gene. While kidney for both). HO-1 levels of treated ADPKD patients were significantly higher both vs
failure typically occurs in adulthood, the disease starts in utero. The best change of untreated ADPKD patients with normal GFR (p=0.04) and vs healthy controls
preserving renal function long term might be the use of agents with few side effects as (p=0.01)
early as possible. For this approach, both better early prognostic stratification and CONCLUSIONS: Tolvaptan is reported to reduce the rate of GFR deterioration of 1.20
novel treatment options are needed. The pediatric phase of ADPKD, while kidney mg/mL/year compared to placebo. Several animal studies have demonstrated the
function is still normal and before significant tissue destruction has occurred could be ability of tolvaptan to reduce OxSt and increase HO-1. Our study showed “ex vivo” in
the best stage both to identify and study prognostic biomarkers as well as to identify humans that in ADPKD patients tolvaptan reduces the OxSt state compared to
novel targets for early treatment. Copeptin (a surrogate for vasopressin), epidermal untreated ADPKD with normal GFR and increases the antioxidant HO-1, in addition
growth factor (EGF) ( a measure for functional tubular mass) and monocyte to reduce Rho kinase activation, further supporting its renoprotective effect also in
chemoattractant protein-1 (MCP-1) ( a chemoattractant for macrophages) are terms of OxSt inhibition.
associated with severity and hold prognostic value in adults but remain unstudied in This study confirms for the first time in humans that tolvaptan is effective on the
the early disease stage. Kidneys from adults with ADPKD exhibit macrophage reduction of intracellular OxSt and may impair the biochemical/molecular
infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells is mechanisms that contribute to the worsening of renal function, endothelial damage
suggested from rodent models. and hypertension.
METHOD: A monocentric cross-sectional study in a tertiary referral center was
performed. All consenting genotyped ADPKD patients attending the outpatient
pediatric ADPKD clinic of the university hospital of Leuven and age, sex and BMI MO023 FLANK PAIN HAS A MAJOR NEGATIVE IMPACT ON HEALTH-
matched healthy controls were included between June and October 2017. Plasma RELATED QUALITY OF LIFE IN ADPKD: THE CYSTIC I STUDY
copeptin, urinary EGF and urinary MCP-1 were evaluated. MCP-1 was studied in
mouse collecting duct cells, human proximal tubular cells and fetal kidney tissue. Jean Winterbottom1, Roslyn Simms2, Anna Caroli3, Emilie Cornec-Le Gall4,
RESULTS: 53 genotyped ADPKD patients and 53 controls were included. Mean (SD) Nathalie Demoulin5, Monica Furlano6, Esther Meijer7, Olivier Devuyst5,
age was 10.4 (5.9) vs 10.5 (6.1) years (P=0.543), and eGFR 122.7 (39.8) vs 114.5 (23.1) Ronald Gansevoort7, Yannick LeMeur4, Norberto Perico3, Roser Torra6,
ml/min/1.73 m2 (P= 0.177) in patients vs controls respectively. Outcome parameters in Albert Ong1
table. Plasma copeptin and EGF secretion were comparable between both groups. 1
Median (IQR) urinary MCP-1 (pg/mg creatinine) was significantly higher in ADPKD University of Sheffield Medical School, Academic Nephrology Unit, Department of
patients (185.4 (213.8)) compared to controls (154.7 (98.0)) (P= 0.010). Human Infection, Immunity & Cardiovascular Disease, Sheffield, United Kingdom, 2University of
proximal tubular cells with a heterozygous PKD1 mutation and mouse collecting duct Sheffield Medical School, Academic Nephrology Unit, Department of Infection,
cells with a PKD1 knockout exhibited increased MCP-1 secretion triggered by fetal Immunity & Cardiovascular Disease, Sheffield, United Kingdom, 3Mario Negri Institute
bovine serum. Human fetal ADPKD kidneys displayed prominent MCP-1 for Pharmacological Research, Ranica, Italy, 4Centre Hospitalier Régional Universitaire
immunoreactivity and M2 macrophage infiltration. de Brest, Service de Néphrologie, Hémodialyse et Transplantation Rénale, Hôpital La
CONCLUSION: An increase in tubular MCP-1 secretion is an early event in ADPKD, Cavale Blanche, Brest, France, 5Cliniques universitaires Saint-Luc (UCLouvain),
long before kidney function decline and in children with few kidney cysts. MCP-1 is a Université catholique de Louvain Medical School, Bruxelles, Belgium, 6Fundaci o
promising early disease severity marker and a potential treatment target. Puigvert, Barcelona, Spain and 7University Medical Center Groningen, Department of
Nephrology, Groningen, Netherlands

MO021 BACKGROUND AND AIMS: ADPKD is the most common inherited kidney disease
in man, a major cause of end-stage renal disease and is a significant medical and
Variable Median (IQR) P economic burden worldwide. However, the impact of this major disease on the quality
of life of patients with preserved kidney function has not been systematically explored.
uEGF (ng/mg) ADPKD 43.5 (40.0)
METHOD: The CYSTic I study was an observational, prospective study designed to
Control 42.0 (31.6) 0.714 study the natural history of ADPKD in adult patients with preserved kidney function
Serum Copeptin (pmol/L) ADPKD 5.2 (4.3) (eGFR 30 ml/min/1.73m2). 465 patients were recruited from six expert centres across
Europe (Belgium, France, Italy, Netherlands, Spain and UK) with baseline data
Control 5.8 (3.4) 0.319 recorded including HR-QoL (Health-Related Quality of Life) incorporating a Kidney
uMCP-1 (pg/mg) ADPKD 185.4 (213.8) Disease QOL short form questionnaire (KDQoL-SF v1.3), MRI for Total Kidney
Control 154.7 (98.0) 0.010 Volume (TKV) and DNA for genotyping. The cohort was stratified by baseline eGFR,
Ht-TKV or genotype and correlated with HR-QOL scores. Bivariate and multivariate
analyses were applied to examine the relationship between HRQoL and variables of
interest. KDQoL-SF scores were calculated using an online tool provided by the Rand
organisation.
MO022 EVALUATION OF THE EFFECT OF TOLVAPTAN ON RESULTS: Mean age of the participants was 44 years, 54.6% were female with a mean
OXIDATIVE STRESS IN PATIENTS WITH AUTOSOMAL eGFR of 77ml/min/1.73m2 and Ht-TKV of 849ml/m. 72.3% had PKD1 mutations.
DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) 32.5% of participants reported flank pain that was not significantly correlated with
eGFR, Ht-TKV or genotype. Of all the variables examined, flank pain showed
Matteo Rigato1, Giovanni Bertoldi1, Verdiana Ravarotto1, Gianni Carraro1, significant negative associations with the highest number of KDQoL-SF subscale scores
Lorenzo Calo 1 assessed (12/20).
1
University of Padova, Department of Medicine, Nephrology, Dialysis and CONCLUSION: Our results indicate that flank pain is common, likely to be under-
Transplantation Unit, Padua, Italy reported in routine care but has a major negative impact on patient-reported quality of
life.
BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease
(ADPKD) is the most frequent monogenic kidney disease, with approximately 12.5
million affected people worldwide, and it is responsible for over 10% of patients with
end-stage renal disease (ESRD) with an important impact on public health. It causes
progressive renal failure and other extrarenal manifestations, including endothelial
dysfunction and hypertension. These complications are both linked to reduced nitric
oxide levels related to excessive Oxidative Stress (OxSt) that different studies confirm
occurring in the early stages of ADPKD.

i102 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO024 THE ROLE AND MECHANISM OF DECOY RECEPTOR DCR2 withdraw therapy because of CKD’s progression to stage 5 after 2 years of therapy.
IN EMBRYONIC KIDNEY DEVELOPMENT CONCLUSION: Results of this observational study show that Tolvaptan therapy was
well tolerated and the incidence of liver damage was superimposed on that described in
Jia Chen1, Yani He1 the literature.
1
Daping Hospital, Army medical University, Department of Nephrology, Chongqing, P.R. It will be necessary to continue clinical observation over the time and apply
China Tolvaptan’s therapy to a larger population in order to assess its effects on disease
progression.
BACKGROUND AND AIMS: Decoy receptor 2 (DcR2), a transmembrane receptor of
tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), has been regarded as
a hallmark of cell senescence. This study aimed to explore the role and the potential MO026 CLINICAL AND MUTATIONAL SPECTRUM OF CHILDREN
mechanism of DcR2 in the embryonic kidney development. WITH AUTOSOMAL RECESSIVE AND AUTOSOMAL
METHOD: The 12.5d, 16.5d, 20.5d embryonic kidney and mature renal tissue (8w) DOMINANT POLYCYSTIC KIDNEY DISEASE
form WT and DcR2-KO mice were obtained. The ureteric buds, S-shaped bodies, renal
vesicles were observed by periodic Acid-Schiff staining. The expression of DcR2 were Ozum Tutal1, Bora Gulhan2, Emine Atayar3, Selcuk Yuksel4, Z. Birsin Ozcakar5,
detected by IHC. The co-expression of DcR2 and proximal tubular markers (AQP-1, Oguz Soylemezoglu6, Seha Saygili7, Mihriban Inozu8, Esra Baskin9, Ali Duzova2,
villin), distal tubular markers (AQP-2), senescent markers (P16, LaminB1), Mutlu Hayran10, Rezan Topaloglu2, Fatih Ozaltin2,3
proliferation markers (Ki-67, PCNA, Edu) were analyzed by confocal. 1
RESULTS: In WT kidneys, DcR2 were specifically expressed in the tubules and the Hacettepe University Faculty of Medicine, Department of Pediatrics, Ankara, Turkey,
2
percentage of DcR2 expression were higher than mature renal tissue. In addition, the Hacettepe University Faculty of Medicine, Division of Pediatric Nephrology, Ankara,
expression of tubular DcR2 were significantly decreased in DcR2-KO kidney than WT. Turkey, 3Hacettepe University Faculty of Medicine, Division of Pediatric Nephrology,
The number of ureteric buds, S-shaped bodies, renal vesicles were decreased in DcR2- Nephrogenetics Laboratory, Ankara, Turkey, 4Pamukkale University Faculty of Medicine,
KO kidney than WT. And the cortex of DcR2-KO kidney were thinner and medullar Division of Pediatric Nephrology, Denizli, Turkey, 5Ankara University Faculty of Medicine,
were enlarger than WT. DcR2 were co-expressed with proximal tubular markers AQP- Division of Pediatric Nephrology, Ankara, Turkey, 6Gazi University Faculty of Medicine,
1 and villin, but not with distal tubular markers AQP-2. Furthermore, DcR2 were co- Division of Pediatric Nephrology, Ankara, Turkey, 7Istanbul University Cerrahpasa
expressed with senescent markers P16 and LaminB1, but not with proliferation Faculty of Medicine, Division of Pediatric Nephrology, Istanbul, Turkey, 8Ankara City
markers Ki-67, PCNA, Edu. Hospital, Division of Pediatric Nephrology, Ankara, Turkey, 9Baskent University Faculty
CONCLUSION: DcR2 is specifically expressed in proximal tubular cells in embryonic of Medicine, Division of Pediatric Nephrology, Ankara, Turkey and 10Hacettepe
kidney, and DcR2 is involved in early renal development. The potential mechanism is University Faculty of Medicine, Department of Preventive Oncology, Ankara, Turkey
related to cell senescence participating in tissue remodeling and inhibiting cell
proliferation. BACKGROUND AND AIMS: Cystic kidney diseases are a heterogeneous group of
chronic renal disease. Autosomal recessive polycystic kidney disease (ARPKD) is
generally diagnosed in utero or at birth due to mutations in PKHD1 gene. Autosomal
dominant polycystic kidney disease (ADPKD) is the most common inherited kidney
MO025 TREATMENT WITH TOLVAPTAN IN ADPKD PATIENTS: disease commonly associated with mutations in PKD1 or PKD2. In this study, we
RESULTS FROM AN OBSERVATIONAL, MULTICENTRIC aimed to investigate clinical and genetic features of ARPKD and ADPKD in a group of
STUDY Turkish patients.
METHOD: A total of 69 children with genetically confirmed ARPKD (10 females, 11
Marco Galliani1, Elio Vitaliano1, Silvana Chicca1, Antonio Paone1, males) or ADPKD (28 females, 20 males) from seven pediatric nephrology centers were
Valentina Pistolesi2, Santo Morabito2, Luca Di Lullo3, Fulvio Floccari4, included in this study. Demographic features, family history, clinical and laboratory
Fulvio Marrocco4, Massimiliano Cioffi5, Nunzio Rifici5, Rossella Iacono6, findings at presentation and during 12 months intervals were collected.
Sandro Feriozzi6, Cynthia Pasquarelli7, Massimo Morosetti7, Eleonora Bernabei8, RESULTS: For ARPKD patients, the median age at diagnosis was 10.5 (IQR; 0.75-58.5)
Maria Teresa Ferrazzano8, Antonella Orossi9, Riziero Fini9, Silvia Lai10, months. Consanguinity between parents was present in 11 patients (52.4%). At the
Sandro Mazzaferro10, Pierluigi Fulignati11, Giuseppe Grandaliano11 time of diagnosis, 14 (66.7%) patients had eGFR<90 ml/min/1.73 m2. Mean duration
1
UOC Nefrologia, Dialisi e Litotrissia, Ospedale Sandro Pertini - ASL Roma 2, Roma, of follow-up was 4.163,7 years. At the last visit, median eGFR was 74 (IQR; 43-126)
Italy, 2UOSD Dialisi, Azienda Ospedaliera Universitaria, Policlinico Umberto I, Roma, ml/min/1.73m2. A total of 6 patients (28,6%) underwent a renal replacement therapy
Italy, 3UOC Nefrologia e Dialisi, Ospedale Leopoldo Parodi Delfino - ASL Roma 5, (RRT), 3 of them died in infancy and 2 of them had renal transplantation during follow
Colleferro, Italy, 4UOC Dialisi Ospedale e Territorio, Ospedale San Paolo - ASL Roma 4, up. All patients had bi-allelic PKHD1 mutation.
Civitavecchia, Italy, 5UOC Nefrologia e Dialisi, Ospedale Santa Maria Goretti - ASL For ADPKD patients, the mean age at diagnosis was 5.564.6 years. At the time of
Latina, Latina, Italy, 6UOC Nefrologia e Dialisi, Ospedale di Belcolle, Viterbo, Italy, 7UOC diagnosis 11 (22.9%) patients had eGFR<90 ml/min/1.73m2. Mean duration of follow-
Nefrologia e Dialisi, Presidio Ospedaliero G.B. Grassi - ASL Roma3, Lido di Ostia, Italy, up was 2,762.3 years. At the last visit, median eGFR was 114 (IQR; 98-135) ml/min/
8
UOCA Nefrologia e Dialisi, Ospedale dei Castelli - ASL Roma 6, Ariccia, , 9UOC 1.73m2. Only one patient underwent a renal transplantation. A total of 42 patients
Nefrologia e Dialisi, Ospedale Fabrizio Spaziani - ASL Frosinone, Frosinone, Italy, (87.5%) had a heterozygous PKD1 mutation while 6 (12.5%) had a heterozygous PKD2
10
Dipartimento Medicina Translazionale e di Precisione, Sapienza Universit a di Roma, mutation. The rate of growth retardation, hypertension at diagnosis and progression to
UOC Nefrologia, Policlinico Umberto I, Roma, Italy and 11UOC Nefrologia, Fondazione chronic kidney disease (CKD) were higher in patients with PKHD1 mutation than the
Policlinico Universitario A. Gemelli, IRCCS, Universita Cattolica del Sacro Cuore, Roma, patients with PKD1 or PKD2 mutation (p < 0.001, p < 0.001 and p = 0.001,
Italy respectively). In kidney survival analysis, mutation type, growth retardation at
presentation, increased renal echogenity in ultrasonography were found as
BACKGROUND AND AIMS: In recent years, treatment of ADPKD (Autosomal independent risk factors for progression to CKD.
Dominant Polycystic Kidney of the Adult) has been based on the antisecretive and CONCLUSION: Cystic kidney diseases are one of the most clinically and genetically
antiproliferative effect of several drugs. Tolvaptan, a vasopressin receptor antagonist, heterogenous diseases. Differentiating them and establishing the predictors for CKD
has been shown to slow disease progression in the face of side effects such as aquaresis development is important to provide appropriate management including choosing
and liver damage. Currently, the drug’s reimbursability is allowed in patients aged up appropriate donor in renal transplantation.
to 55 years, CKD 2-4 (GFR  25 ml/min) with evidence of rapid disease progression.
METHOD: We report the experience with Tolvaptan in 62 patients with ADPKD who
were recruited from 11 Nephrology Units in Lazio (Italy). MO027 ROLE OF ANGIOTENSIN II TYPE 1 RECEPTOR GENE
Baseline characteristics of patients are reported in Table 1. POLYMORPHISM IN PROGRESSION OF CHRONIC KIDNEY
Renal volume was evaluated by MRI (26 patients), CT scan (3 patients), or DISEASE AND ITS ASSOCIATION WITH HYPERTENSION
ultrasonography (28 patients). AMONG AUTOSOMAL DOMINANT POLYCYSIC KIDNEY
Rapid progression’s criteria were the following: Mayo Clinic classification, PRO-PKD DISEASE PATIENTS
score and the annual loss of GFR. Mean duration of Tolvaptan’s treatment was 522
days (range 56-867). Anand Sasidharan1, R Gnanasambandan2, Kevin T John Keeppallil3,
The Tolvaptan dosage used at the beginning of therapy was 60 mg/day in 95% of Elumalai Ramprasad3
patients; at the end of follow-up, 37% were still taking 60 mg/day, while 38.7% were 1
taking 90 mg/day and 16.1% were taking 120 mg/day. Sri Ramachandra Institute of Higher Education and Research, Department of General
RESULTS: Median diuresis was 5-6 liters over 24 hours. A mean reduction in GFR of Medicine, Chennai, India, 2Sri Ramachandra Institute of Higher Education and
12.5% (which was maintained for the next 12 months) was observed after initiation of Research, Department of Biomedical Sciences, Chennai, India and 3Sri Ramachandra
therapy as a likely effect of tubulo-glomerular feedback. Institute of Higher Education and Research, Department of Nephrology, Chennai, India
Monthly blood tests were performed to monitor side effects (hyper/hyponatremia,
increased bilirubin and/or transaminases, etc.). BACKGROUND AND AIMS: Autosomal dominant polycystic kidney diseases
Therapy was withdrawn by 2 patients (3.2%) due to aquaresis, while it was (ADPKD) are the most common hereditary renal disorder that is characterized by the
discontinued in 3 patients (4.8%) according to clinicians’ decision due to hepatic development of hypertension, Chronic Kidney Disease and leads to morbidity and
damage (3-fold increase in transaminases and/or bilirubin normal values). No mortality. Hypertension is one of the most important traits of ADPKD patients. The
significant alteration in natremia was observed in any patient. An increase in CK was activation of rennin-angiotension system contributes to the early development of
observed in one patient, leading to momentary discontinuation of therapy. One patient hypertension and CKD progression in ADPKD. This study aimed to investigate the

10.1093/ndt/gfab081 | i103
Abstracts Nephrology Dialysis Transplantation

AT1R gene polymorphisms and its involvement in CKD progression in ADPKD and
its relation to the presence of hypertension among the ADPKD.
METHOD: It was a case control study which included 85 patients with the diagnosis of
Autosomal Dominant Polycystic Kidney Disease who came to the Nephrology OPD of
Sri Ramachandra Medical Centre, Chennai and 94 healthy volunteers without diabetes,
hypertension and any kidney related disease as controls. Patients with other end stage
renal disorder were excluded from the study. Among the ADPKD patients, the
glomerular filtration rate (eGFR) and chronic kidney disease (CKD) stages were
assessed based on Modification of Diet in Renal Disease (MDRD) formula and KDOQI
CKD guidelines respectively (120). Further, the ADPKD patients were divided into two
groups such as early stages (CKD stages 1-3; n=45) and advanced (CKD stages 4 & 5;
n=40) stages. Furthermore the ADPKD cases were classified into two groups such as
hypertensive (n=70) and normotensive (n=15). All the study participants were tested
for AT1R A1166C polymorphisms by PCR-RFLP method. Allele frequencies and
genotypes were compared between groups. SPSS V16.0 used for statistical analysis and
p> 0.05 considered significant.
RESULTS: The study included a total of 85 (58.8% Male and 41.1% Female) patients
with ADPKD and 94 (62.7% Male and 37.2% Female) unrelated healthy individuals
included as control subjects. The mean age of control group were 53.3 6 12.4 yrs and
ADPKD group were 46.9 6 10.4 yrs and the difference is statistically significant
(P<0.001). Among the ADPKD, 40 (47%) subjects showed advanced CKD stage and MO027 Figure 3: The Genotype distribution between the non hypertensive &
45 (52.9%) subjects showed early stage and found statistical significant differences hypertensive groups among ADPKD cases.
(P<0.008) between the stages. Furthermore, based on the presence and absence of
hypertension in the ADPKD cases, there was no significant difference found between
the non hypertensive and hypertensive groups (p=0.734). AT1R A1166C
polymorphism was genotyped for 85 ADPKD patients and 94 unrelated healthy
individuals. The distribution of A1166C genotypes between the ADPKD patients and
control subjects was documented. Of the studied 94 control subjects the AA 87 MO028 AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE:
(92.5%), AC 7 (7.45%) and CC 0 (0%) and the genotypes of 85 ADPKD patients were REGISTRY OF NORTHERN CYPRUS
AA 78 (91.7%), AC 7 (8.24%) and CC 0 (0%). There was no significant association
observed between the ADPKD cases and controls in genetic model AA vs AC Simge Bardak1, Düriye Deren Oygar1, Ahmet Behlul1
1
(OR=1.11; 95% CI=0.37-3.32; p=0.844) and allelic model A vs C (OR=1.11; 95% DOKTOR BURHAN NALBANTOGLU GOVERNMENT HOSPITAL, NEPHROLOGY, NICOSIA,
CI=0.38-3.32; p=0.847). Similarly, between the CKD stages AA vs AC (OR=3.07; 95% Cyprus
CI=0.56-16.8; p=0.177) and allelic model A vs C (OR=2.13; 95% CI=0.40-11.3;
p=0.364) there was no significant association. BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease
CONCLUSION: Analysis for AT1R A1166C polymorphism revealed that there is no (ADPCK) is the most prevelant inherited kidney disease in adults, and the fourth
significant association between the ADPKD patients and controls. Similarly there was common cause for renal replacement therapy worldwide and preventive measures
no significant association between between the CKD stages (early & advanced) and should be taken to slow the decline in renal functions. From previous studies we
non hypertensive, hypertensive groups. Our study reveals that the AT1R gene already know that hereditary kidney diseases such as medullary kidney disease and
polymorphism does not have any impact on ADPKD, CKD progression and the tubular kidney diseases are frequent in Cyprus. In this study, we aim to find out the
hypertension induced ADPKD and /or CKD development. situation for ADPKC in North Cyprus and declare the overall magnitude of the
problem in our region.
METHOD: From January 2004 to January 2021, we collected data from all patients
with ADPCK irrespective of whether they were on RRT or not and who were followed
in nephrology departments within Northern Cyprus. Clinical and demographic data of
all the patients aged above 18 were collected. The affected families and their route of
inheritance were determined. Need for renal replacement therapy (RRT) and types of
RRT were noted. RRT rate and death rate were calculated.
RESULTS: We collected information from a total of 79 patients with the diagnosis of
ADPCK; 3 patients were excluded due to lost to follow up. There was no family history
in 11% of patients. Inheritence was maternal in 53% and paternal in 42% whereas both
maternal and paternal inheritence route were identified in 5%. 68 patients with family
history were grouped in 24 families (2.8 patients/ family). The demographic and
clinical data can be seen on Table 1. At some point during follow up 31 patients started
with RRT. Mean age for RRT was 55 years (23-81). 5 (16%) patients initiated RRT with
peritoneal dialysis, wheras 23 (74%) with hemodialysis, and 3 (10%) had preemptive
renal transplantation. At the end of follow up period we found out that 35% (11/31) of
patients who had RRT had transplantation, 32% (10/31) experienced peritoneal
dialysis whereas 77% (24/31) experienced hemodialysis. 18 out of 76 (24%) patients
died during the follow up period. The mean age of death was 71 years (53-81).
MO027 Figure 1: The genotype distribution between the Controls and ADPKD cases CONCLUSION: The prevalance of the disease when living patients were considered
was 1.3 cases/10000 inhabitants which is low when compared with other studies.
Hence ADPCK was not a common diagnosis in North Cyprus as other hereditary
kidney diseases. This may show that some patients are underdiagnosed in the
population. The frequency of patients without family history was high and also the
number of patients per family was low when compared with other studies; these
findings may also indicate an underdiagnosed problem. The patients were diagnosed
late at a mean age of 47 Hence we need to perform further studies on ADPCK in our
population since identifiying ADPCK patients and their families may help to adress the
needs adequately, to plan lifelong supportive measures and to decrease high mortality
rate of these patients.

MO027 Figure 2: The AT1R A1166C genotype distribution between early and
advanced stages of ADPKD patients

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Nephrology Dialysis Transplantation Abstracts
MO028 Table 1: Demographic and clinical data of the patients with autosomal
dominant polycystic kidney disease

Age at diagnosis (mean, years) 47 (21-81)


Sex (F/M) n, (%) 40/36 (53%/47%)
Cypriot ethnicity (n) 44 (58%)
Hypertension 50 (66%)
Diabetes mellitus 8 (11%)
Body mass index (mean, kg/m2) 29
SBP/DBP at first admission (mean, mmHg) 115/60
Microscopic hematuria (þ/-) 19 (44%)
Macroscopic hematuria (þ/-) 13 (23%)
Urinary tract infection (proven with urine culture) (þ/-) 4 (8%)
Neprolithiasis 6 (10%)
Complicated renal cysts 7 (13%)
Liver cysts 35 (65%)

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Nephrology Dialysis Transplantation 36 (Supplement 1): i106–i119, 2021
10.1093/ndt/gfab080

GENETIC DISEASES AND MOLECULAR GENETICS develop a single glomerulus which is attached to a pair of tubules. Like in mammals,
the glomerular filtration barrier consists of a fenestrated endothelium, the glomerular
basement membrane and interdigitating podocyte foot processes bridged by a slit
diaphragm. By using genetically modified zebrafish strains with fluorescently labeled
MO029 CLINICAL CHARACTERISTICS AND PATHOGENIC GENES podocytes, it is possible to study alterations of the glomerulus during the development
OF CONGENITAL SOLITARY KIDNEY WITH REPRODUCTIVE of renal disease like focal segmental glomerulosclerosis (FSGS) directly in vivo. FSGS is
SYSTEM MALFORMATION* characterized by podocyte loss, the effacement of their foot processes as well as scarring
of the glomerulus. To study FSGS in zebrafish larvae, we induced podocyte detachment
Rongrong HU1, Lubin Xu1, Minting Chen1, Na Chen2, Tiantian Ma1, Peili Ji1, by the use of a zebrafish strain expressing the enzyme nitroreductase converting
Zhenzhen Liu3, Lan Zhu2, Limeng Chen1 metronidazole into a toxic substance specifically in podocytes. The aim of our study
1
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, was to collect glomeruli for the identification of mRNAs as well as miRNAs by
Department of Nephrology, Beijing, P.R. China, 2Peking Union Medical College Hospital, RNA_Seq that are up- and down-regulated in the glomeruli of this FSGS-like disease
Chinese Academy of Medical Sciences, Beijing, Department of Obstetrics and model.
Gynecology Department, Beijing, P.R. China and 3Peking Union Medical College METHOD: The transgenic zebrafish strain Cherry (Tg(nphs2:GAL4);
Hospital, Chinese Academy of Medical Sciences, Beijing, Department of Ultrasound Tg(UAS:Eco.nfsB-mCherry); mitfaw2/w2; mpv17a9/a9) which expresses the
diagnosis, Beijing, P.R. China prokaryotic enzyme nitroreductase (NTR) fused to mCherry, a red fluorescent protein,
under the control of the podocyte-specific podocin (nphs2) promoter in a transparent
zebrafish strain, was utilized. After addition of metronidazole (MTZ) into the tank
BACKGROUND AND AIMS: Congenital solitary kidney – one category of congenital water, MTZ is converted into a cytotoxin by NTR leading to dose-dependent apoptosis
anomalies of the kidney and urinary tract (CAKUT) may combine with other system exclusively in podocytes. Cherry larvae were treated at 4 days post fertilization (dpf) for
malformations such as reproductive, cardiac, skeletal system, and so on. Our study 48 h with 80 mM MTZ. MTZ-treated and control larvae were homogenized at 6 dpf.
analysed the clinical characteristics among congenital solitary kidney patients and their The cell suspension was diluted, and red-fluorescent glomeruli were collected using a
reproductive system malformations. And further work about probable pathogenic micropipette and a microscope. Total RNA was isolated, and integrity was checked by
genes was explored. a Bioanalyzer. Libraries were generated with a MACE kit and True Quant small RNA
METHOD: The information of CAKUT patients who were indicated by Doppler seq kit by GenXPro. Constructs were amplified by PCR and sequenced on an Illumina
ultrasound was collected. The clinical and imaging features including reproductive Hiseq 2000. Normalization and statistical analysis for differential gene expression were
system abnormalities were retrospectively reviewed in patients with congenital solitary done using DESeq2.
kidney. In patients with Mayer-Rokitansky- Küster-Hauser (MRKH) syndrome, a RESULTS: Zebrafish larvae showed severe whole-body edema, proteinuria, loss of
disorder of congenital agenesis of uterus and vagina, whole exome sequencing was podocytes and an increased mortality rate after MTZ-treatment. The glomerular
performed. Rare variants in CAKUT-related genes were analysed. Trio analysis was histology resembled mammalian FSGS. We found that only the RNA of manually
conducted to identify de novo mutations. collected glomeruli had an excellent quality. Using RNA_Seq, we identified a total of
RESULTS: We identified 209 patients with congenital solitary kidney from July 20, 16941 genes. DESeq2 analysis showed 494 up-regulated and 473 down-regulated genes.
2017 to July 19, 2020 among 1160 CAKUT patients in Peking Union Medical College Gene ontology (GO) enrichment analysis of up-regulated genes revealed a total of 167
Hospital. There were 152 females. The average age of congenital solitary kidney that are significantly enriched in GO terms (e.g. metabolic processes, immune response
patients was 35.26618.42 years when they were diagnosed. 53.2% showed different and ion transport). Down-regulated genes were enriched in 14 GO terms and most of
degrees of proteinuria and hematuria. Serum creatinine elevating was proved 13.1% them are linked to normal glomerular function and the slit diaphragm. DESeq2
and 40% in women and men separately. Among 81 females who also had a analysis identified 200 miRNAs of 777 small RNAs. Some of these miRNA are already
gynecological ultrasound report, 88.9% combined with genital malformation, oblique described to be regulated in different glomerular diseases like FSGS, lupus nephritis,
vaginal septum syndrome 48.7%, the Mayer-Rokitansky-Küster-Hauser (MRKH) IgA nephropathy and diabetic nephropathy.
syndrome 22.2%, malformed uterus 23.5%, vaginal atresia and other genital CONCLUSION: We analyzed isolated glomeruli from transgenic zebrafish larvae that
malformation 7%. Congenital heart disease, complete transposition of viscera, and developed a FSGS-like disease. By sequencing, we have found mRNAs and miRNAs
scoliosis were also found in some patients with congenital solitary kidney. that were significantly regulated after the onset of disease. Detailed knowledge of these
Furthermore, based on the whole exome data of 443 patients with MRKH syndrome, mRNAs and miRNA-based gene regulation will help to uncover the pathomechanism
seven function-lost mutations were confirmed. And also two De nove mutations as well as to develop therapeutics for the treatment of FSGS.
(NOTCH2 (NM_024408.3: c.703A>T(p.Thr235Ser), ESRRG (NM_001243512.1:c.-
169-8delT)), one homozygous patients with parents heterozygous
(NM_133433.3:c.8084C>T(p.Thr2695Me) were identified as possible pathogenic
genes caused CAKUT. MO031 KLOTHO GENE PROMOTER METHYLATION IN THE
CONCLUSION: We should be aware of reproductive system malformations in VASCULATURE IS RELATED TO INFLAMMATION IN HUMAN
CAKUT patients. Whole exome sequencing may suggest common pathogenic genes ATHEROSCLEROSIS.
between the two kinds of diseases.
Ernesto Martın-Nu n~ez1, Javier Donate-Correa1, Carla Ferri1, Vıctor G Tagua1,
Ainhoa Gonz alez-Luis1, Sergio Rodrıguez-Lopez1, Purificacio n Cerro-Lo pez1,
Angel Lopez-Castillo1, Alejandro Delgado-Molinos1, Eduardo Ontoria-Aguilera1,
Carmen Mora-Ferna ndez1, Juan F. Navarro-Gonz alez1
1
Hospital Universitario Nuestra Se~
nora de Candelaria, Unidad de Investigaci
on, SANTA
CRUZ DE TENERIFE, Spain
MO030 IDENTIFICATION OF REGULATED MRNAS AND MIRNAS IN
GLOMERULI ISOLATED FROM AN FSGS-LIKE ZEBRAFISH
BACKGROUND AND AIMS: Atherosclerosis, a vascular pathological process with an
MODEL
important inflammatory component, underlies most of the cardiovascular diseases
(CVD). Deficiencies in the antiaging factor a-Klotho (KL) have been related to the
Anna Iervolino1,2, Tim Lange2, Sabrina Siccardi1,3, Florian Siegerist2, Francesca
appearance and progression of atherosclerotic damage associated with CVD. In
Pia Caruso1,4, Michele Ceccarelli1,4, Karlhans Endlich2,
addition, some studies have demonstrated that KL gene is expressed in human arteries
Giovambattista Capasso1,3, Nicole Endlich2
1
and that low vascular KL expression levels are related with clinical atherosclerotic
Biogem S.c.a.r.l., Department of Translational Nephrology, Ariano Irpino, Italy, disease. Among the epigenetic mechanisms that regulate the expression of the KL gene,
2
University Medicine Greifswald, Department of Anatomy and Cell Biology, Greifswald, methylation of the CpG islands in the promoter region is one of the most studied. In
Germany, 3University of Campania “Luigi Vanvitelli”, Department of Translational this pilot study, we propose that this mechanism participates in the regulation of
Medical Sciences, Napoli, Italy and 4University of Naples “Federico II”, Department of vascular KL expression and contributes to the deficiency in vascular KL levels observed
Electrical Engineering and Information Technology (DIETI), Napoli, Italy in CVD. Moreover, we determined the influence of different inflammatory
components in the methylation status of KL promoter.
BACKGROUND AND AIMS: The zebrafish (Danio rerio) is a powerful animal model METHOD: We developed a case-control study that included 25 patients with
to study glomerular morphology and the function of the permselectivity of the diagnosis of clinical atherosclerotic vascular disease undergoing elective vascular
glomerular filtration barrier. surgery and 15 cadaveric organ donors with no medical history of CVD, respectively.
Since zebrafish larvae develop quickly and can be bred to become transparent, in vivo Vascular fragments were retrieved from all subjects, and the degree of methylation of
observation of these animals is possible. At 48 hours post fertilization, zebrafish larvae the KL gene promoter was assessed by bisulfite sequencing. Additionally, vascular gene
expression in both groups was assessed by qPCR for KL, two DNA methyltransferases
(DNMT1 and DNMT3A), and three inflammatory-related loci (TNF, IL10 and

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
NFKB1). Serum concentrations of TNFa and IL10 were measured by ELISA Although the diagnosis can be suspected based on presenting features, the clinical
immunoassay, and complementary inflammatory parameters (CRP and neutrophil/ diagnosis of BS and GS can be challenging, as they are rare and phenotypically
lymphocyte ratio) by standardized routine methods. overlapping. As a consequence, the current clinical classification lacks of specificity and
RESULTS: The vascular tissue of patients in the case group presented a higher percent genetic testing represents the gold standard for the diagnosis. Driven by the rapidly
level of methylated positions in the KL promoter region (71.468.3% vs. 39.4612.3%, decreasing costs and turn-around time, next-generation sequencing technologies are
P<0.05), as well as a significant decrease in the expression of KL gene (a 40% reduction increasingly utilized in diagnostics and research of inherited tubulopathies, including
as compared to controls, P<0.05). Considering the whole study population, the BS and GS. Recently, sequencing of selected gene panels provided the advantage of
methylation degree was inversely related to the endogenous transcript levels of KL gene achieving high coverage of genes of interest at lower costs, providing high diagnostic
(r=-0.66, P<0.0001). Moreover, the expression of DNMT1 was significantly increased yield and new insights into the phenotypic spectrum of these rare disorders. However,
in the case group (P<0.05), as well as those of the proinflammatory genes TNF and whole-exome (WES) is not routinely performed for the molecular diagnosis of BS and
NFKB1 (P<0.0001 and P<0.05, respectively), being all of them directly associated with GS. The aim of our study was to assess the diagnostic performance of WES in BS and
the vascular methylation levels of KL gene (r=0.51, P<0.0001 for DNMT1; r=0.45, GS and to establish genotype-phenotype correlations.
P<0.001 for TNF; r= 0.37, P<0.05 for NFKB1). Furthermore, vascular expression of METHOD: We performed WES in all consecutive patients referred for genetic testing
DNMT1 and DNMT3A directly correlated with both inflammatory markers in this with a clinical suspect of BS or GS. Variant prioritization was carried out according to
tissue (P<0.0001, for all). Systemic levels of IL10 presented a direct association with the American College of Medical Genetics and Genomics guidelines (ACMG). Parents
vascular KL gene expression (r=0.28, P<0.05), while inverse associations were and first-degree relatives were included, whenever available. Demographic, clinical and
observed with the methylation degree of KL gene (r=-0.38, P<0.05) and DNMT1 laboratory data were collected retrospectively, in order to establish genotype-
expression (r=-0,29, P<0.05). phenotype correlations.
CONCLUSION: These results suggest that the methylation of KL gene promoter in the RESULTS: We enrolled 50 patients (22 males, 46 Caucasians) with a clinical diagnosis
vasculature is a mechanism associated with the inflammatory response that would of BS (19), GS (24) or BS/GS (7). All the patients showed hypokalemic metabolic
partly explain its reduction during atherosclerotic injury. alkalosis at onset (serum bicarbonate=29.5 mEq/l 6 4.4, potassium= 2.7 mEq/l 6 0.6).
The median age at clinical diagnosis was 7 years (range 0-67 years). Three patients had
familial history of tubulopathies. WES showed pathogenic variants in 42/50 patients
(84%), thus establishing a conclusive diagnosis. Interestingly, a dedicated analytic
MO032 URINARY EXCRETION DISORDER IN 125 PATIENTS WITH
pipeline allowed us to identify copy number variations (CNVs) in 7/42 patients with a
GITELMAN SYNDROME
confirmed genetic diagnosis. In detail, WES allowed us to confirm the clinical diagnosis
in 33/50 patients, with an improvement in classification in at least 14 cases (i.e. subtype
Bingbin Zhao1, Lei Zhang1, Xiaoxiao Shi1, Peili Ji1, Lubin Xu1, Limeng Chen1
1
I-V of BS). In 9 additional patients, genetic testing changed the clinical diagnosis: 6
State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of patients with a clinical of BS turned out to have pathogenic variants in SLC12A3,
Medical Sciences & Peking Union Medical College Hospital, Department of Nephrology, resulting in GS; in 3 patients, genetic testing revised the clinical diagnosis indicating
Beijing, P.R. China inherited disorders outside the BS/GS spectrum (HELIX syndrome, Primary familial
hypoparatiroidism, Type 2 renal hypomagnesemia). Only 38% of patients with a
BACKGROUND AND AIMS: Long-term oral prescription of thiazide diuretics, genetic diagnosis of BS showed nephrocalcinosis. Strikingly, this was present in 8% of
which can block the sodium chloride co-transporter (NCC) of the distal tubule, has patients with GS. On the other hand, hypomagnesemia, a distinctive feature of GS, was
been recognized to affect the function of the proximal tubule. But the underlying similarly distributed among BS and GS patients (45% vs. 68%, respectively). Finally,
mechanism is largely unknown. Gitelman syndrome (GS) is a recessively inherited salt- although patients with GS showed a median age at onset higher than patients with BS,
losing tubulopathy due to the loss-of-function mutation of NCC, which can be used as some overlap did exist, making differential diagnosis challenging at single-patient level.
a good model to understand the pathophysiological mechanism of thiazide-related CONCLUSION: The results of our study demonstrate that WES ensures a high
disorders. In this study, we summarized the clinical characteristics of proximal tubular diagnostic yield (84%) in patients with a clinical diagnosis of BS or GS, especially if
function in the cohort of patients with GS, and explore the possible mechanisms of coupled with analysis of CNVs. This approach showed to be useful in dealing with the
proximal tubular dysfunction secondary to distal tubular disorder. phenotypic heterogeneity typical of these rare disorders, improving differential
METHOD: Patients who were diagnosed with GS (confirmed by gene sequencing) in diagnosis by detecting phenocopies also outside the BS/GS spectrum, enabling
our hospital from August 1, 2005 to December 31, 2019 were enrolled, as well as the additional specific work-up, genetic counseling, and screening of at-risk relatives.
selected gender- and age-matched healthy controls. For patients whose SLC12A3 gene
was sequenced as a single heterozygous mutation, further whole exome sequencing was
performed to clarify the gene mutation. Clinical data including demographic
MO034 A SUBGROUP ANALYSIS OF FEMALE PATIENTS IN A PHASE
information, symptoms, and hematuria tests were collected. The hydrochlorothiazide
3 OPEN-LABEL STUDY TO ASSESS THE SAFETY AND
test was performed to assess the function of NCC. Characteristics of calcium and
EFFICACY OF PEGUNIGALSIDASE ALFA IN PATIENTS WITH
phosphate metabolism and uric acid of patients were analyzed.
FABRY DISEASE PREVIOUSLY TREATED WITH AGALSIDASE
RESULTS: A total of 125 patients with genetic diagnosed GS were enrolled, and 33
ALFA
patients (26.4%) were with only a single heterozygous mutation. Twenty-five patients
completed whole exome sequencing, and 9 patients (36%) were finally diagnosed with
Derralynn Hughes1, Gabriela Dostalova2, Kathy Nicholls3, Michael West4,
compound heterozygous mutations. Seven mutation sites were newly detected by ~¸ndel5, Ana Jovanovic6, Pilar Giraldo Castellano7, Bojan Vujkovac8,
Camilla Ta
whole exome sequencing, including 3 missense mutations, 1 splice-site point mutation
Tarekegn Geberhiwot9, Einat Almon10, Sari Alon10, Mali Szlaifer10,
and 3 intron mutations. Serum uric acid in GS patients was significantly higher than
Raul Chertkoff10, Ales Linhart11
that in healthy controls (347.5691.7 vs 309.9685.3lmol/L; P<0.001). The proportions 1
of men and women with hyperuricemia were 19.4% and 34.5%, respectively. Urinary University College London, 2General University Hospital in Prague, First Faculty of
fraction excretion of uric acid in the hyperuricemia group was significantly lower than Medicine, Charles University, 2nd Department of Internal Cardiovascular Medicine,
that of patients with normal serum uric acid. Compared with healthy controls, GS Prague, Czech Republic, 3Royal Melbourne Hospital, Australia, 4Dalhousie University,
patients had higher blood calcium level (2.4160.17 vs 2.3260.09mmol/L; P<0.001). Division of Nephrology , Department of Medicine, Canada, 5University of Bergen,
However, urinary calcium, parathyroid hormone (26.79614.21 vs 33.18611.58lmol/ Department of Clinical Medicine, Bergen, Norway, 6Salford Royal NHS Foundation
L; P=0.005), and 25-hydroxyvitamin D (15.8866.46 vs 19.5666.06 nmol/L; P=0.001) Trust, Department of Endocrinology and Metabolic Medicine, Salford, United Kingdom,
7
were lower in GS patients. Lower blood magnesium level was associated with lower Hospital Universitario Miguel Servet, Unidad de Investigacion Traslacional - Instituto
parathyroid hormone level. de Investigaci
on Sanitaria Arag on, Zaragoza, Spain, 8General Hospital Slovenj Gradec,
CONCLUSION: In GS patients, low urinary calcium, high serum calcium and high Fabry Center, Slovenj Gradec, Slovenia, 9University of Birmingham, Institute of
serum uric acid levels were related with the compensation of proximal tubular Metabolism and Systems Research, Birmingham, United Kingdom, 10Protalix
function. Biotherapeutics, Karmiel, Israel and 11General University Hospital in Prague, Head of
Clinic, Prague, Czech Republic

BACKGROUND AND AIMS: Females with Fabry disease (FD) often develop
MO033 WHOLE-EXOME SEQUENCING AS A FIST-LINE DIAGNOSTIC
symptoms and disease complications later in life than males. However, they can
TOOL IN BARTTER AND GITELMAN SYNDROME
experience significant health declines, including renal function impairment.
Pegunigalsidase alfa is a novel PEGylated alpha-galactosidase A enzyme in
Francesca Becherucci1, Viviana Palazzo2, Luigi Cirillo1, Benedetta Mazzinghi1,
development for the treatment of patients with FD with potential pharmacokinetic
Samuela Landini2, Valentina Raglianti1, Paola Romagnani1
1
benefits. We previously reported that males with FD showed improvements in several
Meyer Children’s Hospital, Nephrology and Dialysis Unit, Florence, Italy and 2Meyer parameters including median (minimum, maximum) estimated glomerular filtration
Children’s Hospital, Medical Genetics Unit, Florence, Italy rate (eGFR) slope from -4.6 (-20.5, 4.8) to -1.1 (-18.6, 14.2) mL/min/1.73m2/year after
treatment with pegunigalsidase alfa.(Tondel et al. ASN 2020. PO0562. www.asn.
BACKGROUND AND AIMS: Bartter (BS) and Gitelman syndrome (GS) are scientificposters.com) Here we report a subgroup analysis of the safety and efficacy of
autosomal recessive rare inherited disorders characterized by hypokalemic metabolic pegunigalsidase alfa treatment in females with FD.
alkalosis and secondary hyperaldosteronism. The primary defect is a genetically METHOD: BRIDGE (PB-102-F30; NCT03018730) is a phase 3, open-label, switch-
determined impairment of sodium chloride reabsorption in the renal tubule, thus over study designed to assess the safety and efficacy of pegunigalsidase alfa in adults
resulting in salt loss, dehydration and acid-base homeostasis perturbations. with FD previously treated with agalsidase alfa for at least 2 years. Patients received
intravenous pegunigalsidase alfa at 1 mg/kg every other week for 12 months.

10.1093/ndt/gfab080 | i107
Abstracts Nephrology Dialysis Transplantation

RESULTS: Twenty-two patients were enrolled in the study; of the 20 patients who compared with the ones harboring frameshift mutations leading to truncated Kir4.1
completed 12 months of study treatment, 7 were female. Females had a mean age of 46. channel (Figure. 1).
7 years (range: 26–59 years), and had the following median (minimum, maximum) Furthermore, computational modeling of wild-type NKCC2 and frameshift mutation
baseline measurements: residual enzymatic activity in leucocytes of 23.7% (16, 46) of Arg302Glyfs*3 variant clearly demonstrated that Arg302Glyfs*3 results in a loss of
the normal laboratory mean; plasma lyso-Gb3 of 12.9 (7.4, 23.2) nmol/L; eGFR of 87.7 large part of the protein, indicating that NKCC2-Arg302Glyfs*3 is practically
(55.3, 109.2) mL/min/1.73m2; and an annualized eGFR slope of 3.7 (-11.2, 1.5) mL/ nonfunctional (Figure. 2).
min/1.73m2/year. After 12 months of pegunigalsidase alfa treatment, the annualized
eGFR slope was 1.4 (-6.3, 4.1) mL/min/1.73m2/year, indicating an improvement from
baseline of 5.9 mL/min/1.73m2/year. In addition, plasma lyso-Gb3 had a reduction of
23.3% (-45.7, -17.3). Although all females had baseline mean residual enzyme activity
> 5% and were previously treated with agalsidase alfa, only 2 had stable kidney disease
(eGFR slope  -3 mL/min/1.73m2/year), while 2 had moderately progressing kidney
disease (eGFR slope between -5 and < -3 mL/min/1.73m2/year), and 3 had fast
progressing kidney disease (eGFR slope < -5 mL/min/1.73 m2/year).( Wanner et al.
2018 Mol Genet Metab 124:189-203) After treatment all but 1 patient experienced
categorical improvement or remained stable; this patient had a decline of < 3 mL/min/
1.73m2/year and remained in the fast progressing disease category. Mean left
ventricular mass index in females increased from 66.9 g/m2 at baseline to 74.1 g/m2 at
month 12, but remained within normal ranges(47–77 g/m2).(Kawel-Boehm et al. 2015
J Cardiovasc Magn Reson 17:29) All females had at least 1 treatment-emergent adverse
event (TEAE), and all TEAEs were mild or moderate. The most common TEAEs
reported in female were nasopharyngitis (n=2), oropharyngeal pain (n=2), and
headache (n=2). None of these TEAEs were considered related to treatment. However,
2 females had injection site reactions and 2 developed transient, non-neutralizing anti-
drug antibodies to pegunigalsidase alfa treatment.
CONCLUSION: The current study included females with symptoms of Fabry disease
comparable to the disease presentation of males enrolled in this study. At baseline most
females had eGFR decline characterizing progressive or rapidly progressive kidney
disease. Most females showed improvements in disease status following 12 months of
pegunigalsidase alfa treatment, as previously reported for males enrolled in this study.
This long-term, controlled study suggests a potential benefit and a favorable safety
profile for pegunigalsidase alfa on renal function in females with FD previously treated
with agalsidase alfa. While this subgroup analysis should be interpreted with caution
due to the small number of patients, these findings may provide valuable insight for
future studies.

MO035 COMPUTATIONAL MODELING APPROACH FOR THE


COMPREHENSIVE INTERPRETATION OF RARE
TUBULOPATHIES

Yoko Suzumoto1,2, Valeria Columbano2, Giovanna Capolongo2,


Mariadelina Simeoni2, Alessandra Perna2, Miriam Zacchia2, Davide Viggiano1,2,3,
Giovambattista Capasso1,2, Francesco Trepiccione1,2
1
Biogem A. C. S. R. L., Ariano Irpino (AV), Italy, 2University of Campania Luigi Vanvitelli,
Department of Translational Medical Sciences, Naples, Italy and 3University of Molise,
Department of Medicine and Health Sciences, Campobasso, Italy

BACKGROUND AND AIMS: Kidney plays a central role on the maintenance of


water homeostasis, acid-base and electrolytes balances through the activity of different
types of ion channels/transporters expressed along the nephron segments. Mutations
in genes encoding these transporters could subsequently lead to aberrant transporter
activities, resulting in abnormal renal handling of electrolytes, thus represent CONCLUSION: Computational modeling of disease-related mutations in various ion
monogenic form of rare kidney diseases. channels/transporters represents a novel, powerful approach for comprehensive
Accumulating number of mutations identified in genes responsible for such interpretation of the disease phenotypes observed in patients with rare tubulopathies.
monogenic disorders demonstrated that eventual disease phenotypes may vary In addition, combination of in silico modeling and clinical data could provide us with
according to the type and localization of the mutation within the gene. Thus, careful further insight into molecular mechanisms underlying the renal transporter activities.
evaluation of gene variation would be crucial prior to designing the strategy for the Furthermore, this in silico computational modeling approach can be applicable and
therapy in each case. suggestive for novel pharmacological intervention as well as the visual disease severity
Here we present various mutations from our patients, identified in genes including assessment.
kcnj10, SLC12A1, SLC26A4 and clcn7 which are associated with rare tubulopathies
EAST/SeSAME syndrome, Bartter’s syndrome, Pendred syndrome and Fanconi
syndrome, respectively.
MO036 DAPAGLIFLOZIN RESCUES THE RENAL PHENOTYPE OF
In order to explore molecular mechanisms underlying the observed disease conditions
GLYCOGEN STORAGE DISEASE TYPE IB
in our patients, we have performed computational modeling analyses of these
mutations in comparison with wild-type models.
Mariavittoria D’Acierno1,2, Roberta Resaz3, Sabrina Siccardi1,2, Anna Iervolino2,
METHOD: Three-dimensional homology models of Kir4.1, NKCC2, Pendrin and
Donato Sardella2, Giovambattista Capasso1,2, Alessandra Eva3,
CLC-7 proteins were generated by Swiss-Model protein structure homology-modelling
Francesco Trepiccione1,2
server (http://swissmodel. expasy.org) and I-TASSER server (https://zhanglab.ccmb. 1
med.umich.edu/I-TASSER/). Disease-related mutations including novel mutations University “Luigi Vanvitelli”, Department of Translational Medical Sciences, Naples,
identified from our patients were mapped onto the three-dimensional models and Italy, 2Biogem scarl, Genetics and Translational Medicine, Ariano Irpino, Italy and 3
compared with wild-type models in terms of atomic interactions as well as secondary, Istituto Giannina Gaslini, Laboratory of Molecular Biology, Department of Translational
tertiary and quaternary structures. Furthermore, we assessed possible effects of Research, Laboratory Medicine, Diagnosis and Services, Genoa, Italy
missense mutations on the function of ion channels/transporters using online
bioinformatic prediction tools PolyPhen-2, Mutation taster, PROVEAN and SIFT. BACKGROUND AND AIMS: Glycogenosis I type b (GsdI-b) is a rare metabolic
RESULTS: The three-dimensional model comparison between wild-type Kir4.1 and disease and immune disorder characterized by hepato-renal glycogen accumulation
Ala167Val variant, which is related to EAST/SeSAME syndrome, revealed that caused by a deficiency in the Glucose-6-phosphate transporter (G6PT). G6PT
Ala167Val located at the junction between transmembrane domain 2 (TM2) and C- transports glucose-6-phosphate (G6P) from cytoplasm to endoplasmic reticulum (ER)
terminus is predicted not to interrupt the sequence of the hydrogen bonds, thus not where a G6Pase catalyses the hydrolysis of G6P in glucose and phosphate. G6PT
altering the TM2 alpha-helix structure. In addition, while PolyPhen-2 and Mutation deficiency lead to impaired glucose homeostasis, myeloid disfunction and long-term
taster evaluated Ala167Val as ‘probably damaging’, PROVEAN and SIFT predicted risk of hepatocellular adenomas. No causal therapy is so far available for GSDI-b
Ala167Val as ‘neutral’ and ‘tolerated’. These observations are in line with the clinical patients besides a dietary approach to control glycemia and the use of Granulocyte
data demonstrating the milder phenotype in patients with Ala167Val mutation Colony-Stimulating Factor (GCSF) to improve neutropenia. Over time, these supports

i108 | Abstracts
Nephrology Dialysis Transplantation Abstracts
increase the chronicity of GSDI-b with some complications. A mouse model MO038 SCARF EXPRESSION IN KIDNEY DISEASE
recapitulating the GDSI-b has been recently generated by inducing G6PT suppression
after tamoxifen injection. Here, we characterized the renal phenotype of TM-G6PT-/- Sol Carriazo1, Maria Dolores Sanchez-Nino2, Maria Vanessa Perez Gomez1,
mice model focusing on the molecular mechanisms that lead to renal dysfunction. Laura Castan ~eda-Infante1, Catalina Martin1, Guillermo Gonzalez-Martin1,
Finally, we evaluated the efficiency of Dapagliflozin, a selective inhibitor of SGLT2, on Elena Goma 1, Marina Gonzalez-Rivera1, Alberto Ortiz1
1
kidney functions in terms of therapeutic effect. Fundacion Jiménez Dıaz, Nephrology, Madrid, Spain and 2Instituto de Investigaci
on
METHOD: Machine learning approach to computer based evaluation of renal sanitaria, Fundaci
on Jiménez Dıaz Hospital, Nephrology, Madrid, Spain
morphology was used to analyze the renal sections from TM-G6PT-/- treated with or
without dapagliflozin. BACKGROUND AND AIMS: Chronic kidney disease (CKD) is the most common
Results: G6PT is expressed in all renal zones and a severe downregulation of G6PT risk factor for lethal COVID19 and the risk factor that most increases the risk of death
mRNA expression in whole kidney of TM-G6PT-/- mice can be observed. TM- of COVID19 patients. Additionally, acute kidney injury (AKI) is frequent in COVID19
G6PT-/- mice show tubular vacuolization and overall cellular dysfunction of PT due to and AKI increases the risk of death. However, the underlying cellular and molecular
a high glycogen accumulation. TM-G6PT-/- mice manifest glycosuria, phosphaturia mechanisms of such increased risk are unclear. SARS-CoV-2 and coronavirus-
and polyuria associated with a down regulation of main transporters of PT cells. The associated receptors and factors (SCARFs) are required for and/or regulate (in a
urine concentrating defect is due to a primarily role of G6PT in CNT/CD cells positive or negative manner) coronary cell entry and/or viral replication. We have now
confirmed by a downregulation of AQP2, main water channel along CD segments. studied changes in the expression of genes encoding for SCARF in the context of acute
This mouse model recapitulates the human GSD-Ib renal phenotype characterized by a and chronic kidney disease.
disfunction of PT but also CNT/CD cells. In order to evaluate whether targeting the METHOD: Data mining of in-house (experimental models of AKI -folic acid
glucose metabolism would improve the renal phenotype of these mice we limited nephropathy- and CKD -Unilateral ureteral obstruction- in mice) and publicly
glucose flux across the apical membrane of PT cells, applying the SGLT2-inhibitor available databases (Nephroseq, published single cell transcriptomics studies) of kidney
dapagliflozin to reduce new glycogen formation. After one month of treatment, tissue transcriptomics as well as the Protein Atlas database.
Dapagliflozin prevents glycogen accumulation in TM-G6PT-/- mice and ameliorates RESULTS: Out of 28 SCARF genes identified by Singh et al (Cell Reports 2020), 26
the main dysregulated markers of PT function. This finding was paralleled by an were represented in the experimental AKI database. Of them 7 (27%) were
improvement of the histological features of kidney morphology in dapagliflozin treated differentially expressed during AKI (FDR <0.05), 4 of them upregulated and 3
TM-G6PT-/- mice. downregulated (Figure 1.A). Additionally, 27 were represented in the experimental
CONCLUSION: Our data provide evidence that treatment with dapagliflozin CKD database. Of them 17 (63%) were differentially expressed during experimental
ameliorates intracellular glycogen storage and improves the renal functions in TM- CKD, 6 of them upregulated and 11 downregulated (Figure 1.B). Two genes were
G6PT-/- mice. consistently upregulated (Ctsl and Ifitm3) and two consistently downregulated
(Tmprss2 and Top3b) in both experimental AKI and CKD (Figure 1.A and B). They
encode cathepsin L, interferon induced transmembrane protein 3, transmembrane
MO037 EPIGENETIC REGULATION OF KLOTHO IN PERIPHERAL serine protease 2, DNA topoisomerase III beta, respectively. Single cell transcriptomics
BLOOD CIRCULATING CELLS IS ASSOCIATED CELLS IS databases localized Ctsl expression mainly to podocytes and tubular cells while protein
ASSOCIATED WITH SOLUBLE PROTEIN SERUM IN atlas showed clear tubular staining. The main site of Ifitm3 was endothelium in both
CARDIOVASCULAR DISEASE datasets and it was also localized to leukocytes by single cell transcriptomics. Tmprss2
was mainly localized to tubular cells in both datasets while Top3b was widely expressed
Atteneri Pérez-Castro1, Ernesto Martın-Nu ~ez1, Javier Donate-Correa1,
n in parenchymal renal cells, endothelium and leucocytes in single cell transcriptomics.
Carla Ferri1, Vıctor G. Tagua1, Ainhoa Gonz alez-Luis1, Alejandro Delgado- Increased kidney expression of Ifitm3 and decreased expression of Tmprss2 and Top3b
Molinos1, Angel Lo pez-Castillo1, Sergio Rodrıguez-Lo pez1, Purificacio
n Cerro- were confirmed in diverse CKD datasets in Nephroseq.
Lopez1, Carmen Mora-Ferna ndez1, Juan F. Navarro-Gonz alez1
1
Hospital Universitario Nuestra Se~
nora de Candelaria, Unidad de Investigaci
on, SANTA
CRUZ DE TENERIFE, Spain

BACKGROUND AND AIMS: The antiaging factor a-Klotho (KL) has been related to
cardiovascular diseases (CVD), including coronary artery disease, heart failure and
peripheral arterial disease. The soluble form of this protein (sKL), which is mainly
produced by the kidneys, have demonstrated to display different protective effects on
the cardiovascular system, e.g., prevention of vascular calcification, oxidative stress, or
cardiac fibrosis. Likewise, different clinical studies have pointed out that CVD is a state
of sKL deficiency, even when the renal function is still preserved. It has been
demonstrated that peripheral blood circulating cells (PBCCs) also express KL, but little
is known about its expression profile during CVD. The aim of this work is to
determinate if the expression of KL gene and its promoter methylation in PBCCs are
correlated with serum levels of the soluble protein, and if there exist any association
with the underlying inflammatory process that occurs during CVD.
METHOD: Forty-four patients diagnosed with clinical atherosclerotic vascular disease
(case group) and 15 subjects without CVD background (control group) were included
in the study. Whole blood and serum samples were obtained from all participants. We
performed gene expression analysis for KL expression in PBCCs by qPCR, as well as
for DNMT1 and DNMT3A (members of the DNA-methyltransferases family), TNF,
IL10 and NFKB1 (inflammatory parameters). We assessed the degree of methylation of
the KL gene promoter in these cells by bisulfite sequencing. Furthermore, we
determined circulating levels of sKL, TNFa and IL10 by ELISA immunoassay in serum
samples of both groups.
RESULTS: Results showed a lower expression of KL gene in PBCCs of patients with
CVD compared to controls (45% reduction, P<0.001), which was accompanied by a
higher degree of methylation of its promoter (36.766.3% vs. 15.964.8%, P<0.05). The
case group also presented significantly higher levels of DNMT1 and DNMT3A
transcripts in these cells (P<0.0001 for both), as well as higher values of
proinflammatory parameters (gene expression of TNF and NFKB1, and TNF/IL10
ratio; P<0.001 for all of them). Serum levels of sKL were decreased in the CVD group
compared to controls (a reduction of 57.5%, P<0.0001). KL expression in PBCCs
correlated directly with systemic levels of sKL (r=0.20, P<0.05), but inversely with
expression of DNMT1 (r=-0.33, P<0.01) and inflammatory parameters (r=-0.37,
P<0.01 for NFKB1 expression; r=-0.38, P<0.01 for TNF/IL10 expression ratio; and r=-
0.39, P<0.01 for serum TNFa/IL10 ratio). No significant associations were found
between inflammatory markers and methylation degree of KL gene promoter.
CONCLUSION: These results indicate an association between epigenetic regulation of
KL gene in PBCC and systemic levels of the soluble protein in CVD, which could be CONCLUSION: Both AKI and CKD are associated with differential expression of
influenced by the proinflammatory state present in these disorders. SCARF genes in kidney tissue, the impact of CKD appearing to be larger.
Characterization of these changes and their functional impact in kidney tissue and

10.1093/ndt/gfab080 | i109
Abstracts Nephrology Dialysis Transplantation

beyond the kidneys may provide clues to the increased risk of severe or lethal slopes, predicted time to reach CKD stage 5 with and without tolvaptan therapy. Given
COVID19 in kidney disease patients. this was a retrospective review, eGFR were estimated during clinic visits whilst on
Kidney SCARF gene expression tolvaptan treatment, rather than after a drug washout period.
RESULTS: The cohort of patients included 20 from Newcastle upon Tyne Hospitals
and 2 from Sunderland Royal Infirmary. The mean rate of eGFR decline prior to
treatment was -5.92 ml/min/1.73m2 per year for the cohort. Following tolvaptan
MO039 IDENTIFICATION OF A RECURRENT SYNONYMOUS
treatment, the average decline in eGFR was reduced to -2.57 ml/min/1.73m2 per year.
GENETIC VARIANT IN NPHP3 LEADING TO
Therefore, tolvaptan lessened average eGFR decline within this cohort by 3.35 ml/min/
NEPHRONOPHTHISIS AND CONGENITAL HEPATIC FIBROSIS
1.73m2 per year, gaining 7 years and 9 months delay until CKD stage 5. The majority
of patients (n=19) received full dose tolvaptan (90mg/30mg). At an individual level, 3
Eric Olinger1, Intisar Al Alawi1,2, Elisa Molinari1, Eissa Ali Faqeih3, Mohamed Al
patients failed to respond at all to tolvaptan, with no improvement in decline of GFR
Hamed4, Miguel Barroso-Gil1, Ian Wilson5, Genomics England Research
and 2 others had a very mild improvement only (change in eGFR slope of <0.5 ml/
Consortium6, John Sayer1,7,8
1
min/1.73m2 per year). 6 patients had a dramatic improvement in eGFR slope (>5 ml/
Translational and Clinical Research Institute, Newcastle University, Newcastle upon min/1.73m2 per year).
Tyne, United Kingdom, 2Ministry of Health, National Genetic Center, Muscat, Oman, CONCLUSION: The real life use of tolvaptan seemed to give a dramatic improvement
3
Children’s Specialist Hospital, King Fahad Medical City, Section of Medical Genetics, in eGFR slopes, much more than the previously reported clinical studies have shown.
Riyadh, Saudi Arabia, 4King Faisal Specialist Hospital and Research Center, Department This may be in part due to patient selection and only including patients who tolerated
of Genetics, Riyadh, Saudi Arabia, 5Biosciences Institute, Newcastle University, therapy, a “tolvaptan clinic” effect where great personal care is given to these patients
Newcastle upon Tyne, United Kingdom, 6Department of Health & Social Care, London, and to excellent compliance with medication. Reasons for both non-response and
United Kingdom, 7Newcastle Upon Tyne Hospitals NHS Foundation Trust, Renal exaggerated response need to be evaluated carefully to determine how individualisation
Services, Newcastle upon Tyne, United Kingdom and 8NIHR Newcastle Biomedical of tolvaptan therapy can be best used.
Research Centre, Newcastle upon Tyne, United Kingdom

BACKGROUND AND AIMS: Whole exome sequencing (WES) is becoming part of


routine clinical and diagnostic practice and has been extensively applied in research
studies as well as for diagnostic utility to detect various novel genes and variants.
Filtering of variants and scoring variants in terms of pathogenicity still represents a
major challenge and may explain why 50% of patients remain without diagnosis after
initial assessment.
METHOD: In this study, we performed WES to determine the genetic cause of a
hepato-renal ciliopathy syndrome in a genetically unsolved consanguineous family
from Oman with 2 affected children. For variants filtering and annotation Qiagen
Clinical Insight tool was used. Database searches for identical alleles in patients with
similar phenotypes were performed using Genomics England, UK Biobank and a Saudi
Arabian cohort. RNA studies were used to confirm a splicing defect. This research was
made possible through access to the data and findings generated by the 100,000
Genomes Project and from UK Biobank, a major biomedical database.
RESULTS: Initial bioinformatic analysis of WES data from 2 affected sibs excluded
obvious pathogenic variants in known genes associated with primary ciliopathy
syndromes with liver and kidney phenotypes. However, by manual curation of variants
in candidate genes, a rare homozygous synonymous allele in NPHP3 was identified
(c.2805C>T; p.(Gly935Gly)), mid-exon 20 and within a region of shared homozygosity
on chromosome 3. Correct segregation was confirmed via Sanger sequencing in the
parents and the 2 affected sibs. The variant was rare in gnomAD (2/251374 alleles) and
was found heterozygously in just one individual within the UK Biobank cohort of
200,000 exomes. Using various in silico tools, the allele was shown to activate a cryptic
splice donor site in the middle of exon 20. RT-PCR with sequencing of parental whole MO041 STABILIZATION OF KIDNEY FUNCTION DECLINE AND
blood RNA confirmed alternative splicing leading to frameshift p.Gly935GlyfsTer47. CARDIOMYOPATHY IN MALE PATIENTS WITH CLASSIC
The identical homozygous allele was identified in 2 additional unsolved families within FABRY DISEASE: A PRE- VS. POST-AGALSIDASE BETA
the Genomics England 100,000 Genomes Project and in 1 Saudi Arabian family with TREATMENT FABRY REGISTRY ANALYSIS
similar hepato-renal phenotypes.
CONCLUSION: This study shows that automated filtering of WES data may exclude Alberto Ortiz1, Michael Mauer2, Elvira Ponce3, Meng Yang4, Badari Gudivada4,
synonymous variants which are pathogenic, especially if they are mid-exon. Here we Geu-Ru Hong5, John L Jefferies6
identified a recurrent synonymous NPHP3 variant leading to a splice defect as the 1
Hospital Universitario Fundacion Jiménez Dıaz, Unidad de Dialisis, Madrid, Spain,
cause of a hepato-renal ciliopathy phenotype in four families. In unsolved cases, rare 2
University of Minnesota, Departments of Pediatrics and Medicine, Minneapolis, United
synonymous alleles in candidate genes need to be reassessed for impact on RNA 3
States of America, Sanofi Genzyme, Global Medical Affairs Rare Diseases, Cambridge,
splicing and possible pathogenicity. United States of America, 4Sanofi Genzyme, Epidemiology & Biostatistics, Cambridge,
United States of America, 5Yonsei University College of Medicine, Department of
Cardiology, Seoul, Korea, Rep. of South and 6University of Tennessee Health Science
MO040 REAL-WORLD USE OF TOLVAPTAN AND ITS IMPACT ON Center, The Cardiovascular Institute, Memphis, United States of America
EGFR IN A NORTH EAST UK COHORT
BACKGROUND AND AIMS: Fabry disease (FD) is an X-linked lysosomal storage
Eleftherios Gkekas1, Tsz Yau Tiffany Tang1, Alan Green2, Han Davidson2, disorder caused by pathogenic GLA gene variants. Males with the classic (more severe)
Rachel Fraser2, John Sayer2,3, Shalabh Srivastava3,4 phenotype have markedly deficient or no a-galactosidase A activity and early,
1
Newcastle University, Medical School, Newcastle, United Kingdom, 2Newcastle Upon progressive accumulation of glycosphingolipids (e.g. globotriaosylceramide [GL-3] and
Tyne Hospitals NHS Foundation Trust, Renal Services, Newcastle, United Kingdom, deacylated GL-3 [lyso-GL-3]) in cells and body fluids. Particularly compromised are
3
Newcastle University, Translational and Clinical Research Institute, Newcastle, United vascular endothelial and smooth muscle cells, most kidney cell types (particularly
Kingdom and 4Sunderland Royal Hospital, Renal Department, Sunderland, United podocytes), cardiomyocytes and neural cells. Cellular injury triggers inflammatory
Kingdom responses leading to fibrosis with multisystem involvement. Symptoms associated with
small fiber neuropathy (e.g. neuropathic pain) appear in childhood, typically followed
in adulthood by chronic nephropathy (proteinuria, reduced glomerular filtration rate
BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease [GFR]) that may evolve to end-stage renal disease, and progressive cardiomyopathy
(ADPKD) is a cause of progressive chronic kidney failure (CKD) and end stage kidney with left ventricular hypertrophy and early demise. We compared kidney function and
disease (ESKD). Tolvaptan has been shown within clinical trials to slow down decline cardiomyopathy outcomes after enzyme replacement therapy with agalsidase beta with
of kidney function in patients with ADPKD at risk of rapid progression. We performed treatment-naive outcomes in male patients with the classic form of FD.
a retrospective review of a cohort of ADPKD patients who had been established on METHOD: The self-controlled comparison (piecewise mixed linear modelling) used
tolvaptan therapy to determine its efficacy in a real- world clinic setting. Fabry Registry (NCT00196742) data from males with GLA variants associated with the
METHOD: Subjects who had a clinical diagnosis of ADPKD and who had been classic FD phenotype (dbfgp.org/dbFgp/fabry/). The patients had received agalsidase
established on tolvaptan for a period of >18 months were reviewed retrospectively in beta (average dose of 0.9  1.1 mg/kg every 2 weeks) and had 2 pre- and 2 post-
terms of their eGFR. Subjects were between the ages of 18-65 years old and both males baseline assessments. Baseline was defined as up to 6 months after start of treatment.
and females were included in this study. Other inclusion criteria involved a pre- Follow-up spanned from 5 years pre-treatment (preTx) to 5 years post-treatment
treatment slope of <-2.5 ml/min/1.73m2 based on readings for a 3 year period, a pre- (postTx). Patients on dialysis or with a kidney transplant were excluded. Assessed were
treatment eGFR of 30-90 ml/min/1.73m2 and ability to tolerate tolvaptan treatment slopes of estimated GFR (eGFR, CKDEPI equation), ultrasound derived
and be maintained on treatment for at least12 months. We calculated based on eGFR

i110 | Abstracts
Nephrology Dialysis Transplantation Abstracts
interventricular septum thickness (IVSTd) and left ventricular posterior wall thickness MO043 HYPERURICEMIA IS RELATIVELY COMMON IN CHILDREN
(LVPWTd) during the preTx and postTx periods. Data were stratified by low renal WITH HNF1B MUTATION, BUT ITS UTILITY AS A CLINICALLY
involvement (LRI, ratios [g/g] urine protein-to-creatinine 0.5 or albumin-to- USEFUL MARKER FOR PREDICTING THE MUTATION IS
creatinine 0.3) and high renal involvement (HRI, ratios [g/g] >0.5 or >0.3, LIMITED
respectively). Ages at start of treatment (ageTx) and follow-up durations are expressed
as medians. Marcin Kołbuc1, Beata Bienias2, Sandra Habbig3, Mateusz Kołek4,
RESULTS: Compared with 1.1-year preTx data, eGFR decline was similar during 4.1- Maria Szczepanska5, Katarzyna Kilis-Pstrusin ska6, Anna Wasilewska7,
year postTx follow-up in 254 males, ageTx 30.8 years. eGFR slopes (preTx vs. postTx) Piotr Adamczyk8, Rafał Motyka9, Marcin Tkaczyk10, Przemysław Sikora2, Bodo
were -2.22 vs. -2.66 ml/min/1.73 m2/year (Ppre-post difference=0.24). The changing B. Beck11, Marcin Zaniew1
1
patterns among the 165 LRI males, ageTx 25.4 years (slopes preTx vs. postTx: -1.73 vs. University of Zielona Gora, Department of Pediatrics, Zielona Gora, Poland, 2Medical
-1.92 ml/min/1.73 m2/year; Ppre-post difference=0.66), and the 68 HRI males, ageTx University of Lublin, Department of Pediatric Nephrology, Lublin, Poland, 3University
38.2 years (slopes: -2.93 vs. -4.31 ml/min/1.73 m2/year; Ppre-post difference=0.04), Hospital of Cologne, Department of Pediatrics, Cologne, Germany, 4University of
were statistically different (Pinteraction<0.01). IVSTd remained stable among 73 Warsaw, Department of Animal Physiology, Faculty of Biology, Warsaw, Poland,
5
males, ageTx 34.2 years, during 1.0-year preTx (slope=þ0.02 mm/year, P0>0.05) and Medical University of Silesia in Katowice, Department of Pediatrics, Faculty of Medical
4.1-year postTx follow-up (slopes=-0.02 mm/year, P0>0.05) (Ppre-post Sciences in Zabrze, Zabrze, Poland, 6Wroclaw Medical University, Department of
difference=0.83), where a P0 <0.05 indicates that the slope is significantly different Paediatric Nephrology, Wrocław, Poland, 7University Hospital, Department of Pediatric
from zero. LVPWTd increased preTx (slope=þ0.33 mm/year, P0=0.01) but stabilized Nephrology, Białystok, Poland, 8Medical University of Silesia in Katowice, Department of
during postTx follow-up (slope=-0.09 mm/year, P0>0.05) in 87 males, ageTx 35.1 Pediatrics, Faculty of Medical Sciences in Katowice, Katowice, Poland, 9University of
years (Ppre-post difference<0.01). Overall, patients with LRI had more stable cardiac Zielona G ora, Poland, 10Polish Mother’s Memorial Hospital Research
ora, Zielona G
ultrasound indices throughout follow-up. Institute, Department of Pediatrics, Immunology and Nephrology, Ł odz , Poland and
11
CONCLUSION: In males with classic FD, treatment with agalsidase beta appeared to University of Cologne, Institute of Human Genetics and Center for Molecular Medicine
stabilize eGFR decline in LRI males. Overall, IVSTd remained stable throughout Cologne, Cologne, Germany
follow-up and LVPWTd, increasing during pre-treatment follow-up, stabilized post-
treatment. BACKGROUND AND AIMS: Hyperuricemia is recognized as an important feature of
Funding: Fabry Registry, abstract: Sanofi Genzyme. HNF1B nephropathy, and could serve as a good marker of the disease facilitating
selection of patients for genetic testing. However, neither the casual relationship nor its
predictive value have been proven yet. We thus decided to assess this in a cohort of
MO042 PREVALENCE OF FABRY DISEASE CAUSING VARIANTS IN children with renal malformations with (mutþ) and without HNF1B mutations (mut-
THE UK BIOBANK ).
METHOD: We performed a retrospective analysis of clinical and genetic results of
Mark Gilchrist1, Francesco Casanova1, Jessica Tyrrell1, Nicole Fife1, pediatric patients tested for HNF1B mutations, whose data were collected in a national
Katie Young1, Richard Oram1, Michael Weedon1 registry. Hyperuricemia was assessed by using the newest, age- and gender-dependent
1 reference values for serum uric acid (sUA) in children.
University of Exeter, United Kingdom
RESULTS: A total of 108 children were included into the study comprising 43 mutþ
patients, and 65 mut- subjects. Mean sUA was higher in mutþ than in mut- subjects (p
BACKGROUND AND AIMS: Fabry disease (FD) is an X-linked lysosomal storage = 0.006), and hyperuricemia was more prevalent in those with HNF1B mutations
disorder resulting from deficiency of the alpha-galactosidase A enzyme. This leads to (42.5% vs. 15.4%, p = 0.002). Renal phenotype analysis revealed renal
the accumulation of globotriaosylceramide in multiple organ sites with prominent hyperechogenicity and multicystic dysplastic kidney disease were more frequent in
renal involvement, cardio and cerebrovascular disease, as well as neurological, mutþ patients, but no influence of any renal features/phenotypes on hyperuricemia
dermatological, and gastrointestinal pathology in affected individuals. Clinical was found. The two patient cohorts were different with regard to pancreatic anomaly
manifestations are highly heterogeneous with considerable variation depending on the (p < 0.001), glucose metabolism disorders (p = 0.003), hypomagnesemia (p < 0.001),
specific variant and even within families with the same variant. Prevalence estimates and hyperparathyroidism (p < 0.001). In a multivariate linear stepwise regression
from studies of case control cohorts range from 1 in 40,000 to 1 in 140,000. We sought model, eGFR, fractional excretion of uric acid, impairments in glucose metabolism and
to determine the prevalence of Fabry disease causing mutations in an unbiased adult pancreatic anomaly were found to be independent predictive variables of sUA
population sample using the UK Biobank. (R2=0.67, F=13.27, p < 0.001). Mutation was not identified as a determinant of sUA.
METHOD: UK Biobank comprises approximately 500,000 participants with extensive After exclusion of patients with hyperglycemia and/or pancreatic malformations, the
phenotyping and genetic data linked to clinical care records. Exome sequencing data difference in hyperuricemia prevalence did not persist between mutþ and mut-.
from 200643 individuals from the UK Biobank were examined for variants in the GLA Potential of hyperuricemia for mutation prediction was tested in a model with
gene. Likely mutations were searched for in ClinVar and HGMD with subsequent hypomagnesemia and hyperparathyroidism, which showed an accuracy of 85%
review of supporting literature. We used ACMG guidelines to classify the pathogenicity (sensitivity: 83%, specificity: 86%). Adding hyperuricemia to the model did not
of variants. increase the accuracy (79%; sensitivity: 77%, specificity: 82%). Information gain, which
RESULTS: Eighty one coding variants were identified in GLA. Nine of these variants informs selective potential of each parameter, was the lowest for hyperuricemia (0.34
were rare (<1 in 10,000 individuals) and either protein truncating variants or compared with 0.99 and 0.63 for hyperparathyroidism and hypomagnesemia,
previously reported to cause Fabry’s disease. Thirty seven individuals, (14 males, 22 respectively).
females, 1 missing data) carried one of these GLA variants. The most common variant CONCLUSION: Hyperuricemia is relatively common in children with HNF1B
was the cardiac predominant phenotype causing N215S variant (18/37). 6/37 had the mutation, however its direct association with this molecular defect remains still
R363C variant, 4/37 had R356Q. The R112H, R301Q, I198T variants were each unproven. Its dependence on renal function and hyperglycemia diminishes the utility
identified in 2 individuals. There were single individuals with I232T, K240fs, and E66G as a clinically useful marker for predicting HNF1B disease.
variants.
Two male individuals (with I232T, K240fs variants) had HES codes compatible with a
known diagnosis of Fabry disease. The remaining 12/14 males did not have evidence of
an existing diagnosis of Fabry disease. No female participants had HES codes MO044 TARGETED NEXT GENERATION SEQUENCING AND
indicating an existing diagnosis of Fabry disease. MULTIDISCIPLINARY APPROACH IN AUTOSOMAL
The overall prevalence of Fabry disease causing variants in the UK Biobank is 1 in DOMINANT POLYCYSTIC KIDNEY DISEASE, ALPORT
5,422. The N215 variant alone has a prevalence of 1 in 11,147. DISEASE AND FAMILIAL HAEMATURIA: GENETIC
CONCLUSION: Reported Fabry disease causing GLA variants are far more prevalent SPECTRUM AND CLINICAL UTILITY IN A SPANISH COHORT
in an unselected population sample than would be expected from the reported
prevalence of Fabry disease. This may be because some of the reported variants are not Isabel Galan Carrillo1, Liliana Galbis2, Vıctor Martınez Jiménez3, Juan
pathogenic, or are predominantly later-onset causing variants with reduced David Castro4, Fernanda Ramos1, Susana Roca5, Lidia Rodrıguez6, Juan Pin ~ero7,
penetrance. The true prevalence of Fabry disease may be substantially higher than Encarnacion Guillén6
1
current estimates. Reina Sofia Hospital, Nephrology, Murcia, Spain, 2Virgen de la Arrixaca Hospital,
Biochemistry and Clinical Genetics, Murcia, Spain, 3Virgen de la Arrixaca Hospital,
Nephrology, Murcia, Spain, 4Santa Lucia Hospital, Pediatrics, Cartagena, Spain, 5Santa
Lucia Hospital, Nephrology, Cartagena, Spain, 6Virgen de la Arrixaca Hospital, Genetics,
Murcia, Spain and 7Virgen de la Arrixaca Hospital, Pediatrics, Murcia, Spain

BACKGROUND AND AIMS: Autosomal Polycystic kidney Disease (ADPKD;


ORPHA 730), Alport Syndrome (AS; ORPHA 63) and Familial Haematuria (FH) are
the most frequent inherited kidney diseases. Next-generation Sequencing (NGS) has
facilitated their molecular identification. A multidisciplinary team from four hospitals,
with nephrologists, pediatricians, and clinical and molecular geneticists, has been
formed in the Spanish region of Murcia (1.5 million inhabitants) with the lab
implementation of NGS. Our aim is to evaluate the genetic spectrum in AS, FH and
ADPKD and the clinical utility of this comprehensive approach.

10.1093/ndt/gfab080 | i111
Abstracts Nephrology Dialysis Transplantation

METHOD: During 1-year activity, 114 individuals with diagnostic suspicion of MO046 NGS PANEL PERFORMANCE IN THE DIAGNOSIS OF
ADPKD, AS or FH have been evaluated by a coordinated clinical protocol with HEREDITARY RENAL DISEASE IN SOUTHERN SPAIN
periodic cases discussions. A customized Agilent panel was designed to capture 113 
genes associated with several genetic diseases, including some related to PKD, AS or Marıa del Mar Del Aguila Garcıa1, Antonio M Poyatos Andu jar2, Ana
Familial Haematuria (FH): PKD1, PKD2, PKHD1, HNF1b, COL4A1, COL4A3, Isabel Morales Garcıa3, Margarita Martınez Atienza4, Susana Garcıa Linares2,
COL4A4 and COL4A5. Interpretation of sequence variants was performed according Rafael Jose Esteban de la Rosa5
1
to the American College of Medical Genetics and Genomics (ACMG) Guidelines. Hospital Universitario Virgen de las Nieves, Servicio de An alisis Clınicos, Granada,
Sanger sequencing was performed to confirm variants identified by NGS and to Spain, 2Hospital Universitario Clınico San Cecilio, Laboratorio de Genética, Servicio de
3
segregate them in the families. Exon 1 of PKD1 gene was also sequenced by Sanger Analisis Clınicos, Granada, Spain, Hospital Universitario Clınico San Cecilio, Servicio de
method, due to the suboptimal capture of this region by NGS. Nefrologıa, Granada, Spain, 4Hospital Universitario Virgen de las Nieves, Laboratorio de
RESULTS: We detected genetic variants in 63 patients (55.3%), pathogenic or probably Genética, Servicio de An alisis Clınicos, Granada, Spain and 5Hospital Universitario
pathogenic variants in 54 (47.8%). 31 patients had a variant in AS associated genes: 10 Virgen de las Nieves, Servicio de Nefrologıa, Granada, Spain
in COL4A3, 18 in COL4A4, 2 in COL4A1 and 1 in COL4A5. There were 13 pathogenic
variants, 12 probably pathogenic variants and 6 variants of uncertain clinical BACKGROUND AND AIMS: Hereditary renal disease (HRD) is still underdiagnosed:
significance (VUCS). Among them, 27 had an AD inheritance, 1 AR and 3 were although we know aspects related to autosomal dominant polycystic kidney disease
sporadic. All the patients with any variant had microhaematuria, a 68% had also (ADPKD), we know little about the incidence and prevalence of other entities such as
proteinuria, and mean eGFR at diagnostic was 63.79621 ml/min/1.73m2. 61% had Alport syndrome. Altogether, HRD can represent 15% of individuals undergoing renal
auditory disturbances and 11% ophthalmologic alterations. 4 of them had underwent replacement therapy (RRT) or could even be higher.
kidney biopsy previously, but 3 were not adequately diagnosed, so they were The advancement of genetics at the healthcare level let to achieve accurate and early
reclassified after the molecular diagnosis. In total, 16 kidney biopsies were avoided by renal diagnoses, as well as the incorporation of genetic counseling to families, all of
the genetic diagnosis. On the other hand, 29 patients had a variant in the ADPKD which will result in better management of the disease in its initial stages and the
associated genes: 24 in PKD1 and 5 in PKD2. There were 20 pathogenic variants and 4 possibility of offering reproductive options that avoid transmission to offspring.
probably pathogenic variants, and their inheritance was confirmed AD in 27 patients, Our objective is to know the performance offered by the implementation of the ERH
whereas new sporadic mutations were identified in 2 patients. 22 patients had big or panel through Next Generation Sequencing (NGS) in our healthcare area.
enormous kidneys on sonography, although 7 had normal size. Hepatic cysts were METHOD: Observational-descriptive study of 259 probands (141 men / 118 women),
present on 5%. 19 patients had hypertension, with a mean age of diagnosis of 47614 mean age of 46 years (30 pediatric / 123 over 50 years), with chronic kidney disease and
years. Additionally, 1 patient was diagnosed on AR polycystic disease with suspected hereditary cause attended in the specialized consultation of our centers from
homozygosity PKHD1 pathogenic variant. Among all the scope, familial history was October 2018 to October 2020. The DNA extracted from leukocytes obtained by
clearly present in 43 patients, uncertain in 11, and not present in 9 patients. venipuncture was processed with Nephropathies Solution version 3 panel (SOPHiA
CONCLUSION: The multidisciplinary approach to hereditary kidney diseases, with Genetics) according to the manufacturer’s protocol. This panel covers the coding regions
the active participation of nephrologists and clinical geneticists, has allowed a and splicing junctions of 44 HRD-related genes such as nephrotic syndromes, polycystic
molecular diagnostic yield of 48% among patients with AS and ADPKD, employing kidney diseases, Bartter syndromes, Alport syndrome, CAKUT or tubulopathies (table 1).
NGS technology. This has led to a quicker diagnostic result in our region, the
reclassification of some patient’s diagnosis, a decrease in invasive diagnostic procedures MO046 Table 1: Genes included in the SOPHiA Genetics Nephropaties solution
(such as kidney biopsy) and the correspondent adverse events and cost savings. panel.
Additionally, the AD inheritance pattern in AS has been confirmed as the most
frequent in the region. The active participation of nephrologists in genomic medicine
teams results in a better characterization of the hereditary kidney diseases, helping in
the genetic variant interpretation and management of these patients and their families.

MO045 THE APPLICATION OF A NGS KIDNEY PANEL REVEALED


KEY CHALLENGES OF PKD1-2 ANALYSIS: INTERPRETATION
OF MISSENSE VARIANTS, SIGNIFICANCE OF VARIANTS IN
DUPLICATED REGIONS AND HIGH ALLELIC
HETEROGENEITY
The sequencing of the libraries was done in a MiSeq (Illumina Inc), the bioinformatic
Giancarlo Blasio1, Miriam Zacchia1, Francesca Del Vecchio Blanco2, analysis of the data and annotation of variants was performed using the SOPHiA DDM
Giovanna Capolongo1, Alessandra Perna2, Vincenzo Nigro1, 5.8.0.3 software, and the revision of variants by consulting the main databases
Giovambattista Capasso2 (ClinVar, Exac, HGMD, NCBI, PKD Foundation, LOVD).
1
University of Campania, L. Vanvitelli , Italy and 2University of Campania, L. Vanvitelli , RESULTS: The panel was informative (pathogenic or probably pathogenic) in 80/259
Naples, Italy patients (31%) and 56/259 cases (21.66%) of variants of uncertain significance (VSI)
were detected.
BACKGROUND AND AIMS: Genetic testing has changed the clinical management Autosomal dominant polycystic kidney disease accounted for 76.2% of the variants
of inherited kidney diseases patients, improving prognosis, surveillance and therapy. identified (56.2% PKD1, 20% PKD2), following Alport syndrome with 15% and the
On the other hand, it has put geneticists and clinicians in front of new challenges, as alterations in the PKHD1 gene associated with renal polycystic disease in its recessive
the heterogeneity of these disorders and the high number of variants, with no clear form with about 4% (Figure 1). We have also identified a case of autosomal dominant
genotype-phenotype correlation. tubulointerstitial kidney disease associated with the UMOD gene that was not
METHOD: 108 patients underwent genetic analysis through a kidney focused NGS suspected until the genetic study was performed. We highlight that 45% (36/80) of the
panel, named Nephroplex, containing 119 genetic loci associated with inherited kidney variants identified as responsible for the renal disease are not yet described. Overall, the
disorders. The study aimed to addressed the genetic landscape of cystic individuals and most prevalent type of mutation is that which produces displacement in the reading
to analyze PKD1 and PKD2 variants in non-cystic individuals. frame or frameshift (Figure 2). Individually, frameshift is the most frequent alteration
RESULTS: Following diagnostic criteria, patients were divided as cystic kidney diseases in PKD1, PKD2 and COL4A5, while for PKHD1, COL4A3 and COL4A4 it is missense.
(n=36) and non-cystic kidney diseases (n=72). Among the group of cystic patients, a
causative mutation was detected in 51% of cases. We found thirty-seven PKD1 and PKD2
variants in 26 out of 35 individuals. In particular, 12 variants were shown to be damaging
and nine of that were reported in public database, as CLINVAR and Mayo Clinic
databases. Among pathogenic variants, twelve were truncating and the remaining were
missense variants. Of note, 7 out of 12 damaging PKD1 mutations were located in
duplicated regions. Moreover, in three cystic patients, we found a (i) a frameshift
hemizygote OFD1 mutation (ii) compound heterozygote PKHD1 variants and (iii) a
frameshift MUC1 variant, framing the diagnosis of oro-facio-digital type 1, autosomal
recessive polycystic kidney disease and autosomal dominant tubulointerstitial disease,
respectively. Interestingly, we detected 28 PKD1-2 rare variants in 21 out of 75 adult non
cystic patients (28%). The most were observed in PKD1 genes (82% vs 18% in PKD2).
Eighteen of 28 variants were described in the literature as likely benign or as mutations of
uncertain significance, while we found 10 novel variants. In silico analysis revealed as
pathogenic a frameshift mutation located in exon 15. Of note, the great part of these
variations reside into the duplicated PKD1 regions.
CONCLUSION: Our data showed that genetic analysis of ADPKD retains unique
challenges, given the high degree of homology of PKD1 with his pseudogenes and the MO046 Figure 2: Types of mutations according to frequency.
high allelic heterogeneity in non-cystic individuals.

i112 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Our NGS HRD panel a) offers an adequate diagnostic performance at presenting with end-stage kidney disease (ESKD) and no evidence of nephrolithiasis or
the healthcare level, with definitive results in 1 out of 3 cases and has also allowed the nephrocalcinosis.
performance of many carrier studies among family members b) is able of diagnosing METHOD: Two white British brothers presented to a different regional centre over 20
the most frequent disease, ADPKD and Alport syndrome, as well as unresolved or years ago with ESKD of unknown aetiology. The UK 100,000 Genomes Project
poorly characterized cases, and c) opens the horizon for new diagnoses, all without provided a unique opportunity to make a molecular diagnosis using whole-genome
increasing costs by outsourcing services. All this makes the genetic study of renal sequencing linked to clinical records.
pathology a useful and efficient strategy. RESULTS: The older brother presented with ESKD aged 23 with bilateral small
These results encourage us to enhance the resources in this area that we consider to be kidneys and no evidence of nephrolithiasis or nephrocalcinosis on ultrasound. He had
of strategic value. various musculoskeletal pains, ’cutaneous ectopic calcification’ and secondary
hyperparathyroidism, all of which improved post parathyroidectomy. Investigation of
his 17-year-old brother for consideration of kidney transplant donation revealed
progressive chronic kidney disease (CKD), microscopic haematuria, proteinuria (3g/
MO047 STABLE EGFR IN PATIENTS WITH PRIMARY
24hours) and hypokalaemia. There was no nephrocalcinosis or renal calculi on
HYPEROXALURIA TYPE 1 TREATED WITH LUMASIRAN,
ultrasound or cystoscopy. Renal biopsy showed tubulointerstitial changes with patchy
REGARDLESS OF KIDNEY FUNCTION AT START OF
fibrosis and marked chronic inflammatory cell infiltrates. He had a history of enuresis,
TREATMENT
polydipsia, delayed bone age and general developmental delay. ESKD by the age of 22
was complicated by hypertension and hyperparathyroidism requiring
Wesley Hayes1, Sander Garrelfs2, David Sas3, John Lieske4, Taylor Ngo5,
parathyroidectomy. Right knee pain with ’unusual osteochondral abnormality’ on MRI
John Gansner5, Tracy McGregor5, Yaacov Frishberg6
1
resulted in a supracondylar femoral osteotomy. Early serum and urine biochemistry
Great Ormond Street Hospital for Children, London, United Kingdom, 2Emma results were not available. A hemizygous nonsense variant p.Arg417Ter in CLCN5 was
Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, identified by whole-genome sequencing via the 100,000 Genomes Project. Sanger
Netherlands, 3Mayo Clinic, Division of Pediatric Nephrology and Hypertension, sequencing at the Wessex Regional Genetics Laboratory confirmed this. This variant
Rochester, MN, United States of America, 4Mayo Clinic, Division of Nephrology and was predicted to be protein-truncating, was absent in the genome aggregation database
Hypertension, Rochester, MN, United States of America, 5Alnylam Pharmaceuticals, (gnomAD) and equivalent to a variant associated with Dent disease in other patients
Cambridge, MA, United States of America and 6Shaare Zedek Medical Center, Division therefore classified as a class 5 pathogenic variant according to ACMG guidelines.
of Pediatric Nephrology, Jerusalem, Israel Three male children with Dent disease have previously been reported with the
pathogenic variant p.Arg347Ter. A seven and a twelve year old from two different
BACKGROUND AND AIMS: Primary hyperoxaluria type 1 (PH1) is a rare genetic families in Japan had microscopic haematuria, proteinuria, elevated b2-microglobulin
disorder characterized by hepatic oxalate overproduction. Excess oxalate is excreted by and normal renal function. The twelve-year-old had mild hypercalciuria, but neither
the kidneys, leading to recurrent kidney stones, nephrocalcinosis, and progressive had a history of nephrolithiasis or nephrocalcinosis. A four-year-old Turkish boy
kidney disease. Patients with PH1 generally experience a slow decline in kidney manifested hypophosphataemia, nephrolithiasis and nephrocalcinosis. Unusually for
function over time that can be punctuated by abrupt worsening precipitated by Dent disease, he also had hypokalaemic hypochloraemic metabolic alkalosis and
infection, obstructing stones, or dehydration. Approximately half of patients with PH1 hyper-reninaemic hyperaldosteronism more characteristic of Bartter syndrome, but
progress to kidney failure by early adulthood, and nearly all by 60 years of age. with elevated b2-microglobulin more typical of Dent disease. None of these cases had
Lumasiran is an RNAi therapeutic indicated for the treatment of PH1 in all age groups. CKD but were all reported at a very young age.
In clinical trials, treatment with lumasiran resulted in substantial reductions in urinary CONCLUSION: Approximately 15% of patients with ESKD in Europe have an
and plasma oxalate in pediatric and adult patients, with an acceptable safety profile. unknown aetiology. Dent disease has a variable phenotype and screening of patients for
This analysis evaluates the change in kidney function of patients with PH1 with an low molecular weight proteinuria such as b2-microglobulin is not routinely performed.
eGFR of 30 mL/min/1.73m2 enrolled in clinical trials of lumasiran. Dent disease type 1 should be considered in patients presenting with unexplained renal
METHOD: We analyzed kidney function from 75 patients with PH1, age 12 months failure even without typical clinical features.
old, eGFR 30 mL/min/1.73m2, enrolled in 3 clinical trials of lumasiran (Phase 2
open-label extension, and Phase 3 ILLUMINATE-A and ILLUMINATE-B). In these
trials, eGFR was calculated with the Modification of Diet in Renal Disease (MDRD)
MO049 FUNCTIONAL IMPORTANCE OF MAPKBP1 PROTEIN
Study equation in adults or the bedside Schwartz equation in children. The effect of
DOMAINS IN NEPHRONOPHTHISIS
lumasiran on eGFR was assessed by baseline eGFR subgroup: 90, <90, 60 to <90, 45
to <60, and 30 to <45 mL/min/1.73m2.
Christin Hartig1, Ria Schönauer1, Sebastian Sewerin1, Anastasia Ertel1,
RESULTS: Of 75 patients available for analysis, 46 were treated with lumasiran from
Wenjun Jin1, Elena Hantmann1, Sophie Saunier2, Alexandre Benmerah2,
the start of the study through the Month 12 visit. eGFR remained stable in all eGFR
Jan Halbritter1
subgroups. Patients with eGFR 90 mL/min/1.73m2 at baseline (N=16) demonstrated 1
fluctuations in mean values by timepoint, with a mean change (95% CI) from baseline University Hospital Leipzig, Department of Internal Medicine, Division of Nephrology,
of -1 (-8, 6) mL/min/1.73m2 at Month 12. In patients with eGFR <90 mL/min/1.73m2 Leipzig, Germany and 2Université de Paris, Imagine Institute, Laboratory of inherited
(N=30), no change in mean eGFR from baseline was observed at Month 12; the mean kidney diseases, INSERM UMR1163, Paris, France
change (95% CI) was 0 (-3, 3). When evaluating subgroups with impaired kidney
function, variations in the mean change were observed at Month 12 due to small BACKGROUND AND AIMS: Nephronophthisis is an autosomal-recessive kidney
sample sizes. For patients with eGFR 60 to <90 mL/min/1.73m2 (N=22), the mean disease that accounts for a significant proportion of end-stage renal disease (ESRD) in
change (95% CI) was -2 (-5, 1). For patients with eGFR 45 to <60 mL/min/1.73m2 childhood, adolescence and early adulthood. Biallelic pathogenic variants in
(N=5), the mean change (95% CI) was 3 (-8, 14). For patients with eGFR 30 to <45 MAPKBP1, encoding the c-Jun N-terminale kinase (JNK)-binding protein 1, are
mL/min/1.73m2 (N=3), the mean change (95% CI) was 9 (7, 11). associated with development of Nephronophthisis and subsequent chronic kidney
CONCLUSION: Patients with PH1 had stable kidney function over time with disease (CKD) (Macia et al, AJHG, 2017). We recently characterized MAPKBP1 as
lumasiran treatment, regardless of kidney function at baseline. Given the progressive microtubule-associated protein that is able to localize to centrioles and the base of
kidney function decline that is characteristic of PH1, the eGFR stability observed primary cilia depending on dimerization via its C-terminal coiled-coil domain
during 12 months of treatment with lumasiran is encouraging. Kidney function will (Schönauer et al, Kidney Int, 2020). However, the physiological function of its N-
continue to be monitored for the duration of the lumasiran clinical trials. terminal WD40 and intermediate JNK-binding domain is still poorly understood. By in
vitro comparison of artificial domain deletions with known and novel patient variants,
we aim at pinpointing functional consequences of pathogenic MAPKBP1 in cilia and
cell cycle control.
MO048 PATHOGENIC VARIANTS IN CHLORIDE VOLTAGE-GATED
METHOD: N-terminally GFP-tagged MAPKBP1 constructs with either full-domain
CHANNEL 5 (CLCN5), ASSOCIATED WITH DENT DISEASE
deletions or patient-derived variants were expressed in non-ciliated HeLa and ciliated
TYPE 1, SHOULD BE CONSIDERED IN END-STAGE KIDNEY
H69 cells for fluorescence microscopy studies. Furthermore, RNA-seq analysis using
DISEASE OF UNKNOWN AETIOLOGY
primary patient cells was conducted to investigate differentially regulated molecular
pathways compared to healthy control individuals.
Gary Leggatt1,2,3, Christine Gast1,2, Rodney Gilbert1,4, Kristin Veighey1,2,3,
RESULTS: Immunofluorescence microscopy revealed inappropriate intracellular
Tahmina Rahman2, Sarah Ennis1
1
localization upon single or combined deletion of any MAPKBP1 protein domain.
University of Southampton, Human Development and Health, Southampton, United Compared to wild type, all deletion variants showed reduced intensity at the centrosome
Kingdom, 2Queen Alexandra Hospital, Wessex Kidney Centre, Portsmouth, United and ciliary base. Despite preserved dimerization ability, loss of the intermediate JNK-
Kingdom, 3University Hospital Southampton NHS Foundation Trust, Renal, binding domain (JBD) most effectively abolished centrosomal or ciliary targeting, whereas
Southampton, United Kingdom and 4Southampton University Hospital NHS loss of the N-terminal WD40-domain induced strongest mitotic aberrations. Unlike wild
Foundation Trust, Southampton Children’s Hospital, Southampton, United Kingdom type, both, artificial and patient-derived truncating variants were able to enter the nucleus.
RNA-seq analysis using primary patient fibroblasts with varying C-terminal truncations
BACKGROUND AND AIMS: Hemizygous variants in chloride voltage-gated channel will allow important insights into common gene expression profiles unveiling
5 (CLCN5) on chromosome Xp11.22 cause Dent disease type 1, characterised by low- consequences of aberrant intracellular trafficking.
molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and CONCLUSION: In the present work, we demonstrate that all protein domains are
progressive renal failure. We describe a truncating pathogenic variant in two brothers indispensable for appropriate MAPKBP1 intracellular localization and function. Most

10.1093/ndt/gfab080 | i113
Abstracts Nephrology Dialysis Transplantation

of clinically reported patient variants exhibiting C-terminal truncation of varying higher in the normal-to-mild RD group. Between the groups, there were no differences
lengths resulted in comparable intracellular behavior in presence of an intact N- in urine protein (0.12 [0.0–0.3] vs. 0.16 [0.08–0.29] g/day; P = 0.31) and DeGFR (98%
terminal WD40 domain. Surprisingly, deletion of the JNK-binding domain alone [88–123] vs. 106% [102–112]; P = 0.45), which was calculated as post-/pre-treatment
aggravated functional disturbances hinting at a prominent regulatory role of this annual eGFR change. Although both groups experienced the therapeutic effects of TV,
protein part interdepending with dimerization. Further insights into domain-specific the efficacy was poorer in the moderate-to-severe RD group (DTKV, 82% [76–85] vs.
functions will explain molecular disease mechanisms of MAPKBP1. 96% [86–97]; P = 0.001).
CONCLUSION: The efficacy of TV patients with moderate-to-severe RD in ADPKD
might be modest.
MO050 MUTATION TYPES AND ENZYME LEVELS IN FABRY
DISEASE IN A MULTICENTER STUDY

Luciana Sodre1, Rosalia Huaira1, Luciane Braga1, Carlos Contreras2,


Fernando Colugnati1, Marcelo Coutinho3, Natalia Maria Da Silva Fernandes1
1
Universidade Federal de Juiz de Fora, Medicine, Juiz de Fora, Brazil, 2Universidade
Federal de Juiz de Fora, Statistics, Juiz de Fora, Brazil and 3Faculdade de Medicina de
Campos, Medicine, Campos, Brazil

BACKGROUND AND AIMS: Fabry disease is a chronic, progressive and multi-


systemic hereditary condition, related to a Xq22 mutation in X chromosome, which
results in deficiency of acid alpha-galactosidase, hence reduced capacity of
globotriaosylceramide (Gb3) degradation. Gb3 accumulates in lysosomes throughout
virtually every organ, thus causing considerable morbidity and mortality. Objectives:
To evaluate the types of Fabry disease mutations and enzyme levels of Alpha
Galactosidase and Lyso Gb3 in a multicenter study; the RIM FABRY BRASIL
PROJECT.
METHOD: We conducted a transversal study that consists of data analysis secondary
to the multicenter project: Clinical and Epidemiological Analysis of Fabry’s Disease in
Dialysis Centers in Brazil, “PROJETO RIM FABRY BRASIL”. Included 854 dialysis
centers throughout Brazil and 75059 individuals screened using a questionnaire and
signing an Informed Consent Form. The data were entered into a computer program
(algorithm) that filters the possible carriers of Fabry’s disease. The program / algorithm
discarded those who probably did not have Fabry’s disease and sent blood suspects to
filter enzyme dosage and genetic testing of those suspected of the disease.
RESULTS: 75059 individuals from the RIM FABRY BRASIL project were screened,
where 58.37% were men and 41.54% women. 408 individuals with mutations for Fabry MO052 COL4A3/COL4A4 AS A CAUSE OF MULTICYSTIC KIDNEY
disease were identified, including patients with kidney and Family history of the DISEASE
disease, 34.6% men and 65.4% women with a mean age of 42.7 years. 47 different
mutations were identified, with a higher prevalence of c.352C> T p.Arg118Cys Teresa Bada Bosch1, Angel Sevillano1, Sara Afonso1, Eduardo Gutierrez1,
(24.8%), followed by c.376A> G p.Ser126Gly (13.1%), c.1102G> A p.Ala368Thr ( Teresa Cavero Escribano1, Elena Gutiérrez1, Florencio Garcia1, Enrique Morales1,
7.8%), c.937G> T p.Asp313Tyr (7.8%), c.870G> C p.Met290Ile (7.3%). Alfa GalA Paula Jara Caro Espada1, Manuel Praga2
dosage was performed in 120 men, with 90% of them showing decreased enzyme and 1
Hospital Universitario 12 de Octubre, Nephrology, Madrid, Spain and 2
Lyso Gb3 dosage of 320 individuals, (36.2% men and 63.8% women) 72.5% normal and
27.5% increased.
CONCLUSION: The most frequent mutations were: c.352C> T p.Arg118Cys, BACKGROUND AND AIMS: Thin basement membrane nephropathy (TBMN), the
followed by c.376A> G p.Ser126Gly, c.1102G> A p.Ala368Thr, c.937G> T most common cause of persistent microhaematuria (mH), is due to mutations in genes
p.Asp313Tyr, c.870G> C p.Met290Ile. 90% of men showed a decrease in the enzyme codifying alfa-3 and alfa-4 collagen IV chains (COL4A4/COL4A3). Initially
Alpha GalA and 27.5% of individuals had increased Lyso Gb3. considered as a benign condition, subsequent studies have shown that an important
number of patients develop proteinuria and CKD. We reported in a previous small
study the presence of multicystic kidney disease (MCD) in some TBMD patients. In
this study we aimed to evaluate the presence of MCD in a larger cohort of TBMD
MO051 EFFECT OF TOLVAPTAN ON THE SUPPRESSION OF TOTAL patients and analyze its association with renal outcomes.
KIDNEY VOLUME INCREASE IN PATIENTS WITH METHOD: We collected 50 patients with a diagnosis of TBMD based on the presence
MODERATE-TO-SEVERE RENAL DYSFUNCTION IN of persistent mH (>5 erythocytes per high power field in more than 90% of urinary
AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE sediments and radiological examinations to exclude other causes of mH) and at least
one first-degree relative with persistent mH. TBMD diagnosis was confirmed by renal
Hiroki Nomi1, Daisuke Mori1, Shinjiro Tamai1, Maho Tokuchi1, Natsumi Inoue1, biopsy (glomerular basement membrane thickness less than 150nm) in 18 patients and
Hideaki Kawai1, Naoyuki Shimada1, Ryota Haga1, Katsuyuki Nagatoya1, by genetic test (pathogenic mutations in COL4A3/COL4A4) in 6 patients. MCD was
Atsushi Yamauchi1 diagnosed by the presence of uncountable cysts on renal ultrasonography.
1
Osaka Rosai Hospital, Nephrology, Sakai,Osaka, Japan RESULTS: Mean age at diagnosis was 43.7 years, 34% were males and 18% had
hypertension. At baseline, serum creatinine (SCr) was 0.9 mg/dL, proteinuria 0.48 gr/
BACKGROUND AND AIMS: Tolvaptan (TV) slows down the increase in total 24h and 9 patients (18%) had CKD (estimated glomerular filtration rate -eGFR- lower
kidney volume (TKV) in patients with autosomal dominant polycystic kidney disease than <60 mL/min/1.73m2). 7 patients (14%) had CKD G3 and 2 (4%) CKD G4.
(ADPKD). The efficacy of TV in patients with moderate-to-severe renal dysfunction Kidney cysts were found in 34 patients (68%) and 19 (38%) met MCD criteria. After a
(RD) in ADPKD remains unknown. mean follow-up of 14.7611.5 years, 23 patients (46%) had CKD. Among them, 17
METHOD: This was a single-centre retrospective study involving 27 patients with patients (34%) had CKD G3, 2 (4%) CKD G4, and 4 (8%) CKD G5. Hypertension was
ADPKD who took TV and visited our hospital in the past six years. The participants more frequent among CKD patients as compared with no-CKD patients (39 vs 0%, p
were divided into two groups: the normal-to-mild RD (estimated glomerular filtration 0.00), proteinuria was higher (0.5860.68 vs 0.3960.58 g/24h, p 0.05) and MCD more
rate (eGFR)  45mL/min/1.73m2) group and the moderate-to-severe RD (eGFR < frequent (65.2% vs 14.8%, p 0.00). Patients with MCD had higher SCr (2.1 vs 1.1 mg/
45mL/min/1.73m2) group. Treatment effects were evaluated using DTKV, which was dL, p 0.004) and lower eGFR (41.7 vs 77.2 mL/min/1.73m2, p 0.00) at the end of
calculated as post-/pre-treatment annual TKV change. Continuous variables are follow-up, and MCD was the only risk factor for the occurrence of CKD (OR 6.49, 95%
presented using the median [interquartile range]. CI 1.3-31.6) by multivariable analysis that included age, hypertension and proteinuria.
RESULTS: The moderate-to-severe RD group comprised 11 patients. Baseline CONCLUSION: MCD is frequently observed in TBMD patients and is a risk factor for
characteristics of the normal-to-mild vs. moderate-to-severe RD group were as follows: the progression of CKD.
eGFR, 56 [50–69] vs. 29 [24–38] mL/min/1.73m2; age, 48 [39–55] vs. 49 [43–58] years;
male gender, 57% vs. 36%; body mass index (BMI) , 26 [23–28] vs. 24 [22–27] kg/m2;
TKV 1700 [1084–2574] vs. 1827 [1331–2424] mL; family history of ADPKD, 100% vs.
82%; history of cerebral aneurysm, 19% vs. 36%; hypertension, 81% vs. 82%;
hyperuricemia, 13% vs. 27%; dyslipidaemia, 19% vs. 18%; diabetes, 6.1% vs. 9.1% and
systolic blood pressure (sBP) on admission 138 [129–144] vs. 131 [128-137] mmHg.
No significant differences were noted in all these parameters, except for renal function.
The starting dose of TV was 60 mg/day in all cases (0.9 [0.7–1.0] vs. 0.9 [0.8–1.1] mg/
kg; P = 0.35). Urine volume (7.5 [5.7–9.6] vs. 4.0 [3.3–4.7] L/day; P = 0.006) and
urinary sodium excretion (163 [126–226] vs. 89 [81–120] mEq/day; P = 0.003) were

i114 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO053 GITELMAN’S SYNDROME AND PREGNANCY: TWO (IQR: 16; 49) months. Blood electrolytes levels, ALP, PTH and 24-hour-urine excretion
SUCCESSFUL CASE REPORTS of calcium were evaluated in all children. ALP Z-scores were calculated using age- and
sex-specific mean/standard deviation (SD) lab reference data. Bone mineral density
Chaofan Wang1, Xueyan Chen1, Xubin Yang1, Jinhua Yan1, Bin Yao1 with Z-score were measured in lumbar spine and whole body for all patients using a
1
The Third Affiliated Hospital of Sun Yat-sen University, Endocrinology and Metabolism, dual energy X-ray absorptiometry device. Molecular genetic analysis was performed in
Guangzhou, P.R. China all children using by next generation sequencing.
RESULTS: The median SD score of height at the first and last follow-up was -1.35
BACKGROUND AND AIMS: Gitelman’s Syndrome (GS) is a rare autosomal (IQR: -1.8; -0.87) and -1.51 (IQR: -2.0; -0.66) (p=0.6), respectively, short stature had
recessive hereditary salt-losing tubulopathy characterized by hypokalemic metabolic 33.3% (3/9) of patients at first and 44.4% (4/9) at last follow-up (p=0.7). Treatment
alkalosis with hypomagnesemia and hypocalciuria. Pregnancy in women with GS often with low doses of oral phosphate supplements did not led to normalization of serum
aggravates hypokalemia and hypomagnesemia. However, there are few reports of phosphorus:1.05 (IQR: 0.97; 1.39) vs. 0.93 (IQR: 0.81; 1.27) mmol/l (p=0.13), PTH: 8.3
pregnancies in GS. Here, we report the course of two Chinese women who were (IQR: 5.8; 13.8) vs. 12.9 (IQR: 12.0; 16.0) pg/ml (p=0.34), Z-score in lumbar spine: -1.2
diagnosed as GS during pregnancy in 2019 and 2020 respectively. (IQR: -2.7; -0.1) vs. -1.8 (IQR: -2.8; -1.1) (p=0.48) and Z-score in total body: -2.1 (IQR -
METHOD: Case 1: A 21-year-old woman was referred to our hospital at 9 weeks 2.6; -1.5) vs. -2.4 (IQR: -3.0; -2.0) (p=0.37). Hypercalciuria had 88.8% (8/9) of children
gestation of her first pregnancy. She had complained of muscle weakness and cramps (0.15 (IQR: 0.12; 0.19) mmol/kg/day) at first follow-up and 44.4% (4/9) (0.09 (IQR:
for one year. Before the referral she was diagnosed as hypokalemia and treated by oral 0.08; 0.16) mmol/kg/day) in last examination (p=0.13). ALP blood levels were elevated
potassium supplementation. However, her symptoms became severer after pregnancy. in all patients (9/9) at first and most recent visit, but ALP Z-score were significant
Case 2: A 20-year-old woman was admitted to the hospital because of elevated plasma lower at last follow-up: 3.9 (IQR: 1.2; 5.1) vs. 0.57 (IQR: -0.36; 2.1) (p=0.04). There
glucose level and hypokalemia at 27 weeks gestation of her first pregnancy. The woman were significant correlations between doses of oral phosphate supplements and ALP Z-
was asymptomatic and denied history of chronic diseases. The laboratory examinations score (r=-0.68; p=0.04) and total body Z-score (r=0.78; p=0.03). There was no
were taken after admission. Genetic testing was conducted for pathogenic mutations in significant correlations between ALP Z-score and total body Z-score (r=-0.3) or lumbar
SLC12A3 (GS) and SLC12A1, KCNJ1, CLCKNB and BSND (Bartter syndrome 1-4). spine Z-score (r=-0.1).
RESULTS: Case 1: Initial biochemistry examinations revealed hypokalemia (2.3 mmol/ CONCLUSION: The present study demonstrated that treatment of HHRH with low
L, normal range 3.5-5.3 mmol/L) with inappropriate renal potassium wasting (urine doses (<20 mg/kg/day) of oral phosphorus supplements led to decreasing of ALP Z-
potassium 254 mmol/24h, normal range < 20 mmol/24h), alkalosis (arterial blood gas score in 7/9 (77.8%) and hypercalciuria in 5/9 (55.6%) of patients. However, that
pH 7.49), hypomagnesemia (0.55 mmol/L, normal range 0.67-1.04 mmol/L), therapy didn’t improve significantly height and severity of rickets, as well didn’t led to
hypocalciuria (urine calcium 1.6 mmol/24h, normal range 2.5-7.5 mmol/24h) and normalization of serum phosphorus in children with HHRH. It is therefore conceivable
elevated renin (276 pg/ml, normal range 4-24 pg/ml) and aldosterone (825 pg/ml, that higher daily doses of phosphate supplements are needed to normalize all clinical
normal range 10-160 pg/ml) levels. The blood pressure was normal-low (97/68 mmHg, and radiological features of disease.
12.9/9.0 kPa) and the renal ultrasound was normal. Homozygous mutations Lack of association between ALP Z-score and bone mineral density severity on
[c.179C>T (Thr60Met)] were identified. The woman’s father and sister had a radiographs limits the value of serum ALP as the indicator of rickets activity.
heterozygous c.179C>T, but had no electrolyte disorders. After the treatment of oral
potassium supplementation (KCl 3g tid) and spironolactone (40mg bid), her serum
potassium level increased to 3.4-4.0 mmol/L and muscle weakness was relieved. The MO055 THE IMPACT OF THE COVID-19 PANDEMIC ON MOOD
woman delivered a healthy female infant weighing 2600 g at 39 weeks gestation via STATUS AND TREATMENT ADHERENCE IN PATIENTS WITH
cesarean section. Maternal serum potassium level remained normal and no symptoms FABRY DISEASE
reoccured after delivery. Case 2: Initial biochemistry examinations identified
hypokalemia (2.3 mmol/L, normal range 3.5-5.3 mmol/L) with inappropriate renal Mevlut Tamer Dincer1, Cebrail Karaca1, Betul Sarac2, Saffa Ahmadzada3,
potassium wasting (urine potassium 81 mmol/24h, normal range < 20 mmol/24h), Alev Bakir4, Selma Alagoz5, Ertugrul Kiykim3, Sinan Trabulus1, Nurhan Seyahi1
hypomagnesemia (0.49 mmol/L, normal range 0.67-1.04 mmol/L), hypocalciuria
(urine calcium 0.3 mmol/24h, normal range 2.5-7.5 mmol/24h) and elevated renin (54
1
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Nephrology, _Istanbul,
pg/ml, normal range 4-24 pg/ml) and aldosterone (834 pg/ml, normal range 10-160 pg/ Turkey, 2Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Internal Medicine,
_Istanbul, Turkey, 3Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Pediatric
ml) levels. The blood pressure and renal ultrasound were normal. Heterozygous
mutations [c.179C>T (Thr60Met), c.658G>A (Gly220Ser)] were identified. The Nutrition and Metabolism, _Istanbul, Turkey, 4Halic University, Biostatistics and Medical
woman was treated by oral potassium supplementation (KCl 3g tid) and her serum Informatics, _Istanbul, Turkey and 5Istanbul Training and Research Hospital, Nephrology,
_Istanbul, Turkey
potassium level maintained normal during pregnancy. She had a normal delivery of a
healthy female infant weighing 3050 g at 40 weeks gestation. After delivery she
discontinued oral potassium supplementation and her serum potassium level ranged BACKGROUND AND AIMS: Fabry disease is a rare metabolic disorder, lifelong
from 3.0-3.4 mmol/L without symptoms. enzyme replacement therapy with recombinant human alpha-galactosidase A
CONCLUSION: The outcome of mother and fetus of GS pregnancies appears (agalsidase) constituted the cornerstone of disease-specific therapy. COVID-19
favorable. Intensive monitoring of electrolyte levels and sufficient electrolyte pandemic and epidemic control measures including lockdowns impaired access to
supplementation are advised during pregnancy. health care services. We examined the effect of COVID-19 pandemic and lockdown
measures on mood status and management of Fabry disease patients.
METHOD: We conducted a cross-sectional study between October 2020 and
December 2020. We used the Hospital Anxiety and Depression Scale (HADS) to
MO054 EFFICACY OF ORAL PHOSPHATE SUPPLEMENTATION IN evaluate the mood statuses of FD patients and the Morisky Medication Adherence
CHILDREN WITH HEREDITARY HYPOPHOSPHATEMIC Scale (MMAS-4) to assess patient adherence. We also examined age and sex-matched
RICKETS WITH HYPERCALCIURIA control group to compare mood status.
RESULTS: A total of 68 (Male 48.5 %, mean age 37.0) FD patients were under regular
Svetlana Papizh1, Larisa Prikhodina1, Ekaterina Nikolaeva2 follow-up in our institution, 59 of those patients were taking ERT every other week.
1
Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Two of our patients had reported having a COVID-19 infection, and both of them
Medical University, Department of hereditary and acquired kidney diseases, Moscow, recovered. 25 patients reported to miss an ERT for a median of one dose, 16 of these 25
Russia and 2Research and Clinical Institute for Pediatrics at the Pirogov Russian patients have reported that they did not come to the hospital because of infection fear.
National Research Medical University, Clinical genetics, Moscow, Russia Half of the patients had adopted home-based infusion; they arranged a nurse for home-
based infusion therapy by their own means. According to MMAS-4 FD patients had
BACKGROUND AND AIMS: Hereditary hypophosphatemic rickets with good adherence to their therapy (Median score 0, range 0-2). Mood status of FD
hypercalciuria (HHRH; MIM #241530) is an autosomal recessive renal phosphate- patients and controls are shown in Table 1. Both HADS depression and anxiety scores
wasting disorder caused by mutations in the SLC34A3/NPT2c gene. HHRH were higher in the control group compared to FD patients. Additionally, abnormal
characterized by increased urinary phosphate excretion leading to hypophosphatemic scores were more prevalent for HADS depression scores in controls (Figure 1).
rickets, short stature and elevated serum 1,25(OH)2D levels which result in
hypercalciuria leads to nephrocalcinosis/urolithiasis due to enhanced intestinal calcium
absorption and reduced PTH-dependent calcium reabsorption in the distal renal
tubules.
Treatment of HHRH involves administration of oral phosphate supplements alone to
normalize of serum phosphate, alkaline phosphatase activity (ALP), PTH levels, urine
calcium excretion for prevention of renal calcifications and progression of rickets.
Currently there is no consensus on the optimal dose of oral phosphate in patients with
HHRH. The aim of the study was to evaluate the efficacy of oral phosphate
supplements in Russian cohort of children with HHRH.
METHOD: 9 children (7M/2F) with homozygous (n=6) and compound heterozygous
(n=3) SLC34A3 mutations from unrelated families were examined. Treatment with
oral phosphate supplements was started at the median age of patients 12.0 (IQR: 9.0;
13.0) years. The median dosage of oral phosphate supplements was 14.1 (IQR: 13.8;
14.8) mg/kg/day based on elemental phosphorus. The duration of follow-up was 36.0

10.1093/ndt/gfab080 | i115
Abstracts Nephrology Dialysis Transplantation

using clinical exome sequencing. According to the Human Gene Mutation Database
(HGMD) guideline, this variant is assessed as likely pathogenic. There was no mutation
in the FAN1 gene.
The second case was a 64-year-old female, she had hypertension for eight years, and
was referred to the nephrology clinic due to renal dysfunction. There was a history of
pharyngitis four times a year. There was no history of smoking and alcohol use. She
had been suffering from nocturia for eight years. She did not use alcohol, nephrotoxic
drugs, or herbal substances. There was no history of kidney disease in her family.
Serum creatinine on admission was 1.58 mg/dl and e-GFR was 35.2 ml/min/1.73m2.
Liver function tests, Hepatitis B, C and HIV serologies, and serum complement levels
were normal. Urinalysis, including microscopic examination, did not reveal any
abnormality. In 24-hour collected urine 143 mg proteinuria was detected. Kidney
biopsy revealed global sclerosis in glomeruli, nucleomegaly, intranuclear inclusions,
and hyperchromasia in tubules epithelial cells and endothelial cells. A pathological
diagnosis of KIN was made. The genetic analysis detected c.1972 C>T (p. Arg658Trp)
mutation in the FAN1 gene. According to the HGMD guideline this variant is classified
as an unknown significance. However, the clinical and pathological features of the
MO055 Figure 1. The percentage of the patients classified as abnormal according to the patient were compatible with KIN, we concluded this specific FAN1 mutation was
HADS-anxiety, HADS-depression scores, for each study group. HADS anxiety p=0.062 associated with the disease in our case.
HADS depression p=0.001. CONCLUSION: Despite similar clinical features and histopathological findings, we
found two different gene mutations in these two cases. It is especially interesting that
UMOD mutation which was associated with hyperuricemia and uric acid nephropathy
was associated with KIN. KIN should be included in the differential diagnosis of
patients without a definite diagnosis of CKD, the genetic examination should be carried
MO055 Table 1. Scores of Hospital Anxiety and Depression Scale in the study
out to reveal the underlying mutation.
groups.

Fabry Disease Control group p


MO057 REGIONAL IMPORTANCE OF FIBRINOGEN A A-CHAIN
(n=68) (n=68) MUTATION ON RENAL AMYLOIDOSIS
HADS anxiety score 5.1 6 3.7 8.0 6 4.5 <0.001
(4.0) (8.0) Sofia Homem Melo Marques1, Maria Lopes-de-Almeida2,3, Renata Carvalho1,
Barbara Ribeiro1, Raquel Vaz1, Joana Medeiros1, Rui Costa1, Anto nio Rmalheiro1
HADS depression score 4.4 6 3.4 6.964.0 <0.001 1
Hospital de Braga, Nephrology, Braga, Portugal, 2Hospital de braga, Medical Genetics,
(4.0) (7.0) Braga, Portugal and 3Genetyca ICM S.A., Porto, Portugal
HADS: Hospital Anxiety and Depression Scale.
BACKGROUND AND AIMS: Renal amyloidosis include amyloid A (AA) and light
Data are expressed as mean6SD and (median). chain (AL) as well as amyloidogenic leukocyte chemotactic factor 2 (ALECT2) and
numerous hereditary forms. After identifying amyloidosis by its suggestive pale pink
CONCLUSION: We found that the mood status of FD patients was better than the amorphous appearance in optic microscopy (OM) and Congo red positivity, a correct
control group. Traumatic growth may be an important factor to explain this finding. diagnosis of the amyloidogenic precursor protein is determinant to establish prognosis
Their adherence to therapy was good. Home-based therapy was the preferred method and treatment. Immunohistochemistry (IHC) and immunofluorescence (IF) studies
by the patients. Government-supported home therapy programs might be beneficial use a limited number of antibodies to detect specific epitopes and may be difficult to
for FD patients to increase adherence to the therapy. interpret. The gold standard has become proteomics but laser microdissection and
mass spectroscopy are not routinely available. Other options include electron
microscopy with immunogold staining and complementary exams such as scintigraphy
with 99mTc-DPD to detect transthyretin-related amyloidosis. Since the cause of
MO056 KARYOMEGALIC INTERSTITIAL NEPHRITIS: AN ENTITY amyloidosis vary among regions, analyzing local patterns can help establish a
ASSOCIATED WITH DIFFERENT GENETIC MUTATIONS diagnostic procedure. We aimed at describing cases of kidney amyloidosis identified by
biopsy during a 4-year interval and discuss possible implication for future diagnosis.

S¸eyda Gül Ozcan 1
, Mustafa Tarık Alay2, Aysel Kalaycı Yigin3, Sinan Trabulus4, METHOD: We analyzed our kidney biopsy database and selected all cases of renal
Nurhan Seyahi5 amyloidosis collecting clinical, laboratory and imaging data.
1
Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Internal Medicine, RESULTS: From January 2016 until December 2019, 194 kidney biopsies were
Istanbul, , 2Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Medical performed at the Hospital of Braga in the Portuguese province of Minho. Among these,
Genetics, Istanbul, , 3Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, 8 (4.1%) revealed amyloidosis. Mean age was 63.869.2 years of age, 5 were female, 6
Medical Genetics, 4Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, were referred for nephrotic syndrome and 2 for what seemed like acute kidney injury.
Nephrology and 5Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Mean creatinine at presentation was 3.262.3mg/dL. Among them, 2 had AL
Nephrolgy amyloidosis with light chain restriction by IF, 1 had AA amyloidosis with intense IHC
stain and 5 patients had non-AL and non-AA forms of amyloidosis. Of these, 3 had
BACKGROUND AND AIMS: Karyomegalic interstitial nephritis (KIN) is a rare probable fibrinogen A alpha-chain (AFib) amyloidosis, after a heterozygous mutation
hereditary cause of chronic interstitial nephritis, The disease manifests as a slowly FGA p.Glu545Val was detected, 1, who did not have IHC performed, was assumed as
progressive chronic kidney disease and it is an underdiagnosed cause of interstitial having AA amyloidosis due to a history of serious recurrent infections and 1 is still
nephritis. The presence of karyomegalic tubular epithelial cells in a renal biopsy under study. Four performed scintigraphy with 99mTc-DPD which was negative. The
specimen is the primary marker that makes KIN distinguishable from other common 2 patients with AL amyloidosis had, by OM, in one case glomerular and
causes of chronic tubulointerstitial nephritis. KIN has recently been associated with the tubulointerstitial and on the other, glomerular and vascular involvement and, by IF,
FAN1 (FANCD2 / FANCI-Associated nuclease 1) gene involved in DNA repair. both had k light chain restriction. Both had additional cardiac and neurovegetative
In this article, we present two cases with KIN with different genetic associations. involvement, were treated with cyclophosphamide-bortezomib-dexamethasone and
METHODS: Clinical, laboratory, and kidney biopsy finding along with genetic oral doxycycline with complete hematologic response and stabilization of kidney
examination is presented. function. In 1 case, proteinuria only showed a slow decline 2 years after treatment. The
RESULTS: The first case was a 42-year-old male, who was diagnosed with gout eight 2 patients with AA amyloidosis had glomerular, vascular and tubular deposits. One
years ago and renal dysfunction was found in routine examinations. He was admitted had bronchiectasis and allergic bronchopulmonary aspergillosis and the other had
to the nephrology clinic with pain in both feet and legs for the last six months. He had a common variable immunodeficiency with recurrent gastrointestinal and urinary
history of frequent upper respiratory tract infections in his childhood. There was no infections with frequent bacteremia. None of them had confirmed extra-renal
family member with kidney disease. There was a ten pack/year smoking history. He did involvement, although the latter had hepatic fibrosis awaiting biopsy. Both progressed
not use alcohol, nephrotoxic drugs, or herbal substances. Physical examination was to dialysis soon after diagnosis. The 3 patients with AFib amyloidosis all had
unremarkable. On admission, serum creatinine was 2.71 mg/ dl and the estimated glomerular amyloidosis with additional amyloid deposition at tubular, vascular and
glomerular filtration rate (e-GFR) was 28 ml/min/1.73m2. Liver function tests, both respectively. Two had had an increased creatinine and subnephrotic proteinuria
Hepatitis B, C, and HIV serologies, and serum complement levels were normal. for some years whereas 1 had kidney function decline and nephrotic syndrome in the
Urinalysis, including microscopic examination, did not reveal any abnormality. In 24- course of few months. All were hypertensive and none had evident extra-renal deposits.
hour collected urine, 182 mg proteinuria was detected. Kidney biopsy revealed the CONCLUSION: Identifying the amyloidogenic precursor may be difficult. Algorithms
following findings; mild tubular atrophy, nucleomegaly in tubular epithelial nuclei, rare for diagnosis may vary according to local prevalence of specific types and available
multinucleation, and prominence in nuclei. There were no immune deposits present in resources. AFib amyloidosis was very significant in our series. It was also described in
immunofluorescence microscopy. A pathological diagnosis of KIN was made. In the 4.5% of hemodialysis patients in the district of Braga making it one of the first causes of
genetic analysis, we detected c.358T>C (p.Cys120Arg) mutation in UMOD gene by

i116 | Abstracts
Nephrology Dialysis Transplantation Abstracts
amyloidosis in our region. This high prevalence may justify early genetic testing for the MO060 CYSTINURIA: DISEASE PRESENTATION, PROGNOSIS AND
specific mutation in non-AL and non-AA forms. QUALITY OF LIFE ANALYSIS OF A WEB-BASED COHORT

Rocco Baccaro1,2, Viola D’Ambrosio2, Pietro Manuel Ferraro1,2


1
Fondazione Policlinico Universitario A.Gemelli IRCCS, UOC Nefrologia, Rome, Italy and
MO058 PREDICTORS OF MORTALITY IN PATIENTS WITH 2
Universit
a Cattolica del Sacro Cuore, Roma, Italy
NEPHROBLASTOMA: A SYSTEMATIC REVIEW AND META-
ANALYSIS
BACKGROUND AND AIMS: Cystinuria is considered a rare condition as
Firdian Makrufardi1, Erri Larene Safika2 approximately 1% of adult and 6% of pediatric kidney stones are due to this defect.
1 Prevalence varies by geographic region, with good representation in the Mediterranean
Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada,
area. Given the low prevalence and the lack of a defined clinical pathway for these
Department of Medicine, Yogyakarta, Indonesia and 2Faculty of Medicine, Public
patients, only partial data are available on the long-term course of the disease.
Health, and Nursing, Universitas Gadjah Mada, Department of Biostatistics,
A group of cystinuria patients has gathered on Facebook to exchange advice on
Epidemiology, and Population Health, Yogyakarta, Indonesia
symptom management and therapy.
The use of this type of platform, in cases of low-prevalence diseases, is a good method
BACKGROUND AND AIMS: Nephroblastoma constitutes 90-95% of the 5 types of of collecting patients who otherwise would be difficult to reach.
kidney tumors that are most common in children. Studies for clinical management of We proposed an online survey to further analyze clinical, therapy, and quality of life of
patients with nephroblastoma are continuing today and several factors are thought to cystinuria patients.
influence the mortality. This study is aimed to evaluate the outcome of patients with METHOD: An online survey was proposed to an Italian social media group restricted
nephroblastoma and its associated factors. to cystinuric patients with the agreement of the administrator. Before participating to
METHOD: The dataset was defined by searching PubMed, EMBASE, Google Scholar the survey, patients provided documentation on their diagnosis and signed an
that had been published until December 2020. No language or date restriction was informed consent. The survey was structured in four sections: a thorough medical
performed during literature searching. The meta-analysis was conducted using Review history focused on kidney stone and cystinuria, the SF-36 questionnaire, the Fatigue
Manager Software version 5.4. Factors investigated included gender, age, and site of Severity Scale, The Brief Pain Inventory.
tumor with p <0.05 considered significant. Data was managed and analyzed anonymously.
RESULTS: The final analysis was conducted on 5 studies, and 2 were multi- RESULTS: Our survey was sent to 55 patients, but only 18 completed all
institutional. Overall, 17279 patients with nephroblastoma were included in this study. questionnaires. Our cohort is composed of 5 men and 13 women, with a mean age of
The pooled data demonstrate there was significant difference in the mortality incidence 39.5 years (SD 17.6), mean height 156.4 cm (SD 18.5), mean weight 60.8 kg (SD 17.9),
of nephroblastoma patients with gender, (OR=1.25 [1.02, 1.52], p=0.03). Significant mean BMI 24.1 (SD 4.5).
difference result was also seen in the incidence of mortality with age (OR=2.05 [1.86, About medical history, 15/18 patients have had at least 4 episodes of renal sstons in
2.26], p<0.00001). There was no association in the mortality of nephroblastoma their lifetime, of these 10/15 reported stone expulsion in most episodes. The first
patients with site of tumor (OR=1.28 [0.79, 2.09], p=0.31). No publication bias was episode occurred on average at 14.9 years (SD 9.3), while confirmed diagnosis of
found in our study. cystinuria arises at 20.1 years (SD 15.1).
CONCLUSION: The incidence of mortality in nephroblastoma patients still has to be Most patients experienced bilateral stones (12/18). The diagnosis was confirmed
a concern in patient management. Gender and age are factors that associate with generally by: stone composition analysis (39%), urinary cystine levels (24%), cystine
incidence of mortality in nephroblastoma patients. crystals revealed at fresh urine exam (22%), genetic findings (7%), Brand test (2%),
other (5%). About 33% of our cohort performed a genetic test.
Almost 95% of patients are in follow-up with a clinic. Routine exams include: renal
MO059 COLEC10 AND 3MC SYNDROME: EXPANDING THE ultrasound (30%), nephrologist evaluation (27%), urine 24h evaluation (25%), urology
GENOTYPIC AND PHENOTYPIC SPECTRUM OF A VERY visit (13%), abdominal CT (4%), kidney x-ray (2%).
RARE DISEASE All the patients of our cohort received urological or surgical procedures for kidney
stones: generally endoscopic procedures (32%), or lithotripsy (30%), or open surgery
Martina Migliorero1, Silvia Kalantari2, Valeria Bracciam a2, Monica Sorbini1, (23%). Four patients underwent a nephrectomy.
Francesca Arruga1, Licia Peruzzi3, Elisa Biamino4, Antonio Amoroso1,2,
Tiziana Vaisitti1, Silvia Deaglio1,2
1
Department of Medical Sciences, University of Turin, Italy, Italy, 2Immunogenetics and
Transplant Biology Service, Citt
a della Salute e della Scienza University Hospital, Turin,
Italy, 3Pediatric Nephrology Dialysis and Transplantation Unit, Citt a della Salute e della
Scienza University Hospital, Turin, Italy and 4Department of Pediatrics, Citt a della Salute
e della Scienza University Hospital, Turin, Italy

BACKGROUND AND AIMS: 3MC syndrome is an autosomal recessive disorder


encompassing a variable spectrum of abnormalities, among which facial
dysmorphisms are characteristic. Mutations in genes which encode proteins involved
in the lectin complement pathway MASP1, COLEC11 and recently COLEC10 have
been identified in patients with 3MC syndrome, supporting their key role during
human development. We present a 5 years old patient with typical 3MC phenotypic
characteristics, including blepharophimosis, telecanthus, high arched eyebrows, fifth
finger clinodactyly, horseshoe kidneys, diastasis recti, umbilical depression and sacral
dimple. The diagnosis was confirmed by sequencing of COLEC10 gene and the
putative pathogenic variant was functionally validated through in vitro assays.
METHOD: COLEC10 gene was analyzed through Sanger sequencing. The secreted
protein CL-L1 was investigated in the plasma of the patient and her parents by
Western blot. The variant was introduced by a site-specific mutagenesis approach into
a plasmid encoding wild-type human CL-L1. HeLa cells were then transfected with the
mutated or wild-type plasmid and culture supernatant evaluated in a migration assay.
RESULTS: A homozygous frameshift variant c.807_810delCTGT p.(Cys270Serfs*33)
was identified in the patient. Segregation studies confirmed the parents’ carrier status
for the variant. Functionally, the variant affects the chemo-attractive feature of CL-L1,
as HeLa cells are less sensitive to the mutant protein compared to the WT one,
resulting in a reduced migratory response.
CONCLUSION: We report a patient affected by 3MC syndrome who, besides typical
phenotypic signs, presents a patent ductus arteriosus, never described in association to
COLEC10 before. The variant causative role was functionally confirmed in an in vitro
assay, where the mutated protein failed to act as a chemo-attractant. We thus provide
further evidence for CL-L1 role during embryonic development

10.1093/ndt/gfab080 | i117
Abstracts Nephrology Dialysis Transplantation

Patienst reportes an average of 31 painful episodes of renal colic (min 0; max 200) in MO062 A RARE COMBINATION OF POLYCYTHEMIA VERA WITH A
their history. Of these episodes almost 6 ended with a stone expulsion (min 0; max 50), THROMBOPHILIA FACTOR V MUTATION IN A
while haematuria was reported by 12 patients (up to 20 episodes in a patient lifetime). HEMODIALYSIS PATIENT :CASE REPORT
A secondary stone composition in addition to cystine was reported by 5/18: calcium
oxalate in 100% of these cases, even with struvite and calcium phosphate. Faten Ghabi1,2, Toumi Salma1,2, Asma Amouri1,2, Hanen Chaker1,2,
Most of these patients (78%) received some nutritional recommendation: generally by Ikram Agerbi1,2, Najla Damak1,2, Khawla Kammoun1,2, Soumaya Yaich1,2,
nephrologist (50%), or dietician (23%), or urologist (18%). Indications were not easy to Mohamed Benhamida1,2
1
follow: a 0-100 visual scale about compliance showed a mean of 45 (SD 27). university hospital center hedi chaker, nephrology, Sfax, Tunisia and 2Medical school
The 78% were currently on drug therapy: most used therapy included citrate (45%), Sfax, Renal pathology reserch laboratory UR12ES14, Sfax, Tunisia
tiopronin (40%), or bicarbonate (10%). Drugs compliance is very low (26/100 scale SD
23.3). INTRODUCTION: Anemia is an almost constant complication in patients with end
Nobody in our cohort showed a GFR of less than 60 mL/min/1.73 m2. 4/18 reported a stage renal disease. In contrast, primary polycythemia is extremely rare, with only a few
positive family history of cystinuria, while 7/18 relatives with renal stones without a cases that have been reported in the literature. We report in this work a rare association
diagnosis. of thrombophilia and acquired polycythemia in a chronic hemodialysis patient.
CONCLUSION: Patients affected by cystinuria show a very poor quality of life, with OBSERVATION: This is a 47-year-old man, non-smoking, hypertensive, with CKD in
high levels of pain, fatigue, and emotional wellness. The diagnosis is delayed from the hemodialysis since 2015 secondary to undetermined nephropathy. The change in the
first event, and they are exhausted by an high frequency of pain stone passages. More patient’s condition on hemodialysis was marked by the occurrence of repeated
attention to quality of life aspects is needed in patients with this rare but life- thrombosis of these arteriovenous fistulas(AVFs), including exploration that revealed
threatening condition. a coagulation factor V mutation, hence his initiation of antivitamin K. The patient
initially presented with severe anemia at the start of the extra renal purification , the
average hemoglobin (Hb) level between 2015 and 2018 was 7.4 g / dl thus requiring the
MO061 IS THE PM290I MUTATION RELATED TO ORGAN use of iron supplementation (IV iron) and stimulating agents erythropoiesis (ESA). In
INVOLVEMENT OF FABRY DISEASE? february 2019, erythropoietin requirements were reduced due to the increase in Hb
levels and then stopped in April 2019. The Hb level continued to increase to reach 16.8
Francisca Silva1, Nicole Pestana1, José Dura ~es1, Nuno Guimar~
aes Rosa1, g / dl in february 2020 without receiving ESAs or iron supplements. From where an
Gil Silva1 etiological investigation was initiated to search for the origin of this polycythemia
1 going up to the genetic study for the JAK2V617F mutation which came back positive.
Hospital Dr. Nélio Mendonça, Funchal, Portugal
Furthermore, gas scans, chest x-rays and abdominal ultrasounds are normal, hence
polycythemia vera was retained in this patient. For fear of losing his AVF, the patient
BACKGROUND AND AIMS: Fabry disease (FD) is an X-linked hereditary disease. It underwent intermittent phlebotomies during dialysis associated with the prescription
results from mutations in the GLA gene, leading to deficient activity of the enzyme of IEC and his Hb level rose to 14.5g / dl.
alpha-galactosidase A and progressive accumulation of undegraded glycosphingolipids CONCLUSION: Primary erythrosis remains rare in dialysis, the pathophysiological
in cell lysosomes. Enzyme replacement therapy improved the natural course of this mechanism of which remains poorly understood. Iterative phlebotomies remain the
disease, but an early diagnosis is crucial for a successful treatment. solution sometimes coupled with the prescription of IEC.
METHOD: A screening study for GLA gene mutations was conducted for all patients
under dialysis, from a single centre. All the probands with a detectable mutation were
analysed individually. Data on the patient’s family and personal pathological history
were retrospectively collected, by consulting the clinical file. MO063 DESCRIPTION OF GENETIC VARIANTS IN A COHORT OF
RESULTS: 35 years-old female diagnosed with chronic proteinuric kidney disease in TOLVAPTAN ADPKD PATIENTS
the postpartum period. Despite optimal medical treatment the disease progressed, and
she started renal replacement therapy with peritoneal dialysis. Five years later she was Valentina Corradi1,2, Carlotta Caprara2, Ofelia Pegoraro2, Barbara Mancini3,
enrolled in a pilot screening study for FD and the heterozygous mutation c.870G>C Anna Giuliani1, Fiorella Gastaldon1, Davide Giavarina3,4, Claudio Ronco1,2,5
1
(p.Met290Ile; M290I) in exon 6 of the GLA gene was found. The proband didn’t meet AULSS 8 BERICA - Ospedale San Bortolo, UOC Nefrologia, Vicenza, Italy, 2International
the criteria for a definitive FD diagnosis, but she remained under follow-up at our Renal Research Institute of Vicenza, IRRIV, Vicenza, Italy, 3AULSS 8 BERICA - Ospedale
nephrology metabolic diseases consultation, as the mutation was described as San Bortolo, UOS Laboratorio di Genetica - UOC Medicina di Laboratorio, Vicenza, Italy,
4
pathogenic and associated with a classic FD phenotype. Later that same year, AULSS 8 BERICA, UOC Medicina di Laboratorio, Vicenza, Italy and 5University of
reassessment exams revealed a worsening left ventricle mass index, a new ischemic Padova, DIMED, Padova, Italy
cerebral lesion and a substantial increase in serum globotriaosylsphingosine (LysoGb3)
levels. These clinical changes led to the decision to initiate enzyme replacement BACKGROUND AND AIMS: Autosomal Dominant Polycystic Kidney Disease
therapy. (ADPKD) is the most common inherited renal cystic disease. It is genetically
Until now there are only a few descriptions of this genetic variant in the scientific heterogeneous: 72-75% of ADPKD cases are related to mutations in the PKD1, 15-18 %
literature. A Portuguese study analysed a total of 11 FD patients and described 2 to PKD2 and the remaining 7–10% of affected are genetically unresolved (GUR).
patients with p.M290I mutation, without detectable Gb3 accumulation. Another study Recent years, new drugs have emerged as promising agents that may retard the
was designed to evaluate the genotype-phenotype relationship in 73 Chinese FD progression of ADPKD, such as Tolvaptan. In Italy Tolvaptan is available since 2016
patients. Contrary to other reports, the p.M290I mutation was not associated to the and commonly used since 2017 in ADPKD patients, which fulfill the criteria of “rapid
classic FD phenotype. A Swiss investigation with a similar design analysed 69 FD disease progression”, according to the European recommendations. High intra-
patients during their routine annual examinations. M290I mutant enzyme was found interfamilial variability in pedigrees was observed, despite the same germ-line
in a 48-year-old heterozygous female with a classic FD phenotype but with a low serum mutation. This could be explained by other clinical or genetic factors (environmental,
LysoGb3. A Spanish newborn screening identified one male patient with FD and the modifier genes, etc), that may affect disease severity. The aim of the study is to describe
p.M290I genetic variant but was unable to provide any information about the clinical the genetic variants in a cohort of Tolvaptan ADPKD patients (pts) referral to Renal
expression of this mutation, since the diagnosis was made between the third and fifth Genetic Disease Ambulatory of Nephrology Department.
days of life. The study describing the most patients carrying the M290I mutant enzyme METHOD: Patients with ADPKD and in Tolvaptan treatment were enrolled.
is Brazilian and screened a total of 25,223 dialysis patients. Among 89 FD-positive Diagnosis of ADPKD was made upon the revised Ravine’s criteria and Eligibility
patients, the p.M290I mutation was present in 22. However, the authors did not Criteria for Tolvaptan was made upon Italian indication for Tolvaptan prescription
provide detailed information about the clinical manifestations or a-Gal A activity and according to Italian Medicine Agency (AIFA) and European Medicines Agency
LysoGb3 levels of these patients. Finally, a recent Portuguese screening of 150 (EMA). We performed genetic analysis (PKD1, PKD2 and PKHD1 genes) to identify
hypertrophic cardiomyopathy patients found 25 patients with FD. Of these, one female mutations by NGS capture-based target enrichment kit (Sophia GeneticTM),
carried the GLA gene variant p.M290I, with a non-detectable LysoGb3 plasma level. sequencing on Illumina MySeq PlatformV R and Sanger Sequencing on 3500 Series
CONCLUSION: We describe a case of FD due to a previously known but still poorly Genetic Analyzer (Applied BiosystemsTM).
described GLA mutation, which offers strong evidence of its pathogenicity. To our RESULTS: Eighteen pts [median age 46 (IQR 39-48) yrs ], 12 male, were included in
knowledge, this is the first report of p.M290I mutation-associated disease activity the analysis. We manage to perform genetic analysis in all pts. Genetic analysis was
evidenced by elevated levels of serum LysoGb3. Despite the absence of classic FD essential in 4 patients without family history for Tolvaptan eligibility. Sixteen pts
symptoms such as neuropathic pain, cornea verticillata and angiokeratoma, the (88,9%) have mutations in PKD1, confirming what is already known from the
presence of severe multiple organ evolvement, characterized by renal failure, cardiac literature for rapid progressor subjects; 2 pts are characterized by PKD2 mutations,
disease and ischaemic stroke, strongly suggests a classic phenotype. Consequently, it is both truncating. In only one pt, concomitant with a PKD1 mutation, also a PKHD1
our opinion that the presence of a p.M290I GLA mutation should require a strict mutation was found. In order to better characterize the cohort it was decided to
ongoing patient follow-up, as it may cause clinically significant disease. subdivide the pts into 3 groups, by gene involvement and mutation type:
1st group: 12 Subjects with truncated PKD1 mutation (66.7%). In 7 pts (58,3%) the
mutations are within exons (5 and from exon 11 to 15 inclusive) that encode for
Immunoglobulin-like repeats or PKD domain of Polycystin 1 (PC1).
2nd group: 4 Subjects with non-truncated PKD1 mutations (22.2%). 3 pts (75.0%) are
characterized by missense variants, as previous studies highlighted (a higher percentage
of missense mutations in subjects with non-truncating mutations). In 2 pts (50%) the

i118 | Abstracts
Nephrology Dialysis Transplantation Abstracts
mutations are within exons (2 and 6) that encode for C-type lectin domain (CTLs) di METHOD: Studies are carried out in 23 families affected in which a genetic study has
PC1 and typical domain of extracellular protein. previously been the variant identified. For the survival analysis, the Kaplan-Meier test
3rd group: 2 Subjects with a PKD2 mutation (11.1%), both truncating. These data was performed. Data are expressed in terms of mean 6 SD, median and %.
confirmed the lower mutation rate of PKD2 compared to PKD1 and highlighted an RESULTS: The data described in Table 1 show that there is huge variability of access to
effective prevalence of truncation mutations in rapid disease progressors as previous RRT according to the type of variant found in the family. We found families in which
reported. the age at which kidney failure occurred ranged from 48.03 (28.38-67.68) years to
CONCLUSION: Although our cohort of patients is small, we manage to perform families in which RRT began with 78.04 (65.06-91.03).
genetic analysis in all pts reaching a detection rate of 100%. In 9 of 16 pts (56,3%) with We observed that those families that present a variant with a stop or frameshift codon
PKD1 mutation the presence of mutations in exons coding PKD domain in PC1 or suffer a loss of kidney function before those that present a missense variant. In the
Immunoglobulin-like repeats or typical domain of extracellular protein allows us to variants with a stop or frameshift codon, we observed that they ranged from 48.03
hypothesize that the resulting alteration of the polycystin-mediated cell recognition (28.38-67.68) for the variant c.7480G> T (p.Glu2494 *) to 73.75 (61.52-85, 98) in
and communication processes play a crucial role in the pathogenesis of ADPKD. variant c.9616C> T p.Gln3203 *. In those missense variants, the age of access to RRT
ranges from 62.17 (60.43-63.91) to 77.13 (71.56-82.71)
CONCLUSION: Advances in studies of the genes involved in ADPKD are expanding
the identification of new variants and the knowledge about their involvement in the
MO064 ASSESSMENT OF KIDNEY SURVIVAL IN PATIENTS
progression of the disease.
AFFECTED BY ADPKD
The correlation between genotype and kidney disease will provide a useful clinical
prognosis for ADPKD and will allow us to establish current and future treatments.
Carmen Garcıa Rabaneda1, Ana Isabel Morales Garcıa2, Marıa Luz Bellido Dıaz3,

Marıa del Mar Del Aguila Garcıa4, Antonio M Poyatos Andu jar5, Margarita Martınez
Atienza3, Rafael Jose Esteban de la Rosa6
1
Hospital Universitario Clınico San Cecilio, An alisis clınicos, Granada, Spain, 2Hospital
Universitario Clınico San Cecilio, Nefrologıa, Granada, Spain, 3Hospital Virgen de las
Nieves, Genética, Granada, Spain, 4Hospital Virgen de las Nieves, An alisis clınicos,
Granada, Spain, 5Hospital Universitario Clınico San Cecilio, Genética, Granada, Spain
and 6Hospital Virgen de las Nieves, Nefrologıa, Granada, Spain

BACKGROUND AND AIMS: Autosomal dominant polycystic kidney disease


(ADPKD) is the most common hereditary nephropathy that causes kidney failure and
the need for renal replacement therapy (RRT). It has recently been established that
there is a genotype-phenotype relationship for this disease, with differences in the age
of access to TRS if the involvement occurs in the PKD1 or PKD2 gene and if the
variant is truncating or not. Identifying patients at high risk for rapid progression has
become increasingly important given the emergence of potential new treatments such
as tolvaptan.

10.1093/ndt/gfab080 | i119
Nephrology Dialysis Transplantation 36 (Supplement 1): i120–i132, 2021
10.1093/ndt/gfab078

RENAL PATHOLOGY. EXPERIMENTAL AND CLINICAL

MO065 DIAGNOSTIC CRITERIA OF HUMORAL REJECTION IN RENAL


TRANSPLANT RECIPIENTS WITH PRE-EXISTING ANTI-HLA
ANTIBODIES BASED ON SENTINEL SKIN FLAP BIOPSY

Denis Sadouski1, Aleh Kalachyk1, Alexadr Nosik1, Aliaksei Narbin1,


Anna Startsava1, Yuliya Kuzmenka-Maskvina2, Anna Dolgolikova2
1
State Institution «Minsk Scientific and Practical Center for Surgery, Transplantology
and Hematology», Minsk, Belarus and 2Belarusian Medical Academy of Postgraduate
Education, Belarus

BACKGROUND AND AIMS: Twenty years of transplantation of composite


vascularised allografts have revealed the high immunogenicity of the constituent parts,
especially the skin.Several researchers have proposed the use of vascular stalk flaps,
which allow to performe skin biopsy and diagnose rejection without biopsy of the
transplanted solid organ.Pre-existing anti-HLA antibodies represent a serious MO065 Figure 2: Skin flap with rejection (24 hours after transplantation)
immunological barrier to successful kidney transplantation.We are not aware of any
studies on the diagnosis of antibody-associated acute kidney allograft rejection from
deceased donors in recipients with pre-existing antibodies, based on morphological
examination of a sentinel skin flap on a vascular stalk.
The Aim: To determine the morphological features of humoral rejection in renal
transplant recipients with pre-existing anti-HLA antibodies based on sentinel skin flap
biopsy.
METHOD: Three skin-kidney allografts recipients underwent skin flap biopsy on 2nd
day after transplantation. A kidney allograft biopsy was performed on day 7, 30, 60,
90.The results of morphological studies are presented using the Banff classification of
renal allograft and skin allograft pathology. All recipients were female; 35, 44, and 57
years old. Two patients were re-transplanted and the main cause of CKD was chronic
glomerulonephritis. The third patient, with congenital abnormality of the urinary tract,
received her first graft.Pre-existing anti-HLA antibody levels before transplantation
were 50%, 60%, 80%, respectively.
RESULTS: All recipients showed signs of humoral rejection of the skin flap with
thrombosis of the feeding vascular bundle, phlebitis, predominantly intimal arteritis
with median necrosis, detachment and areactive necrosis of epidermis and epithelium
of skin appendages. Clinical rejection, similar to the algorithm proposed by Etra J.W.
et al. to assess preclinical skin rejection in an animal model (2019), was interpreted as
G2 in two cases and G3 in one case. The Banff classification of the skin flap offers a
qualitative assessment of certain biopsy parameters, while the kidney graft has MO065 Figure 3: Removed flap, x200, arterial thrombosis, intimal arteritis, areactive
qualitative-quantitative criteria for assessing rejection. median necrosis
When comparing the two classifications, a quantitative gradation of pathological
changes in the skin flap according to the parameter of intimal arteritis (v) and
immunoreactivity of the C4d marker similar to renal rejection was possible. In
histological examination of skin flap biopsies, the degree of vasculitis was assessed in a
large feeding artery: in all three cases this parameter was equal to v3. C4d expression
was analyzed in the endothelium of microcirculatory blood vessels of the dermis and
hypodermis: C4d1 in one case and C4d3 in the other two. The analysis of renal
allograft biopsies revealed signs of humoral rejection (v1) only at day 30 in two
recipients whose C4d expression in the skin and hypodermis was strong (C4d3).
CONCLUSION: Antibody-mediated rejection of a vascularized sentinel skin flap in
recipients with combined skin-kidney transplantation is characterized by vasculitis
affecting a core vascular bundle in the form of endarteritis with necrosis of
media,phlebitis and associated thrombosis.Further studies are required to determine
the feasibility of using a vascular stalked skin flap in the diagnosis of humoral rejection
after renal transplantation.

MO065 Figure 4: Artery with blood clot, x25

MO065 Figure 1: Skin flap after reperfusion

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts

MO066 CONGO RED DOT TEST AS A DIAGNOSTIC TOOL FOR RENAL and PCR in the NN (r=0.722, p<0.0001) and RA (r=0.605, p=0.013) was determined.
AMYLOIDOSIS IN PATIENTS WITH NEPHROTIC SYNDROME ROC-analysis showed that threshold value for the diagnosis of RA can be taken as
CRR=33.5% with sensitivity 68.8% and specificity 68.4% (Figure 1b). Despite the
Anastasiia Anpilova1, Maria Khrabrova2, Olga Galkina1, Aleksandr Rubel3, absence of differences in the CRR, polarization microscopy showed specific apple-
Yury Chernoff3,4, Alexei Smirnov1 green birefringence of aggregates bound with CR in the sample of patient with AL-
1
First Pavlov State Medical University of St. Petersburg, Research Institute of amyloidosis (Figure 2 a, b) contrary to the sample of patient with IgA-nephropathy
Nephrology, Saint-Petersburg, Russia, 2First Pavlov State Medical University of St. (Figure 2 c, d).
Petersburg, Department of Propaedeutic of Internal Diseases, Saint-Petersburg, Russia,
3
Saint Petersburg State University, Laboratory of Amyloid Biology, Saint-Petersburg,
Russia and 4Georgia Institute of Technology, School of Biological Sciences, Atlanta,
United States of America

BACKGROUND AND AIMS: Amyloidosis is a serious mostly systemic disease


caused by the deposition of abnormal proteins with a cross-b-sheet conformation in
tissues and predominantly affecting kidneys among other organs that are associated
with inferior renal outcome. Nephrotic syndrome is a common clinical manifestation
of renal amyloidosis (RA) among other primary glomerulopathies. Nowadays there is a
lack of non-invasive diagnostic tools for screening RA. The aim of this pilot study was
to investigate the Congo Red Dot (CRD) test supplemented with polarizing microscopy
as a non-invasive technique for detecting RA in patients with nephrotic syndrome.
METHOD: In this cross-sectional study, we enrolled patients with nephrotic
syndrome (NS, n = 41, aged 52612 years, 48.8% of males) and healthy individuals
without proteinuria for control group (CG, n = 32, aged 45̆18 years, 45.5% of males).
The first-morning urine samples from all included persons were used for the CRD test.
In all cases the protein-creatinine ratio (PCR) was assessed at 24-hour urine collection MO066 Figure 1(b): ROC-curve of CRR as renal amyloidosis predictor
as well as estimated glomerular filtration rate (eGFR) using CKD-EPI formula. Kidney
biopsy was carried out for morphological verification of diagnosis in all patients with
nephrotic syndrome. For the Congo Red Dot test, 4 çl of Congo red dye solution (CR)
was mixed with 2 çl of a sample of the patient’s first-morning urine sample. This
mixture was applied in duplicates onto a nitrocellulose membrane (0.45 çm). To
quantify the Congo Red Retention (CRR, %), which means the staining intensity the
membrane was washed in ascending series of ethanol concentrations and
photographed under constant conditions before and after washing in the specially
designed photo camera. The CRR was determined as the ratio of the average brightness
for two spots on the membrane after and before washing in ethanol and calculated
using the ImageJ software. For polarizing microscopy urine samples were centrifuged
at 1500 g for 15 minutes at +4 C, the supernatant was removed, 5 çl of CR was added
to the sediment and 10 çl was applied to a histological slide, and viewed under
polarized light. Data are presented as median and interquartile range (M (25%; 75%)).
To assess the significance of differences between groups, the nonparametric Mann-
Whitney test was used. Spearman’s correlation analysis was used to investigate the
relationships between the variables. Receiving operating characteristic (ROC) curve
was generated to assess the utility of CRR in prediction of RA.
RESULTS: The CRR in the NS group (42.2% (26.8; 74.2)) significantly differs from the
CRR in the CG group (0.0%), p<0.001. PCR in the NS group was 4.8 g/g (2.2; 11.2). MO066 Figure 2: Sample of a patient with AL-amyloidosis under an optical
The examples of CRD test results are shown in Figure 1a. By morphological diagnosis, microscope (a) and with apple-green birefringence under polarized light (arrows) (b)
patients were divided into two groups: renal amyloidosis (RA, n = 16, aged 58.3̆7.5 Sample of a patient with IgA-nephropathy under an optical microscope (c) and
years, 50% of males) and non-amyloid variant of nephropathy (NN, n = 25, aged without apple-green birefringence under polarized light (d)
48.6̆12.1 years, 48% of males). There was no significant difference between CRR in RA
(71.6% (15.0; 91.8)) and NN (41.7% (27.5; 70.4), p=0.41 as well as between PCR (6.5 g/
g (1.4; 15.4) in RA and 3.6 g/g (1.9; 10.4) in NN, p=0.34). Correlation between CRR CONCLUSION: Preliminary results suggest that CRD test supplemented with
polarizing microscopy could be used for RA screening in patients with nephrotic
syndrome but require further validation as far as congophilia of urine samples from
patients with non-amyloid nephropathy also presents.

MO067 DELETION AND BLOCKAGE OF KININ B1 RECEPTOR


EXACERBATES CISPLATIN-INDUCED CKD

Gabriel Estrela1,2, Alexandre Budu3, Leandro Freitas-Lima3, Adriano Arruda2,


Mauro Perilh~ ao2, Jonatan Barrera-Chimal4, Ronaldo Araujo3
1
Federal University of S~
ao Paulo Unifesp, Clinical and Experimental Oncology, S~ ao
Paulo, Brazil, 2Federal University of S~
ao Paulo Unifesp, Nephrology, S~
ao Paulo, Brazil,
3
Federal University of S~ ao Paulo, Brazil and 4Universidad
ao Paulo Unifesp, Biophysics, S~
Nacional Aut onoma de México, Instituto Nacional de Cardiologıa Ignacio Ch
avez,
Mexico

BACKGROUND AND AIMS: Kinins plays a major role in immune response, where
kinin B2 receptor is constitutively expressed and kinin B1 receptor is induced under
inflammatory stimuli. Kinin B1 receptor deletion and blockage has been shown to have
beneficial effects in some models of renal diseases. Multiple acute renal insults, even if
followed by renal recovery, is a risk factor for the future development of chronic kidney
disease (CKD) and end-stage renal disease (ESRD). Our main objective was to
determine the importance of kinin B1 receptor in tubulointerstitial fibrosis induced by
ongoing cisplatin treatment.
METHOD: Male C57/Bl6 mice were divided in 3 groups, vehicle, cisplatin, cisplatin þ
MO066 Figure 1(a): The examples of the CRD test results
R715 (kinin B1 receptor antagonist). Animals has been treated with multiple doses of
cisplatin (7mg/kg i.p) once a week during 4 weeks and R715 (0.8mg/kg i.p) 48, 24 and 1
hour prior to cisplatin injections. We also used B1KO mice (C57Bl6 background) and

10.1093/ndt/gfab078 | i121
Abstracts Nephrology Dialysis Transplantation

WT mice (littermates). Mice were euthanized after 30 days of last cisplatin injection.
Renal parameters, histology, real time PCR were performed to investigate renal injury,
inflammation and fibrosis.
RESULTS: Cisplatin treatment increases most of renal parameters, renal injury and fibrosis
markers. Deletion of B1 receptor exacerbates significantly creatinine (WT CIS 0,60þ0,03
B1KO 0,76þ0,01 mg/dL), urea (WT CIS 111,8þ5,638 B1KO CIS 240,8þ28,60 mg/dL), and
protein excretion (WT CIS 0,0058þ0,0011 B1KO CIS 0,0121þ0,0007 mg/24h). Association
of cisplatin with R715 increased creatinine levels (veh 0,43þ0,03 cisþR715 0,64þ0,04 mg/
dL), exacerbates urea (cis 95,51 þ 3,926 cisþR715 158,9þ14,40 mg/dL) and protein
excretion (cis 0,012þ0,002 cisþR715 0,018þ0,003 mg/24h). Renal injury markers such as
KIM-1 and TNF-a showed no significant differences. NGAL expression exacerbates (cis
2,53þ0,44 cisþR715 5,66þ1,34) and tubular injury score (cis 0,130þ0,021 cisþR715
0,191þ0,020) is higher in cisplatinþR715 group. Fibrosis markers a-SMA (cis 2,56þ0,43
cisþR715 4,67þ0,99), Col4 (cis 2,57þ0,39 cisþR715 5,14þ1,01) and Vimentin (2,69þ0,31 MO068 RENAL HISTOPATHOLOGY IN CANCER PATIENTS: RESULTS
cisþR715 4,62þ0,98) were exacerbated in cisplatin treatment associated with R715. OF A MULTICENTER STUDY
Picrosirius red staining were used to asses tubulointerstitial fibrosis, and we confirmed that
R715 treatment here also exacerbates fibrosis (cis 0,225þ0,025 cisþR715 0,345þ0,042). Monica Bolufer1, Clara Garcia Carro2, Amir Shabaka3, Cristina Rabasco4,
CONCLUSION: Here we show that both deletion and blockage of kinin B1 receptor has Juliana Draibe5, Maria Rosa Melero Martin6, Fabiola Alonso Garcia7,
deleterious effects in renal injury and fibrosis induced by ongoing cisplatin treatment. Anna Buxeda8, Paula Batalha9, Maria Teresa Visus10, Marıa José Soler1
1
Hospital Vall Hebron, Nephrology , Barcelona, Spain, 2Hospital Clinico San Carlos ,
Nephrology , Madrid, Spain, 3Fundacion Alcorcon, Nephrology , Alcorcon , Spain,
4
Hospital de Cordoba, Nephrology , Cordoba, Spain, 5Hospital Bellvitge , Nephrology ,
6
Hospitalet de Llobregat , Spain, Hospital Gregorio Mara~ non , Nephrology , Madrid ,
Spain, 7Hospital Virgen Macarena , Nephrology , Sevilla , Spain, 8Hospital del Mar ,
9
Nephrology , Barcelona, Spain, Hospital Virgen del Rocio , Nephrology , Sevilla , Spain
and 10Hospital de Navarra , Nephrology , Pamplona , Spain

BACKGROUND AND AIMS: Some decades ago, patients with cancer were not
submitted to invasive procedures because of their short life expectancy. This is one of
the main reasons why data about kidney histology in oncological patients with kidney
impairment is very scarce: kidney biopsies were not performed in this population.
However, renal biopsy is an especially useful diagnostic and prognostic tool in these
patients when they develop kidney injury. The aim of our study is to study clinical and
histological characteristics of patients with active solid organ malignancy that
underwent kidney biopsy in a multicenter cohort.
METHOD: We performed a multicenter collaborative retrospective study. Clinical,
demographical, and histological data from patients with an active neoplasia or in active
cancer treatment who underwent kidney biopsy were collected. Statistics: Quantitative
variables are expressed as meanþ/-SD (normal distribution) or median (IQ 25-75)
(non-normal distribution).Qualitative variables are expressed as percentage. Actuarial
survival curves were performed using Kaplan-Meier.
RESULTS: 94 patients with cancer who underwent a kidney biopsy during the study
period, from 9 hospitals were included.63.8% men, 36.2% woman and mean age 66 (SD
þ/- 10,95) years old. The indications for biopsy were acute renal failure (63.8%),
proteinuria (17%), and exacerbation of chronic kidney disease (11.7%).
At the time of the renal biopsy, 27.7% patients presented diabetes, 60.6% high blood
pressure, 10.6% were on non-steroidal anti-inflammatory drugs treatment, and 74.5%
were receiving renin angiotensin system blockers. Malignances were lung (31.9%),
intestinal (13.8%) and prostate (8.5%), with 43.6% metastatic cancer.
As oncospecific treatment, 33% received chemotherapy, 30.8% immunotherapy (of
which 37.93% received more than 1 checkpoint inhibitor (CPI) and 24.13% had
immune-related adverse events), 22.4 % specific therapies, 17 % surgery, and 3.2%
conservative treatment.
Previously to kidney injury, 51.06% presented Cr> 1 mg / dL. At the time of kidney
biopsy, median creatinine was 2,63mg/dL [1,75-3,9 (IQ 25-75)], median urine protein/
creatinine ratio 795 mg/g [221-3182(IQ 25-75)]; 51.1% presented haematuria and
22.3% nephrotic range proteinuria; 8.5% eosinophiluria and 7.44% hemolytic anemia
and /or low platelet. At the time of renal biopsy, 8.5% presented ANCA and 5.31%
decrease in C3 / C4 serum levels.
The renal biopsy diagnosis was: 40.4% acute interstitial nephritis, followed by acute
tubular necrosis (9.6%), thrombotic microangiopathy (6.4%), membranous
nephropathy (5.3%) and IgA nephropathy (6.4%). 62.8% received corticosteroids
(28.81% pulses) for an average of 5.8 months [3.7-9.1(IQ 25-75)]. 12.8% required
kidney replacement therapy. 43.6% showed complete recovery of kidney function at
the end of follow-up. Average follow-up 22.59 months. 40.2% of patients died at the
end of follow-up and 72.34 % presented chronic kidney disease.
As expected, and maybe related to the heterogeneous cancer disease studied, the only
factor associated with mortality was the presence of the metastasis at the moment of
kidney biopsy (p=0.028).
CONCLUSION: Histological kidney diagnosis in patients with active cancer involves
various renal disorders, such as acute interstitial nephritis, thrombotic

i122 | Abstracts
Nephrology Dialysis Transplantation Abstracts
microangiopathy, membranous nephropathy and IgA nephropathy. Renal biopsy in into the mesangium accounts for the advancement from diffuse mesangial sclerosis
this group of patients provides valuable diagnostic and prognostic information. More (DMS) to nodular sclerosis (NS) and to the herniation of the tuft through the
studies are needed to expand the consensus in the diagnosis and treatment of glomerular vascular pole to the outside; the latter is associated with the outgrowth of
oncological patients with renal injury. glomerular capillaries into the peri-glomerular space leading to the destruction of the
juxtaglomerular apparatus. 2.The role of podocytes: Podocytes have frequently been
accused to play a central role in DN. This is correct, but in another way than generally
assumed. Damage to podocytes cannot be seen in DMS. The albuminuria regularly
MO069 SARS-COV-2 RECEPTOR ACE-2, TMPRSS2 AND SOLUBLE
seen during this stage derives, as previously suggested by others, from an increased
ACE-2 IN PATIENTS WITH END STAGE KIDNEY DISEASE
leakiness of the glomerular capillary endothelium based on a deranged glycocalyx.
Podocyte detachments start at the transition from DMS to NS, based on the loss of
Samsul Arefin1, Leah Hernandez1, Liam Ward1, Peter Stenvinkel1,
cross talk signals with the capillary endothelium: the increasing deposition of matrix
Karolina Kublickiene1
1
leads to the collapse of many capillaries. These podocytes contribute little to the further
Karolinska Institute, Department of Clinical Science, Intervention & Technology, progression of the damage: they are lost into primary urine or they undergo cell lysis.In
Division of Renal Medicine, Stockholm, Sweden addition to their role in increased matrix production, podocytes take an active role in
the formation of tuft adhesions to Bowman’s capsule (BC), starting the progression to
BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 NS. Expansion of the matrix within the mesangium has led to expansion of the tuft
(SARS-CoV-2) has led to dramatic loss of lives due to COVID-19. Individuals with (frequently associated with nodules) towards Bowman’s capsule (BC) or towards the
chronic conditions, including patients with kidney failure and/or kidney transplants, urinary orifice. Podocytes on the surface of these expansions are in their majority
are affected more substantially due to multiple comorbidities and altered immune structurally intact, exhibiting an intact pattern of foot processes. These podocytes come
system. The first step of this infection process is the binding of SARS-CoV-2 with into contact with parietal epithelial cells and initiate DN-specific tuft adhesions to BC
angiotensin-converting enzyme 2 (ACE-2) receptor, followed by its priming by allowing the proliferation of glomerular capillaries into BC. There they deliver an
transmembrane protease serine 2 (TMPRSS2). We hypothesized that the expressions of exudate into BC that spreads around the entire circumference of the glomerulus
ACE-2 and TMPRSS2 are increased in microvasculature, in addition to increased presenting as giant insudative spaces. Moreover, this process encroaches via the
circulating soluble ACE-2 levels in patients with end stage kidney disease (ESKD); i.e. glomerulo-tubular junction onto the tubule constituting the major pathway of
prerequisites to explain to why ESKD patients are susceptible to SARS-CoV-2 glomerular damage extending to the tubulointerstitium. 3. Tubulointerstitial
infection. Therefore, we assessed if there is a difference in the expression of ACE-2 and fibrosisIt is current opinion that the tubulointerstitial fibrosis may start from tubular
TMPRSS2 receptors in the resistance artery and subcutaneous adipose tissue, alongside damage resulting in an own, glomerular-independent pathway to nephron loss.
circulating soluble ACE-2 levels in ESKD patients versus controls. However, there is scant evidence for such a mechanism. Studying 162 glomerulo-
METHOD: A total of 210 participants were enrolled, representing 80 ESKD and 73 healthy tubular transitions, we did not see a tubular epithelial or interstitial damage in those
controls for soluble ACE-2 analysis, and 31 ESKD and 26 healthy controls for isolated biopsies without any evidence of a glomerulo-tubular damage transfer. The only exception
subcutaneous vasculature bioassay. Immunofluorescence techniques were performed for the consists of the well-known prominent thickening of the tubular basement membrane, which
detection and evaluation of ACE-2 and TMPRSS2 in isolated subcutaneous resistance artery may result in functional loss but does not lead to structural epithelial damage.
(200-300 mm of internal ^aCEe) and adipose tissue. Soluble ACE-2 protein concentration was CONCLUSION: We consistently found that tubulo-interstitial damage develops after
detected using commercially available ELISA kits. encroachment of the glomerular damage onto the tubule, leading first to a gradual
RESULTS: Soluble ACE-2 levels were significantly higher in ESKD (3.8 ng/mL, IQR degeneration of tubules which subsequently initiate the process of interstitial fibrosis.
2.4-5.5, n=80) vs control groups (2.7 ng/mL, IQR 2.1-3.7 ng/mL, n=73). There was no
difference in soluble ACE-2 between females and males in either group. Soluble ACE-2
was positively correlated with IL-6 (rho=0.257, p=0.02, n=80), while it was negatively
MO071 PROTEINS LINKED TO ATHEROSCLEROSIS AND CELL
correlated with cholesterol (rho= -0.248, p=0.02, n=78) in ESKD patients. The
PROLIFERATION ARE ASSOCIATED WITH SHRUNKEN PORE
expression of ACE-2 receptor was observed both on endothelium and vascular smooth
SYNDROME IN HEART FAILURE PATIENTS
muscle cells (VSMCs) in arteries from both groups. The expression was higher in
ESKD patients (19.1%, n=23) vs controls (15.4%, n=15). Patients with ESKD on ACE-
Liana Xhakollari1,2, Amra Jujic1,3, John Molvin1,3, Peter M Nilsson1,
inhibitor/angiotensin receptor blocker treatment showed higher expression of ACE-2
Hannes Holm1,3, Erasmus Bachus1, Margret Leosdottir1,3, Anders Grubb4,
vs. non-treatment group (treatment: 20.2%, n=12 vs non-treatment: 12.8%, n=11) in
Anders Christensson1,2, Martin Magnusson1,3
resistance artery. In subcutaneous adipose tissue the ACE-2 staining was not 1
statistically different among the groups (ESKD: 2.9%, n=10 vs controls: 3.6%, n=10). In Lund University, Clinical Sciences, Lund, Sweden, 2Skåne University Hospital,
addition, TMPRSS2 was expressed both on endothelium and VSMCs in resistance Nephrology, Malmö, Sweden, 3Skåne University Hospital, Cardiology, Malmö, Sweden
artery, however there was no difference in the expression (ESKD: 8.4%, n=23 vs and 4Skåne University Hospital, Clinical Chemistry, Lund, Sweden
controls: 10.2%, n=15) between the groups.
CONCLUSION: Soluble ACE-2 levels and ACE-2 receptor expression in the BACKGROUND AND AIMS: The “Shrunken pore syndrome” is characterized by a
vasculature were higher in patients with ESKD as compared to controls. The ACE-2 difference in renal filtration between cystatin C and creatinine resulting in a low
receptor is present both in the endothelium and VSMCs from arteries in peripheral eGFRcystatinC/eGFRcreatinine-ratio, and studies have demonstrated a high risk for
microcirculation. This supports the suggestion that the uremic milieu induces an cardiovascular morbidity and mortality for patients with shrunken pore syndrome. In this
optimal environment for SARS-CoV-2 entrance in microcirculation with following observational study, we explored associations between shrunken pore syndrome and
consequence on the vasculature during the COVID-19. Similarly, TMPRSS2 proteins implicated in cardiovascular disease and inflammation in patients with heart failure.
expression was observed in vessels from both groups, while increased expression of METHOD: Plasma samples from 300 individuals HARVEST-Malmö trial hospitalized for
ACE-2 receptor was observed in those ESKD patients receiving ACE-inhibitor/ the diagnosis of heart failure (mean age 75 years; 30% female), were analyzed with a proximity
angiotensin receptor blocker treatment. Further studies are warranted to assess extension assay consisting of 92 proteins, to identify proteins associated with shrunken pore
possible sex differences in the target receptor expressions with further elaboration on syndrome. Shrunken pore syndrome was defined as eGFRcystatinC 60% of eGFRcreatinine.
specific treatment regime(s) for different comorbidities present in patients with ESKD. Proteins associated with shrunken pore syndrome in the initial age and sex-adjusted analyses
(Bonferroni-corrected p 5.4x10-4) were further adjusted for relevant covariates.
RESULTS: In multivariate analyses, Shrunken pore syndrome was associated with elevated
levels of six proteins; scavenger receptor cysteine-rich type 1 protein M130, tumor necrosis
MO070 NEW ASPECTS OF THE PATHOMORPHOLOGIC SEQUENCE
factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor
OF NEPHRON LOSS IN DIABETIC NEPHROPATHY
subunit alpha, and tyrosine-protein kinase receptor UFO (p<0.05).
CONCLUSION: In heart failure patients, shrunken pore syndrome was independently
Hermann Gröne1, Wilhelm Kriz2, Jana Loewen2, Elisabeth Groene3
1
associated with proteins linked to atherosclerosis and cell proliferation.
Institute of Pharmacology, Pharmacology, Marburg, Germany, 2Institute of Anatomy,
Anatomy, Mannheim, Germany and 3German Cancer Research Center (DKFZ), M 220,
Heidelberg, Germany

BACKGROUND AND AIMS: Diabetic nephropathy (DN) is the leading cause of


end-stage-renal disease in western countries. Despite of innumerable studies
undertaken to elucidate the pathogenesis of DN the underlying morphologic
alterations have been insufficiently analyzed.
METHOD: Re-evaluation of more than 800 biopsies was done showing several
unknown features.
RESULTS: 1.: Matrix accumulation in the mesangium: Thickening of the glomerular
basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of
DN, generally considered to emerge from different sites of overproduction: GBM
components from podocytes and mesangial matrix from mesangial cells.
We show, that the accumulation of matrix in the mesangium emerges from an
overproduction of GBM material by podocytes and endothelial cells and an impaired
degradation by mesangial cells. The progressing deposition of worn-out GBM material MO071 Figure 1: Proposed pathophysiology behind the Shrunken pore syndrome.

10.1093/ndt/gfab078 | i123
Abstracts Nephrology Dialysis Transplantation

dose dependently opposed LPS stimulated expression of inflammatory genes: IL6 up to


MO072 APABETALONE DOWNREGULATES FIBROTIC,
94%, IL1B up to 95% & PTGS2 (COX2) up to 94% p<0.001, suggesting
INFLAMMATORY AND CALCIFIC PROCESSES IN RENAL
downregulation of inflammatory processes. In all studies, JQ1 and / or MZ1 had
MESANGIAL CELLS WHICH MAY CONTRIBUTE TO
similar activity as apabetalone, confirming on-target BETi effects.
REDUCED CARDIAC EVENTS OBSERVED IN CKD PATIENTS
In GO Enrichment analysis of RNA-seq from TGF-b1 stimulated HRMCs, multiple
gene sets associated with ECM were in the top 20 affected by BETi, supporting anti-
Dean Gilham1, Li Fu1, Brooke Rakai1, Sylwia Wasiak1, Laura Tsujikawa1,
fibrotic properties. IPA predicted NfkB-RelA and NFkB (complex) were upstream
Christopher Halliday1, Christopher Sarsons1, Stephanie Stotz1, Ravi Jahagirdar1,
regulators inhibited by apabetalone, indicating suppression of NF-kB mediated
Jan Johansson2, Michael Sweeney2, Norman Wong1, Kamyar Kalantar-Zadeh3,
inflammation. IPA also predicted apabetalone activated canonical pathways of glucose
Ewelina Kulikowski1
1
utilization & tolerance of ROS production, including Oxidative Phosphorylation (z-
Resverlogix Corp., Calgary, Canada, 2Resverlogix Corp., San Francisco, United States of score 5.7, p<0.01 at 25mM; z-score 3.5, p>0.05 at 5mM) and NRF2-Mediated Oxidative
America and 3University of California Irvine, Irvine, United States of America Stress Response (z score 2.3, p<0.001 at 25mM; z-score 1.6, p<0.001 at 5mM). PGC-1a,
a key upstream regulator of the Oxidative Phosphorylation pathway, was also predicted
BACKGROUND AND AIMS: Major adverse cardiac events (MACE) remain a to be activated by apabetalone (z score 4.2, p<0.001 at 25mM; z-score 2.3, p<0.001 at
leading cause of mortality in chronic kidney disease (CKD). Apabetalone is an orally 5mM). These changes in energy metabolism pathways may allow HRMC to cope with
available inhibitor of bromodomain & extraterminal (BET) proteins – epigenetic elevated glucose.
readers that modulate gene expression involved in fibrosis, inflammation and CONCLUSION: Apabetalone downregulated responses to TGF-b1 or LPS in HRMCs
calcification. In the phase 3 BETonMACE trial, apabetalone treatment was associated that promote fibrotic, inflammatory and calcific processes which exacerbate kidney
with reduction in MACE in the subpopulation with CKD (eGFR < 60 mL/min/1.73m2; dysfunction. Changes in energy metabolism pathways predicted apabetalone facilitates
HR 0.50 95% CI 0.26,0.96 p=0.04]) implying favorable effects of apabetalone on adaptation to high glucose in the kidney. Together, our results provide mechanistic
cellular responses along the kidney-heart axis. This study examines effects of insight into reductions in MACE in CKD patients receiving apabetalone in the phase 3
apabetalone on primary human renal mesangial cells (HRMCs) in culture on fibrosis, BETonMACE trial. The effect of apabetalone on MACE in patients with diabetes and
inflammation, reactive oxygen species (ROS) and calcification pathways that CKD will be further evaluated in the upcoming BETonMACE2 trial.
contribute to renal pathology.
METHOD: HRMCs from donors without kidney dysfunction were stimulated with
TGF-b1 or lipopolysaccharide (LPS) 6 1-25mM apabetalone, 0.15-0.5mM JQ1 or
MO073 HISTOLOGICAL PREDICTORS OF PROTEINURIA AND RENAL
0.1mM MZ1 (BET inhibitors [BETi] with chemical scaffolds different than
OUTCOMES IN PRIMARY MEMBRANOUS NEPHROPATHY: IS
apabetalone). Gene expression was measured by real-time PCR and RNA-seq. Smooth
INTERSTITIAL FIBROSIS THE MAIN CHARACTER?
muscle actin (a-SMA) was examined by immunofluorescence microscopy, and alkaline
phosphatase enzyme activity in a biochemical assay. RNA-seq from TGF-b1 treated
Elena Naso1, Lisa Gianesello1, Diego Maschio1, Monica Ceol1, Samanta Beggio1,
HRMC 6 BETi was evaluated by Gene Ontology (GO) Enrichment and Ingenuity
Annalisa Angelini2, Marny Fedrigo2, Franca Anglani1, Lorenzo Calo 1, Dorella Del
Pathway Analysis (IPA).
Prete1
RESULTS: TGF-b1 is a pro-fibrotic cytokine that activates HRMC to a fibroblast-like 1
state which over-produces extracellular matrix (ECM). Apabetalone dose dependently Nephrology, Dialysis and Transplantation Unit, Department of Medicine - DIMED,
suppressed TGF-b1 induced gene expression of (a) a-SMA, a marker of fibrotic University of Padova, Italy and 2, Department of Cardiac-Thoracic-Vascular Sciences
activation, up to 90% p<0.001 and de novo a-SMA protein production (b) fibronectin, and Public Health, University of Padova, Italy
a key ECM component, up to 44% p<0.001 (c) NADPH oxidase 4 (NOX4), involved in
production of pro-fibrotic ROS, up to 82% p<0.001 (d) tissue non-specific alkaline BACKGROUND AND AIMS: Membranous nephropathy (MN) is the most common
phosphatase (TNALP), associated with reduced glomerular function & extracellular cause of nephrotic syndrome in older white adults, with an incidence of 12 cases per
calcification, up to 96% as well as TNALP enzyme activity up to 96% p<0.001. An millions of people per year. Primary MN (PMN, 75%-80% of MNs) is an organ-specific
inhibitor of TGF-b receptors reduced or abolished TGF-b1 responses, indicating the autoimmune disease caused by antibodies anti-PLA2R and anti-THSD7A. Regardless
expected signal transduction pathways mediated its downstream effects. Apabetalone of treatment one third of patients progresses to end-stage renal disease and two third

MO074 Figure 1: In a human ex vivo kidney fibrosis model,tilvestamab inhibits markers ofactivationin myofibroblasts and shows synergy with ACE inhibitors
A. Experimenta Iset up for investigation of anti-fibrotic efficacy of tilvestamab and enalapril in Precision cut Kidney slices.
B. Alpha-Smooth Muscle Actin (aSMA ) was sta ined by IHC in FFPE slides 96 hrs after drug administration
C. Secreted Collagen 1a1 were measured in supernatants 96 hrs after drug administration.

i124 | Abstracts
Nephrology Dialysis Transplantation Abstracts
develop non-progressive chronic kidney disease. Renal biopsy is the gold standard for METHOD: Eight weeks old male C57BL/6 mice underwent UUO operation. After 15
MN diagnosis. Several clinical and biochemical markers have been associated with the days, kidneys were dissociated and stained with a high dimensional single cell mass
risk of progressive loss of kidney function while contrasting results have been obtained cytometry 33 markers antibody panel. Data were analysed using JMP Genomics (v.8.2).
by the few studies which have examined the prognostic value of histologic findings. Precision Cut Kidney Slices (PCKSs) from explanted human kidney tissue were
In this study the clinical outcome of patients with PMN has been considered based on propagated in a bioreactor (Paish et al., 2019, FibroFind, UK). PCKS were incubated
the prognostic value of histological findings. for 72hrs in the presence of investigational drugs. Secreted collagen1a1 were quantified
METHOD: Forty-nine patients with PMN of our Nephrology Unit at Padova by ELISA. RNA was reverse transcribed to cDNA and used in qPCRs to measure
University Hospital from 2003 to 2018 were considered. 16 patients were excluded Col1a1 and aSMA. FFPE sections were stained for aSMA. High magnification images
from the study due to missing data. Age, comorbidities, proteinuria (g/day) and renal were taken of each slide and analysed for surface area covered by the stain.
function (eGFR, CKD-EPI) were collected. eGFR decline and decrease of proteinuria RESULTS: Expression pattern of AXL during development of kidney fibrosis in the
were used as clinical outcomes. The follow-up was considered from renal biopsy to the UUO model was investigated using a mass cytometry antibody panel designed for
last visit (in absence of GFR decline or decrease in proteinuria). identifying subpopulations of immune cells as well as cell populations of the fibrotic
Histological grading (0-3) was assigned to parameters (glomerulosclerosis (GS), stroma. Two predominant cell populations were affected by ligation; the mesenchymal
tubular atrophy (TA), interstitial fibrosis (IF), vascular hyalinosis (VH)) and were and the immune island. AXL was a marker characterising several of the key
evaluated separately or in combination (as GSTIV score). Morphometric analysis was populations that expanded upon ligation supporting a role for AXL in kidney fibrosis
used to quantify IF and expressed in percentage as the mean of area covered by pixel. pathogenesis.
Statistical analysis was performed using Fisher’s exact test and Mann-Whitney U-test In an ex vivo model of human PCKS, tilvestamab dose-dependently reduced the levels
where appropriate. Cox regression analyses (univariate and multivariate) were of aSMA. When combined with the lower of two doses of the ACE inhibitor enalapril,
performed to identify variables associated with both renal outcomes and p<0.05 was the lowest dose of tilvestamab synergized to reduce aSMA levels further as well as
considered as significant. reducing secreted Collagen 1a1.
ROC curves were used to determine interstitial fibrosis cut-off values predictive for CONCLUSION: AXL expression is induced in key cell populations during
both outcomes. Area under the curve (AUC) between 0.8 and 1.0 was considered as development of kidney fibrosis supporting AXL as a novel target in CKD. Tilvestamab
significant. Diagnostic accuracy was assessed by Specificity (Sp), Sensibility (Se), represents a promising strategy for the pharmacologic intervention of kidney fibrosis,
positive (PPV) and negative (NPV) predictive values and positive (LRþ) and negative and the potential synergy with current reno-protective therapies warrants further
(LR-) likelihood ratios. exploration.
RESULTS: Patients with no decrease of proteinuria had a greater degree of IF vs those
with a full response (p=0.006).
Univariate Cox analyses identified age 65 years (HR 4.92), pre-existing CKD (HR 12.98)
MO075 KLF11 DEFICIENCY ENHANCES CHEMOKINE GENERATION
and IF (HR3.05) as significant predictors of renal function decline in all patients.
AND INJURY IN MURINE UNILATERAL URETERIC
Multivariate Cox analysis confirmed these variables (age 65 years HR 3.05, CKD HR 6.35,
OBSTRUCTION
IF HR 3.03). In patients without CKD only IF was significantly associated with eGFR decline
in both Cox univariate and multivariate analysis (HR 4.34 and 5.05 respectively).
Silvana DeLorenzo1, Joseph Grande1
ROC analysis showed that IF threshold of 17.80% identified patients with eGFR 1
reduction (AUC 0.65, Se 0.50, Sp 0.79, PPV 0.75, NPV 0.45, LRþ 2.38, LR-0.63) and IF Mayo Clinic, Laboratory Medicine and Pathology, Rochester, United States of America
threshold of 18.04% the lack of proteinuria reduction (AUC 0.78, Se 0.70, Sp 0.83, PPV
0.67, NPV 0.80, LRþ 4.12, LR- 0.36). BACKGROUND AND AIMS: Kruppel-like factors (KLFs) comprise a family of zinc-
CONCLUSION: Our study shows that IF could be used as a histologic predictor of finger transcription factors that play a critical role in development, proliferation, and
renal and proteinuria outcomes. Biopsy report should therefore also include regeneration following injury. There are over 17 members of this family; recent studies
quantitative IF data that could be helpful for the choice of a more appropriate have shown that KLF family members regulate podocyte differentiation, preservation
therapeutic approach. of the glomerular filtration barrier, and regulation of mitochondrial function. However,
a role for KLF11 in renal pathophysiology has not been previously established.
METHOD: Wild-type (WT) and KLF11 knockout (KO) mice were subjected to
unilateral ureteric obstruction (UUO), a well-established model of renal inflammation
MO074 TILVESTAMAB, A FUNCTION-BLOCKING MONOCLONAL
and fibrosis; controls included mice subjected to manipulation of the ureter without
ANTIBODY INHIBITOR OF AXL RTK SIGNALLING, LIMITS THE
ligation. Kidneys were harvested after 9 days (n=8 animals per group).
ONSET OF RENAL FIBROTIC CHANGES IN HUMAN KIDNEYS
Semiquantitative histopathologic analysis of renal atrophy, fibrosis, and inflammation
EX VIVO
was performed in a blinded fashion. Gene expression analysis was performed on renal
cortex employing the Pathway Detect RNA array and RNASeq.
Linn Hodneland Nilsson1, Sturla Magnus Grøndal2, Magnus Blø1,
RESULTS: In UUO, renal atrophy was more severe in KLF11 KO mice than WT mice
Anna Boniecka1, Barbara VanderHoeven1, Lea Zoe Landolt3,4, Tarig Al-
(p<0.001). Deposition of collagen, as assessed by quantitative analysis of Sirus Red
Hadi Osman3,4, David Micklem1, Hans-Peter Marti3,4, James B Lorens2,
stained sections, was greater in KLF11 KO mice, compared to WT mice subjected to
Akil Jackson5, Gro Gausdal1
1
UUO; COL3A1 expression was also increased (p<0.05). Atrophy was associated with
BerGenBio ASA, Bergen, Norway, 2Department of Biomedicine, University of Bergen, an increase in F4/80þ (p<0.01) and CD206þ macrophages (p<0.05), but not CD3þ T
Bergen, Norway, 3Department of Clinical Medicine, University of Bergen, Bergen, cells in KLF11 KO vs. WT mice. Induction of CC chemokines, including CCL2, CCL5,
Norway, 4Department of Medicine, Haukeland University Hospital, Bergen, Norway and CCL7, CCL12, and CCL2 as well as CCR2 was significantly higher in KLF11 KO versus
5
BerGenBio Ltd, Oxford, United Kingdom WT mice subjected to UUO (all p<0.001). Expression of NF-kB (p<0.01) and TNF
alpha (p<0.01), but not IL-1 beta, IL-6, or IL-10 were significantly higher in KLF11 KO
BACKGROUND AND AIMS: Interstitial fibrosis, characterised by the accumulation than WT mice with UUO. Expression of TGF-beta 1, Smad2, and Smad3 were also
of extracellular matrix in the cortical interstitium, is directly correlated with higher in KLF11 KO mice than WT mice with UUO (p<0.05).
progressive chronic kidney disease secondary to inflammatory, immunologic, CONCLUSION: Renal injury in UUO is exacerbated in KLF11 KO mice, compared to
obstructive or metabolic causes. An invariant histologic marker of this progression is WT mice. Injury is associated with increased macrophage influx and production of
the accumulation of fibroblasts, with the phenotypic appearance of activated pro-inflammatory chemokines. Future studies will determine how KLF11 deficiency
myofibroblasts expressing alpha smooth muscle actin (aSMA) within intracellular directs transcription of pro-inflammatory and pro-fibrotic genes.
contractile stress fibres. Once present, these myofibroblasts are prognostic indicators of
expansion of fibrotic matrix and progressive tubular atrophy, leading towards end-
stage disease.
MO076 REGULATION OF DIFFERENTIAL CELLULAR RESPONSE TO
The Receptor Tyrosine Kinase AXL is involved in a range of kidney pathologies, with OXIDATIVE STIMULI IN SYSTEMIC LUPUS
increased activity associated with Epithelial to Mesenchymal Transition (EMT) and ERYTHEMATOSUS
tubular proliferation following podocyte loss. In mice treated with an angiotensin-
converting enzyme (ACE) inhibitor, enhancement of AXL expression is localised to Corina-Daniela Ene1,2, Mircea Penescu1,2, Simona Roxana Georgescu3,4,
tubular segments within the medulla and there is evidence of parallel regulatory control Mircea Tampa3,4, Ilinca Nicolae4
of ACE and AXL. We have demonstrated enhanced expression of AXL and the 1
Carol Davila University of Medicine and Pharmacy, Nephrology, Bucures, ti, Romania,
mesenchymal marker, vimentin in diseased human kidney tissue secondary to diabetes 2
Nephrology Hospital Dr. Carol Davila, Nephrology, Bucures, ti, Romania, 3Carol Davila
or hypertension. University of Medicine and Pharmacy, Dermatology, Bucures, ti, Romania and 4Victor
Targeting AXL with a small-molecule inhibitor has previously been reported to Babes, Hospital, Research in Dermatology, Bucures, ti, Romania
attenuate fibrosis and reduce inflammation in the unilateral ureteric-outflow
obstruction (UUO) model of kidney fibrosis in mice (Landolt et al., 2019). Tilvestamab
is a novel function blocking humanized anti-AXL antibody. Tilvestamab blocks GAS6- BACKGROUND AND AIMS: Interaction of reactive oxygen species (ROS) with
mediated AXL receptor activation in fibroblasts and renal tubule epithelial cells and lipids, proteins, nucleic acids and hydro carbonates promotes acute and chronic tissue
mediates AXL receptor internalization and degradation. damage, mediates immunomodulation and triggers autoimmunity in systemic lupus
In this study we aimed to further characterise AXL as a target in CKD and to erythematous (SLE) patients. The aim of the study was to determine the
investigate anti-fibrotic efficacy of tilvestamab. pathophysiological mechanisms of the oxidative stress-related damage and molecular
mechanisms to counteract oxidative stimuli in lupus nephritis.

10.1093/ndt/gfab078 | i125
Abstracts Nephrology Dialysis Transplantation

METHOD: Our study included 82 volunteers with SLE: 38 SLE volunteers with lupus intersection over union (IoU) and Matthews correlation coefficient (MCC) against the
nephritis (LN group) and 44 SLE volunteers without renal impairment (non-LN nephropathologist’s segmentation as ground truth.
group) and a control group of 40 healthy volunteers. LN was diagnosed by histological RESULTS: Over all classes (artery, arteriole, glomerulus) Cohen’s kappa was 0.86.
exam (optic microscopy, electronic microscopy and immunofluorescence). Disease
activity was measured by systemic SLE disease activity index (SLEDAI), urinary IoU was 0.716 for artery, 0.491 for arteriole and 0.829 for glomerulus.
protein/creatinine ration, anti-dsDNA, C3, C4 and urinary b2-microglobulin. MCC was 0.837 for artery, 0.664 for arteriole and 0.907 for glomerulus.
In the present paper, we evaluated in serum:

• lipid peroxidation by malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), thio-


barbituric acid reactive substances (TBARS), F2-isoprostane;
• DNA oxidation by 8-hydroxy 2 deoxyguanosine (8-OHdG);
• oxidized proteins by carbonylated proteins (PCO), thiol – disulphide homeostasis
, protein nitrotyrosine;
• carbohydrates oxidation by advanced glycation end products (AGE) and
pentosidine
• endogenous protective systems like overall antioxidant capacity (ImAnOx), DNA
repair enzyme 8-Oxoguanine DNA glycosylase (OGG1), soluble receptor for
advanced glycation end-products (sRAGE), thiol-disulfide homeostasis (TDH).

RESULTS: We detected high lipid peroxidation, elevated oxidative DNA damage,


excess accumulation of reactive carbonylic compounds, important oxidation of
carbohydrates, disulphide bonds formation and high nitrotyrosination with statistically
significant differences between groups, when compared LN and non-LN groups with
control group.When compared LN and non-LN groups, our results showed:

• elevated oxidative DNA damage levels and decreased enzymatic activity of OGG1 MO077 Figure: The figure shows the performance of our segmentation model on the
in LN group [8-OHdG (ng/mL): 4.3160.81 in LN group, 3.5860.68 in non-LN holdout set with Cohen’s kappa, intersection of union (IoU) and Matthews correlation
group (p<0.05); OGG1(pg/mL): 16.2163.31 in LN group, 20.8062.26 in non- coefficient (MCC).
LN group (p<0.001)];
• increased sRAGE in LN group [sRAGE (pg/mL): 1198.46 201.7 in LN group, CONCLUSION: We achieved good automatic segmentation of arteries, arterioles and
963.16 164.3 in non-LN group (p<0.05)]; glomeruli, even with severe pathological distortion on routine histopathological slides.
• decreased serum thiols in LN group [native thiols (lmol/L): 324.21619.32 in LN We will further improve this segmentation technology in order to enable the bulk
group, 355.92618.53 in non-LN group (p<0.01)]; analysis of these descisive tissue compartments in large clinicopathological repositories
• disulphide bonds formation [Disulphides (lmol/L): 31.9562.97 in LN group, of native kidney biopsies with TMA using supervised and unsupervised machine
25.6561.62 in non-LN group (p<0.01)]; learning algorithms.
• increased nitrotyrosination in LN group [3-Nitrotyrosine (lmol/L): 0.4060.11 in
LN group, 0.2960.04 in non-LN group (p<0.01)].
MO078 DEEP LEARNING DIAGNOSIS OF ANTIBODY-MEDIATED
3-Nitrotyrosine levels, the decrease of total and native serum thiols, pentosidine levels, REJECTION (AMR) ON GLOMERULAR TRANSECTIONS
sRAGE level and OGG1 activity correlated with disease activity markers in both LN
and non-LN groups, while AGE correlated with disease activity only in non-LN group. Pietro A. Cicalese1, Syed A. Rizvi1, Candice Roufosse2, Ibrahim Batal3,
CONCLUSION: The cellular response to oxidative stimuli in SLE is concreted in the Martin Hellmich4, Angela Ernst4, Katharina Moos4, Marian Clahsen-van
amplification of oxidative degradation of lipids, proteins, nucleic acid, hydro Groningen5, Alexander Weidemann6, Chandra Mohan1, Hien V. Nguyen1, Jan
carbonates and in alteration of endogenous strategies for suppression /modulating Ulrich Becker7
oxidative stress. The defective DNA repair mechanism via OGG1 and the reduced 1
University of Houston, Department of Electrical and Computer Engineering, Houston,
regulatory effect of sRAGE in activation AGE-RAGE axis in LN group versus non-LN TX, United States of America, 2Imperial College London, Department of Immunology
could explain alteration of renal architecture and development of renal injury. and Inflammation, London, United Kingdom, 3Columbia University, Department of
Pathology and Cell Biology, New York, NY, United States of America, 4University
Hospital of Cologne, Institute of Medical Statistics and Bioinformatics, Köln, Germany,
5
MO077 AUTOMATIC SEGMENTATION OF ARTERIES, ARTERIOLES Erasmus Medical Center, Department of Pathology, Rotterdam, The Netherlands,
6
AND GLOMERULI IN NATIVE BIOPSIES WITH THROMBOTIC Kliniken der Stadt Köln, Medizinische Klinik I, Köln, Germany and 7University Hospital of
MICROANGIOPATHY AND OTHER VASCULAR DISEASES Cologne, Institute of Pathology, Köln, Germany

Brendon Lutnick1, Katharina Moos2, Surya V. Seshan3, Jesper Kers4, BACKGROUND AND AIMS: Antibody-mediated rejection (AMR) is among the
Joris Roelofs4, Martin Hellmich2, Savino Sciascia5, Pietro Antonio Cicalese6, most common causes for kidney transplant loss. The histological diagnosis is
Brandon Ginley1, Pinaki Sarder1, Jan Ulrich Becker7 hampered by significant intra- and interobserver variability. Training a deep learning
1 classifier for the recognition of AMR on glomerular transections as the most decisive
Department of Medicine, The State University of New York, Pathology and Anatomical
Sciences, Buffalo, United States of America, 2University of Cologne, IMSIE, Köln, compartment could establish a reliable and perfectly reproducible diagnostic method.
Germany, 3Weill Cornell Medicine, Department of Pathology, New York, United States METHOD: We identified 48 biopsies with AMR (all positive for donor-specific
of America, 4Amsterdam Medical Center, Department of Pathology, Amsterdam, The antibody) and 38 biopsies without AMR according to Banff 2017 from our archive.
Netherlands, 5University of Turin, Department of Clinical and Biological Sciences, Center Photographs were taken from all non-globally sclerosed glomeruli on two PAS-stained
of Research of Immunopathology and Rare Diseases and SCDU Nephrology and level sections, yielding a total of 1,655 images as a training set. 1,503 images could be
Dialysis, Turin, Italy, 6University of Houston, Cullen School of Engineering, Houston, labeled by three experienced nephropathologists conclusively as AMR or non-AMR in
United States of America and 7University Hospital of Cologne, Institute of Pathology, a blinded fashion.We trained a DenseNet-121 classifier (pre-trained on ImageNet) with
Köln, Germany basic online augmentation. In addition, we implemented StyPathþþ, a data
augmentation algorithm that leverages a style transfer mechanism, addressing
BACKGROUND AND AIMS: Thrombotic microangiopathies (TMAs) manifest significant domain shifts in histopathology. Each sample was assigned a consensus
themselves in arteries, arterioles and glomeruli. Nephropathologists need to label generated by the pathologists.
differentiate TMAs from mimickers like hypertensive nephropathy and vasculitis RESULTS: Five-fold cross validation schemes produced a weighted glomerular level
which can be problematic due to interobserver disagreement and poorly defined performance of 88.1%, exceeding the baseline performance by 5%. The improved
diagnostic criteria over a wide spectrum of morphological changes with partial overlap. generalization ability of the StyPathþþ augmented model shows that it is possible to
As a first step towards a machine learning analysis of TMAs, we developed a computer construct reliable glomerular classification algorithms with scarce datasets.
vision model for segmenting arteries, arterioles and glomeruli in TMA and mimickers. CONCLUSION: We created a deep learning classifier with excellent performance and
METHOD: We manually segmented n=939 arteries, n=6,023 arterioles, n=4,507 reproducibility for the diagnosis of AMR on glomerular transections. We plan to
glomeruli on whole slide images (WSIs) of 34 renal biopsies and their HE, PAS, expand the training set, including challenging cases of differential diagnoses like
trichrome and Jones sections (19 TMA, 11 hypertensive nephropathy, 4 vasculitis with glomerulonephritis or other glomerulopathies. We are also interested in external
preglomerular involvement). As a segmentation model we used DeepLab V3, clinicopathological datasets to further validate our results.
pretrained on 61,734 segmented glomeruli from 768 WSIs. 58 randomly chosen WSIs
served as the intrainstitutional holdout testing set after training of the model on the
remaining slides. Automatic segmentation accuracies were reported as Cohen’s kappa,

i126 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO079 SOY PROTEINS PREVENT HEART REMODELING IN WISTAR
RATS ON HIGH SODIUM CHLORIDE DIET diagnosis, between 2013 and 2018. Several histopathological data were analysed,
including percentage of cellular, fibrocellular and fibrous crescents; presence of
Olga Beresneva1, Marina Parastaeva1, Galina Ivanova2, Aleksander Kulikov3, fibrinoid necrosis, interstitial hemorrhage, tubular atrophy ant interstitial fibrosis.
Anatoly Kucher4, Kirill Smirnov4, Mokhamad Khasun4, Ivan Kayukov,5 Clinical data such as need of dialysis at presentation and death, during a 2 year follow
1
First Pavlov St.-Petersburg State Medical University Institute of Nephrology Laboratory up period, were also examined.
of Clinical Physiology of the Kidney , Saint Petersburg, Russia, 2I. P. Pavlov Institute of The patients were classified accordingly to the histopathological Berden classification.
Physiology, Russian Academy of Sciences, Saint Petersburg, Russia, 3First Pavlov St.- For statistical analysis purposes they were divided in two groups: mixed and non-
Petersburg State Medical University, Research and clinical research center, Department mixed.
of clinical physiology and functional diagnostics, head, Saint Petersburg, Russia, 4First Categorical variables are presented as frequencies and percentages, continuous
Pavlov St.-Petersburg State Medical University Institute of Nephrology, Saint Petersburg, variables as means and standard deviations, or medians and interquartile ranges (IQR)
Russia and 5First Pavlov St.-Petersburg State Medical University Institute of Nephrology for variables with skewed distributions. Statistical analysis was performed using SPSS
Laboratory of Clinical Physiology of the Kidney, Saint Petersburg, Russia version 25 for Windows.
RESULTS: We observed 51 ANCA GN kidney biopsies: 68.5% (n=35) from mixed,
BACKGROUND AND AIMS: Increased salt intake has been linked to a number of 11.8% (n=6) from crescentic and sclerotic and 7.8% (n=4) from focal category. In
poor effects, such as myocardial remodeling [1], independently of blood pressure level. average, the biopsies contained 10.464.8 glomeruli. The percentage of fibrous
Yet, many aspects of this remodeling are not well understood. The aim of the study was crescents was significantly higher in mixed than non-mixed group (16.1618.6% vs
to find echocardiographic myocardial changes in Wistar rats on high sodium chloride 7.2617.9%; p=0.037). Although not statistically significant, the percentage of
(NaCl) diet, as well as to prove protective effects of diet, containing soy proteins. fibrocellular crescents was higher (10.3620.9 vs 6.2612.5; p=0.512) and the percentage
METHOD: 28 male Wistar rats (age of 2.5-3.0 months) were enrolled in the of cellular crescents was lower (15.4618.2 vs 34.3637.7; p=0.072) in mixed group. The
observational prospective study (4 month) and subdivided into several groups. 1) presence of fibrinoid necrosis (54.3% vs 87.5%; p=0.021) and fibrinoid necrosis with
Standard diet-Control group (C, n = 8, 20.16% protein of animal origin and 0.34% cellular crescents (34.3% vs 68.8%; p=0.022) were both lower in mixed category.
NaCl); 2) High salt diet (n = 10, 8% NaCl); 3) Low-protein diet (n=10, 10% soy protein There was no difference in the need of dialysis at presentation between both groups,
(SUPRO 760) and 8% NaCl). but the percentage of fibrous crescents was a predictor of dialysis induction at
Tail systolic blood pressure (BP) measurement, as well as echocardiographic admission in all cases [p=0.009; adjusted odds ratio (OR) 1.053 (CI: 1.013–1.096)].
examination were performed in anesthetized rats. Statistical analysis was performed Deaths were significantly higher in mixed group (34.3% vs 6.3%; p=0.033).
with STATISTICA 10 software package. Fisher’s LSD test was used. The significance CONCLUSION: There are other morphological aspects that seem to be relevant in the
level was <0.05. All data are presented as mean 6 SEM. characterization of different histological classes of ANCA GN. Having more chronic
RESULTS: Keeping rats on a diet with 8% NaCl did not lead to significant changes in lesions, like the percentage of fibrous crescents, and a less frequency of acute lesions,
blood pressure (group 2 - 138.0 þ 5.0, group 3 - 134.0 þ 5.0 mm Hg), compared to C such as fibrinoid necrosis, proved to be relevant in the mixed group and may be
(135.0 þ 5.0 mm Hg). On the contrary, left ventricle back wall width in rats of group 2 associated to the higher mortality in this class. Besides, the percentage of fibrous
was significantly higher (1.83 6 0.09 mm, p <0.02), than in C (1.49 6 0.10 mm) or crescents was itself a predictor of the need of dialysis, which highlights the importance
animals from group 3 (1, 47 6 0.09mm). of assess other characteristics, in addition to those included in the current ANCA GN
The values of end systolic left ventricle size, interventricular septum width, mitral valve classification. However, further studies and larger samples are needed to evaluate better
systolic movement and tricuspid valve systolic movement in group 3 were the importance of other morphological features in this classification and their influence
significantly lower (1.67 6 0.08 mm, 2.18 6 0.13 mm, 2.70 6 0.23 mm), than in group on survival and renal outcome of these patients.
2 (3.26 6 0.33mm, p <0.037; 2.00 6 0.12mm, p <0.043; 2.67mm 6 0.15, p <0.0124;
3.56 6 0.34mm , p <0.0148, respectively). At the same time, left ventricular chamber
size and thickness of interventricular septum did not differ significantly. In C animals, MO081 THE INFLUENCE OF VITAMIN D3 ON PODOCYTE
mitral valve movement (1.96 6 0.09 mm; p <0.0008) and tricuspid valve movement DIFFERENTIATION IN SITU AND IN VITRO
(2.35 6 0.07 mm; p<0.0012) were significantly lower than in rats of group 2 but not
differed much from the values found in group 3. Tim Lange1, Laura Kuhn1, Marie-Christin Böttcher1, Stefan Simm2,
CONCLUSION: High sodium containing diet does not necessarily lead to the Elke Hammer3, Lars Kaderali2, Uwe Völker3, Claudia Weber1, Karlhans Endlich1,
development of arterial hypertension in Wistar rats, but may cause heart remodeling, Nicole Endlich1
while soy proteins counteracts the development of left ventricle hypertrophy, even in 1
case of high sodium consumption. Department of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald,
Germany, 2Institute of Bioinformatics, University Medicine Greifswald, Greifswald,
Germany and 3Interfaculty Institute for Genetics and Functional Genomics, University
Medicine Greifswald, Greifswald, Germany
MO080 HISTOLOGIC CLASSIFICATION OF ANCA-ASSOCIATED
GLOMERULONEPHRITIS – ARE THERE OTHER BACKGROUND AND AIMS: Dedifferentiation of podocytes affects their complex 3
MORPHOLOGICAL FEATURES THAT CAN BETTER D morphology and is the main initiator for the development of chronic kidney disease
DESCRIBE MIXED GROUP? (CKD). Unfortunately, there is no causal therapy for CKD until today. Thus,
inadequate and late treatment lead to end-stage renal disease which subsequently
Catia Figueiredo1, Patricia Valerio2, Teofilo Yan3, Helena Sousa4, M is4,
ario Go makes renal replacement therapy inevitable. To address this, new treatment options are
Fernando Nolasco4 of high significance for CKD patients. Recently, vitamin D3 (VitD) became a
1
Rainha Santa Isabel Hospital - Centro Hospitalar Médio Tejo, EPE, Nephrology, Torres promising candidate, but it is controversially discussed. In the present study, we
Novas, Portugal, 2Sao Bernardo Hospital - Centro Hospitalar de Setubal, Nephrology, investigated the influence of VitD on podocyte differentiation and the related pathways
Setubal, Portugal, 3Amato Lusitano Hospital, Nephrology, Castelo Branco, Portugal and in situ and in vitro.
4
Curry Cabral Hospital - Centro Hospitalar Lisboa Central, Nephrology, Lisbon, Portugal METHOD: We combined a podocyte dedifferentiation model (GlomAssay) with an
automated imaging procedure (Aquifer Imaging Machine). We analyzed cultured
BACKGROUND AND AIMS: In 2010 a new histopatological classification for glomeruli from transgenic mice expressing cyan-fluorescent protein (CFP) under the
ANCA-associated GN (ANCA GN) was developed – the Berden classification. It is control of the nephrin promoter which were treated with VitD and itsanalogue
composed of four categories – focal, crescentic, sclerotic and mixed - based on the (calcipotriol). In this model, the decreasing CFP fluorescence is as a read out for
predominance (50%) of normal glomeruli, cellular crescents, and globally sclerotic podocyte (de)differentiation. Additionally, VitD-, calcipotriol- and VitD receptor
glomeruli, respectively. The mixed category, related to an intermediate renal outcome, (VDR) inhibitor (PS121912)-treated glomeruli were investigated by RNA-Seq and LC-
has no glomerular feature predominating. Our aim was to evaluate other MS/MS to reveal the molecular effects of VitD on podocyte differentiation.
histopathological characteristics that could be significant in the mixed group and their Furthermore, we treated cultured murine podocytes with VitD, calcipotriol and
impact on survival and renal outcome. PS121912 to elucidate the morphological and molecular changes by
METHOD: This is a multi-center retrospective observational study which included immunofluorescence staining, RT-qPCR and Western blot.
patients with ANCA GN who were submitted to kidney biopsy at the time of clinical

10.1093/ndt/gfab078 | i127
Abstracts Nephrology Dialysis Transplantation

RESULTS: VitD- and calcipotriol-treated glomeruli showed a significantly higher (AAV). We have previously reported that severe deterioration of kidney function is
intensity of CFP fluorescence after 9 days, indicating higher level of nephrin compared associated with necrotizing and crescentic ANCA glomerulonephritis (GN), classified
to the control. This was verified by RT-qPCR and Western blot for nephrin and CFP. into Berden’s crescentic class or ANCA renal risk score (ARRS) high risk. However,
Additionally, we found an upregulation of VDR in VitD- and calcipotriol-treated tubulointerstitial inflammation associated with either histopathological subgrouping or
glomeruli compared to controls. By transcriptomic and proteomic analysis, we ARRS remains elusive. Furthermore, clinical and laboratory markers of AAV disease
identified molecular patterns that are specific for the different treated groups. Thus, we severity or deterioration of kidney function in association with inflammatory findings
observed differential gene expression in VitD- and Wnt-signaling pathway as well as in the kidney have not been described yet. Since aggressive immunosuppressive
regulated genes that are essential for the actin cytoskeleton, focal adhesion formation therapy is recommended for remission induction especially in severe cases of AAV, we
and the slit membrane. Beside this, cultured podocytes showed a significant here aimed to expand our current knowledge with regard to histopathological
upregulation of the slit membrane protein nephrin, VDR and CYP24A1 by VitD. This classification of tubulointerstitial injury and inflammatory findings analogous to the
is accompanied by an altered morphology of the podocytes due to a reorganization of Banff classification.
the actin cytoskeleton. METHOD: A total number of 50 renal biopsies with confirmed renal involvement of
CONCLUSION: Our results show that VitD influences podocyte differentiation in situ AAV were retrospectively included between 2015 till 2020 in a single-center
and in vitro by the regulation of specific signaling pathways. observational study. Renal biopsies were evaluated for either focal, crescentic, mixed or
sclerotic class (according to Berden et al.) and ARRS low, intermediate or high risk
(according to Brix et al.). Inflammatory and fibrotic tubulointerstital alterations were
evaluated analogous to Banff scoring system for allograft pathology.
MO082 THE EFFECTS OF DIFFERENT MICROMOLAR
RESULTS: We here show that distinct inflammatory lesions are associated with
CONCENTRATIONS OF CADMIUM IONS ON THE
glomerular findings classified into either histopathological subgrouping or ARRS.
PERITUBULAR MEMBRANE POTENTIAL OF PROXIMAL
Furthermore, interstitial inflammation and tubulitis correlate with disease severity and
TUBULAR CELLS IN PERFUSED FROG KIDNEYS
decline of kidney function in AAV. Finally, we provide data that tubulointerstitial
injury and inflammatory findings correlate with short-term outcome in response to
Sanjin Kovacevic1, Svetolik Spasic1, Srdjan Lopicic1, Jasna Todorovic1,
aggressive immunosuppression and remission induction therapy.
Marko Dincic1, Marija Stanojevic1, Jelena Nesovic - Ostojic1
1
CONCLUSION: In summary, we here provide evidence that a systematic scoring of
Medical Faculty, University of Belgrade, Department of Pathophysiology, Belgrade, inflammatory and degenerative tubulointerstitial lesions correlate with severe renal
Serbia impairment and short-term response to remission induction therapy. Since aggressive
immunosuppressive therapy is recommended for remission induction especially in
BACKGROUND AND AIMS: Cadmium (Cd2þ) is toxic metal and environmental severe cases of AAV, systematic histopathological scoring of tubuloinsterstital lesions
pollutant. Accumulation of cadmium in the kidney results initially in proximal tubule could further improve our current knowledge of ANCA GN progression.
dysfunction. Although Cd2þ toxicity is well documented, all mechanisms that are
involved in the early stages of nephrotoxicity, especially considering low micromolar
concentrations of Cd2þ ions are still unknown. The Aim of this study was to investigate
MO084 THE INFLUENCE OF INTRAVENOUS CORTICOSTEROIDS ON
the effects acute exposure to different peritubular micromolar concentrations of
PLASMA SIRTUIN-1 AND SCLEROSTIN LEVELS IN PATIENTS
cadmium (0.25, 0.50, 1.0, 2.0, 3.0, 5.0 lmol/L) on the peritubular cell membrane
WITH PRIMARY GLOMERULAR DISEASE
potential in proximal tubular cells of frog kidney.
METHOD: The experiments were performed on isolated, doubly perfused kidneys of
Katarzyna Peczek1, Michal Nowicki1
Rana esculenta of both sexes. Aortic and portal vein were cannulated in order to 1
perfusate luminal and peritubular cell membraine. In controled conditions, Ringer Medical University of Lodz, Department of Nephrology, Hypertension and Kidney
solution was simultaneously used to perfusate both cell membraines. Cadmium Transplantation, Lodz, Poland
chloride (different concentrations: 0.25, 0.50, 1.0, 2.0, 3.0, 5.0 lmol/L) were added to
the peritubular perfusate separately, by switching the peritubular perfusate from the BACKGROUND AND AIMS: SIRT-1 is member of seven protein family that are
control Ringer solution to Ringer solution with addition of cadmium ions. Peritubular involved in the cellular response to inflammatory, metabolic, and oxidative stress. The
cell membrane potentials (PD) were measured with conventional 3 mol/L KCl sirtuin family is a group of class III histone deacetylases. The best known of the family
microelectrodes. is SIRT-1. It may induce organ protection through inactivation of apoptosis and anti-
RESULTS: The peritubular application of different micromolar Cd2þ concentrations inflammatory action.
led to a rapid, sustained, reversible hyperpolarization of the peritubular cell membrane: Sclerostin is a glycoprotein produced by the osteocytes and an inhibitor of Wnt
0.25 mmol/L, by 3.360.4 mV (n=8, p<0.001); 0.50 mmol/L, by 3.060.5 mV (n=11, signaling. Increased activity of sclerostin increases the resorption of bone tissue and
p<0.001); 1.0 mmol/L, by 2.960.6 mV (n=8, p<0.01); 2.0 mmol/L, by 4.260.4 mV inhibits osteogenesis. It has been hypothesized that by deacetylating histones SIRT-1
(n=13, p<0.01); 3.0 mmol/L, by 3.460.3 mV (n=14, p<0.001); 5.0 mmol/L, by could negatively regulate sclerostin gene. That mechanism requires a confirmation in
3.060.4 mV (n=10, p<0.001). After switching the perfusion from Ringer solution clinical setting.
with addition of cadmium ions to control Ringer, the peritubular membraine potential This exploratory study was designed to assess the influence of high doses of
returned to the average values that were maintained before the peritubular Cd2þ intravenous methylprednisolone on plasma SIRT-1 and sclerostin levels in patients
application (p>0.05). Comparing the effect of different Cd2þ concentrations, there was with primary glomerular disease.
no difference in the hyperpolarization of the peritubular cell membrane (p>0.05).Each METHOD: The study included 40 patients (25 M, 15 F; mean age 53.1614 years,
cell served as its own control. mean eGFR 58.9631.3 ml/min) in different stages of chronic kidney disease. 20
CONCLUSION: Different low micromolar concentrations of Cd2þ provoked rapid patients had eGFR below the median value of 46 ml/min. The main inclusion criterion
and sustained hyperpolarization of peritubular membrane potential that did not show was the clinical and histopathological diagnosis of primary glomerular disease and
concentration-dependent response. urine protein excretion >2.0 g/24h. The main biopsy-proven diagnoses were IgA
nephropathy (13 patients) and focal segmental glomerulonephritis (FSGS) (13
patients). The patients were hospitalized to receive scheduled intravenous pulses of
methylprednisolone 20-30 mg/kg/day for three consecutive days followed by oral
MO083 SYSTEMATIC HISTOLOGICAL SCORING OF
prednisone 0.8-1.0 mg/kg/day.
TUBULOINTERSTITIAL LESIONS CORRELATE WITH
The blood was taken before the administration of methylprednisolone to assess SIRT-
CLINICAL PARAMETERS IN ANCA-ASSOCIATED
1, sclerostin, calcium, phosphate and PTH and urine for was taken for the
GLOMERULONEPHRITIS
measurement of calcium, phosphate and albumin to creatinine ratio. The same
laboratory tests were repeated after 4, 7 and 30 days of steroid therapy.
Björn Tampe1, Samy Hakroush2
1
RESULTS: Plasma SIRT-1 during increased significantly during steroid administration
University Medical Center Göttingen, Department of Nephrology and Rheumatology, (Fig.1). Plasma sclerostin did not change significantly during the study however a
Göttingen, Germany and 2University Medical Center Göttingen, Institute of Pathology, statistically significant correlation between the changes of SIRT-1 levels and sclerostin
Göttingen, Germany

BACKGROUND AND AIMS: Renal involvement is a common and severe


complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

i128 | Abstracts
Nephrology Dialysis Transplantation Abstracts
was found. In a multiple regression model the changes of plasma sclerotin induced by
steroid therapy explained the largest part of the variance of the respective changes of
plasma SIRT-1.

MO084 Figure 1: Plasma SIRT-1 during steroid therapy

CONCLUSION: Plasma SIRT-1 increases during high-dose corticosteroids therapy.


The negative relation between the changes of plasma SIRT-1 and plasma sclerostin
may suggest a protective role of SIRT-1 against the rapid bone loss induced by
corticosteroids.
MO085 Figure 1: Study flow of MPGN patients with paraproteinemia

MO085 MONOCLONAL GAMMOPATHY OF UNKNOWN


SIGNIFICANCE AMONG MEMBRANOPROLIFERATIVE RESULTS: MGUS was diagnosed in 15/60 (25%) of patients. Clinical variables are
GLOMERULONEPHRITIS PATIENTS summarized in Table 1. The mean age at presentation was 59 years (37-79), 47-% were
males. Smoldering myeloma was diagnosed in 2 (13%) patients and overt malignancy
Marja Kovala1, Minna Seppala2, Kati Kaartinen2, Seppo Meri3, Eero in 3 (20%) patients.
Olavi Honkanen2, Anne Ra €nen-Sokolowski1
€isa
1
Helsinki, Department of Pathology, Helsinki University Hospital and Helsinki University,
Helsinki, Finland, 2Helsinki, Department of Nephrology, Helsinki University Hospital and
Helsinki University, Helsinki, Finland and 3Helsinki, Department of Immunology, Helsinki MO085 Table 1. Demographic clinical variables at the time of diagnostic renal
University Hospital and Helsinki University, Helsinki, Finland biopsy in MPGN patients. Values are expressed a means (range) or as number of
patients (percentage). Overt malignancy denotes multiple myeloma, chronic
lymphocytic leukemia, marginal zone lymphoma, and lymphoma. MGUS=
BACKGROUND AND AIMS: Monoclonal gammopathy is an entity where a B-cell or monoclonal gammopathy of undetermined significance. MGRS= monoclonal
plasma cell clone produces monoclonal immunoglobulin. When paraproteinemia and gammopathy of renal significance.
a kidney disease is discovered without criteria for treatment of haematological
malignangy, the entity is called monoclonal gammopathy of unknown significance
(MGUS) or of renal significance (MGRS). It can cause variable histology, among which Variable MPGN, n=
membranoproliferative glomerulonephritis (MPGN) has been described. Direct 15
entrapment of paraprotein in glomeruli/tubules can be observed by Age (range) 59 (37-79)
immunofluorescence (IF), but IF can also be negative as paraprotein can cause
complement-associated disease by acting as an activator of the classical pathway or as a Male sex, n (%) 7 (47)
dysregulator of the alternative pathway. Electron microscopy (EM) is needed to Paraprotein finding
differentiate possible organized deposits.
METHOD: We investigated the prevalence, clinical parameters, histology, and the type
Only in blood, n (%) 11 (73)
of monoclonal gammopathy in biopsy-proven MPGN between 2006-2017. A total of Only in urine, n (%) 1 (7)
15 adult patients with a detected urine and/or serum paraprotein with concurrent Both in blood and urine, n (%) 3 (20)
biopsy-proven diagnosis were discovered among 60 patients (Figure 1). Two
diagnostic biopsies were from transplants. Type of paraprotein
IgG kappa, n (%) 7 (47)
IgG lambda, n (%) 1 (7)
IgM kappa, n (%) 3 (20)
IgM lambda, n (%) 2 (13)
Two serum paraproteins, n (%) 1 (7)
Kappa light chain only, n (%) 1 (7)
Classification of hematologic disease
MGRS or MGUS, n (%) 10 (67)
Smoldering myeloma, n (%) 2 (13)
Overt, malignany, n (%) 3 (20)

Histological features are summarized in Table 2. There were 7 (47%) with dominant
staining for C3 (6 with C3 glomerulonephritis, 1 Dense Deposition Disease) and 8
(53%) with dominant staining for Ig, of which 4 (31%) had mesangioproliferative, 4
(31%) membranoproliferative, 3 (23%) minimal change, 2 (15%) crescentic and 1 (8%)
exudative pattern in light microscopy (LM). Seven (47%) biopsies, which did not stain
for kappa or lambda light chains. The most common EM deposit location was
subendothelial (69%).

10.1093/ndt/gfab078 | i129
Abstracts Nephrology Dialysis Transplantation

MO085 Table 2. Histological findings at diagnostic biopsy. MO087 PLASMALEMMAL VESICLE-ASSOCIATED PROTEIN-1
(PLVAP) INDICATES THE FORMATION OF DIAPHRAGM-
BRIDGED FENESTRATIONS OF GLOMERULAR
Variable Result ENDOTHELIAL CELLS IN KIDNEY DISEASE
Morphology, n (%) 14* (93) Björn Tampe1, Laura Schridde2, Samy Hakroush2
Crescentic, n (%) 2 (15) 1
University Medical Center Göttingen, Department of Nephrology and Rheumatology,
Minimal histology, n (%) 3 (23) Göttingen, Germany and 2University Medical Center Göttingen, Institute of Pathology,
Göttingen, Germany
Excudative, n (%) 1 (8)
Mesangioproliferative, n (%) 4 (31) BACKGROUND AND AIMS: Plasmalemmal vesicle-associated protein-1 (PLVAP or
Membranoproliferative, n (%) 4 (31) PV-1) is a major protein of diaphragm-bridged fenestrated endothelial cells found in
IF staining, n (%) 15 (100) capillaries of neuroendocrine glands and peritubular capillaries. In contrast to
peritubular capillaries, the glomerulus is known for its unique fenestrated endothelium
C3 dominant, n (%) 7 (47) without any diaphragm formation thereby ensuring free filtration. Here we aimed to
Ig dominant, n (%) 8 (53) investigate whether PLVAP is expressed in glomerular endothelial cells in various
glomerular diseases and whether PLVAP expression is associated with the formation of
Kappa, n (%) 6 (40) diaphragm-bridged endothelial cells.
Lambda, n (%) 6 (40) METHOD: A total number of 114 biopsy samples of glomerular diseases including
No kappa or lambda staining, n (%) 6 (40)** diabetic nephropathy, FSGS, IgA-Nephritis, ANCA-GN and Lupus–Nephritis were
analyzed immunohistochemistically for glomerular PLVAP expression. A fraction of
Any deposits on EM, n (%) 10 (77) PLVAP positive cases was subsequently investigated ultrastrucurally for the formation
Subendothelial, n (%) 9 (69) of diaphragm-bridged glomerular endothelial cells.
Subepithelial, n (%) 3 (23) RESULTS: One third of all cases showed at least one glomerulus with one single
circumferential PLVAP staining. Interestingly, the most prominent staining, affecting
Intramembranous, n (%) 4 (31) the entire glomerular tuft, was observed in diabetic nephropathy and ANCA-GN.
Mesangial, n (%) 5 (38) Ultrastructurally, such cases exhibited injured endothelium with focal detachment
from the glomerular basement membrane, loss of pore formation and frequently
*One biopsy lacked sufficient light microscopy material, **One frozen diaphragm-bridged fenestrations reminiscent of peritubular capillaries.
CONCLUSION: Our data show that injured glomerular endothelium is capable of
section biopsy was not dyed with kappa or lambda stains forming true diaphragm-bridged fenestrations, suggesting a possible role in preventing
glomerular protein leakage and limiting its detachment from the GBM.
CONCLUSION: MPGN was associated with a significant risk of underlying
monoclonal gammopathy, as many (25%) patients were diagnosed with concurrent
MGUS. When MPGN is observed, it should prompt investigations of the possible MO088 CLINICOPATHOLOGICAL FEATURES OF THROMBOTIC
underlying monoclonal gammopathy and possibly, hematological neoplasm. MICROANGIOPATHY

Maria Do Mar Menezes1, Elsa Soares2, Helena Viana1, Ma is1,


rio Go
MO086 THE EFFECT OF HIGH SODIUM CHLORIDE INTAKE ON Fernando Nolasco1
1
CARDIOVASCULAR SYSTEM AND KIDNEYS IN Hospital Curry Cabral, Nephrology Department, Lisboa, Portugal and 2Hospital S~
ao
SPONTANEOUSLY HYPERTENSIVE RATS Bernardo, Nephrology Department, Setubal, Portugal

Ivan Kayukov,1, Olga Beresneva2, Marina Parastaeva2, Galina Ivanova3, BACKGROUND AND AIMS: TMA is a rare and severe endothelial lesion with
Mikhail Zaraiski4, Anatoly Kucher1, Kirill Smirnov1, Mokhamad Khasun1, thrombus formation and vascular occlusion with organ damage. It can be a
Alexei Smirnov5 complication of several clinical conditions. The aim of this study was to characterize
1
First Pavlov St.-Petersburg State Medical University Institute of Nephrology, Saint clinical and pathological findings of patients with confirmed kidney TMA.
Petersburg, Russia, 2First Pavlov St.-Petersburg State Medical University Institute of METHOD: We performed a retrospective observational descriptive study that
Nephrology Laboratory of Clinical Physiology of the Kidney, Saint Petersburg, Russia, analyzed all patients with TMA diagnosed by kidney biopsy, in two hospital centers,
3
Pavlov Institute of Physiology Russian Academy of Sciences, Laboratory of physiology from January 2015 until December 2020. Clinical, laboratorial, pathologic
of cardiovascular and lymphatic systems, Saint Petersburg, Russia, 4Department of characteristics were analyzed as also therapeutic performed and kidney and patient
Clinical Laboratory Diagnostics with a Course of Molecular Medicine, First Pavlov State outcomes.
Medical University of St. Petersburg, Saint Petersburg, Russia and 5Pavlov University, RESULTS: Our sample had 14 patients, the majority female (n=11, 78%) with a mean
Research Institute of Nephrology, Director, Saint Petersburg, Russia age of 45610 years-old and 12 (80%) were Caucasian. Six (40%) had past medical
history of HTA, 2 (13%) had Multiple Myeloma, 4 (26%) transplant (3 kidney, 1 lung)
BACKGROUND AND AIMS: It is believed that high consumption of sodium and none had positive viral serology’s. Prodromal symptoms included diarrhea in 2
chloride (NaCl) leads to the development of arterial hypertension, which result in heart (13%) patients, neurological in 3 (20%) and previous infection in 3 (20%).
remodeling, however, NaCl can probably cause direct heart damage. We aimed to Mean laboratorial values were: Hemoglobin 7.8 g/dL, platelets 161.000/uL; LDH 586
evaluate the effects of high and normal NaCl containing diets on blood pressure (BP), UL; bilirubin 1.38 mg/dL, haptoglobin 1,55 g/L. Only 5 had schistocytes. ADAMTS13
myocardial remodeling, as well as on the level of nuclear transcription factor jB activity was >10% in all performed and in all, Coombs test were negative.
(NFjB) expression in myocardium and kidneys. C3 was consumed in 3 (20%) patients and C4 in 2 (13%) but complement phenotypic
METHOD: 49 spontaneously hypertensive rats (SHR) were enrolled and subdivided study was normal in all performed patients. Auto-immune study revealed: 1 positive
into 2 groups: Group 1 (n=24) received standard diet (NaCl=0,34%); Group 2 (n=25) ANA, dsDNA negative in all but one with positive c1q antibody. One had positive
was on high sodium diet (NaCl=8%). In 2 months, systolic BP, myocardial and renal antiphospholipid syndrome (AFS) antibodies and one scleroderma antibodies.
mass indices, morphological changes, as well as NFjB expression in heart and kidneys Main kidney presentation was acute kidney injury in 8 (53%) patients, with mean
were assessed. Results are presented as mean 6 SD. eGFR 14ml/min/1,73m2. Mean proteinuria was 2,5 g/24h and half (50%) had
RESULTS: BP in group 2 did not change significantly (190 6 10 mm Hg, p> 0.05) hematuria.
compared to group 1, yet left ventricle muscle mass indices as well as, right and left Kidney biopsies had a mean of 11,85 glomerulus, of which 14% sclerotic, mean
kidney mass indices were higher. Hypertrophy of cardiomyocytes (CMC) was found in interstitial fibrosis and tubular atrophy score 1,7. Acute tubular necrosis was present in
group2: (area of the nucleus- 43.55 6 17.39 lm2 (p <0.001); area of CMC-21799.31 6 7 (46%) and inflammatory infiltrate in all, endotheliosis in 13 (86%), mesangiolysis in 3
579.89 lm2 (p <0.001), compared to group 1: (area of the nucleus- 36.14 6 4.67 lm2 (20%), arteriolar thrombus in 10 (66%), glomerular thrombus in 6 (40%), ischemic
(p <0.001); area of CMC-19011.13 6 571.8 lm2 (p <0.001). Also, perivascular fibrosis glomerulus in 12 (80%) and double-contour appearance in 7 (46%).
was found in group2 (area of perivascular connective tissue(APCT)- 4038.96 6 28.58 TMA etiologies were the following: 2 malignant hypertension, 2 proteasome inhibitor
lm2 (p <0.001), compared to group1 (APCT-3718.36 6 91.8 lm2, p <0.001). An (PI), 1 scleroderma, 1 lupus, 1 AFS, 2 calcineurin and mammalian target of rapamycin
increase in arterial wall thickness was noted in group 2 (15.71 6 6.28 lm, p<0,001), inhibitors, 2 antibody mediated rejection (AMR), 1 methylmalonic acidemia and 2
compared to group 1 (13.51 6 8 ,68 lm, p<0,001). The expression level of NFjB in undetermined.
myocardial tissue (n = 7) in group 2 was 33 times higher, and in kidney tissue (n = 5) Treatment performed encompassed: hypertension management, withdrawal od PI,
12 times higher than in group 1 (n = 8). changing immunosuppression, AMR treatment, cyanocobalamin, lupus induction
CONCLUSION: High consumption of NaCl induces NFjB activation in kidneys and treatment and eculizumab.
myocardium, and may cause myocardial remodeling, probably via NFjB - associated Kidney recovery was observed in 8 patients (53%). Patient survival at 6 months was
signaling pathways. 73%.

i130 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: These study results highlight the vast context of conditions that TMA because of intracranial haemorrhage (17 donors) or cerebral trauma due to accident
can appear. Most of them had only with mild or even absent clinical and laboratory (23 donors). Histomorphometric analysis was performed using “Olympus BX51”
features. Therefore, a high index of suspicion is required to diagnose TMA, allowing microscope (Olympus, Tokyo, Japan) coupled with “Olympus BX50” camera and the
targeted treatment to preserve of kidney function. “cellSens Standard” software (Olympus, Tokyo, Japan). Weibel-Gomez formula was
adapted to calculate glomerular volume.
RESULTS: No significant differences were found between mean kidneys length [115.8
(112.4-119.1) vs.115.5 (112.5-118.5) mm], glomerular volume [2.59 (2.24-2.93) vs 2.49
MO089 HISTOMORPHOMETRIC ANALYSIS OF GLOMERULI AND
(2.15-2.84) lm3 x106 ], glomerular density [3.43 (3.07-3.80) vs 3.24 (2.87-3.61) n/
CAPILLARIES DENSITY IN THE INTERSTITIUM IN
mm2] and interstitial capillaries density [233.58 (211.26) vs 217.80 (199.45-236.47) n/
PREIMPLANTATION NEEDLE BIOPSIES OF PAIRED KIDNEYS
mm2] of both kidneys harvested from the same deceased donor.
HARVESTED FROM ADULT CADAVERIC DONORS
CONCLUSIONS: 1. Both kidneys harvested from the same deceased donor did not
differ significantly in kidney length, glomerular volume, glomerular density and
Marcin Adamczak1, Katarzyna Kwiecien1, Henryk Karkoszka1, Robert Krol2,
capillary density. 2. Our results justify to preimplantation biopsy of only one kidney
Andrzej Jan Wiecek1
1
and the results from the histomorphometric analysis may be used in the future also for
Medical University of Silesia in Katowice, Department of Nephrology, Transplantation assessment of the second kidney.
and Internal Medicine, Katowice, Poland and 2Medical University of Silesia in Katowice,
Department of General, Vascular and Transplant Surgery, Katowice, Poland

MO090 TRANSPLANT KIDNEY BIOPSY FINDINGS IN COVID-19: A


BACKGROUND AND AIMS: Preimplantation needle biopsy of kidney allows more
SYSTEMATIC REVIEW
precise interpretation of subsequent kidney biopsies performed after transplantation
and potentially also may predict kidney graft survival. It is unknown, whether it is
Henry Wu1,2, Vishnu Jeyalan1, Rajkumar Chinnadurai1, Arvind Ponnusamy1
justified to perform the biopsy of one kidney only and then to transmit obtained results 1
also to the second kidney or biopsies of both kidneys are mandatory. The aim of the Lancashire Teaching Hospitals NHS Foundation Trust, Department of Renal Medicine,
study was to assess differences regarding glomerular volume, glomerular density and Preston, United Kingdom and 2University of Manchester, Faculty of Medical and
capillary density in the interstitium of both kidneys harvested from the same deceased Human Sciences, Manchester, United Kingdom
donor.
METHOD: The study involved 40 pairs of kidneys (all together 80 kidneys) in which BACKGROUND AND AIMS: Patients with transplanted kidneys are more
preimplantation kidney biopsies were performed. Kidneys were harvested from 40 susceptible to COVID-19 infections compared to those with native kidneys because of
deceased donors (17 females and 23 males; mean age 42.3 [37.6-47.0] years old) died chronic immunosuppression and co-existing co-morbidities. A wide spectrum of renal

MO090 Table 1: Transplant Kidney Biopsy Findings from Positive COVID-19 Cases

10.1093/ndt/gfab078 | i131
Abstracts Nephrology Dialysis Transplantation

pathologies has been reported from renal biopsies taken from patients with native
kidneys following COVID-19 presentation. In comparison, biopsy-proven findings in
the setting of kidney transplantation and COVID-19 diagnosis are seldom described.
Our study aims to review early reported histological findings of transplant kidney
biopsies from patients testing positive for COVID-19.
METHOD: This is a secondary analysis of a larger study (PROSPERO registration
number: CRD42020218048) which reviewed the histopathological findings of kidney
biopsies in adults with concurrent COVID-19 infection. A systematic literature search
was conducted independently by two authors (HW, VJ) through ‘PubMed’, ‘Web of
Science’, ‘Embase’ and ‘Medline-ProQuest’ using the following keywords: “COVID-19
AND Kidney Biopsy”, “COVID-19 AND Renal Biopsy”, “SARS-CoV-2 AND Kidney
Biopsy” and “SARS-CoV-2 AND Renal Biopsy”. Articles were screened by three
authors (HW, VJ, RC) for relevance and duplicates were removed. The study selection
process was carried out as per the PRISMA guideline. In this analysis, we included all
research articles reporting biopsies in transplanted kidneys in adults over age > 18 who
tested positive with COVID-19 following a PCR swab test. We only included articles
published in the English language. All relevant articles published before November 1st
2020 were included in this review. Information regarding demographic data, co- MO091 Figure 1: B-Mode ultrasound shows diffuse hyperechogenic images associated
morbidities, renal presentation, renal parameters at time of COVID-19 diagnosis, with some reverberation artefacts (yellow arrows) in left kidney pelvis.
management, need for renal replacement therapy and outcomes were extracted from
selected articles.
RESULTS: Our review identified 11 cases reporting transplant kidney biopsies in
patients with positive COVID-19 status. These 11 cases were reported from 7 articles,
which were either single case reports or part of a case series. Mean age of the reported
cases was 43.6 years 6 10.7. Transplant kidney biopsies were taken from 4 female and
7 male patients, where 7 patients were of black ethnicity. The review involved 3 live
donor and 6 deceased donor transplanted kidneys, and 2 cases did not report type of
kidney transplant received. All of the documented cases presented with acute kidney
injury. 9 patients have essential hypertension or hypertension secondary to other co-
morbidities. Biopsy findings revealed 2 cases of acute T-cell mediated and antibody
mediated rejection, 2 cases of acute tubular injury, 5 cases of either FSGS or collapsing
FSGS and 1 report of post-transplant kidney infarction. Acute treatment received
involved different regimes. All 11 patients were eventually discharged from hospital,
where 2 patients required dialysis following discharge. Table 1 describes data from the
extracted cases.
CONCLUSION: There are multiple histological pathologies observed amongst
transplant kidney biopsies taken from patients admitted following COVID-19
diagnosis. Early results suggest aggressive medical treatment to manage inflammation,
transplant rejection and co-morbidities such as hypertension may optimize general and MO091 Figure 2: B-mode ultrasound shows diffuse hyperechogenic images associated
renal-specific outcomes. Collation of further cases is required to determine a clearer with some reverberation artefacts (yellow arrows) in right kidney pelvis.
association between COVID-19 and characteristics demonstrated from transplant
kidney biopsies. Reverberation artifacts give rise the suspicion of gas presence in kidney pelvises, usually
absent in case of staghorn calculi and encrusted pyelitis. CT confirmed the diagnosis of
bilateral emphysematous pyelitis due to the diffuse presence of gas within the renal
calyces, also extending to the ureters and bladder lumen (Fig. 3).
MO091 BILATERAL EMPHYSEMATOUS PYELITIS: A CASE REPORT
AND ULTRASONOGRAPHY FEATURES

Angela Maria Pellegrino1, Michele Vergura1, Michele antonio Prencipe1,


Giuseppe Gatta1, Filippo Aucella1
1
IRCCS “Casa Sollievo Della Sofferenza”, Department of Medical Sciences, Division of
Nephrology an Dialysis, San Giovanni Rotondo, Italy

BACKGROUND AND AIMS: Emphysematous pyelitis is a rare urinary infection with


gas formation in the excretory system. Diabetes mellitus and urinary tract obstruction
are the main risk factors. Most patients are women over 60 years old. The pathogenesis
is unknown. Diabetes mellitus and the elevated glucose levels may create a favorable
microenvironment for gas-forming microbes, but it does not exhaustively explain
clinical and pathological symptoms. Escherichia Coli and Klebsiella Pneumoniae are
the most involved bacteria. Clinical features are the same as other forms of
pyelonephritis e.g. fever, chills, flank abdominal pain, nausea and vomiting.
Ultrasonography, and especially computed tomography (CT) are important diagnostic
tools for demonstration of gas within pelvicalyceal system, urethers or even in bladder.
Use of parenteral antibiotic, relief of urinary tract obstruction if present, percutaneous
catheter drainage of gas and purulent material and nephrectomy are the mainstays of
therapy. This report introduces a case of bilateral emphysematous pyelitis with MO091 Figure 3: Axial CT scan of the abdomen without IV contrast demonstrating
emphasis on its ultrasound presentation. This is one of the few cases of bilateral the presence of gas in the kidney pelvises, ureters and in the bladder lumen (yellow
emphysematous pyelitis reported in literature. arrows).
METHOD: A 49-year-old female presented to the emergency with asthenia, epistaxis, MO091 Fig. 4 B-mode ultrasound shows left kidney (on the left) and right kidney (on
orthostatic hypotension and nocturnal cramps. Two months before she was referred to the right) after one week of parental antimicrobial therapy.
Department of Nephrology for proteinuria. In that occasion, renal ultrasound showed
normal kidneys and renal biopsy was performed. She started oral therapy with We promptly started parental antimicrobial therapy with cefalosporine. After one week
corticosteroid for ANCA-negative vasculitis and iatrogenic diabetes mellitus occurred. we observed a clinical and laboratory improvement, and the renal ultrasound revealed
She was admitted again to our Department of Nephrology, blood test was performed the resolution of bilateral pelvises alteration (Fig. 4).
and revealed: white cell count 20.500/ml; glucose 243 mg/dl; serum creatinine 2.3 mg/ CONCLUSION: In emphysematous pyelitis, renal ultrasound is characteristic due to
dl; C-reactive protein, 0.65 mg/dl ( < 0.5), procalcitonin 2.05 mg/l (nv < 0.5). Urine the presence of diffuse hyperechogenic images located in the renal pelvis associated
culture was positive for E. Coli. with some reverberation artifacts, usually absent in case of renal stones.
RESULTS: Renal ultrasound revealed the presence, in both kidney pelvises, of multiple Therefore, the renal ultrasound in association with clinical and laboratory findings,
and diffuse hyperechogenic images associated with some reverberation artefacts. The especially in patient with positive urine culture, should arouse the suspicion of
ultrasound findings were unusual and of doubtful interpretation: staghorn calculi, emphysematous pyelitis to start promptly antimicrobial therapy, even when CT
encrusted pyelitis, gas? (Fig. 1, 2). examination is not immediately available.

i132 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i133–i141, 2021
10.1093/ndt/gfab106

HYPERTENSION. EXPERIMENTAL investigate the impact of angioprotectin on the organism, rats were treated with
angiotensin II in the absence and presence of PLP. The blood pressure was used as
read-out of the effect of the treatment.
RESULTS: The incubation of angiotensin II with pyridoxal-5’-phosphate in vitro
MO092 THE ROLE OF CALCIUM IN UROMODULIN EXPRESSION AND caused in increased amount of angioprotectin. Since the first two amino acids aspartic
SECRETION FROM RENAL MEDULLARY EPITHELIAL CELLS acid and arginine of further peptides like angiotensin I, angiotensin (1-6) and
OF HYPERTENSIVE AND NORMOTENSIVE RATS cortistatin-17 were also metabolized to proline and glutamic acid, the underlying
mechanism is not specific for angiotensin II, but for aspartic acid and arginine. In
Philipp Boder1, Sheon Mary1, Lesley Graham1, Christian Delles1 accordance with this, the blood pressure of spontaneously hypertensive rats (SHR)
1
University of Glasgow, Institute of Cardiovascular & Medical Sciences, British Heart treated with PLP decreases after three days. The blood pressure of Wistar Kyoto rats
Foundation Glasgow Cardiovascular Research Centre, Glasgow, United Kingdom (WKY) treated with angiotensin II increases, whereas the blood pressure of WKY rats
treated with angiotensin II and PLP decreases to normal level.
CONCLUSION: Angiotensin II is obviously metabolized by pyridoxal-5’-phosphate
BACKGROUND AND AIMS: Uromodulin (UMOD) is the most abundantly secreted (PLP) to angioprotectin. PLP decreases the blood pressure in spontaneously
protein found within the urine, primarily produced by medullary thick ascending limb hypertensive rats and in Wistar Kyoto rats. The first two amino acids aspartic acid and
(mTAL) epithelial cells of the kidneys. There is accruing genetic evidence implicating arginine are also metabolized to proline and glutamic acid in other peptides.
UMOD in blood pressure regulation and consequently hypertension. The molecular
signaling induced by calcium in the kidney and its influence on blood pressure are not
well understood. The aim of this study was to investigate the potential role of
extracellular calcium and the calcium-sensing receptor (CaSR) in mTAL on UMOD MO094 SALT INFLUENCES UROMODULIN EXCRETION
production and secretion in TAL cells with the hope of defining novel clinical targets INDEPENDENT OF BLOOD PRESSURE
for the treatment of hypertension.
METHOD: Kidneys were harvested from normotensive Wistar-Kyoto (WKY) and Sheon Mary1, Philipp Boder1, Giacomo Rossitto1, Lesley Graham1, Kayley Scott1,
stroke-prone spontaneously hypertensive (SHRSP) female rats. To determine the effect Arun Flynn1, David Kipgen2, Delyth Graham1, Christian Delles1
1
of extracellular calcium on UMOD secretion, mTAL tubules were incubated in media Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom and
2
with and without 1mM calcium, nifedipine (10mM), NPS2143 (1 or 5 mM) and Department of Pathology, Queen Elizabeth University Hospital, Glasgow, United
spermine (2mM). Extracellular and intracellular UMOD protein levels were detected Kingdom
by Western blot. Gene expression of Umod was determined by qRT-PCR.
RESULTS: Calcium increased mTAL tubule UMOD secretion in WKY and SHRSP. BACKGROUND AND AIMS: Uromodulin (UMOD) is the most abundant renal
Nifedipine slightly decreased UMOD secretion in WKY without calcium. In both protein secreted into urine by the thick ascending epithelial (TAL) cells of the loop of
strains, NPS2143 increased calcium-induced UMOD secretion, with an enhanced Henle. Genetic studies have demonstrated an association between UMOD risk variants
effect in SHRSP. Stimulation of CaSR with spermine decreased UMOD secretion in and hypertension. Studies on UMOD overexpressing transgenic mice have shown that
WKY. Analysis of intracellular UMOD levels in these conditions demonstrated UMOD increases the tubular salt reabsorption via enhanced NKCC2 activity. We
increased accumulation when extracellular secretion was low, and vice versa. aimed to dissect the effect of salt-loading and blood pressure on the excretion of
Incubation of primary mTAL cells with calcium confirmed increased localisation of UMOD.
UMOD at the membrane compared to the cytosol, without any major differences in METHOD: Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive
cell morphology. The Umod mRNA level changes were not statistically significant (SHRSP) rats (n=8/sex/strain) were maintained on 1% NaCl for three weeks. Salt-
among conditions. loaded SHRSP were treated with nifedipine. Tubule isolation and ex vivo incubation
CONCLUSION: Trafficking of UMOD in the mTAL is influenced by the type of CaSR with nifedipine were used to assess its direct effect on TAL.
ligand and the biased nature of G-protein coupled CaSR signalling. Unravelling the RESULTS: Urinary UMOD excretion was significantly reduced after salt loading in
signalling events post-calcium will be necessary for identification of key regulators of both strains (figure). In salt-loaded SHRSP, nifedipine treatment reduced blood
UMOD secretion and provide new sites for therapeutic intervention in hypertension. pressure and urinary UMOD excretion. The reductions in urinary UMOD excretion
were dissociated from unchanged kidney UMOD protein and mRNA levels, however,
were associated with UMOD endoplasmic reticulum accumulation, thus suggesting
secretion as a key regulatory step. Ex vivo experiments with TAL tubules showed that
nifedipine did not have a direct effect on UMOD secretion.
CONCLUSION: Our data suggest a direct effect of salt on UMOD secretion
independent of blood pressure and a potential role of endoplasmic reticulum stress on
MO093 CLARIFICATION OF BIOSYNTHESIS OF ANGIOPROTECTIN
the control of UMOD secretion. The role of UMOD as a cardiovascular risk marker
deserves mechanistic reappraisal and further investigations based on our findings.
Michaela Lellig1, Juan. R Mun ~oz-Castan ~eda2,3,4,5, Juliane Hermann1,
Mariano Rodriguez2,3,4,5,6, Joachim Jankowski1,6,7, Vera Jankowski1,6
1
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University,
Aachen, Germany, 2Maimonides Biomedical Research Institute of Cordoba (IMIBIC),
Reina Sofia University Hospital/ University of Cordoba, Cordoba, Spain, 3School of
Medicine, Department of Medicine/ University of Cordoba, Cordoba, Spain,
4
ordoba, Spain, 5Spanish Renal
Nephrology Service, Reina Sofia University Hospital, C
Research Network (REDinRED)/ Institute of Health Carlos III, Department of Science and
Innovation/ Department of Health, Madrid, Spain, 6European Uremic Toxin Work
Group (EUTox) and 7School for Cardiovascular Diseases (CARIM), Maastricht University,
Maastricht, The Netherlands

BACKGROUND AND AIMS: The renin-angiotensin-aldosterone system (RAAS) is


involved in the regulation of the blood pressure, water- and electrolyte balance.
Pathophysiologically, this system is essential for the development and pathogenesis of
both cardiovascular and renal diseases. Recently, the angiotensin peptide
angioprotectinwas identified as an antagonist of the contractile effect of angiotensin II.
The amino acid sequence of angioprotectin (pro-glu-val-tyr-ile-his-pro-phe) compared
to the amino acid sequence of angiotensin II (asp-arg-val-tyr-ile-his-pro-phe) differs in
the n-terminal amino acids asp1 and arg2, which are transformed to pro1 and glu2 by
endothelial cells (Jankowski et al., 2011). The aim of the study is the identification of
the underlying mechanism of the transformation of angiotensin II to angioprotectin.
METHOD: To clarify the transformation of angioprotectin diverse angiotensin
peptides were incubated with enzymes like glutamic oxaloacetic transaminase (GOT),
cofactors like pyridoxal-5’-phosphate (PLP) and other substances like vitamin B6-
derivates. Aliquots were collected time-dependently and analyzed by matrix-assisted
laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). To

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

MO095 THE FECAL ABUNDANCE OF SHORT CHAIN FATTY ACIDS IS Although confirmatory data in larger cohorts are required, our original observations
INCREASED IN MEN WITH A NON-DIPPING BLOOD unravel innovative pathophysiological pathways in the field of the circadian regulation
PRESSURE PROFILE of BP levels.
Justine Huart1, Arianna Cirillo2, Annie Saint-Remy1, Jean-Marie Krzesinski1,
Pascal De Tullio2, François Jouret2
1
University of Liège, Nephrology, Liège, Belgium and 2University of Liège, Metabolomics MO096 ROLE OF THE ENDOTHELIN SYSTEM IN THE INTERACTIONS
group, Liège, Belgium OF THE VASOPRESSOR SYSTEMS IN VIVO IN MEN -
IMPORTANCE OF GENETIC HOST FACTORS
BACKGROUND AND AIMS: Gut microbiota (GM) has been involved in the Bastian Brune1, Johannes Korth2, Sebastian Dolff3, Benjamin Wilde2,
pathophysiology of hypertension (HT), possibly via its role in the production of short Winfried Siffert4, Andreas Kribben2, Oliver Witzke3
chain fatty acids (SCFAs) from diet carbohydrate fermentation. The absence of a 1
significant drop in night-time BP (also known as the non-dipping BP profile) measured University Hospital Essen, Department of Trauma, Hand and Reconstructive Surgery,
by 24-hour ambulatory BP monitoring (24h-ABPM) has been associated with poor Essen, Germany, 2University Hospital Essen, Department of Nephrology, Essen,
renal and cardiovascular outcomes, independently of HT. The putative link between Germany, 3University Hospital Essen, Department of Infectious Diseases, West German
GM-derived metabolites and BP dipping status is still unknown. Centre of Infectious Diseases, Essen, Germany and 4University Hospital Essen, Institute
METHOD: We investigated a cohort of male volunteers who were prospectively for Pharmacogenetics, Essen, Germany
recruited and subjected to 24h-ABPM, stool sample collection and a medical
questionnaire. A patient was categorized as non-dipper if the ratio between night and BACKGROUND AND AIMS: Arterial hypertension is one of the most common
day systolic BP was >0.9. The patients were categorized in two groups, i.e. NT or HT, diseases of the cardiovascular system worldwide and is still the cause of most deaths in
on the basis of the European Society of Hypertension criteria. Metabolomics analyses Germany. Data on interactions of the endothelin-system with the renin-angiotensin-
were conducted using Nuclear Magnetic Resonance. Fecal concentrations of acetate, and the sympathoadrenergic system in the regulation of systemic hemodynamics in
butyrate and propionate were obtained by integrating the signals at 1.93 ppm, 1.56 humans are lacking. In our present investigation we study the effects of Endothelin A-,
ppm and 1.05 ppm, respectively. Mann-Whitney test and Chi-square test were used to Alpha1- and Angiotensin II-type-1-receptor antagonization on the systemic pressor
compare continuous and categorical variables, respectively. effects of intravenous Endothelin-1-application in young, healthy men. In addition, we
RESULTS: Our 44-case cohort included 13 non-dippers (29.6%) and 31 dippers, with analyzed the effects of the genetic variations of the GNB3 C825T-polymorphism on
35 HT (79.4%) and 9 NT patients. Ten non-dippers (28.6%) and 25 dippers were HT. hemodynamic changes. GNB3 825CT/TT-allele-carriers are considered to have a
Nineteen HT patients were under anti-hypertensive medications (43.1%), including 7 higher risk for multiple diseases with structural, vascular degeneration, such as arterial
non-dippers and 12 dippers. The mean age and body mass index (BMI) of the cohort hypertension, diabetes mellitus and obesity.
were 50.869.5 years and 26.363.5 kg/m2, respectively. No significant difference in age, METHOD: 21 healthy male volunteers were included in this double- blind,
BMI, smoking habits, alcohol consumption, familial HT, personal history of diabetes, randomized, placebo-controlled cross-over study and were studied on four days.
cardiovascular or gastro-intestinal disorders was observed between dippers and non- Endothelin-1 (ET-1) (0.5, 1, 2.5, 5 ng/kg/min for 20 min each) was given intravenous
dippers. The relative quantification of fecal SCFAs showed higher amounts of acetate, 2.0 hours after oral application of either placebo or Doxazosin, 3.5 hours after oral
butyrate and propionate in the stools of non-dippers versus dippers (p=0.0252, application of Candesartan (Candesartan 8 mg) or in the presence of a continuous
p=0.0468, and p=0.0496, respectively; n=44 in toto) (Figure 1A). Similarly, the fecal infusion of the ET-A-selective antagonist BQ123 (60 lg/min). Blood pressure (BP) and
amounts of acetate, butyrate and propionate were higher in non-dippers versus dippers heart rate (HR) were recorded and total peripheral resistance (TPR) was measured
in patients without anti-hypertensive medications (p=0.0414, p=0.0108, and p=0.0602, using impedance cardiography. ET-1-dose-response curves were analyzed with
respectively; n=25 in toto) (Figure 1B). When focusing only on HT patients without ANOVA. Data are presented as mean 6 SD. Since we suspected an effect of the GNB3
any anti-hypertensive medications, a not significant trend for higher amounts of the 3 C825T-polymorphism we divided the overall collective into 2 sub-collectives according
main SCFAs was still found in the stools of non-dippers versus dippers (p=0.0556; to the GNB3 C825T-genotypes (n = 21, GNB3 825CC: n = 10, GNB3 825CT/TT: n =
n=16 in toto). 11). Our analyses considered the overall collective and compared the sub-collectives
intraday and interday.

CONCLUSION: Our pilot study highlights a putative link between GM-derived RESULTS: ET-1 increased systolic blood pressure (SBD) (p  0,01), diastolic blood
SCFAs and the BP dipping status, despite the BP status itself or the anti-hypertensive pressure (DBD) and mean arterial pressure (MBP) as well as total peripheral resistance
medications. No significant confounding factors were found between dippers and non- (TPR) (each p  0,001) with decreasing heart rate (HR5) (p  0,05). Elevation of blood
dippers in our cohort. The non-dipping BP profile is thought to reflect the disruption pressure existed in both sub-collectives (GNB3 825CC: SBD & MBD: p  0,01, DBP &
of the circadian BP rhythm. A circadian misalignment between peripheral and central TPR: p  0,05, GNB3 825CT/TT: DBD, MBD & TPR: p  0,01, SBP p  0,05).
clocks has also been described in the GM of jetlagged animals and patients, which may Antagonization of ETA-receptors reversed the effect in the overall collective as well as
in turn perturb the rhythmic secretion of metabolites. One may thus speculate that the in the sub-collectives. Both, Doxazosin, as well as Candesartan led to a decrease in
non-dipping BP profile may be linked to an altered homeostasis of GM-derived SCFAs. blood pressure, however, dose-response relationship was influenced more by doxazosin

i134 | Abstracts
Nephrology Dialysis Transplantation Abstracts
(DBD: p  0,001, MBD: p  0,01) than by candesartan (all values: p > 0,05). For both We, therefore, tested the hypothesis that beta blocker therapy prevents fetal gene
drugs, blood pressure and TPR remained elevated under maximum ET-1-application induction and pathological cardiac remodelling in experimental uraemia.
compared to baseline measurement. Blood pressure dependent heart rate changes were METHOD: Wistar rats (n=32) had subtotal nephrectomy (STNx) [Frontiers in
observed in the overall collective and in GNB3 825CC-allele-carriers under sole ET-1- physiology, 10: 1365, 2019] or sham surgery and were followed up for 10 weeks. The
therapy (p  0.05) (Fig. 1). Candesartan reversed the effect of ET-1 on the sub- animals were randomly allocated to metoprolol (10mg/kg/day) or vehicle. In vivo and
collectives (p > 0.05). GNB3 825CT/TT-allele-carriers showed no reduction in heart in vitro cardiac assessments were performed, and changes in myocardial fetal gene
rate under ET-1-application, but with accompanying candesartan therapy (p  0.01) expression were also studied.
(Fig. 2). The genotype collectives thus behaved oppositely to the drugs in this respect. RESULTS: Heart rate was significantly lower in metoprolol groups compared to
untreated groups demonstrating effective beta blockade (Fig 1A). Echocardiographic
LV mass was significantly higher in untreated STNx group compared to the metoprolol
group (896.4 vs 632.2g, P=0.0004). Similar changes were seen with heart weight to tibia
ratio (Fig 1B). There was no significant difference in blood pressure (BP) between
treated and untreated STNx animals (123 vs 119 mmHg, P=0.359) (Fig 1A). STNx
increased mRNA expression of fetal genes and there was a trend towards attenuation of
this increase with beta blocker therapy (Fig 1C).
CONCLUSION: Beta blocker therapy ameliorates uraemic pathological cardiac
remodelling irrespective of changes to BP. This benefit appears be associated with a
reduction of induced fetal gene expression. Further translational research on the
benefits of beta blockade in the treatment of uraemic cardiomyopathy is required.

MO097 Figure 1: 1A shows significant reduction in heart rate in metoprolol treated


groups compared to untreated groups. Fig 1A also shows the absence of difference in
blood pressure between treated and untreated STNx animals. Figure 1B shows the
significantly higher LV mass and heart weight to tibia ratio in untreated STNx
CONCLUSION: In summary, ET-1 increased systolic, diastolic and mean arterial
compared to metoprolol treated STNx. Fig 1C shows increased expression of mRNA
blood pressure as well as systemic vascular resistance. Doxazosin, Candesartan and
for fetal genes with STNx and its prevention with metoprolol treatment.
BQ123 led to a decrease in blood pressure. Blood pressure and TPR remained elevated
HR: heart rate, BP: blood pressure, Met: metoprolol, STNx: subtotal nephrectomy,
under maximum ET-1 application plus Candesartan or Doxazosin. The heart rate
CTGF & MEF2a are fetal genes associated with cardiac remodelling.
changes of the genotype-separated sub-collectives were opposite when ET-1 was
administered compared to ET-1 and Candesartan.

MO097 BETA BLOCKER PREVENTS CARDIAC MOLECULAR AND


MO098 HUMAN STOOL METABOLOME DIFFERS UPON 24-HOUR
MORPHOLOGICAL REMODELLING IN EXPERIMENTAL
BLOOD PRESSURE LEVELS AND THE NON-DIPPING BLOOD
URAEMIA
PRESSURE PROFILE
Shanmugakumar Chinnappa1,2, Azhar Maqbool1, Laura Denby3,
Justine Huart1, Arianna Cirillo2, Bernard Taminiau3, Julie Descy4, Annie Saint-
Andrew Mooney4, Mark Drinkhill1
1
Remy1, Georges Daube3, Jean-Marie Krzesinski1, Pierrette Melin4, Pascal De
University of Leeds, L.I.C.A.M.M, Leeds, United Kingdom, 2Doncaster and Bassetlaw Tullio2, François Jouret1
Teaching Hospitals, Nephrology, Doncaster, United Kingdom, 3University of Edinburgh, 1
University of Liège, Nephrology, Liege, Belgium, 2University of Liège, Center for
Edinburgh, United Kingdom and 4Leeds Teaching Hospitals, Nephrology, Leeds, United
Interdisciplinary Research on Medicines (CIRM), Metabolomics group, Liege, Belgium,
Kingdom 3
University of Liège, Fundamental and Applied Research Center for Animal & Health
(FARAH), Department of Food Sciences, Faculty of Veterinary Medicine, Liège, Belgium
BACKGROUND AND AIMS: Fifty years of heart failure research has shown that and 4University of Liège, Clinical Microbiology, Liege, Belgium
pathological cardiac remodelling forms a vicious cycle with myocardial dysfunction
leading to progressive heart failure (HF) [Circulation, 102: IV14-23, 2000]. Fetal gene
BACKGROUND AND AIMS: Dysbiosis of gut microbiota (GM) has been involved in
induction is associated with this process and beta blocker therapy has been shown to
the pathophysiology of arterial hypertension (HT), via a putative role of food-derived
prevent it. Although chronic kidney disease (CKD) and HF share similar mediators of
short chain fatty acids (SCFAs). Among the clinical manifestations of HT, the absence
cardiac remodelling, the benefits of beta blocker therapy in CKD has not been studied.

10.1093/ndt/gfab106 | i135
Abstracts Nephrology Dialysis Transplantation

of a significant drop in blood pressure (BP) overnight (i.e. non-dipping BP profile) has using GC-MS method. Fecal microbial community was analyzed using a combination
been associated with poor cardiovascular outcomes. The link between GM and non- of 16S rRNA gene and fecal metagenome sequence analysis.
dipping BP profile is unknown. RESULTS: Garlic supplementation during pregnancy and lactation protected against
METHOD: After informed consent, 16 male patients and their female partners (n=10) programmed hypertension in adult male offspring fed with HF diet. Garlic oil
were subjected to 24-hours ambulatory BP monitoring and were categorized in 2 supplementation caused a significant increase in plasma levels of acetate, propionate,
groups: HT (n=7; 6 men) and normotension (NT) (n=19). According to the and butyrate. NO bioavailability was augmented by garlic oil supplementation,
conventional night–day systolic BP ratio >0.9, 15 individuals (8 men and 7 women) represented by decreases of plasma levels of asymmetric and symmetric
were categorized as non-dippers. Metabolomics using Nuclear Magnetic Resonance dimethylarginine (ADMA and SDMA) levels, and increased plasma L-arginine-to-
was performed on stool samples, including the quantification of the 3 main SCFAs (i.e. ADMA ratio (AAR). HF intake associated with decreased a-diversity was quantified by
acetate, propionate and butyrate). Shannon diversity index. The Analysis of similarities (ANOSIM) demonstrated the
RESULTS: Multivariate analysis (principal component analyses (PCA) and partial difference in the gut microbiota among the four groups existed (All p < 0.05),
least squares (PLS-DA)) of stool metabolomics were not able to statistically separate indicating that four groups had distinct enterotypes. Additionally, garlic oil
HT versus NT groups. However, this approach discriminated dippers versus non- supplementation increased abundance of genus Lactobacillus, but decreased genera
dippers groups in both male and female cohorts (Q2=0.87 and 0.98, respectively), as Turicibacter and Staphylococcus. Moreover, the linear discriminant analysis effect size
well as in the entire cohort (Q2=0.68). As previously described, fecal amounts of (LEfSe) algorithm analysis identified several microbial markers including genera
acetate, propionate and butyrate were higher in HT patients than in NT patients in the Lactobacillus, Staphylococcus, and Turicibacter.
entire cohort (p=0.027; p=0.015 and p=0.015, respectively). Fecal amounts of acetate, CONCLUSION: The beneficial effects of garlic oil were associated with increased renal
propionate and butyrate were also significantly higher in non-dippers versus dippers in mRNA expression and activity of H2S-generating enzymes, increased NO
the entire cohort (p=0.027; p=0.038 and p=0.036, respectively). Significant correlations bioavailability, increased plasma SCFA levels, and alterations of gut microbiota
between stool metabolomes and the 24h-mean BP levels were found in male and composition. Our data revealed associations between H2S-generating pathway in the
female cohorts (R2=0.63 and 0.79 respectively) as well as in the entire cohort (R2=0.54). gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in
CONCLUSION: In conclusion, this 26-patient cohort highlights significant hypertension programmed by HF intake and provided insight to garlic oil as a
correlations between stool metabolome and (i) BP levels and (ii) non-dipping BP hypertension reprogramming strategy for further translational research.
profile in both men and women.

MO100 WNT/B-CATENIN SIGNALING PATHWAY IS ASSOCIATED


MO099 REPROGRAMMING HYPERTENSION PROGRAMMED BY WITH HYPERTENSIVE CARDIAC AND RENAL
HIGH-FAT DIET: THE ROLE OF GARLIC OIL FIBROSIS

You-Lin Tain1, Chien-Ning Hsu2 Evdokia Bogdanova1, Natalia Semenova2, Olga Galkina1, Irina Zubina1,
1
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Olga Beresneva1, Galina Ivanova3, Marina Parastaeva1, Vladimir Dobronravov1
Medicine, Pediatrics, Kaohsiung, Taiwan, R.O.C. and 2Kaohsiung Chang Gung Memorial 1
Pavlov University, Nephrology Research Institute, Saint Petersburg, Russia, 2Almazov
Hospital, Pharmacy, Kaohsiung, Taiwan, R.O.C. National Medical Research Center, Institute of Experimental Medicine, Saint Petersburg,
Russia and 3Pavlov Institute of Physiology, Laboratory of cardiovascular and lymphatic
BACKGROUND AND AIMS: Perinatal high-fat (HF) diet programs high blood systems physiology, Saint Petersburg, Russia
pressure (BP) in adult offspring. Hydrogen sulfide (H2S) has shown benefits in
hypertension by restoration of nitric oxide (NO) bioavailability and alterations of gut BACKGROUND AND AIMS: Arterial hypertension (AH) causes a cardiac
microbiota. Garlic, a naturally dietary source of H2S donors, supplementation has remodeling and renal fibrosis which considered to be mediated by reactivation of fetal
shown benefits in hypertension. We aimed to examine whether maternal garlic oil and pro-fibrotic signaling pathways. Signal transduction of canonical Wnt (b-catenin
supplementation can prevent hypertension programmed by maternal and post- expression) evaluation in the settings of heart and kidney hypertensive alterations was
weaning high-fat diet in adult offspring and whether its protective effects are related to the subject of the study.
mediation of H2S-genetaing system, alterations of gut microbiota composition, and METHOD: Systolic blood pressure (BP), serum and urinary creatinine (Cr),
microbiota metabolite short chain fatty acids (SCFAs). proteinuria (uTP), inorganic phosphate (sPi), intact parathyroid hormone (PTH),
METHOD: Pregnant rats received either a normal diet (ND) or HF diet (D12331, intact fibroblast growth factor 23 (FGF23), Klotho protein, were estimated in
Research Diets, Inc.) Garlic oil (GO) or vesicle was administered daily by oral gavage at spontaneously hypertensive rats after 1 (SHR1, n=6), 2 (SHR2, n=6), 4 (SHR4, n=6) b 6
100 mg/kg/day during pregnancy and lactation. Male offspring were weaned at 3 weeks (SHR6, n=6) months of exposure. Perivascular and interstitial fibrosis (Masson’s
of age, and onto either ND or HF diet to 16 weeks of age. Male offspring were assigned trichrome), and b-catenin expression (IHC) were analyzed by light microscopy of
to four groups (n=8/group): ND, HF, NDþGO, and HFþGO. Garlic supplementation myocardium and kidney tissues and calculated quantitatively. Statistical comparisons
during pregnancy and lactation protected against programmed hypertension in adult among groups were performed using Mann–Whitney U-test and Kruskal-Wallis H-
male offspring fed with HF diet. All offspring were killed at 16 weeks of age. NO- test. The association between biochemical and morphological variables was estimated
related parameters were analyzed by HPLC. Plasma levels of SCFA were determined by Spearman’s correlation.

MO100 Figure 1: (a) Representative micro pictures of myocardium Massons’ trichrome stainand antibetacatenin IHC of SHR1 and SHR2 and b) correlation between areas of
myocardialbeta-catenlnexpression and perlvascular fibrosis, c) evaluated by Orbit Image Analysis

i136 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: In all groups BP increased compared to baseline values (p = 0.011). The BP 8669 vs. 7068 mmHg; (p<0.001) and the mean ACR was 29665 vs. 5.662.7 mg/
decline of renal function was obvious in SHR6 (vs SHR2, p=0.001). Klotho level g, (p<0.001) respectively. Around 20% hypertensives had albuminuria. Urinary
decreased in SHR2 vs SHR1 (p = 0.026) and in SHR4-6 vs SHR2 (p < 0.013). There potassium excretion was lower in hypertensives (51631 vs. 69631, mEq/g; p<0.02).
were no differences in sPi (p = 0.50), PTH (p = 0.63), FGF23 (p = 0.62) between The median urUMOD in hypertensive subjects was 3.38 (1.73-9.06) and in
experimental groups. Perivascular myocardial fibrosis was already increased in SHR2 normotensives 3.85(2.28-5.69) mg/g (P=NS).Multivariate analysis showed significant
(vs SHR1, p=0.026, Figure 1a), renal interstitial fibrosis - since 6mo exposure (p = inverse association between diastolic blood pressure and urinary uromodulin
0.012, Figure 2a). Both cardiac and renal fibrosis were associated with redistribution of excretion. An urURMOD cut-off of 2.9 (25th percentile in normotensives) showed
b-catenin in cardiomyocytes and tubular epithelial cells (Figure 1a, 2a: decrease in eGFR, urinary sodium & potassium excretions were significantly lower at low
membrane and increase in cytoplasm) without significant changes in tissue b-catenin uromodulin cut-off and this was seen in38%subjects.
expression. In heart b-catenin expression correlated with to perivascular fibrosis CONCLUSION: The glomerular involvement was found in 20% hypertensives as
(Figure 1 b). Renal b-catenin expression correlated with interstitial fibrosis (Figure 2b), evidenced by albuminuria. In general urinary uromodulin level was not different
but not with sCr (r=-0.03, p>0.05) b uTP (r=0.04, p>0.05). between hypertensive and normotensive subjects. Association of low uromodulin cut-
off with lower eGFR, Naþ and Kþ excretion indicates simultaneous tubule glomerular
involvement in 38%.

MO100 Figure 2: (a) Representative micro pictures of kidney Massons’trichrome stain


and antibeta-catenin IHC of SHR2 and SHR6 and b) correlation between areas of
kidney beta-catenln expression and Interstitial fibrosis, c) evaluated by Orbit Image
Analysis

CONCLUSION: Reactivation of Wnt/ b-catenin signal transduction is possibly a basic


molecular mechanism of cardiac and renal fibrosis in arterial hypertension. The data
suggests involvement of Klotho decline mediated activation of canonical Wnt.
Targeting these signaling molecules is promising therapeutic strategy for protecting
both organs in cardiorenal pathology and requires further research.

MO101 ASSESSING EARLY RENAL INVOLVEMENT IN ESSENTIAL


HYPERTENSION BY MEASURING URINARY ALBUMIN AND
UROMODULIN EXCRETION

Raquib Morshed1, Kazi Shahnoor Alam1, Babrul Alam1, Sajal Krishna Banerjee2,
MZ Hassan3, SR Chaudhury4, Maa Chowdhury1, Md M Iqbal1
1
National Institute of kidney Diseases & Urology (NIKDU), department of nephrology,
Dhaka, Bangladesh, 2BSMMU, Department of cardiology, Dhaka, Bangladesh, 3BUHS,
Department of physiology & molecular biology, Dhaka, Bangladesh and 4NHFRI,
Department of Epidemiology & Research, Dhaka, Bangladesh

BACKGROUND AND AIMS: Kidneys are target organs in hypertension.


Hypertensive damage results in glomerular as well as tubular dysfunction. Albuminuria MO101 Figure: Clinical and biochemical variables between urine uromodulin-
is a known marker of glomerular damage. Whereas, urinary uromodulin is creatinine (urURMOD) groups.
increasingly considered as potential biomarker of early tubular dysfunction. The aim of
this study was to identify the pattern of early renal involvement based on glomerular
and tubular function assessment by measuring urinary albumin and uromodulin in
hypertensive patients
METHOD: In this cross-sectional study 122 hypertensive subjects with age>30 years,
duration of hypertension <5years, without accelerated or malignant BP, absence of
dipstick proteinuria and eGFR>60ml/min. Subjects with possibility of secondary
hypertension were excluded. There were also 33 normotensive volunteers included as
healthy referents. Morning spot urine for albumin-creatinine ratio (ACR mg/g), urine
uromodulin-creatinine ratio (urUMODlg=g), urinary sodium-creatinine ratio (mEq/
g) and potassium-creatinine ratio (mEq/g) were measured in single urine sample.
Urine uromodulin was measured by ELISA method.
RESULTS: The hypertensive and healthy subjects were matched for age 48611 vs.
47611, years (P=NS). The systolic BP was 145615 vs. 112612 mmHg and diastolic

10.1093/ndt/gfab106 | i137
Abstracts Nephrology Dialysis Transplantation

Uromodulin-creatinine ratio(mg/g)
Variables Low (<2.29) Not low (2.29) p- MO103 PREDICTION OF CARDIOVASCULAR OUTCOMES WITH
PERIDIALYTIC, INTRADIALYTIC, SCHEDULED
n=60 n=95 value INTERDIALYTIC AND AMBULATORY BP RECORDINGS IN
Mean6SD HEMODIALYSIS PATIENTS
Age (years) 47.41611.25 49.40612.03 0.30 Foteini Iatridi1, Marieta Theodorakopoulou1, Charalampos Loutradis1,
SBP (mmHg) 138.24616.29 135.9562.65 0.44 Antonios Karpetas2, Athanasios Bikos3, Maria Eleni Alexandrou1,
DBP (mmHg) 84.82610.44 82.03612.49 0.15 Ioannis Tsouchnikas1, Christopher Mayer4, Anna-Bettina Haidich5,
Aikaterini Papagianni1, Pantelis Sarafidis1
BMI (kg/m2) 25.8463.85 24.7665.35 0.18 1
Aristotle University of Thessaloniki, Department of Nephrology, Hippokration Hospital,
eGFR (ml/min/ 89.62617.74 96.37621.01 0.04 Thessaloniki, Greece, 2Therapeutiki Hemodialysis Unit, Thessaloniki, Greece, 3Protypo
1.73 m2) Hemodialysis Unit, Thessaloniki, Greece, 4Austrian Institute of Technology, Center for
Health & Bioresources, Biomedical Systems, Vienna, Austria and 5Aristotle University of
Urine ACR(mg/g)* 8.18 (5.33, 2.43) 12.90 (6.17, 30.37) 0.77 Thessaloniki, Department of Hygiene, Social-Preventative Medicine and Medical
Urine Naþ- 111.14669.70 143.19697.33 0.03 Statistics, School of Medicine, Thessaloniki, Greece
creatinine
(mEq/g) BACKGROUND AND AIMS: Ambulatory-BP-monitoring (ABPM) is recommended
for hypertension diagnosis and management in hemodialysis subjects due to high
Urine Kþ- 47.06622.89 56.18628.04 0.03 accuracy and strong associations with outcomes. The agreement and prediction of
creatinine averaged intradialytic BP readings and home BP readings with ABPM and clinical
outcomes is not known. This study assesses in parallel the association of pre-dialysis,
(mEq/g) intradialytic, scheduled interdialytic and ambulatory BP recordings with cardiovascular
outcomes and mortality in this population.
Independent t test was done. METHOD: We prospectively followed for 49.1625.6 months 242 hemodialysis
patients with valid 48-hour ABPMs to examine the association of pre-dialysis,
*Median (IQR) and Mann-Whitney U test was done.
intradialytic, intradialytic plus pre/post-dialysis readings, scheduled interdialytic BP
(the average of out-of-dialysis day readings at 8:00 am and 8:00 pm) and 44-hour
ambulatory BP with outcomes. The primary end-point was a composite of
cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation
after cardiac arrest, hospitalization for heart failure, coronary revascularization
MO102 LUNG ULTRASOUND-GUIDED DRY-WEIGHT REDUCTION procedure or peripheral revascularization procedure.
DECREASES AMBULATORY BLOOD PRESSURE LEVELS IN RESULTS: Cumulative freedom from the primary end-point was significantly lower
HYPERTENSIVE HEMODIALYSIS PATIENTS: LONG-TERM with increasing 44-hour SBP (group 1, <120 mmHg, 64.2%; group 2, 120 to <130
ANALYSIS OF A LUST SUB-STUDY* mmHg 60.4%, group 3, 130 to <140 mmHg 45.3%; group 4, 140 mmHg 45.5%;
logrank-p=0.016). Similar were the results for intradialytic (logrank-p=0.039),
Charalampos Loutradis1, Pantelis Sarafidis1, Robert Ekart2, Ioannis Tsouchnikas1, intradialytic plus pre/post-dialysis (logrank-p=0.044), and scheduled interdialytic SBP
Christodoulos Papadopoulos3, Vasileios Kamperidis4, Maria Eleni Alexandrou1, (logrank-p=0.030), but not for pre-dialysis SBP (logrank-p=0.570). With group 1 as the
Charles Ferro5, Aikaterini Papagianni1, Gérard London6, Francesca Mallamaci7, reference group, the Hazard Ratios of the primary end-point showed a gradual increase
Carmine Zoccali7 with higher BP levels with all BP metrics, except pre-dialysis SBP. An inverse
1
Hippokration Hospital, Aristotle University of Thessaloniki, Department of Nephrology, association of DBP levels with outcomes was shown with all BP metrics.
Thessaloniki, Greece, 2University Clinical Centre Maribor, Clinic for Internal Medicine, CONCLUSION: Averaged intradialytic and scheduled home BP measurements (but
Department of Nephrology, Maribor, Slovenia, 3Hippokration Hospital, Aristotle not pre-dialysis readings) display similar patterns of prognostic associations with 44-
University of Thessaloniki, 3rd Department of Cardiology, Thessaloniki, Greece, 4AHEPA hour ambulatory BP in hemodialysis patients and represent valid metrics for
Hospital, Aristotle University of Thessaloniki, 1st Department of Cardiology, Thessaloniki, hypertension management in these individuals.
Greece, 5University Hospitals Birmingham NHS Foundation Trust, Department of Renal
Medicine, Birmingham, United Kingdom, 6Manhes Hospital and FCRIN INI-CRCTC,
Manhes, France and 7CNR-IFC Clinical Epidemiology of Renal Diseases and
Hypertension, Reggio Calabria, Italy MO104 RISK OF END-STAGE RENAL DISEASE: PREDICTION USING
CUMULATIVE NUMBER OF HYPERTENSION DIAGNOSES
BACKGROUND AND AIMS: Hypertension is highly prevalent and independently Chang Seong Kim1, Hong Sang Choi1, Tae Ryom Oh1, Eun hui Bae1, Soo
associated with adverse outcomes in patients undergoing hemodialysis. The main Wan Kim1
mechanism leading to BP elevation in these individuals is their inability to maintain 1
water homeostasis. This study examines the long-term effects of dry-weight reduction Chonnam National University Medical School, Internal Medicine, GWANGJU, Korea,
with a standardized lung-ultrasound-guided strategy on ambulatory BP in Rep. of South
hypertensive hemodialysis patients.
METHOD: This is the report of the 12-month trial phase of a randomized controlled BACKGROUND AND AIMS: Hypertension is the leading risk factor for end-stage
trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were renal disease (ESRD). However, the association between repeated measurements of
randomized (1:1 ratio) in the active group (23 male and 12 female), following dry- high blood pressure and ESRD is not well-established. This study investigated whether
weight reduction guided by the total number of US-B lines prior to a mid-week dialysis the cumulative number of diagnoses of hypertension is a substantial risk factor for
session and the control group (24 male and 12 female), following standard-of-care ESRD.
treatment. A 48-hour ABPM was performed in all study participants at baseline and METHOD: The incidence of ESRD among 2,144,801 participants, identified from the
after 12 months. Korean National Health Insurance Service database, who did not have a history of
RESULTS: During follow-up more patients in the active compared to control group antihypertensive therapy and had documented blood pressure assessments for 4
had dry weight reduction (71.4% vs 22.2%; p<0.001). US-B lines -4.83613.73 vs consecutive years was determined retrospectively. Data were extracted from the
5.53616.01; p=0.005) and dry-weight (-1.6862.38 vs 0.5462.32; p<0.001) decreased database where events of hypertension were defined as systolic blood pressure 140
in the active and slightly increased in the control group. At 12 months, 48-hour SBP mmHg or diastolic blood pressure 90 mmHg.
(136.19614.78 vs 130.31613.57; p=0.034) and DBP (80.7269.83 vs 76.8268.97; RESULTS: Over a median follow-up of 7.2 years, ESRD was identified in 1758 of the
p=0.008) were lower compared to baseline in the active but similar in the control 2,144,801 participants. In a multivariable Cox model adjusted for age, sex, smoking,
group. Changes in 48-hour SBP (-7.78613.29 vs -0.10614.75; p=0.021) were alcohol consumption, exercise, and history of diabetes and chronic kidney disease, a
significantly greater in the active compared to the control group. Comparisons for positive dose-dependent relationship between the cumulative number of diagnoses of
intradialytic, 44-hour, Day-1, Day-2 and day- and night-time BP were to the same hypertension and ESRD was found (adjusted hazard ratio for ESRD, 2.70 in 4
direction. The proportion of patients experiencing at least one episode of intradialytic cumulative number of diagnoses of hypertension compared to no history of
hypotension was numerically lower in the active group (71.4% vs 88.9%, p=0.065). hypertension). This association was maintained for the cumulative number of
CONCLUSION: A lung-ultrasound-guided strategy for dry-weight reduction can diagnoses of both systolic and diastolic hypertension.
effectively and safely decrease ambulatory BP levels during a 12-month follow-up CONCLUSION: The cumulative number of diagnoses of systolic or diastolic
period This method is a simple treatment approach to improve hypertension hypertension increases the risk of ESRD. Therefore, preventive treatment to avoid
management in hemodialysis patients. repetitive events of systolic or diastolic hypertension may be important to lower the
risk of ESRD in this clinical population.

i138 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO105 TELEMEDICAL SURVEILLANCE AND OPTIMIZED CONCLUSION: Our findings, though need to be confirmed by further studies,
TREATMENT OF BLOOD PRESSURE IN KIDNEY revealed an association between a higher state of anxiety and a higher blood pressure
TRANSPLANT RECIPIENTS level in HD patients in COVID-19 pandemic era, which was remarkable particularly in
patients not taking a beta-blocker.
Wiebke Duettmann1, Marcel Naik1, Bianca Zukunft1, Danilo Schmidt2,
Petra Glander1, Bilgin Osmanodja1, Manuel Mayrdorfer1, Mira Choi1,
Friederike Bachmann1, Ulrike Weber1, Verena Graf1, Michael Dürr1,
Fabian Halleck1, Klemens Budde1 MO107 CLINICAL CHARACTERISTICS OF A PATIENT POPULATION
1
Charité - Universit€
atsmedzin Berlin, Nephrology and Internal Intensive Care Medicine, WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME AND
Berlin, Germany and 2Charité - Universit€atsmedizin Berlin, IT, Berlin, Germany MALIGNANT HYPERTENSION: THE GLOBAL AHUS
REGISTRY ANALYSIS
BACKGROUND AND AIMS: Patients with chronic kidney disease suffer often from Jean-Michel Halimi1, Imad Al-Dakkak2, Katerina Anokhina3, Gianluigi Ardissino4,
cardiovascular diseases, especially high blood pressure and its complications such as Christoph Licht5, Wai Lim6, Annick Massart7, Franz Schaefer8, Johan Van de
stroke and heart attack. After kidney transplantation, this condition persists and can in Walle9, Eric Rondeau10
addition harm the graft. However, outpatient care surveillance is not ideal to treat high 1
blood pressure sufficiently. mHealth solutions such as remote vital signs seem to have CHRU Tours, Service de Néphrologie-Hypertension Artérielle, Dialyses, Transplantation
the potential to fill in this gap. Rénale, Tours, France, 2Alexion Pharmaceuticals, Inc., Boston, United States of America,
3
METHOD: To optimize the monitoring of kidney transplant recipients (KTR), the Alexion Pharmaceuticals, Inc., Zurich, Sweden, 4Fondazione IRCCS Ca’ Granda
MACCS (Medical Assistant for Chronic Care Solution)-project offers participants an Ospedale Maggiore Policlinico, Center for HUS Control, Prevention and Management,
intensified control of home-measured vital signs via a smartphone app. Additionally, Milan, Italy, 5The Hospital for Sick Children, Division of Nephrology, Toronto, Canada,
6
well-being and medical adherence can be forwarded. A telemedicine team reviews daily Sir Charles Gairdner Hospital, Department of Renal Medicine, Perth, Australia,
7
incoming data and takes action, if necessary. A self-programed telemedicine dashboard Antwerp University Hospital, Department of Nephrology and Hypertension, Edegem,
visualizes the data. KTR receive their updated medication plan and medical support. Belgium, 8Heidelberg University Hospital, Division of Pediatric Nephrology, Heidelberg,
The pilot phase of project started in February 2020 and is ongoing. A randomized Germany, 9Ghent University Hospital, Department of Internal Medicine and Pediatrics,
controlled trial will start in March 2021. The concept sticks to General Data Protection Ghent, Belgium and 10Hôpital Tenon, Urgences Néphrologiques et Transplantation
Regulation (GDPR) of European Union. Rénale, Paris, France
RESULTS: Currently, 335 KTR participate in the project with 26 (7.76%) dropouts
since beginning. Including the 26 dropouts, we received in total 15 973 blood pressure BACKGROUND AND AIMS: Atypical haemolytic uraemic syndrome (aHUS) is a
(BP) values (mmHg) (systolic BP [SBP] mean 128.56, standard deviation [SD] 6103.7, rare disease that manifests as complement-mediated thrombotic microangiopathy
maximum (max) 220, minimum (min) 60; diastolic BP [DBP] mean 78.51, SD 69.97, (TMA), which can lead to severe organ damage. Some patients with aHUS may present
max 120, min 60) and 27 481 heart rate (HR) values in beats per minutes (bpm) (mean with malignant hypertension (MHT); both conditions can result in TMA. The
70, SD 614, max 200, min 40). For 278 times, an adaption of antihypertensive therapy objective of this analysis was to characterise patients with aHUS and MHT.
took place. In total, 170/335 KTR were hospitalized, which made up for 338 METHOD: In this analysis, patients from the Global aHUS Registry (NCT01522183)
hospitalizations (1.99 cases per patient, max 6, min 1), which led to 3 8547 days in were included if they were diagnosed with MHT and were followed 90 days after
hospital (mean 9.34, SD 611.43, max 89, min 1). In 331 cases, the diagnosis (main or initial aHUS symptom presentation or diagnosis date; patients were excluded if they
secondary diagnosis) was related to hypertension, and 196 cases the diagnosis may be a withdrew from the registry or discontinued treatment with eculizumab due to a
hypertension-related complication, e.g. myocardial infarct. Evaluation regarding diagnosis other than aHUS. Demographics and clinical characteristics were evaluated.
significance is in process and requires further data. RESULTS: Seventy-one of 1903 registry patients were included in the analysis. Clinical
CONCLUSION: mHealth solutions including remote vital signs and telemedicine characteristics are presented in the table. Seventeen patients (24%) had a paediatric
personnel for regular evaluation have the potential to optimize blood pressure (<18 years) onset of disease, and 54 (76%) were adults at aHUS diagnosis; female
treatment. Acute onset of hypertensive crisis can be handled sufficiently at home and patients were slightly overrepresented (61%). Sixty-nine percent of patients were
thus reduce treatment at emergency rooms. Since severe complications of high blood reported to have MHT at around the same time as aHUS diagnosis (þ/-2 months),
pressure levels manifest after years, long-term results are required to conduct while 11% and 13% experienced MHT before and after aHUS diagnosis, respectively.
conclusions. aHUS triggering conditions were reported in 6/71 patients (8%) (Table).
Cardiovascular (27%) and gastrointestinal (21%) symptoms were the most commonly
reported extra-renal manifestations. Eight patients (11%) had a reported family history
of aHUS and 40 patients (56%) had a complement pathogenic variant or an anti-CFH-
MO106 A PROSPECTIVE STUDY ON ANXIETY AND BLOOD antibody. Thirty-three patients (46%) had a kidney transplant; of these, 20 were
PRESSURE LEVELS IN HAEMODIALYSIS PATIENTS DURING prescribed eculizumab in the peri- or post-transplant period.
COVID-19 PANDEMIC

Rezzan Eren Sadiog lu1, Merve Aktar1, Berker Duman2, Sim Kutlay1, Sule Sengul1,
Kenan Keven1, Gökhan Nergizoglu1, Kenan Ateş1, S¸ehsuvar Ertürk1
1
Ankara University School of Medicine, Nephrology, Ankara, Turkey and 2Ankara
University School of Medicine, Psychiatry, Ankara, Turkey

BACKGROUND AND AIMS: Coronavirus Disease-19 (COVID-19) pandemic has


currently been one of the leading causes of psychosocial stress worldwide. We
hypothesized that possible changes in anxiety status might affect blood pressure in
haemodialysis (HD) patients during COVID-19 pandemic.
METHOD: Seventy one prevalent HD patients were included in this prospective study.
Hospital Anxiety and Depression Scale (HADS) and State-Trait Anxiety Inventory
(STAI) were applied to assess psychological status of the patients. Peridialysis blood
pressure measurements were performed and average of 6 consecutive HD sessions’
pre-dialysis systolic blood pressure measurements were used for statistical analyses. All
assessments were performed both at the beginning (March) and after ending (June) of
the partial lock-down, which was officially instituted by the Government in parallel
with the status of the pandemic in Turkey.
RESULTS: Mean age (6SD) was 59.2614.8 years and 52% of the patients were female.
Dose of medications including antihypertensives, dry weight, interdialytic weight gain,
and Kt/Vurea were stable during the study period. STAI-state score was higher in
March than that in June (44.6612.6 vs 42.3611.5, respectively, p=0.047), whereas
HADS-anxiety, HADS-depression, and STAI-trait scores were not different. Pre-
dialysis systolic blood pressure was significantly higher in March than in June
(127.9620.3 vs 124.8622.8 mmHg, respectively, p=0.029). Change in state anxiety
score from March to June was remarkable particularly in patients not taking a beta-
blocker (49.369.6 to 43.8611.1, p=0.001) and in patients younger than the median age
of 64 years (48.6612.8 to 45.3612.5, p=0.029). Change in blood pressure level from
March to June was found to be significant only in patients not taking a beta-blocker
(123.4620.2 to 118.2620.6 mmHg, p<0.001), while did not reach a statistically
significant level in the others.

10.1093/ndt/gfab106 | i139
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: In this analysis of patients with aHUS and MHT, the observed high m2 vs 2864 kg/m2), serum phosphate (3.960.7 mg/dL vs 3.760.8 mg/dL), CRP
prevalence of pathogenic variants in complement genes or anti-CFH antibodies, (median: 3.2 mg/L, IQR: 1.6-6.5 vs 3.2 mg/L, IQR: 1.6-6.5 vs 2.1 mg/L, 0.9-5.1 mg/L),
alongside the high proportion of patients with extrarenal manifestations and/or 24h urinary protein (median: 1.0 g/24h, IQR: 0.4-2.3 vs median: 0.5 g/24h, IQR: 0.2-1.0
requiring kidney transplant, indicate a high severity of presentation and poor g/24h) and lower serum albumin (4.160.5 g/dL vs 4.260.5 g/dL) and eGFR (34613
prognosis of aHUS associated with MHT. ml/min/1.73m2 vs 37614 ml/min/1.73m2 as compared to remaining patients (all
P<0.03). In a multiple logistic regression model, 24h proteinuria [odds ratio (OR):
1.31, 95% CI: 1.13-1.53, P<0.001] and BMI [OR: 1.08, 95% CI: 1.03-1.13, P=0.001]
resulted to be the first factors in rank explaining resistant hypertension followed by
MO108 ACCURACY OF PERIDIALYTIC, INTRADIALYTIC AND
diabetes (OR: 1.83, 95% CI: 1.18-2.85, P=0.008). Age, background CV comorbidities,
SCHEDULED INTERDIALYTIC RECORDINGS FOR
serum phosphate, serum CRP, albumin, and eGFR failed to be associated with resistant
DIAGNOSING HIGH AMBULATORY BLOOD PRESSURE IN
hypertension after multiple data adjustment (P ranging from: 0.14 to 0.61). Of note, the
HEMODIALYSIS
combination of 24h proteinuria, BMI and diabetes had a relevant discriminatory
power for resistant hypertension because the area under the ROC curve area of these
Marieta Theodorakopoulou1, Foteini Iatridi1, Charalampos Loutradis1,
risk factors was 0.71 (95% CI: 0.66-0.76) (P<0.001).
Maria Eleni Alexandrou1, Antonios Karpetas2, Georgios Koutroumpas3,
CONCLUSION: A rigorously defined phenotype of resistant hypertension has a 20%
Vasileios Raptis4, Charles Ferro5, Aikaterini Papagianni1, Pantelis Sarafidis1
1
prevalence in the CKD population. Proteinuria, high BMI and obesity are the main
Aristotle University of Thessaloniki, Department of Nephrology, Hippokration Hospital, risk factors associated with this phenotype. Optimization of diabetes control, weight
Thessaloniki, Greece, 2Therapeutiki Hemodialysis Unit, Thessaloniki, Greece, loss and pharmacotherapy targeting proteinuria may mitigate resistant hypertension in
3
Achillopouleion General Hospital, Hemodialysis Unit, Volos, Greece, 4Pieria the CKD population.
Hemodialysis Unit, Katerini, Greece and 5University Hospitals Birmingham, Department
of Renal Medicine, Birmingham, United Kingdom

MO110 ARE BIG-DATA TECHNIQUES USEFUL IN SCREENING FOR


BACKGROUND AND AIMS: Hypertension is highly prevalent in hemodialysis
PRIMARY HYPERALDOSTERONISM? RESULTS OF A PILOT
patients. Current recommendations suggest the use of ambulatory-BP-monitoring
STUDY AND THEIR PROSPECTIVE APPLICATION
(ABPM) as the gold-standard for hypertension diagnosis and management in these
subjects. This study assessed the accuracy of peridialytic, intradialytic and scheduled ~o1, Arturo Quesada2, Consolacio n Rosado1, Rosario Manzanedo1,
Gilda Carren
interdialytic recordings in diagnosing high 44-h interdialytic BP.
Dolores Barreda1, David Mena ndez1, Maria Carmen Felipe1,
METHOD: A total of 242 hemodialysis patients that underwent valid 48-h ABPM
Jesus Martin-Centellas3, Alba Martın-centellas4, JESUS MARTIN GARCIA1
were included in the analysis. We used ambulatory BP as reference standard and tested 1 
COMPLEJO ASISTENCIAL DE AVILA, NEFROLOGIA, AVILA,
 Spain, 2COMPLEJO
the accuracy of the following BP metrics: Pre- and post-dialysis, Intradialytic,

ASISTENCIAL DE AVILA, 
INFORMATICA, AVILA, Spain, 3HOSPITAL UNIVERSITARIO DEL
Intradialytic plus pre/post-dialysis readings and Scheduled interdialytic BP (out-of-
dialysis day: readings at 8:00 am, 8:00 pm or their average). HENARES, NEFROLOGIA, MADRID, Spain and 4HOSPITAL UNIVERSITARIO DE LEON,
RESULTS: 44-h SBP/DBP levels had significant differences with and pre- or post- CARDIOLOGIA, Le
on, Spain
dialysis BP, but no or minor differences with any of the other BP metrics. 44-h SBP and
DBP correlated strongly with Intradialytic (r=0.713/0.753, p<0.001), Intradialytic plus BACKGROUND AND AIMS: Primary aldosteronism is a rare cause of high blood
pre/post-dialysis (r=0.725/0.758, p<0.001) and averaged Scheduled interdialytic BP pressure (BP). Guidelines recommend a screening in several situations, such as
(r=0.874/0.823, p<0.001). Bland-Altman plots showed absence of systemic bias for all hypertension with hypokalemia, sleeping apnea or adrenal mass, by determining the
index metrics, but large between-method difference and wider 95% limits of agreement baseline aldosterone/renin ratio. Recent studies point out that hyperaldosteronism may
for pre- and post-dialysis BP compared to Intradialytic, Intradialytic plus pre/post- be more frequent than expected in patients who do not have an arbitrary high
dialysis and averaged Scheduled interdialytic BP. In ROC-analysis for diagnosing 44-h aldosterone/renin ratio. The application of big data techniques could generate “red
SBP130mmHg, the Area-Under-the-Curve of pre-dialysis (0.723) and post-dialysis flags” that help clinicians to anticipate the diagnosis.
SBP (0.746) were significantly lower than that of Intradialytic (0.850), Intradialytic plus We have evaluated the usefulness of big data in the diagnosis of hyperaldosteronism.
pre/post-dialysis (0.850) and Scheduled interdialytic SBP (0.917) (z-test, p<0.001 for METHOD: We have used 3 data sources: patient management, laboratory data
all pairwise comparisons). The corresponding sensitivity/specificity values were 76.6%/ management and clinical record. With them, Oracle database management system
54.5%, 78.7%/59.4%, 73.0%/81.2%, 68.1%/88.1% and 82.3%/89.1%, respectively. extracts demographic data, blood pressure and analytical values in a single collection.
Similar observations were made for DBP. This data are stored in a MongoDB database, where two collections are generated:
CONCLUSION: In contrast to pre- and post-dialysis BP, the average of intradialytic, "patients" (data we are collecting) and "variables" (values obtained from the identifiers
intradialytic plus pre/post-dialysis or scheduled interdialytic BP recordings show of the latest data obtained from the source systems are saved to guide the collection
reasonable agreement with ambulatory BP and may be used for hypertension diagnosis process).
and management in hemodialysis. Since MongoDB is a schemaless system, it is possible to easily add new variables and
their results to the collection "patients", if it is necessary, in order to generate alerts. In
order to diagnose hyperaldosteronism, age between 18 and 55 years, BP > 139/89
mmHg, K 3.5 mEq/l and plasma bicarbonate > 26 mEq/L were used.
MO109 CHARACTERIZATION OF RESISTANT HYPERTENSION IN
RESULTS: From January 2019 to 30th March 2020, 952,520 data were collected and
CKD PATIENTS
281,661 outcome variables from 80,410 patients were analyzed. The method generated
alerts of possible hyperaldosteronism in 33 patients (18 men, mean age 46.8 þ 6.8 years
Giovanni Luigi Tripepi1, Graziella D’Arrigo1, Daniela Leonardis1, Graziella Caridi2,
old). The retrospective study of the clinical record of these patients showed that 11
Giovanna Parlongo2, Francesco Marino2, Vincenzo Antonio Panuccio2,
(33%) had sustained hypertension and 54.5% of them needed 3 antihypertensive drugs.
Patrizia Pizzini1, Carmine Zoccali3, Francesca Mallamaci1,2, on behalf of the
2 patients suffered a severe cardiovascular event (intracranial hemorrhage). Of these 33
MAURO Working Group1
1
patients, aldosterone/renin screening was performed in 2, 2 other patients had an
IFC-CNR, Section of Epidemiology and Physiopathology of Renal Disease and abdominal CT scan, in which no adrenal masses were found. No specific studies were
Hypertension, Reggio Calabria, Italy, 2Grande Ospedale Metropolitano BMM, performed to definitively rule out hyperaldosteronism in any patient.
Nephrology, Dialysis, and Transplantation Unit, Reggio Calabria, Italy and In this period of application of big data, the hospital archive coded 3
3
Associazione per le Ricerche su Ipertensione, Nefrologia e Trapianto Renale, IPNET, hyperaldosteronisms: 1 of them was due to Bartter syndrome, another was a
Reggio Calabria, Italy misdiagnosis (androgenic syndrome) and the third one was due to medical background
of hyperaldosteronism which had been operated years ago.
BACKGROUND AND AIMS: Hypertension resistant to drug treatment is common These results were followed by a prospective screening carried on from 30th March
among CKD patients. However, the phenotype of resistant hypertension in the CKD 2020 to 1th January 2021. 776,878 supplementary data were extracted, and 232,425
population is still loosely defined and scarcely characterized. variables from 13,958 patients were analyzed. The system have generated an alert for 12
METHOD: In a cohort of 759 stage 2-5 CKD patients, we identified a subgroup of 647 patients: 2 of them have been diagnosed of primary hyperaldosteronism, another one
patients with >4 longitudinal visits (range 4-7 visits) over a median follow-up time of have an adrenal mass, which is in surgical waiting list, and 3 patients (total: 50%) are
36 months. These patients did not differ from the original study population as for age waiting medical tests due to a high suspicion of hyperaldosteronism.
(62611 years vs 62611), gender (59% vs 60%), diabetes (34% vs 35%) and eGFR CONCLUSION: Big data techniques allow us to create “red flags” for the screening of
(36613 versus 36613 ml/min/1.73m2). We adopted a conservative definition of rare diseases and might be an important tool in their diagnosis. Its systematic
resistant hypertension i.e. as a BP above the 2020 KDIGO guideline threshold (130/80 application guides us to perform specific diagnostic tests in at least 50% of the cases, in
mmHg) in spite of concurrent use of 3 antihypertensive agents (at maximum order to improve the diagnostic accuracy in these selected patients.
tolerated doses) of different classes including a diuretic or BP controlled with four or
more medications in at least 75% of visits. Adherence to drug treatment in this cohort
was systematically checked by attending physicians across all visits. Data are given as
mean 6 SD or as median and interquartile range (IQR).
RESULTS: Across the 36 months follow-up, 131 out of 647 patients (20%) had
resistant hypertension in >75% of visits. Resistant hypertensive patients were older
(6468 years vs 61611), more frequently diabetics (53% vs 29%) and with background
cardiovascular comorbidities (38% vs 29%) , higher body mass index (BMI) (3065 kg/

i140 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO111 PATTERN OF CARDIAC AND RENAL RISK FACTORS morning urine and fasting blood sample was collected for glycemic profile, lipid profile,
PREVAILING IN HYPERTENSIVE SUBJECTS OF RURAL serum creatinine, eGFR (MDRD equation) and urine ACR estimations for identifying
COMMUNITY: PRIMARY RESULTS FROM AN ONGOING diabetes, dyslipidemia and nephropathy. Results from an early group are presented
SYSTEMATIC SURVEY IN BANGLADESH here.
RESULTS: From surveyed population consequative 300 hypertensive subjects with 100
Sajal Krishna Banerjee1, Md M Iqbal2,3,4, MAA Chowdhury3, Sarwar Iqbal5, normotensive subjects were analyzed. Male/female distribution was 66% and 34%. Age
S Islam1, MZ Hassan6, SR Chaudhury7, RM Hossain1, MN Islam8, MS Hassan5, in 75% was between 25-55 years and BMI overweight to obese in 45%. Etiology wise in
MI Arslan1 81% it was essential hypertension followed by diabetes 18% and nephropathies in rest.
1
BSMMU, 2NIKDU, Bangladesh, 3KDRG, 4NIKDU, Nephrology, Dhaka, Bangladesh, Mean systolic BP was 147616 and diastolic BP 7169 mmHg. Comparison of
5
BIRDEM, 6BUHS, 7NHFRI and 8UHL hypertensive vs. normotensives showed FBS 6.763 vs. 5.861.0 mmol/l, (p<0.001).
Lipids as cardiac markers were TG 1706107 vs. 130676 g/dl, (p<0.001); Cholesterol
BACKGROUND AND AIMS: Hypertension is the leading entity of non 195650 vs. 180649 g/dl, (p<0.001); LDL 1706107 vs. 130676 g/dl, (p<0.04); and
communicable diseases (NCD). Some 15-30% adult population is identified suffering HDL 4267 vs. 4668 g/dl, (p<0.001). Renal parameters like eGFR was 88622 vs.
from hypertension at any given time worldwide. Complications of hypertension cause 98626 ml/min, (p<0.001); and ACR 996556 vs. 30687 mg/g, (p<0.04). These
severe functional deficit and a major decline in quality of life for the patient and family. comparisons showed fasting hyperglycemia with most of the lipids higher and HDL
This study was carried out to identify the presence and pattern of cardiac and renal risk lower in hypertensives. Renal parameters like eGFR was lower and albuminuria was
factors influencing major morbidity and mortality in hypertensive subject by significantly higher with similar urinary Na and K excretion in hypertensives. Other
performing relevant clinical and laboratory evaluations. cardio renal markers like Uric Acid and hCRP was similar in both groups. Pearson’s
METHOD: In this survey adult subjects were selected randomly from a defined rural correlations showed a positive correlation of systolic and diastolic BP with major
area. Their demographic, anthropometric and clinical information was recorded by components of cardiac, renal and metabolic risk factors.
WHO STEP wise approach surveillance-Instrument v.3.1. Information on prevailing CONCLUSION: It is found that hypertension is essential in nature among 81% of
NCDs and related risk factor were collected on a short questionnaire by face-to-face rural subjects. Nearly half of the study subjects are overweight. Dyslipidemia,
interview. Blood Pressure (BP) was measured by digital blood pressure monitor albuminuria and low GFR is more pronounced in hypertensives in comparison to the
(Omron) with standard sized cuff after 10-15 minutes of rest in sitting posture by normotensive counterparts. So, hypertension is mostly associated with adverse cardio-
taking mean of two readings. Systolic BP 140 and/or diastolic BP 90mmHg or renal risk markers.
subjects taking antihypertensive medications were considered for hypertension. Early

10.1093/ndt/gfab106 | i141
Nephrology Dialysis Transplantation 36 (Supplement 1): i142–i146, 2021
10.1093/ndt/gfab107

NEPHROLITHIASIS AND URIC ACID female, median age 6.06 (range 0.3-31.4 years)), of 149 idiopathic CaOx UL (90/59 m/f,
age 8.5 (0.1-68.6)), of 51 PH 1 patients (31/21, age 12.33 (0.8-63.8)), of 5 PH 2 patients
(3/2, age
5.41 (4.3-12.9)) and of 14 PH 3 patients (8/6, age 8.5 (2.9-29.3)) were analyzed for all
MO112 SYSTEMIC OXALOSIS IN PRIMARY HYPEROXALURIA TYPE 3 necessary components. All patients were in stable kidney function (eGFR > 45 ml/
– ARE THE PATIENTS AT RISK? min).
RESULTS: Uox was higher in the PH patients as compared to the non-PH UL or NC
Bernd Hoppe1, Cristina Martin Higueras2, Ulrike Herberg3, Johannes Birtel4, patients (p < 0.05). However, there was no statistical difference between the Uox in PH
Mark Born5 1 vs PH 2 or PH 3 patients, although, a clear effect of B6 medication was visible in PH1
1 patients. Urinary calcium excretion was lower (not significant) in PH patients as
German Hyperoxaluria Center, Bonn, Germany, 2University of La Laguna, Medicine, compared to NC/UL. There was no difference in ßCaOx when PH were compared to
San Cristobal de La Laguna, Spain, 3UKB University of Bonn, Pediatric Cardiology, Bonn, non-PH patients and it mostly remained in the normal range.
Germany, 4UKB University of Bonn, Opthalmology, Bonn, Germany and 5Pediatric
Radiology, Germany

BACKGROUND AND AIMS: Primary Hyperoxaluria type 3 (PH3) is said to be the Urine value PH 1 PH 2 PH 3 NC UL Normal
less problematic form of PH and with low risk of chronic kidney disease (CKD) and Median Median Median Median Median
end stage renal disease. However, a recent OxalEurope registry evaluation reported
both urine and plasma oxalate levels in a comparable range as in PH1 and PH2 (Range) (Range) (Range) (Range) (Range)
patients. In addition, PH3 patients remain symptomatic with recurrent kidney stones, Oxalate 0.95 1.56 1.26 0.46 0.46 < 0.5
even in adulthood, and 24% of the 95 patients evaluated were on CKD  2 at last
follow up. Hence, it was speculated, that PH3 patients may also be on risk to develop
mmol/ (0.46- (0.73- (0.44- (0.13- (0.13-
systemic oxalate deposition. 1.73m2/d 4.58) 2.91) 2.31) 1.21) 1.32)
METHOD: We retrospectively analyzed the imaging procedures performed so far in Calcium 1.23 1.64 2.15 2.69 3.35 <4
patients regularly seen at the German Hyperoxaluria Center, which included: eye
exams; x-rays of the hand; bone MRI (3 Thesla of the left knee and proximal tibia); and mg/kg/d (0.39- (0.3- (0.51- (0.67- (0.42-
Speckle tracking echocardiography using 2D Cardiac Performance Analysis VC 7.95) 10.48) 6.04) 13.32) 17.01)
(TomTec Imaging Systems GmbH, Germany), which measures changes in global Citrate 2.175 4.85 2.84 2.55 2.2 >1.6
longitudinal strain (GLS), an index of left ventricular contractibility. The normal range
for GLS is 18%. All patients or parents signed an informed consent. mmol/ (0.09- (1.78- (1.92- (0.3- (0.7- (f), > 1.9
RESULTS: From the 49 PH3 patients registered at the German Hyperoxaluria center, 1.73m2/d 5.61) 5.78) 7.56) 11.6) 9.74) (m)
12 pediatric and 4 adult patients are seen on a regular basis, at least twice a year, and
the rest are followed in other centers. All the 16 patients were in stable kidney function
«CaOx 4.3 3.95 5.43 4.2 4.81 < 5.5
and in no less than CKD 2. Eye examination was performed in six patients and was rel-units (1.03- (1.85- (1.09- (1.1- (0.8- (f) < 8.4
normal in all. Four patients received an x-ray of the left hand, which was normal in 3, 18.9) 9.53) 6.04) 21.5) 25.8) (m)
but in one patient with a problematic clinical course (multiple stone removal
procedures, decline in GFR), tiny sclerosing areas, although no true metaphyseal
bands, were seen at caput MCP IV and the thumb. Therefore, MRI of the left knee and CONCLUSION: Urine ßCaOx is similar in PH and non-PH stone formers. Therefore,
proximal tibia was performed in this and another patient, which showed no signs of calculation of ßCaOx using computed programs is not a reliable parameter to define
systemic oxalate deposition. Speckle tracking echocardiography was done in 6 patients the definitively extreme CaOx supersaturation of urine from PH patients. This
and was abnormal in one (GLS – 17.3 and left ventricular hypertrophy) and borderline miscalculation is related to a rather lowish urinary calcium excretion in PH as
in the twin sibling (GLS – 18.6). The patient with the abnormal GLS also had salivary compared to other UL/NC patients. Therefore, we recommend not to use such
stones in the parotid gland, as were also found in his other, older sibling in a routine x- programs to express the risk of recurrent stone disease or nephrocalcinosis in PH.
ray of the jaw before orthodontic treatment.
CONCLUSION: Although this is currently only data of a small cohort of patients, the
parameters available so far show, that systemic oxalate deposition may also occur in
PH3. Based on our experience on PH1, we regard Speckle tracking echocardiography MO114 NEPHROLITHIASIS AS CAUSE OF KIDNEY FAILURE AND
as the best parameter to detect early systemic calcium-oxalate depositions. Hence the MAJOR CARDIOVASCULAR OUTCOMES IN INCIDENT
reduction in global longitudinal strain, thus ventricular contractability, is a clear proof DIALYSIS PATIENTS
of such deposits. Of course, data in more patients are needed to elucidate the true risk
of systemic oxalate deposition and we are therefore currently screening all our PH3 Jingyin Yan1, Wolfgang Winkelmayer1, Jingbo Niu1
patients. 1
Baylor College of Medicine, Medicine-Nephrology, Houston, Texas, United States of
America

BACKGROUND AND AIMS: Symptomatic kidney stone formers experience excess


rates of cardiovascular events and are at increased risk of chronic kidney disease and its
progression. Little is known about the cardiovascular outcomes of persons with kidney
failure in whom nephrolithiasis or urolithiasis was listed as their presumed cause of
MO113 CALCULATED URINARY CALCIUM-OXALATE SATURATION
kidney failure.
(ßCAOX) IS NOT SPECIFICALLY ELEVATED IN PATIENTS
METHOD: We used the United States Renal Data Service (USRDS), a national kidney
WITH PRIMARY HYPEROXALURIA
failure registry, to identify all persons initiating dialysis between 1/1/1996 and 9/30/
2015. Patients were required to have Medicare fee-for-service coverage on day 90 of
Bernd Hoppe1, Wolfgang Böhm2, Cristina Martin Higueras3
1
dialysis, which served as index date. The presumed cause of kidney failure was
, Bonn, Germany, 2Clinical Pediatric Kannerklinik, Luxembourg, Luxembourg and abstracted from information reported on the Medical Evidence Report (form CMS-
3
University of La Laguna, San Crist
obal de La Laguna, Spain 2728) and categorized as: nephro-/urolithiasis, diabetes, hypertension,
glomerulonephritis, cystic kidney disease, other urologic cause, and other cause.
BACKGROUND AND AIMS: In the primary hyperoxalurias (PH; types 1-3) Eligible patients were then followed for the occurrence of a major adverse
recurrent urolithiasis (UL) and/or progressive nephrocalcinosis (NC) are the clinical cardiovascular event (MACE; nonfatal myocardial infarction, nonfatal stroke, or
hallmarks. Three different enzyme defects lead to endogenous oxalate overproduction cardiovascular mortality) using claims-based algorithms and causes of death reported
and to extremely elevated urinary oxalate excretion (UOx). Thus, it seems logical that in the Death Notification (form CMS-2746). Multivariable Cox regression models were
urine is supersaturated for calcium-oxalate (CaOx). It was, hence, speculated that fit while controlling for incident year, sociodemographic characteristics, initial dialysis
urinary CaOx saturation (ßCaOx), calculated by computed programs, is significantly modality, reported comorbidities and disabilities, biometric data (body mass index
higher as compared to that of patients with idiopathic CaOx stones. We now aimed to [BMI], eGFR, serum albumin, hemoglobin). Multiple imputation was used for missing
evaluate and calculate urinary ßCaOx in PH patients according to type, as well as in data. Both cause-specific and Fine-Gray sub-distribution hazard ratios (HR) with
non-PH patients with UL or NC. corresponding 95% confidence intervals (CI) were estimated.
METHOD: The computed equilibrium program EQUIL2 was used for the calculation RESULTS: Of 2,000,072 persons with incident kidney failure, 1,048,006 (52.4%) were
of ßCaOx. For this, 24 h urine specimen of 70 patients with non-PH NC (46 male, 24 alive and satisfied all inclusion criteria on day 90 (71.9% of the excluded due had no

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
Medicare coverage). Among those, 2207 (0.2%) had nephro-/urolithiasis as cause of vitro. Treatment with 6,7-DHC also protected both mice and rats from nephrolithiasis.
kidney failure, while 47% had diabetes, 30.4% had hypertension, 8.1% had GN, and Computational modelling have revealed 6,7-DHC interacts with MLKL and inhibits its
1.6% had cystic kidney disease listed. Persons with nephro-/urolithiasis tended to be phosphorylation by ATP which is a key event in necroptosis signaling cascade.
older, more likely to be female and non-Hispanic white, had lower rates of most CONCLUSION: All together our studies indicates that 6,7-DHC owns a novel
comorbidities, higher serum albumin and hemoglobin concentrations and lower BMI pharmacological inhibitory property towards MLKL and it could serve as a lead
and eGFR at dialysis initiation. The composite cardiovascular event rate (MI, stroke, molecule for further development of novel coumarin based MLKL inhibitors.
cardiovascular death; 721 events) was 74.4/1000 person years for nephro-/urolithiasis. Moreover, our findings also suggests that 6,7-DHC could be used as a therapeutic
Compared with those whose cause was nephro-/urolithiasis, persons whose cause of strategy for combating nephrolithiasis.
kidney failure was listed as diabetes had fully adjusted 57% (95% CI, 46%-69%) higher
hazards of MACE and those in whom it was attributed to hypertension the hazards
were 33% (95% CI, 24%-44%) higher. While no difference in the hazards of MACE was
MO116 COMPARISON OF THE CHARACTERISTICS BETWEEN
observed compared with persons with glomerulonephritis (HR 0.97; 95% CI, 0.90-
UNILATERAL AND BILATERAL RENAL STONES AND THEIR
1.05), those with cystic kidney disease had a 14% (95% CI, 7%-20%) lower hazards of
ASSOCIATION WITH KIDNEY INJURY IN CHINESE
MACE than those with nephro-/urolithiasis. Qualitatively similar results were obtained
POPULATION
when examining the individual components of MACE as well as when considering
kidney transplant and non-cardiovascular death as competing risks. However,
Xiaohong Fan1, Wenling Ye1, Jie Ma1, Liang Wang2, Xuemei Li1
competing risk analysis substantially attenuated the magnitude of the associations with 1
diabetes and hypertension as reported cause of kidney failure. Limitations include Peking Union Medical College Hospital, Nephrology, Beijing, P.R. China and 2Peking
heterogeneity of the underlying pathology among patients with nephro-/urolithiasis as Union Medical College Hospital, Ultrasound, Beijing, P.R. China
well as the possibility that some patients with nephro-/urolithiasis were not captured if
a different cause of kidney disease was listed. BACKGROUND AND AIMS: Urinary stone disease (USD) has been associated with
CONCLUSION: Patients with kidney failure presumably from nephro- or urolithiasis increased risk for chronic kidney disease (CKD) and end-stage renal disease (ESRD) in
have distinct cardiovascular risk profiles, with lower major cardiovascular event rates Western populations. However, the comparison of metabolic disorders between
compared with patients whose kidney failure was due to diabetes or hypertension, but unilateral and bilateral renal stones and their association with CKD have not been fully
slightly higher rates compared with those with cystic kidney disease. examined. It is also unclear whether there is an increased risk for kidney tubular injury
makers such as N-acetyl-ß-D-glucosaminidase (NAG) and alpha-1-microglobulin (a1-
MG) in different stone formers.
METHOD: We performed a cross-sectional study of 10,281 participants in rural China
MO115 6,7-DIHYDROXYCOUMARIN AMELIORATE EXPERIMENTAL
in 2014. All subjects underwent a renal ultrasound to detect USD; stone formers were
NEPHROLITHIASIS BY INHIBITING MLKL
grouped into one or two sides of USD by ultrasound exams. CKD was defined as a
PHOSPHORYLATION
decreased estimated glomerular filtration rate (eGFR, <60mL/min/1.73m2) and/or
albuminuria (ACR30mg/g). Increased urine NAG and a1-MG were defined as the
Smita Prajapati1, Bhawna Tomar1, Anjali Srivastava1, Shrikant Ramesh Mulay1
1
values of NAG and a1-MG above the 75th percentile of the sample distribution.
CSIR-Central Drug Research Institute, Pharmacology, Lucknow, India RESULTS: The mean age of the study population was 55.4610.0 years; 47.1% were
males. Among all participants, 4.9% (n=507) had unilateral renal stone, and 0.7% had
BACKGROUND AND AIMS: Intrarenal deposition of organic and inorganic bilateral renal stones. The proportion of CKD in non-stone formers, unilateral and
minerals attributes towards the pathogenesis of nephrolithiasis. Various current studies bilateral renal stones were 11.0%, 19.2%, and 29.7%, respectively (p for trend<0.001).
implicates crystal mineralization involves necroinflammation for the progression of Bilateral renal stone formers tend to have a higher proportion of hypertension and
crystal induced chronic kidney diseases (CKD). We hypothesized that 6,7- diabetes. In multivariate analyses after adjustment for multiple confounders, bilateral
dihydroxycoumarin (6,7-DHC) inhibits calcium oxalate (CaOx) induced necroptosis renal stones were significantly associated with an increased risk of decreased eGFR (OR
and ameliorates nephrolithiasis. 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18;
METHOD: We used an in vitro unbiased high content screening for identifying 95% CI 1.88-5.36), increased NAG (OR 1.95; 95% CI 1.21-3.16) and a1-MG (OR 2.54;
natural compounds that inhibits CaOx induced necroptosis. Molecular docking and 95% CI 1.56-4.12) compared with non-stone formers.
molecular dynamic simulations were done to study the interaction between 6,7-DHC - CONCLUSION: In the present study, bilateral renal stone formers tend to have a
MLKL. Further, for in vivo studies mice and rats models of nephrolithiasis were used. higher proportion of metabolic disorders and are also associated with a higher risk of
Renal injuries, CaOx deposition and fibrosis were evaluated using histological analysis. CKD and kidney tubular injury. Further studies are needed to confirm the increased
Protein expressions were assessed using immunoblots. Data was analysed using one risk for ESRD.
way ANOVA.
RESULTS: An unbiased in vitro high content screening of a library of 24 natural
compounds identified 6,7-DHC as a potential candidate. Further, pretreatment with
6,7-DHC protected human and mouse cells from CaOx crystal mediated necroptosis in

MO116 Table: Associations of urinary stone disease with chronic kidney disease and markers of kidney tubular injury.

Outcomesa stone status unadjusted OR Adjusted OR P for


(95% CI) (95% CI)b trend
CKD Unilateral vs. no stone 1.919(1.523-2.420) 1.838(1.441-2.345) <0.001
Bilateral vs. no stone 3.418(2.068-5.650) 3.176(1.883-5.356)
ACR(30mg/g) Unilateral vs. no stone 2.001(1.584-2.528) 1.927(1.507-2.462) 0.146
Bilateral vs. no stone 3.202(1.909-5.370) 3.005(1.760-5.131)
eGFR(60ml/ Unilateral vs. no stone 1.321(0.642-2.720) 1.032(0.468-2.278) <0.001
min/1.73m2) Bilateral vs. no stone 4.709(1.691-13.113) 3.377(1.046-10.901)
NAG/Cr Unilateral vs. no stone 1.143(0.934-1.399) 1.051(0.852-1.295) 0.043
Bilateral vs. no stone 1.959(1.226-3.131) 1.953(1.206-3.162)
a1-MG/Cr Unilateral vs. no stone 1.462(1.205-1.773) 1.165(0.944-1.439) <0.001
Bilateral vs. no stone 2.624(1.657-4.155) 2.536(1.560-4.124)

CKD, chronic kidney disease; ACR, albumin-to-creatinine ratio; eGFR, estimate glomerular filtration rate; NAG,N-acetyl-ß-D-glucosaminidase;a1-MG,alpha-
1-microglobulin; Cr, creatinine.
a
Outcomes are expressed as dichotomous variables.
b
Adjust for age, sex, smoking, body mass index, mean arterial pressure, uric acid, hypertriton and diabetes or not

10.1093/ndt/gfab107 | i143
Abstracts Nephrology Dialysis Transplantation

MO117 THE IMPACT OF GESTATIONAL AGE ON ANATOMICAL AND METHOD: This prospective study was conducted in the Department of surgery and
PHYSIOLOGICAL CHANGES OF THE UPPER URINARY radiodiagnosis and Imaging, Era Medical College and RML institute of Medical
TRACT DURING PREGNANCY Sciences , Lucknow over the study period, i.e., November 2016 to May 2018 . The
patients were those referred for non-contrast/contrast CT for the diagnosis/evaluation
Ciciu Elena1, Ana-Maria Pas, atu-Cornea1, Liliana-Ana Tuta1 of urolithiasis from the department of Surgery admitted for PCNL/ESWL/therapeutic
1
Ovidius University, Internal Medicine- Nephrology, Constanta, Romania ureterorenoscopy. DECT ratios of the various stones were noted and compared with
the post extraction analysis of stones for composition. A total of 100 patients were
BACKGROUND AND AIMS: Ureterohydronephrosis (UHN) is a common anatomical included in the study, and their DECT results were compared with the post-extraction
change during the evolution of pregnancy, especially after 20th week of pregnancy. Factors analysis (by infrared spectroscopy as the standard comparative method).
responsible for dilation of pyelocaliceal system are hormonal changes, progressive RESULTS: Mean age of patients was 41.15+/- 10.08 years with 64% being males.
obstruction and modification of the route of uterine and iliac vessels in the pelvic area. DECT was highly sensitive and specific in the diagnosis of various types of calculi
The main symptom of UHN is lumbar pain which is controlled in most of the cases by based on their dual-energy ratio. It was found to be 100% sensitivity and 97.2%
conservatory treatment.The aim of study was to o evaluate the stages of UHN during specificity for differentiating UA stones with level of agreement between chemical and
pregnancy depending on gestational age and to highlight the involvement of the pregnant DECT was almost perfect (k= .951) .However for hydroxyapatite stones was
uterus, as well as monitor the symptomatology and adequate management of these substantial (k=.889). Most of the stones belonged to non-UA category (72%), and only
anatomical and physiological changes, that can associate variable complications, with 28% were UA calculi. The sensitivity and specificity in differentiating a calcium oxalate
maternal-fetal risk, during pregnancy. from non-calcium oxalate calculus was 94.1% and 95.5%, respectively.
METHOD: We performed a descriptive, transversal study for examination of pregnant CONCLUSION: DECT highly sensitive and effective in characterizing chemical
women with symptomatic hydronephrosis. A total number of 104 patients, composition of the urinary stones and can help in determining the management plan
hospitalized in the Obstetrics and Gynecology Department of the Constanta County and reduce the unnecessary burden of surgical interventions.
Emergency Hospital, were included, with nephrological monitoring using biological
and imagistic examination for each pregnancy.
RESULTS: The frequency of UHN in our study was 58% (60 cases) from the total MO119 COMPUTER-DERIVED SOFTWARE IN CLINICAL PRACTICE:
number of 104 pregnant women. Regarding the gestational age, UHN was most RESULTS FROM A SHORT-TERM FOLLOW-UP ACCORDING
commonly seen in the third trimester in 44 cases, followed by second trimester with 14 TO KIDNEY STONE COMPOSITION IN KIDNEY STONE
cases and first semester with only 2 cases. The right UHN was seen in all cases and the FORMERS
left UHN was seen in only 68 % of the cases. Our data showed that grade III of UHN
reached a peak between 28 and 31 weeks of pregnancy and occurred in 37 (49%) Tamara Cunha1, Adrian Rodriguez2, Pietro Manuel Ferraro2
pregnant women. Analyzing the parity, it was observed that 56% of the primiparous 1
women developed UHN and 59% of the multiparous patients, showing us that the Universidade Federal do Rio de Janeiro, Nephrology, Rio de Janeiro, Brazil and
2
association with parity is not statistically significant. The majority of our patients Universit
a Cattolica del Sacro Cuore, Nephrology, Roma, Italy
(96.66%) were symptomatic, and the most common accuse on presentation was the
lumbar pain. According to the visual analog scale (VAS) of the lumbar pain, the group BACKGROUND AND AIMS: Urinary supersaturation (SS) contributes to stone
could be distributed as follows: 17% with severe pain, 37 % with moderate pain and 13 formation, and its assessment in stone formers may be helpful in clinical practice. Several
% with mild pain. Eight pregnant women (13.33%) from our study developed UHN computer programs are available for SS calculation, including EQUIL2, JESS and Lithorisk1.
due to passage of ureteral stone, although, the majority got complicated with urinary The aim of this study was to evaluate changes in SS in 24-hour urine in patients with known
tract infection (asymptomatic bacteriuria, acute cystitis, acute pyelonephritis) and even stone composition before and after about three months of regular treatment.
acute kidney injury (4 cases- 6,66%).97% of the symptomatic UHN responded to METHOD: Patients who submitted their stone/s for composition analysis and had
antispastic and analgesic therapy, antibiotics and adequate hydration. From our study provided an adequate 24-hour urine collection (creatinine 15-20 mg/kg/24-hour)
group, only 2 patients (3,33%) with severe symptomatic UHN needed ureteral stent before and around 90 days under regular treatment were included. Stone composition
insertion, because initially they did not respond to medical, conservative treatment. was defined using morphoconstitutional and infrared spectroscopy. The treatment was
CONCLUSION: Uretrohydronephrosis is a common anatomical change in pregnancy and initiated in accordance with specific guidelines, and included dietary advices and
is depending on the gestational age. Parity did not influence the development of medications2. SS for calcium oxalate (CaOx), calcium phosphate (CaP) and uric acid
hydronephrosis in our study group. The most common symptom of ureterohydronephrosis (UA) using EQUIL2, JESS and Lithorisk were calculated at baseline and after about 90
during pregnancy is the lumbar pain, which can have different types of intensity (usually days on treatment. Continuous variables were reported as means (SD) while categorical
moderate to severe). Conservatory treatment during symptomatic, complicated variables were reported as frequencies and percentages. Baseline and follow-up SS
ureterohydronephrosis is efficient in most cases, otherwise urological interventions with urine values were compared using the Wilcoxon signed-rank test. 3D graphs were
ureteral stent insertion must be initiated, because are effective and safe. plotted using mean SS values of CaOx, CaP and UA obtained from each program

MO118 ROLE OF DUAL ENERGY COMPUTED TOMOGRAPHY IN


PREDICTING THE CHEMICAL COMPOSITION OF STONES

Dr Sanjay Bhat1, Anupma Kaul2


1
Ram Manohar Lohia Institute of Medical Sciences, Surgery, Lucknow, India and
2
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Nephrology, Lucknow, India

BACKGROUND AND AIMS: Dual-energy CT (DECT) has shown excellent


outcomes in differentiating the chemical composition of the urinary stones with a great
accuracy. A reliable determination of the chemical type of the stone help the clinician MO119 Figure 1: 3D plots evaluating mean urinary supersaturations (SS) before and
to better satisfy treatment options for the patient- medical versus surgery We used the after treatment of four major groups of stone formers, using EQUIL2, JESS and
DECT in our study to assess the accuracy of non-invasive differentiation of renal Lithorisk programs. "b" : refers to baseline; "f’: refers to follow-up period. COD: calcium
stones using the 3rd generation dual-source computed tomography (CT) scanner in oxalate dihydrate; COM: calcium oxalate monohydrate; COD: calcium oxalate
determining the chemical composition of renal stones and to determine appropriate dihydrate; CaOx : calcium oxalate; CaP: calcium phosphate; UA : uric acid
management based on DECT determined chemical composition of stones.

i144 | Abstracts
Nephrology Dialysis Transplantation Abstracts
before and after treatment, dividing the stones into 4 groups1: calcium oxalate describe the possible link between stone composition and cardiovascular disease and its
monohydrate (COM), calcium oxalate dihydrate (COD), calcium phosphate (CaP), differential effect among women and men.
and uric acid (UA). Ethical Committee approval was obtained. METHOD: Retrospective review of patients with known stone composition seen in a
RESULTS: 105 patients (61 men, 58%) were followed and provided 24h urine nephrolithiasis unit in the last five years. Anthropometric and clinical data were
collection. Of these, 101 (96%) were recurrent patients. The mean (SD) follow-up was gathered from the hospital records. Stone composition was defined as such if 50% of
94 (14) days. 48 (46%) of all calculi were made of CaOx, either COM or COD, 36 (34%) the stone was made from a single component. Cardiovascular disease included
of UA, and 21 (20%) of CaP. A significant reduction in SS values during treatment was coronary artery disease, stroke and peripheral vascular disease. Unadjusted and
observed in patients with COM (p<0.05) , COD (p<0.001), and UA stones (p<0.001) adjusted logistic regression analysis were applied to describe the potential relationship
with all programs. The reduction in SS values over time in patients with CaP stones between stone composition and cardiovascular disease.
was not significant (Table 1). Figure 1 shows 3D plots with SS before and after RESULTS: 337 patients were included in the study sample. Median age was 57 (IQR
treatment into 4 groups of stone formers. 47-67), 61.1% males. 58.2% suffered from recurrent stone disease and 28.5% from
family history of stone formation. 32.9% of patients had hypertension, 22,4%
diabetes and 13,1% chronic kidney disease. The most common kidney stone
MO119 Table 1. Changes in urinary supersaturation before and during follow-up, component was calcium oxalate (38.6%) followed by calcium phosphate (21.3%),
according to the type of the stone.
uric acid (14.2%), struvite (8%) and brushite (0.9%). Only uric acid as main stone
component was associated with cardiovascular disease among men but not women
Stone Type Urinary Supersaturation p- in our sample in univariate analysis. That relationship was lost in adjusted logistic
value regression analysis.
CONCLUSION: Calcium oxalate and phosphate were the most common components
UA stones UA SS of kidney stones. No relationship was found between stone composition and
(n=36) Baseline Follow-up cardiovascular disease in the study sample.
Equil2 4.72 (2.12) 1.04 (1.02) <0.001
Jess 0.72 (0.19) -0.15 (0.46) <0.001
Lithorisk 1.93 (0.86) 0.39 (0.40) <0.001
COM stones CaOx SS
(n=22) Baseline Follow-up
Equil2 5.76 (6.28) 2,72 (1.73) 0.008
Jess 0.62 (0.39) 0,38 (0.29) 0.006
Lithorisk 3.17 (4.02) 1.39 (0.98) 0.016
COD stones CaOx SS
(n=26) Baseline Follow-up
Equil2 7.61 (4.83) 4.48 (3.46) <0.001
Jess 0.86 (0.28) 0.59 (0.29) <0.001
Lithorisk 4.49 (3.17) 2.41 (1.95) <0.001
CaP stones Bru SS
(n=21) Baseline Follow-up
Equil2 1.28 (1.15) 0.93 (0.66) 0.085
Jess 0.31 (0.39) 0.18 (0.39) 0.191
Lithorisk 1.91 (1.71) 1.37 (0.96) 0.630
MO121 ASSOCIATION BETWEEN BONE MINERAL DENSITY, BODY
COMPOSITION AND SERUM SCLEROSTIN IN MALE STONE-
Mean (SD). COM: calcium oxalate monohydrate; COD: calcium oxalate FORMERS
dihydrate; CaP: calcium phosphate; Bru: brushite; SS: urinary supersatu- Fernanda Guedes Rodrigues1,2, Igor Pietrobom3, Milene Subtil Ormanji3,
ration; CaOx: calcium oxalate; UA: uric acid Priscila Ligeiro Gonçalves Esper3, Ana Cristina Matos3, Daniel Ribeiro da Rocha3,
Adriana Dos Santos Dutra1, Martin De Borst2, Ita Pfeferman Heilberg1,3
1
UNIVERSIDADE FEDERAL DE SAO ~ PAULO, Nutrition Post Graduation Program, S~
ao
CONCLUSION: EQUIL2, JESS and Lithorisk are suitable software currently used for
clinical and research purposes. SS values calculated by EQUIL2, JESS and Lithorisk Paulo, Brazil, 2University of Groningen, University Medical Center Groningen,
3
during follow-up showed a significant reduction among COM, COD and UA stone Department of Nephrology, Groningen, The Netherlands and UNIVERSIDADE FEDERAL
~ PAULO, Department of Nephrology, S~
DE SAO ao Paulo, Brazil
formers. CaP stone formers did not show significant changes in SS over time.

References BACKGROUND AND AIMS: Reduced bone mineral density (BMD) has been
observed in stone-formers (SF). Although obesity is considered a protective factor for
1. Rodriguez A, Cunha TDS, Rodgers AL, Gambaro G, Ferraro PM. Comparison of bone health due to increased mechanical load, the role of muscle mass (lean) or body
supersaturation outputs from different programs and their application in testing fat remains controversial. Sclerostin, an antagonist of the Wnt signaling pathway, is
correspondence with kidney stone composition. J Endourol. 2020; doi: 10.1089/ secreted by osteocytes and its actions involve the inhibition of bone formation, FGF23
end2020.0894. stimulation, and increased urinary calcium and phosphorus excretion. Recent studies
2. Wollin AD, Kaplan AG, Preminger GM, Ferraro PM, Nouvenne A, Tasca A, also indicate its association with body composition. The aim of the present study was
Croppi E, Gambaro G, Heilberg IP. Asian J Urol. 2018; 5(4):235–242. to evaluate the relationship between BMD and body composition with serum sclerostin
levels in male SF.
METHOD: This is a retrospective study, based on medical records of SF with available
data of BMD and body composition, serum and urinary biochemistry and hormonal
measurements including sclerostin. BMD had been assessed at lumbar spine (L1-L4),
MO120 STONE COMPOSITION AND CARDIOVASCULAR DISEASE IN femoral neck (FN) and total femur (TF) and body composition (fat and lean mass) in a
PATIENTS WIITH NEPHROLITHIASIS dual energy X-ray absorptiometry (DXA).
RESULTS: Fifty-five male SF (37.2 6 9.3 years) were included. Patients were divided
Ana Lucıa Valencia1, Armando Coca1, Arturo Lorenzo3, Veronica Fidalgo1, into tertiles according to the percentage of body fat (T1, n = 19, 8.7-20.0 %; T2, n = 20,
Vicente Perez1, Lucila Fernandez1, Carmen Aller1, Sandra Sanz1, 20.1-26.0 %; T3, n = 16, 26.1-38.0 %). There was no statistical difference in BMD in any
Alicia Mendiluce1 of the sites between these tertiles. Higher urinary sodium and serum sclerostin were
1
Hospital Clinico de Valladolid, Nephrology and 3hospital Clinico de Valladolid, observed in T3 versus T1 (280 6 93 vs 199 6 75 mEq/day, p <0.05; 33.6 6 14.7 vs 24.7
Nephrology 6 8.3 pmol/L, p<0.05, respectively). There was an inverse association between serum
sclerostin and lean mass (b= -0.30, p=0.001) and direct association with fat mass
(b=0.40, p=0.001), urinary calcium and phosphorus (b=0.29, p=0.02; b=0.32, p=0.01).
BACKGROUND AND AIMS: Kidney stone disease is widely prevalent in the general In a multivariate linear regression model, lean mass was an independent predictor of
population and has been associated with multiple comorbidities including BMD at L1-L4, FN and TF (b= 0.70, p<0.001; b=0.70, p<0.001; b=0.57, p=0.00,
hypertension, diabetes, chronic kidney disease and cardiovascular disease. We aimed to

10.1093/ndt/gfab107 | i145
Abstracts Nephrology Dialysis Transplantation

respectively) and at the TF there was also an inverse association between body fat and in the past. The reasons for such differences and changes over time are not clear.
PTH (b= –0.51, p= 0.03; b= –0.25, p= 0.03). METHOD: We analyzed the association between sex and the first symptomatic
CONCLUSION: These data suggest that male SF with a higher percentage of body fat incident kidney stone using data from three large, longitudinal cohorts. Incidence rates
had higher levels of serum sclerostin, which were directly associated with calciuria and for men and women overall and across categories of age and calendar time were
phosphaturia but not with BMD. In addition, lean mass was an independent predictor computed and hazard ratios (HRs) and 95% confidence intervals (CIs) generated with
of BMD. Further studies are needed to determine long-term effects of serum sclerostin age-adjusted Cox proportional hazards regression models. Mediation analysis was
levels upon bone formation in SF. performed in order to estimate the amount of excess risk for men explained by
established risk factors, including BMI, waist circumference, history of high blood
pressure, history of diabetes, use of thiazides, dietary intakes of animal protein,
caffeine, fructose, potassium, sodium, oxalate, phytate, dietary and supplemental
MO122 SEX DIFFERENCES IN THE RISK OF KIDNEY STONES
intakes of calcium, vitamin C and vitamin D, sugar-sweetened beverages and total fluid
intake.
Pietro Manuel Ferraro1,2, Eric N Taylor3,4, Gary C Curhan3 RESULTS: The analysis included data from 268,616 participants, contributing
1 5,876,205 person-years of follow-up, during which 10,303 incident stone events were
Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia, U.O.S. Terapia
confirmed. The overall incidence rate of kidney stones was 271 and 158 per 100,000
Conservativa della Malattia Renale Cronica, U.O.C. Nefrologia, Dipartimento di Scienze
person-years for men and women, respectively. The age-adjusted HR for men
Mediche e Chirurgiche, Rome, Italy, 2Universit
a Cattolica del Sacro Cuore, Roma, Italia,
compared with women was 2.32 (95% CI 2.20, 2.45). About 18% of the difference in
Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Rome, Italy, 3Brigham
rates was explained by the risk factors included in the analysis. The risk of stones was
and Women’s Hospital, Harvard Medical School, Channing Division of Network
consistently higher across categories of age among men compared with women. With
Medicine, Department of Medicine, Boston, United States of America and 4Maine
regard to calendar time, the risk remained higher among men, but tended to decrease
Medical Center, Division of Nephrology and Transplantation, Maine, United States of
over time while it increased among women, resulting in a relative risk reduction of 38%
America
for after 2009 compared with before 1990.
CONCLUSION: The risk of kidney stones is higher among men compared with
BACKGROUND AND AIMS: Kidney stone disease is a highly prevalent condition. women. This difference is only partly explained by modifiable risk factors.
Men are at higher risk of developing stones compared with women, however recent
data suggest a changing epidemiology with women being relatively more affected than

i146 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i147–i197, 2021
10.1093/ndt/gfab092

CLINICAL NEPHROLOGY CONCLUSION: Overall, we applied single-cell RNA sequencing to IMN to uncover
intercellular interactions, elucidate key pathways underlying the pathogenesis, and
identify novel therapeutic targets of IMN.

MO123 USE OF RIVAROXABAN VERSUS WARFARIN IN PATIENTS


WITH ATRIAL FIBRILLATION AND ADVANCED CHRONIC
KIDNEY DISEASE*

Sherzod Abdullaev1, Rano Igamberdieva1, Olimkhon Sharapov1


1
Tashkent pediatric medical institute, Internal medicine, Tashkent, Uzbekistan

BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) develop
bleeding and thromboembolic tendencies, so the indication for the use of
anticoagulants for atrial fibrillation (AF) is difficult. AF is the most common chronic
cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are the
main complications. In recent years, new oral anticoagulants (rivaroxaban) have been
developed and have shown superiority over classic anti-vitamin K anticoagulants in
preventing the risk of stroke, systemic embolism and bleeding.
Aim is to evaluate the safety parameters of rivaroxaban in patients with stage 4 chronic
kidney disease (CKD) or a transient sustained decrease in glomerular filtration rate
(GFR) to 15–29 ml/min/1,73 m2 in the presence of atrial fibrillation (AF).
METHOD: Multicenter prospective randomized study that included patients from
cardiology departments in 2019. Of 5448 hospitalized patients, 109 (2%) patients with
AF and CKD stage 4 or a sustained decrease in GFR to 15-29 ml/min/1.73 m2 were
randomized in a 2:1 ratio to rivaroxaban 15 mg/day (n=73) or warfarin (n=36).
Primary endpoint: development of large, small and small clinically significant bleeding
according to the BARC (Bleeding Academic Research Consortium) and ISTH
(International Society on Thrombosis and Hemostasis) scales. The average follow-up
period is 12 months.
RESULTS: Patients taking warfarin were significantly more likely to develop minor MO124 Figure 1: Cell lineage analysis by comprehensive single-cell RNA-
bleeding according to BARC scales (n=26 (72.2%) versus n=31 (42.4%), p<0.01) and sequencing in IMN and control subjects
ISTH (n=22 (61.1%) versus n=27 (36.9%), p<0.01) and all clinically significant (minor (A) Schematic of the scRNA-seq pipeline. kidney (n=6) samples from patients with
clinically significant and major) bleeding according to the ISTH scale [n=10 (27.7%) IMN or healthy control subjects (n=2) were collected at the time of clinically indicated
versus n=8 (10.9%), p=0.03]. The number of readmissions was 32 (43.8% of patients) renal biopsy or live kidney donation, respectively. Kidney biopsies were enzymatically
in the rivaroxaban group, 17 (47.2% of patients) in the warfarin group (p=0.57), of disaggregated into single-cell suspensions and loaded onto a microfluidic device for cell
which 12 (37.5%) and 7 (41.1%) (in the rivaroxaban and warfarin groups, respectively) barcoding, cell lysis, reverse RNA transcription, and then scRNA-seq as well as various
- for urgent reasons (p=0.96). A significant improvement in the dynamics of creatinine analysis. (B)Seventeen distinct cell clusters were visualized by UMAP plotting, with
levels, GFR (according to CKD-EPI) in the rivaroxaban group was revealed. each cell color-coded for its associated subtypes. The color of the cells represented
CONCLUSION: The study provides evidence of a favorable safety profile for group origin. (C) UMAP plot of cell clusters from different subjects of IMN patients
rivaroxaban compared with warfarin in patients with AF and advanced CKD. and control. The color of cells reflected the individual origin. (D) Bar plots of the
percent contribution of cell clusters in kidneys from different subjects. Blocks
represented different subjects, and block height was in proportion to the number of
cells. (E) Heatmap of the top 20 most differentially expressed genes in each cluster to
identify mutually exclusive gene sets, which were then used to determine the cell
lineage of each cluster. Each column represented a cell cluster, and each row
corresponded to a marker gene for the individual cluster. Transcript abundance ranges
MO124 THE SINGLE-CELL TRANSCRIPTOMIC OF HUMAN from low (purple) to high (yellow). (F) Violin plot of selected marker genes that
IDIOPATHIC MEMBRANOUS NEPHROPATHY* identified the clusters generated by UMAP plotting. It was colored by different cell
subtypes.
Yong Zhong1, Qiaoling Zhou1 Abbreviations were as follows: PT, proximal tubule cells; LOH, loop of Henle cells PC,
1
Xiangya hospital,central south university, Nephrology, changsha, P.R. China principal cells; IC, intercalated cells; DT, distal tubule cells; EC, endothelial cells; Pod,
podocytes; MC, mesangial cell; DC, dendritic cells; Mac, macrophages; Mono,
monocytes; Fib, fibroblasts; Per, pericyte.
BACKGROUND AND AIMS: Idiopathic membranous nephropathy (IMN) is an
organ-specific autoimmune disease of the kidney glomerulus. Although substantial
advances have been made in the understanding of the molecular bases of IMN in the
last 10 years, there remain largely unanswered questions.
METHOD: To define the transcriptomic landscape at the single-cell resolution, we
analyzed kidney samples from 6 patients with idiopathic membranous nephropathy MO125 NON-AMYLOID TYPE OF MONOCLONAL GAMMOPATHY OF
(IMN) and 2 healthy control subjects using single-cell RNA sequencing. RENAL SIGNIFICANCE: CLINICAL AND MORPHOLOGICAL
RESULTS: Based on transcriptional expression patterns, we identified all previously SPECTRUM AND LONG-TERM RENAL OUTCOME*
described cell types in the kidney. Also, we identified a novel population of the
epithelial cell which is mainly from IMN patients. GO enrichment analysis showed Maria Khrabrova1, Alexei Smirnov2, Vladimir Dobronravov2, Olga Kudjasheva3
1
that DEGs were enriched in the regulation of apoptosis and type I interferon signaling Pavlov University, Propaedeutics of Internal Diseases, 2Pavlov University, Research
pathway in mesangial cells, while DEGs were enriched in the regulation of Institute of Nephrology and 3Pavlov University, Raisa Gorbacheva Memorial Research
programmed cell death, and various cytokine-mediated signaling pathway in Institute for Pediatric Oncology, Hematology and Transplantation
endothelial cells and the regulation of protein modification in pericytes. KEGG
enrichment analysis revealed that DEGs were mainly associated with the IL-17 BACKGROUND AND AIMS: Monoclonal gammopathy of renal significance
signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway as (MGRS) is a clinically and morphologically diverse kidney damage caused by
well as MAPK signaling pathway in endothelial cells as well as pericytes DEGs of monoclonal immunoglobulin (IG) produced by a "small" B-cell clone. Non-amyloid
proximal tubules cells (PT) and PCs between IMN and control subjects were both type of MGRS is considered to be rare but associated with poor kidney outcome (KO).
enriched in IL-17 signaling, TNF signaling, NOD-like receptor signaling. Moreover, The analysis of the prevalence, clinical and morphological spectrum and long-term
the cell-cell crosstalk highlighted the extensive communication of mesangial cells, renal prognosis in different degrees of hematological response (HR) in patients with
which infers great importance in IMN. IMN with massive proteinuria displayed non-amyloid type of MGRS became the goal of this study.
elevated genes participating in the inflammatory signaling pathways that may be METHOD: In this one-center prospective study performed from 01.01.2011 till
involved in the pathogenesis of the progression of IMN. 01.03.2020 patients with MGRS were enrolled. Criteria of MGRS were following: i)

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

morphologically verified monoclonal IG related kidney damage and ii) an aberrant


clone in the bone marrow and/or the level of serum/urine paraprotein not met the
hematological criteria for treatment initiation. Cases of renal AL-amyloidosis were
excluded. The morphological spectrum of non-amyloid MGRS, treatment,
hematological and renal responses (RR) were analyzed. HR was assessed depending on
the type of monoclonal IG according to the accepted criteria. The presence of RR was
considered as a decrease in daily proteinuria> 30% from the initial level or less than 0.5
g in the absence of a decrease in eGFR> 25% at the time of the end of follow-up. The
progression of renal dysfunction was documented with a decrease in eGFR> 25% from
baseline. KO was determined as initiation of renal replacement therapy or eGFR <15
ml/min/1.73m2 at the end of follow-up. Long-term renal survival was assessed by the
Kaplan-Meier method. The median follow-up period was 18 (4; 38) months.
RESULTS: The prevalence of non-amyloid MGRS was 1.4% (n = 29) of all performed
kidney biopsies (n = 2042). Clinical and demographic parameters of the group are
presented in the figure 1.

MO125 Figure 3: Hematological and renal responses in the non-amyloid MGRS


group.

The five-year cumulative renal survival was 44% in the non-amyloid MGRS group and
did not significantly differ from renal AL-amyloidosis group when compared (Figure
4).

MO125 Figure 1: Clinical and demographic data in patients with monoclonal


gammopathy of renal significance at the time of kidney biopsy.

Serum or/and urine paraprotein was detected in 23 patients as j (30.4%), IgM/j


(21.7%), IgM/k (13.1%), IgG/j (13.1%), k (13.1%), IgA/j (4.3%), IgG/k (4.3%).
Morphological spectrum of non-amyloid MGRS is shown in the figure 2.

MO125 Figure 4: Five-year cumulative renal survival in patients with renal AL-amyl
oidosis and in non-amyloid MGRS group.

CONCLUSION: Non-amyloid type of MGRS is a clinically and morphologically


diverse entity characterized by a poor renal prognosis, especially in the absence of
clone-specific therapy. Treatment of MGRS should be carried out in a timely manner
with the participation of a hematologist and nephrologist in order to prevent loss of
kidney function and increase life expectancy.

MO125 Figure 2: Morphological spectrumof non-amyloid type of monoclonal


gammopathy of renal significance.

Combination of light chain deposition disease and thrombotic microangiopathy was


documented in two cases. The majority of patients (82.7%) was treated with clone-
specific agents. In non-IgM-associated MGRS cases bortezomibþdexamethasone (D)
(n=11), melphalanþD (n=2), cyclophosphamide (CPh) þbortezomibþD (n=1),
lenalidomideþD (n=1) were used. Autologous stem cell transplantation was performed
in 1 case. PrednisoloneþCPh based schemes were applied in 5 patients. In IgM-
associated MGRS 7 patients were treated with rituximab and 1 patient with
bortezomibþD due to contraindication to anti-CD20 agent. 8 patients were missed
from the follow-up. HR and RR were achieved in 76.2% and 62% of the treated
patients, respectively (Figure 3).

i148 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO126 CLINICAL AND BIOMARKER CHARACTERISTICS OF <18 years). Complement biomarkers including, but not limited to, C3, C4, AP activity,
PATIENTS WITH C3G OR IC-MPGN ENROLLED IN TWO classical pathway activity, FD, Ba, Bb, sC5b-9, and C5 were measured in serum or
PHASE II STUDIES INVESTIGATING THE FACTOR D plasma prior to dosing. Spearman correlation coefficients (rs) were determined
INHIBITOR DANICOPAN* between biomarkers of complement, eGFR, and/or proteinuria.
RESULTS: A total of 35 patients were included in this analysis (13 from study 1 and 22
Carla Nester1, Steven Podos2, Jonathan Hogan3, Gerald Appel4, from study 2). The majority of patients were male (9 [69%] in study 1, 12 [55%] in
Andrew Bomback4, Koen Bouman5, Terry Cook6, Erica Daina7, Bradley Dixon8, study 2), with mean (SD) ages at baseline of 25.2 (7.63) years in study 1 and 24.3 (9.90)
Craig Langman9, Liz Lightstone10, Jane Thanassi11, Kara Rice11, years in study 2. Most patients had received prior angiotensin converting enzyme
MingJun Huang2, Samir Parikh12, Matthew Pickering13, John Sperati14, inhibitors/receptor blockers (12 [92%] in study 1, 19 [86%] in study 2), and/or
Howard Trachtman15, James Tumlin16, Jack F.M. Wetzels17, immunosuppressants (10 [77%] in study 1, 12 [55%] in study 2). Baseline clinical and
Giuseppe Remuzzi18 biomarker data are shown in Table 1. Baseline eGFR was moderately correlated with
1
Molecular Otolaryngology and Renal Research Laboratory, Iowa City, United States of proteinuria (uPCR24, rs=-0.40 [p=0.022]); baseline uPCR24 was also moderately
America, 2Alexion Pharmaceuticals, Inc., New Haven, United States of America, correlated with Ba (rs=0.42 [p=0.016]) and FD (rs=0.53 [p=0.002]). Ba and FD
3
Hospital of the University of Pennsylvania, Division of Nephrology, Philiadelphia, elevations showed strong correlations with lower eGFR (rs=-0.79 and -0.88,
United States of America, 4Columbia University Medical Center, Columbia, United respectively [p<0.0001]), as seen in Figure 1A and B. Reduced circulating C3 strongly
States of America, 5ZNA Nierkliniek, Antwerp, Belgium, 6Imperial College London, correlated with increased sC5b-9 (rs=-0.70 [p<0.0001]) and reduced C5 level (rs=0.80
London, United Kingdom, 7Istituto di Ricerche Farmacologiche Mario Negri IRCCS, [p<0.0001]), as seen in Figure 1C and D.
Milan, Italy, 8University of Colorado School of Medicine, Renal Section, Department of CONCLUSION: Data from two danicopan clinical studies in C3G patients show
Pediatrics, Aurora, United States of America, 9Feinberg School of Medicine, correlations with renal impairment and proteinuria were observed for some, but not
Northwestern University, Chicago, United States of America, 10Imperial College London, all, complement biomarkers. Factor Ba and FD are strongly associated with eGFR,
Centre for Inflammatory Disease, Dept of Immunology and Infection, Faculty of suggesting that these biomarkers cannot easily be used as markers of complement
Medicine, United Kingdom, 11Alexion Pharmaceuticals, Inc., Boston, United States of dysregulation or activity. Interpretation of changes in these complement proteins needs
America, 12The Ohio State University Medical Center, Division of Nephrology, to include not only the nature of the complement dysregulation and influence of the
Columbus, United States of America, 13Imperial College London, Division of complement therapeutic being tested, but also eGFR. Additional urinary biomarkers,
Immunology and Inflammation, Faculty of Medicine, London, United Kingdom, 14Johns biopsy findings, autoantibodies, and genetic variants are currently being analysed and
Hopkins University School of Medicine, Baltimore, United States of America, 15NYU findings from this study will contribute to a better understanding of C3G and IC-
Grossman School of Medicine, New York, United States of America, 16Georgia MPGN.
Nephrology, Atlanta, United States of America, 17Radboud University Medical Center
Geert, Department of Nephrology, Nijmegen, The Netherlands and 18Istituto di Ricerche
Farmacologiche Mario Negri IRCCS, Milan, Italy

BACKGROUND AND AIMS: C3 glomerulopathy (C3G) and immune complex


membranoproliferative glomerulonephritis (IC-MPGN) are rare, progressive kidney
diseases requiring a biopsy for definite diagnosis. Both C3G and IC-MPGN are
attributed to complement dysregulation, with dysregulation of the alternative pathway
established in C3G and implicated in IC-MPGN (alongside classical pathway
activation by immune complexes). We describe the baseline biomarker and clinical
characteristics of patients participating in two C3G/IC-MPGN phase II studies of the
investigational, oral complement factor D (FD) inhibitor, danicopan (ALXN2040/
ACH-4471).
METHOD: The first study (NCT03369236) was a double-blind, placebo-controlled,
randomised, 6-month (þopen label extension) trial of patients with biopsy-confirmed
C3G of the native kidney treated with danicopan or placebo. The second study
(NCT03459443) was a single-arm, open-label, 12-month (þextension) trial of patients
with biopsy-confirmed C3G or IC-MPGN treated with danicopan. In both studies, all
patients were to have proteinuria 500 mg/day and estimated glomerular filtration rate
(eGFR) 30 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal

MO126 Figure 1: Baseline (day 1) bioma rker correlat ions. Panel A Correlat ion
between eGFR and Ba; Panel B: Correlat ion between eGFR a nd FD; Panel C: Correlat
ion between C3 a nd sCS b-9; Panel D:
Correlat ion between C3 and CS. Dashed lines represent upper limit of norma l (ULN)
and lowe r limit of norma l (LLN);grey boxes denote norma l bioma rker ranges.

MO127 CLEARED PODOCYTES AND NORMAL KIDNEY FUNCTION IN


CLASSICAL FABRY MALES 15 YEARS AFTER START OF
ENZYME REPLACEMENT THERAPY AT YOUNG AGE*

Camilla Tøndel1, Idunn Riisnes2, Sabine Leh3, Kristin Kampevold Larsen3,


Rannveig Skrunes2, Hans-Peter Marti4, Einar Svarstad4
1
Haukeland University Hospital, Department of Pediatrics, Bergen, Norway, 2Haukeland
University Hospital, Department of Nephrology, Bergen, Norway, 3Haukeland University
Hospital, Department of Pathology, Bergen, Norway and 4University of Bergen,
Department of Clinical Medicine, Bergen, Norway

BACKGROUND AND AIMS: Fabry nephropathy may progress to kidney failure


despite enzyme replacement therapy (ERT) when the treatment is initiated at a
relatively late stage of the disease. This study evaluates long term effects of agalsidase in
serial kidney biopsies and functional measurements in men with classical Fabry disease
MO126 Figure 1: Baseline (day 1) bioma rker correlat ions. Panel A Correlat ion that commenced ERT at a young age.
between eGFR and Ba; Panel B: Correlat ion between eGFR a nd FD; Panel C: Correlat METHOD: Six male Fabry patients with a median age of 20 years (range 7-30 years) at
ion between C3 a nd sCS b-9; Panel D: start of ERT were monitored over a median time of 15 years (range 14.5-17.0 years).
Correlat ion between C3 and CS. Dashed lines represent upper limit of norma l (ULN) The patients were treated with an agalsidase dose of 1.0 mg/kg/every other weak (eow)
and lowe r limit of norma l (LLN);grey boxes denote norma l bioma rker ranges. for 8.3 years (range 5-12 years) and with an agalsidase dose of 0.2-0.5 mg/kg/eow for
7.6 years (range 3-10 years). Kidney biopsies were evaluated with the scoring system of
the International Study Group of Fabry Nephropathy (ISGFN) using both plastic
Disease equation for patients 18 years and the Schwartz equation for patients embedded and paraffin embedded tissue with scoring of podocyte
globotriaocylceramide (Gb3) in semithin toluidine blue sections (maximum score 4.0)

10.1093/ndt/gfab092 | i149
Abstracts Nephrology Dialysis Transplantation

and scoring of vacuolization in PAS-sections (maximum score 3.0). ISGFN composite


score consists of both tissue scores giving a maximum score of 7.0. Renal function was Variables Simple correlation Adjusted for log (sCr)
evaluated with measurement of glomerular filtration rate (GFR) with iohexol clearance
R p beta 6 SE p
(mGFR) and urinary albumin creatinine ratio (uACR). Values are given in median
(range). LDH 0.31 0.008 0.21 6 0.10 0.036
RESULTS: Kidney biopsies at baseline contained 24 (13-42) evaluable glomeruli and log (b2-microglobulin) 0.45 <0.001 0.16 6 0.14 0.3
had an ISGFN composite score of 7.0 (6.9-7.0). After 15 years the ISGFN composite
score had decreased to 0.56 (0-4.29), scored in 24 (9-52) evaluable glomeruli. At Leukocyte count 0.29 0.013 0.15 6 0.10 0.1
baseline mGFR was 106 (86-113) ml/min/1.73 m2 and after 15 years mGFR decreased sTfR 0.32 0.007 0.24 6 0.10 0.018
to 97 (73-134) ml/min/1.73 m2. uACR was 5.6 (0.1-13.6) mg/mmol at baseline and had a-klotho -0.27 0.022 -0.13 6 0.10 0.2
after 15 years increased to 10.0 (1.0-107) mg/mmol. The youngest patient had
significant proteinuria with uACR 107 mg/mmol due to a chronic C3- log (FGF-23) 0.34 0.004 -0.01 6 0.13 0.9
glomerulonephritis superimposed on Fabry disease. Median uACR without this patient log (GDF-15) 0.49 <0.001 0.24 6 0.13 0.07
was at 15 years 5.8 (1.0-17.7) mg/mmol. The two youngest patients had no Gb3 visible
log (sCr) 0.54 <0.001 not applicable -
(ISGFN composite score of 0) in their last biopsy and mGFR was normal in both. In all
patients the reduction of podocyte-Gb3 was higher on an agalsidase dose of 1 mg/kg/ log (sCysC) 0.52 <0.001 0.23 6 0.16 0.2
eow; change composite score -4.66 (-7.9 to -1.8), compared to on an agalsidase dose of eGFR (CKD-EPICr) -0.47 <0.001 not analyzed -
0.2-0.5 mg/kg/eow; change composite score -0.15 (-5.1 to þ 1.0).
CONCLUSION: Initiation of ERT at a relatively young age may clear the long living eGFR (CKD-EPICysC) -0.44 <0.001 not analyzed -
kidney cells of Gb3 and protect the kidneys from significant functional loss over a very eGFR (CKD-EPICr-CysC) -0.45 <0.001 not analyzed -
long time period. The reduction of Gb3 in podocytes is higher on high dose compared log (uNGAL monomer) 0.34 0.003 0.13 6 0.11 0.3
to low dose of agalsidase.
log (uIGFBP-7) 0.33 0.004 0.11 6 0.11 0.3

MO128 RETINOL BINDING PROTEIN (RBP) - NEW BIOMARKER OF


KIDNEY INJURY IN MULTIPLE MYELOMA PATIENTS* MO128 Table 2. Multiple regression models to predict log-transformed serum
RBP concentrations.
1 2 3
Karolina Woziwodzka , Jolanta Malyszko , Małgorzata Banaszkiewicz ,
_
Ewa Koc- Zorawska 4
, Paulina Dumnicka5, Artur Jurczyszyn6, Krzysztof Batko7, Independent variables Model 1 Model 2
Joanna Tison czyk5, Paulina Gołasa7, Marcin Krzanowski7, Marcin Zorawski8,
Jacek Małyszko4,9, Ryszard Drozdz5, Katarzyna Krzanowska7
beta 6 SE p beta 6 SE p
1
Jagiellonian University Medical College, Krak
ow, Poland, Department of Nephrology, log (sCr) 0.46 6 0.13 0.001 not included -
Krakow, Poland, 2Department of Nephrology, Dialysis and Internal Medicine, Medical log (sCysC) not included - 0.39 6 0.14 0.008
University of Warsaw, Warsaw, Poland, Warsaw, Poland, 4Second Department of treatment with steroids 0.25 6 0.10 0.018 0.22 6 0.11 0.041
Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok,
Bialystok, 5Jagiellonian University Medical College, Krak
ow, Poland, Department of ISS II -0.002 6 0.11 0.98 -0.06 6 0.12 0.6
Medical Diagnostics, 6Jagiellonian University Medical College, Krak
ow, Poland, ISS III 0.08 6 0.14 0.5 0.13 6 0.14 0.4
Department of Hematology, 7Jagiellonian University Medical College, Krak ow, Poland,
Department of Nephrology, 8Department of Clinical Medicine, Medical University of
R2 and p for the model 0.35 <0.001 0.32 <0.001
Bialystok and 9First Department of Nephrology and Transplantology With Dialysis Unit,
Moreover, RBP correlated with b2-microglobulin, LDH, leukocyte count, a-klotho,
Medical University of Bialystok
FGF-23, GDF-15, uNGAL and uIGFBP-7, however, only the associations with b2-
microglobulin and sTfR were independent of serum creatinine in multiple regression
BACKGROUND AND AIMS: The aim of the study was to analyse the utility of (Table 1).
retinol binding protein (RBP) in case of renal impairment in MM patients and Baseline serum RBP concentration was significantly correlated with eGFR after a
investigate its relationship with acclaimed parameters of renal failure and markers of median of 19 months follow-up (range 1-24 months) (R=-0.35; p=0.003), however, the
MM stages. correlation was not independent of baseline serum creatinine ((beta 6 SE: 0.06 6 0.10;
METHOD: We recruited 73 patients (35 women, 38 men, in age range of 29-90 years, p=0.5). To the contrary, baseline serum cystatin C (beta 6 SE: -0.36 6 0.13; p=0.009)
mean 70 6 10 years) with multiple myeloma (MM), including 6 (8%) with smoldering predicted final eGFR independently of baseline serum creatinine.
MM, 40 (55%) with International Staging System (ISS) stage I, 15 (21%) with ISS II and CONCLUSION: RBP may be useful marker in renal damage in patients with chronic
12 (16%) with ISS III. The majority of patients (65, 89%) received at least one treatment kidney injury among patients with MM. This can lead to noninvasive biomarker-
scheme. Thirty patients (41%) received maintenance treatment at recruitment. Median targeted diagnostic interventions and contribute to early beginning of treatment that
eGFR based on serum creatinine (CKD-EPICr) equaled 67 (range 9 – 117) ml/min/1.73 may improve life expectancy quality of life in MM.
m2.
RESULTS: Significant correlation was observed between RBP and the ordered variable
describing MM stage from smoldering myeloma to ISS III (R=0.36; p=0.002). There
were no differences between patients in CR, PR, SD and PD at the time of samples’ MO129 COMPARATIVE EFFECTIVENESS OF SGLT2I VERSUS DPP4I
collection. Patients who were on maintenance treatment at recruitment tended to have ON CARDIOVASCULAR AND RENAL OUTCOMES IN
higher serum RBP (median 42.6 versus 37.7 mg/l), however, the difference was not ROUTINE-CARE SETTINGS
statistically significant (p=0.068). The patients who received steroid treatment had
significantly higher RBP concentrations. There were no such association with other Edouard Fu1,2, Marco Trevisan2, Vivekananda Lanka2, Catherine M. Clase3,
medications. There was no association between RBP and the number of previous Yang Xu2, Friedo W. Dekker1, Merel Van Diepen1, Juan Jesus Carrero2
1
treatment lines (p=0.8). Serum RBP did not differ between men and women (p=0.7) Leiden University Medical Center, Department of Clinical Epidemiology, Leiden, The
and did not correlate with age (p=0.6). Netherlands, 2Karolinska Institute, Department of Medical Epidemiology and
Significant correlations were found between RBP and serum creatinine, cystatin C and Biostatistics, Stockholm, Sweden and 3McMaster University, Department of Medicine
eGFR values calculated based on creatinine and/or cystatin C (Table 1). In multiple and Health Research Methods, Evidence and Impact, Hamilton, Canada
regression, serum creatinine or cystatin C and the treatment with steroids were
associated with RBP independently of ISS stage (Table 2). BACKGROUND AND AIMS: While clinical trials have demonstrated the efficacy of
SGLT2 inhibitors on preventing cardiovascular and renal damage, few studies have
expanded this evidence to routine-care settings.
METHOD: We compared clinical outcomes of adults who started SGLT2i or DPP4i
therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was a
composite of cardiovascular (CV) death and hospitalization for heart failure (HF).
Secondary outcomes included major adverse cardiovascular events (MACE; composite
of cardiovascular death, myocardial infarction, stroke), all-cause mortality and the rate
of eGFR decline (eGFR slope). Propensity score weighted Cox regression was used to
balance 55 variables and estimate intention-to-treat hazard ratios with 95% confidence
intervals. Differences in eGFR slope were calculated with linear mixed models.
RESULTS: We identified 7136 individuals starting SGLT2i and 13,618 starting DPP4i
therapy. Median age was 64 years (37% women) and median eGFR 86 ml/min/1.73m2.
During median follow-up of 2.1 years, 211 individuals developed the primary outcome,
269 experienced MACE and 178 died. After propensity score weighting, patients
starting SGLT2i therapy were at lower risk for the composite of CV death/HF
hospitalization (HR 0.71; 95% CI 0.53-0.94) compared with DPP4i, and showed a

i150 | Abstracts
Nephrology Dialysis Transplantation Abstracts
tendency towards lower MACE (0.84; 95% CI 0.67-1.04) and all-cause mortality (0.85; MO131 THE SHRUNKEN PORE SYNDROME IS ASSOCIATED WITH
95% CI 0.62-1.18). There were a median of 4 (interquartile range: 2-8) eGFR POOR PROGNOSIS AND LOWER QUALITY OF LIFE IN HEART
€ STUDY
FAILURE PATIENTS- THE HARVEST-MALMO
measurements during follow-up per patient to estimate their eGFR slopes. In adjusted
models, new users of SGLT2i had a slower rate of kidney function decline compared
with DPP4i (eGFR slope difference of 0.43 (95% CI 0.15-0.72) ml/min/1.73m2 per Liana Xhakollari1,2, Anders Grubb3, Amra Jujic2,4, Erasmus Bachus2, Peter
year). Results for the primary outcome were consistent across 7 pre-specified M Nilsson2, Margret Leosdottir2,4, Anders Christensson1,2,
subgroups, including eGFR (eGFR 60: HR 0.79 [95% CI 0.57-1.08]; eGFR <60: HR Martin Magnusson2,4,5,6
1
0.62 [0.38-0.99], p-value for interaction 0.40). Skåne University Hospital Malmö Sweden, Department of nephrology, Malmö,
CONCLUSION: In patients undergoing routine care, initiation of SGLT2i was Sweden, 2Lund University, Clinical Sciences, Malmö, Sweden, 3Skåne University Hospital,
associated with fewer cardiovascular outcomes and less rapid kidney function decline Clinical Chemistry, Lund, Sweden, 4Skåne University Hospital, Cardiology, Malmö,
compared with DPP4i initiation. Sweden, 5Lund University, Wallenberg Center for Molecular Medicin, Sweden and
6
North West University, Hypertension in Africa Research Team, Potchefstroom, South
Africa
MO130 GLOMERULAR FILTRATION RATE IS THE MAIN PREDICTOR
OF URINE OUTPUT IN AUTOSOMAL DOMINANT BACKGROUND AND AIMS: The cardiorenal syndrome was studied in heart failure
POLYCYSTIC KIDNEY DISEASE (ADPKD) PATIENTS (HF) patients with respect to the “Shrunken pore syndrome” (SPS) that is characterized
TREATED WITH TOLVAPTAN by a difference in renal filtration between cystatin C and creatinine, resulting in a low
eGFRcystatin C/eGFRcreatinine-ratio.
Francisco-Jose Borrego-Utiel1, Enoc Merino Garcia1, Maria Luisa Garnica METHOD: 373 patients hospitalized for HF were retrieved from the HeARt and brain
Alvarez1, Clara Moriana Dominguez1 failure inVESTigation trial (HARVEST-Malmö). We used CKD-EPI formulas for
1 estimated glomerular filtration rate (eGFR). Presence of SPS was defined as
Hospital Universitario de Jaén, UGC Nefrologıa, Jaén, Spain eGFRcystatinC 60% of eGFRcreatinine. In Cox regression multivariate models,
associations between SPS, risk of death and risk of 30-day re-hospitalization were
BACKGROUND AND AIMS: Tolvaptan was approved to treat autosomal dominant studied. Associations between SPS and impaired quality of life (QoL) were studied
polycystic kidney disease (ADPKD) to slow the rate of kidney growth and renal using multivariate logistic regressions.
function decline. Tolvaptan blocks the V2 vasopressin receptor in renal collecting ducts RESULTS: SPS was associated with all-cause mortality (124 events; hazard ratio (HR)
and distal nephron causing intense polyuria. Few authors have analyzed what factors 2.35; confidence interval (CI95%) 1.17-4.71; p=0.016 and with 30-day re-
influence the volume of diuresis in patients taking tolvaptan. hospitalization (70 events; HR 1.82; CI95% 1.04-3.18; p=0.036). Analyses of QoL, based
METHOD: We have analyzed the influence of solute excretion and glomerular on a Kansas City Cardiomyopathy Questionnaire overall score <50, revealed that SPS
filtration rate, besides age and gender as predictors of urine output, using multivariable was associated with increased risk of low health-related QoL (odds ratios (OR) 2.15
analysis. In concret, we have searched the importance of osmolar excretion as predictor (CI95% 1.03-4.49; p=0.042).
of volume of diuresis. CONCLUSION: The results of this observational study show for the first time an
RESULTS: We studied 24 h-urine samples from 18 ADPKD patients on treatment association between SPS and poor prognosis in HF. Further studies are needed to
with tolvaptan, who had received the three doses: 45/15, 60/30 and 90/30 mg. Each confirm the results in HF cohorts and experimental settings to identify
patient was represented once per dose, for a total of 54 urine samples (Table 1). pathophysiological mechanisms.
Tolvaptan increased urine volume, which was roughly doubled, and roughly halved
urine solute concentrations expressed by volume and calculated osmolality. By
contrast, solute concentrations expressed as ratios with creatinine remained constant as
did osmolality corrected with urinary creatinine, indicating that there was no change in MO132 IMPACT OF MONOCYTE CHEMOATTRACTANTS ON IN-
solute excretion after tolvaptan. HOSPITAL MORTALITY IN RELATION TO KIDNEY FUNCTION
Urine volume was correlated with serum creatinine (Rho= -0.36, p= 0.008), urinary IN PATIENTS WITH COVID-19
creatinine (Rho = -0.29, p = 0.034) and GFR-MDRD4 (Rho = 0.44, p= 0.001). Urine
volume was correlated with calculated daily osmolar excretion in Osm/day (Rho = Senka Sendic1, Ladan Mansouri2, Sebastian Havervall3, Charlotte Thålin3,
0.76, p <0.001). Urine volume was not correlated with calculated urinary osmolality in Joachim Lundahl2, Stefan H. Jacobson1
1
mOsm/Kg (Rho= -0.04, p= 0.77) or as urinary osmolality/creatinine ratio (Rho= 0.23, Karolinska Institutet, Department of Clinical Sciences, Division of Nephrology,
p= 0.1). Correlation of urine volume with osmolar excretion was lost when urine Danderyd Hospital, Stockholm, Sweden, 2Karolinska Institutet, Clinical Science and
volume was removed from the predictor variable. Urine volume was additionally not Education, Södersjukhuset, Stockholm, Sweden and 3Karolinska Institutet, Department
correlated with urinary urea o sodium concentrations nor their solute/creatinine ratios, of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden
and although it was correlated with urinary potassium concentration (Rho = -0.33,
p=0.014), it was not correlated with potassium/creatinine ratio. BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) are at
We also performed a linear regression analysis searching predictors of urine volume. higher risk of severe complications and mortality due to Covid-19 than patients with
Only GFR and the osmolality/creatinine ratio were significant predictors of urine other known risk factors. The association between CKD and mortality persist in
volume (urine volume= 55.35 x GFR þ 4.74 x Osmolality/Cr; r2= 0.41, p<0.001) but analyses adjusted for covariates known to associate with worse Covid-19 outcomes,
individual solute assessments or tolvaptan dose did not predict urine volume. suggesting that CKD confers a risk beyond that associated to comorbid conditions. The
CONCLUSIONS: Therefore, urine volume after initiating tolvaptan in patients with mechanisms underlying the increased susceptibility to severe Covid-19 in CKD
ADPKD is influenced mainly by the degree of renal function. There might also be a remains unclear but morphologic and functional differences in monocytes have been
contribution of urinary solute load but it can not be studied using total solute excretion due associated with prolonged hospitalization in other cohorts of patients. The monocyte is
to collinearity. We propose that the urinary solute/creatinine ratio and osmolality/creatinine capable to contribute to the pathophysiology through different mechanisms. There is
ratio should be used to search for predictors of urine output in patients on tolvaptan. however insufficient information on factors that orchestrate different aspects of
monocyte function and how these factors relate to outcomes. Increased knowledge into
which features of monocyte function that contribute to risks in CKD patients with
Covid-19 is important to guide treatment strategies.
The aim of the present study was to examine the concentrations of monocyte
chemoattractant markers MCP-1 (Monocyte Chemoattractant Protein-1; CCL2) and
MIP-1a (Macrophage Inflammatory Protein 1-a; CCL3) in patients with Covid-19 and
normal or impaired kidney function and to compare that to CKD patients matched for
sex and eGFR, and sex matched healthy subjects. We analyzed the impact of these
monocyte chemoattractant markers on in-hospital and 30 days mortality by logistic
and multiple regression analyses. We related this to established risk factors for
morbidity and mortality in Covid-19 patients, e.g. CRP and IL-6.
METHOD: We prospectively included 110 patients with Covid-19 (mean age 59 yr.,
mean eGFR 75 ml/min/1.73m2) admitted to Danderyd University Hospital,
Stockholm, Sweden, during the first pandemic wave in April to May 2020 and 33 sex
and eGFR-matched patients (mean age 51 yr., eGFR 52 ml/min/1.73m2) with CKD and
35 sex matched healthy subjects (mean age 47 yr., eGFR 101 ml/min/1.73m2).We used
Luminex assays to analyze MCP-1, MIP-1a and IL-6 and routine laboratory tests to
determine white blood cell count (WBC) and CRP.
RESULTS: Patients with Covid-19 had significantly lower concentrations of MIP-1a
MO125 Figure 1: Clinical and demographic data in patients with monoclonal (p<0.001), and higher IL-6 (p<0.001) and CRP (p<0.001) than patients with CKD
gammopathy of renal significance at the time of kidney biopsy. and healthy subjects (Kruskal-Wallis), there were no differences in MCP-1 between
groups. We found significant negative correlations between MCP-1 (p<0.05), MIP-1a
(p<0.05) and IL-6 (p<0.05) with eGFR in patients with Covid-19 (Spearmans rank
correlation). Logistic regression analysis (Odds ratio, OR, 95% Confidence Intervals
(CI)) and Cox proportional hazard models (Hazard ratio, HR), both adjusted for age,

10.1093/ndt/gfab092 | i151
Abstracts Nephrology Dialysis Transplantation

showed significant associations between in-hospital mortality and WBC, CRP, IL-6, 89.1, 101.3) mL/min/1.73m̂2. According to CKD G class, 70% were I and 30% were II.
MCP-1 and MIP-1a (Table, Figure). Similar findings were observed also for 30 days The cohort was divided in two groups according type of surgery: 44% as RN and 56%
mortality. as PN. Differences between the two groups were detected for Gender (Radical M/F
ratio: 3.2; Partial M/F ratio: 1.8; p=0.4), basal eGFR (Radical Median:92.3 (88.0, 99.8)
mL/min/1.73m2; Partial Median:95.4 (90.1, 102.0) mL/min/1.73m2; p=0.01) and CKD
MO132 Table. Logistic regression analysis, odds ratio (OR) and Cox proportional G class (Radical I:64%, II:36%; Partial I:76%, II:24%; p=0.03). Two-way Anova for time
hazard ratio (HR) both adjusted for age with 95% CI of in-hospital mortality in patients
variation of eGFR according other parameters, enlightened a significative difference for
with Covid-19
the type of surgery (p<0.001): in particular, the analysis showed the presence of a
variation over time of the eGFR (p<0.001) that depends also on the surgery type
Logistic regression analysis Cox proportional hazard analysis (p<0.001). Post-hoc analysis showed the impact of the differences in term of eGFR
p-value OR 95% CI p-value HR 95% CI decay at different time points: at 6 months the radical nephrectomy groups had a mean
decay higher (p<0.001) by 19 mL/min/1.73m2.(13.2, 24.9), at 12 months (p<0.001) by
Lower Upper Lower Upper 19.6 mL/min/1.73m2.(14.9, 24.3), at 24 months (p<0.001) by 18 mL/min/
White BC =0.001 1.438 1.167 1.771 <0.001 1.251 1.128 1.387 1.73m2.(11.9, 25.2), at 36 months (p<0.001) by 15.4 (9.4, 21.4), at 48 months
CRP =0.01 1.008 1.002 1.015 0.004 1.008 1.003 1.013 (p<0.001) by 16,4 (10.4, 22.3) and at 60 months (p<0.001) by 15 (11.2, 18.7) mL/min/
1.73m2 (Figure 1)
IL-6 =0.05 1.007 1.000 1.013 0.001 1.001 1.001 1.002 CONCLUSION: Our study highlights that both RN than PN harbor a non negligible
MCP-1 <0.05 1.001 1.000 1.002 0.001 1.000 1.000 1.001 risk of post-operative CKD events even in normal renal function patients without renal
abnormalities at 5 years from the operations. However, RN patients display a different
MIP-1a =0.006 1.006 1.002 1.011 0.001 1.005 1.002 1.008
behavior in term of renal compensation in respect of PN. In fact, RN pts tend to replace
the acute loss of function derived from the absence of the contralateral kidney with an
increase of eGFR , whereas PN pts tend to remain stable over time without any effort of
hyperfiltration. A prospective comparison multicentric study with kidney living donor
is on going.

CONCLUSION: We demonstrate that factors related to monocyte recruitment and


activation, MCP-1 and MIP-1a, are associated with in-hospital and 30-days mortality
in CKD patients with Covid-19. In this patient group general inflammatory markers as
IL-6 and CRP are also associated with risk of mortality. These data contribute to an
increased understanding of the impact of monocyte activation in Covid-19 and may be
of value when treatment strategies are evaluated.

MO133 RENAL FUNCTIONAL OUTCOMES AT 5 YEARS FROM


RADICAL AND PARTIAL NEPRHECTOMIES IN NORMAL
RENAL FUNCTION PATIENTS : AN UNTOLD STORY OF
FAILED RENAL HYPERFILTRATIONS

Francesco Trevisani1, Federico Di Marco2, Giuseppe Rosiello1, Francesco Fiorio1,


Alessandra Cinque2, Arianna Bettiga2, Umberto Capitanio1,2, Andrea Salonia1,2,
Francesco Montorsi1
1
San Raffaele Scientific Institute, Urology, Milan, Italy and 2Urological Research Institute
(URI), Division of Experimental Oncology, Milan, Italy MO134 COVID-19-ASSOCIATED KIDNEY INJURY IS
CHARACTERIZED BY ACUTE TUBULAR NECROSIS AND
BACKGROUND AND AIMS: Despite major advance in surgical techniques in the CAPILLARY CONGESTION WITH EVIDENCE FOR SARS-COV-
last decade, Chronic Kidney Disease (CKD) is still a major postoperative long-term 2 IN THE NEPHRON
complication in renal surgery for renal cancer, both in radical than in partial
nephrectomy. However, it is still debatable if the renal hyperfiltration mechanism Antoine Bouquegneau1, Pauline Erpicum1, Stéphanie Grosch1, Lionel Habran2,
which happens after an acute loss of nephron mass could promote in oncological Olivier Hougrand2, Justine Huart1, Jean-Marie Krzesinski1, Benoit Misset3, Marie-
patients an effective vicariant process over time able to replace a new renal function Pierre Hayette4, Philippe Delvenne2, Christophe Bovy2, Dominik Kylies5, Tobias
comparable with the pre-operative one. Aim of our study was to compare the eGFR B. Huber5, Victor Puelles5, Pierre Delanaye1, François Jouret1
1
decay over time from pre-operative time surgery to 5 years follow up in the two major ULiège Academic Hospital (ULiège CHU), Division of Nephrology-Dialysis-
renal surgeries approaches (radical-RN- and partial nephrectomies- PN) in a selected Transplantation, Liege, Belgium, 2ULiège Academic Hospital (ULiège CHU), Department
cohort of patients with normal renal function at baseline. of Pathology, Liege, Belgium, 3ULiège Academic Hospital (ULiège CHU), Department of
METHOD: We performed a retrospective cohort-study of 271 consecutive patients Intensive Care, Liege, Belgium, 4ULiège Academic Hospital (ULiège CHU), Department of
who underwent radical (RN) or partial nephrectomy (PN) due to the presence of a Clinical Microbiology, Liege, Belgium and 5University Medical Center Hamburg-
kidney mass suspected of malignancy from 2000-2020 in a tertiary care urological Eppendorf, Department of Medicine for Nephrology, Transplantation and Translational
Institution. Inclusion criteria were: 1) Age > 18 years old 2) eGFR > 80 ml/min/1,73 Immunology, Hamburg, Germany
using CKD-EPI formula 2012 3) absence of urinary abnormalities . The following data
were considered: age, gender, body mass index (BMI), TNM staging, hypertension, BACKGROUND AND AIMS: Kidney damage has been reported in COVID-19
diabetes. Glomerular Filtration rate (GFR) was estimated at each time point using patients. Despite numerous reports about COVID-19-associated nephropathy, the
creatinine-based estimated glomerular filtration rate (eGFR) formula. We evaluated factual presence of the SARS-CoV-2 in the renal parenchyma remains controversial.
eGFR variation at the pre-surgical value, hospital dismissal, 6,12,24,36,48,60 months. METHOD: We consecutively performed 16 immediate (3h) post-mortem renal
eGFR categories were created according to the KDIGO guidelines for G categories in biopsies in patients diagnosed with COVID-19. Kidney samples from 5 patients who
GFR setting different thresholds. Comparisons between groups were performed using died from sepsis and were free from COVID-19 were used as controls. Samples were
Kruskal-Wallis ranks sum test for numerical variables and Pearson’s Chi square test for methodically evaluated by 3 pathologists. Virus detection in the renal parenchyma was
categorical variables. Logistic regression was used to identify variables ODDS Ratio for performed in all samples by bulk RNA RT-PCR (E and N1/N2 genes), immunostaining
AKI onset after surgery. (nCoV2019 N-Protein), fluorescent in situ hybridization (nCoV2019-S) and electron
RESULTS: The study cohort was composed by 271 patients with median Age 56 (IQR: microscopy.
48, 64), M/F ratio 2.3, median BMI 25.7 (IQR: 23.3, 28.3), median eGFR 94.3 (IQR:

i152 | Abstracts
Nephrology Dialysis Transplantation Abstracts
checkpoint (group 4). Kidney biopsies were not performed because of increased risk or
for improvement of RI when changes in TT were performed.
Renal injury (RI) occurred on average after 8.9 months from the start of TT. We
compared the effects of the different therapeutic interventions on changes of renal
function between T0 (before TT) and T1 (during TT). We also documented changes in
oncologic therapeutic prescription due to renal injury and their effects at T2 (follow
up). Kidney biopsies were not performed because of increased risk or for improvement
of RI when changes in TT were performed.
A two way repeated measures ANOVA (group x time) was used to compare the effects
of the four groups on serum creatinine (sCr), creatinine clearance and proteinuria 24 h
(PU) at T0 and T1.
RESULTS: Mean basal sCr of pts taking antiVEGF was 0.95 mg/dl, eGFR (MDRD)
81.9 ml/min and PU 196 mg 24h. At T1 (8.37 months on average) sCr was 1.74 mg/dl,
eGFR 62 ml/min and PU 1777 mg 24h.
Mean basal sCr of pts taking tyrosine kinase inhib was 1.24 mg/dl, eGFR 55 ml/min
and PU 145 mg 24h. At T1 (13 months on average) sCr was 1.59 mg/dl, eGFR 46 ml/
min, and PU 916 mg 24h.
Mean basal sCr of pts taking mTOR inhib was 1.28 mg/dl, eGFR 57 ml/min and PU
150 mg 24 h. At T1 (6.3 months on average) sCr was 2.1 mg/dl, eGFR 31.7 ml/min and
Pu 345 mg 24 h.
Mean basal sCr of pts taking immune-checkpoint was 1.27 mg/dl, eGFR 59 ml/min
and PU 150 mg 24h. At T1 (months on average) sCr was 3.74 mg/dl, eGFR 30 ml/min
and PU 257 mg 24h.
A significant increase in sCr was observed when comparing T0 and T1 among the four
groups but only a statistical trend (P = 0.088) was found for the group by time
interaction thus not allowing us to speculate on potential differences between the
different pharmacological interventions.
Lower Creatinine clearance and higher PU, were found at T1 in pts on anti-VEGF
compared to those on immune-checkpoint inhibitors.
We generally observed an improvement of renal function after reduction of TT dose or
its temporary discontinuation (27.8%), but definitive interruption was required in
31.8% of cases. In 2 diabetics pts on tyrosine kinase inhib we observed persistent
nephrotic proteinuria and progressive worsening of renal function and beginning of
chronic hemodialysis neverthless discontinuation.
At the end of follow-up 5 pts reached end-stage renal disease (1 pt was taking
antiVEGF, 2 pts tyrosine kinase inhib, 2 immune-checkpoint) and 6 pts were dead (4
pts were taking antiVEGF and 2 pts tyrosin kinasi inhib).
CONCLUSION: Our findings suggest that careful monitoring of renal function is
needed to optimize the use of TT, also considering that RI can be multifactorial.
Onconephrologists work with the aim of trying to ensure the continuity of anti-
tumoral therapy, knowing how far they can go to maintain a balance between kidney
MO134 Figure: Detection and spatial distribution of viral RNA using fluorescence
function (even sacrificing part of it) and patient survival. In conclusion, nephrologists
in situ hybridization
should be increasingly familiar with the diagnosis, management and treatment of renal
The first (overview) and second (targeted zoom) columns display positive signal for diseases and the complexity of this field may benefit from well-defined
viral RNA in different renal compartments, including proximal and distal tubules, multidisciplinary management by a dedicated team
glomeruli and vessels. nCoV2019-S RNA is in green; Lotus tetragonolobus lectin (LTL)
is in red; DAPI is in blue.

RESULTS: The mean age of our COVID-19 cohort was 68.2612.8 years, most of
whom were males (68.7%). Proteinuria was observed in 53.3% of cases, while acute
kidney injury occurred in 60% of cases. Acute tubular necrosis of variable severity was
found in all cases, with no tubular or interstitial inflammation. There was no difference
in acute tubular necrosis severity between the patients with COVID-19 versus control
samples. Congestion in glomerular and peri-tubular capillaries was respectively
observed in 56.3 and 87.5% of patients with COVID-19 compared to 20% of controls,
with no evidence of thrombi. The nCoV2019 N-Protein was detected in proximal
tubules and also at the basolateral pole of scattered cells of the distal tubules in 9/16
cases. In situ hybridization confirmed these findings. RT-PCR of kidney total RNA
detected SARS-CoV-2 N gene in one case. Electron microscopy did not show typical
viral inclusions.
CONCLUSION: Our immediate post-mortem kidney samples from patients with
COVID-19 highlight a congestive pattern of acute kidney injury, with no significant
glomerular or interstitial inflammation. Immunostaining and in situ hybridization
suggest that SARS-CoV-2 is present in various segments of the nephron.

MO135 THE NEW FIELD OF ONCONEPGROLOGY: EXPERIENCE OF A


SINGLE DEDICATED CLINIC

Chiara Gonzi1, Anna Maria Aschelter2, Francescaromana Festuccia1,


Paolo Mene’1, Claudia Fofi1 Types of Target Therapy N pts Mean time of TT
1
Sant’Andrea Hospital, Division of Nephrology, Rome, Italy and 2Sant’Andrea Hospital, (months)
Division of Medical Oncology, Rome, Italy
Group 1 antiVEGf 12 8,37
BACKGROUND AND AIMS: The bidirectional relationship between renal disease Group2 Tirosin-chinasi inibitori 26 13,8
and malignancy is well known and requires specialized approaches. For this reason, Group 3 mTOR inibitori 7 6,3
onconephrology has emerged as a new evolving field in the last few years. Group 4 Immuno-checkpoint 9 7,9
METHOD: In a dedicated nephrology clinic, we followed 54 metastatic cancer patients
(pts) (23 F, 31 M; mean age 68.3 6 9.8 yrs) during target therapy (TT). They were in
treatment for different types of cancer (kidney n=32, colo-rectal n 6=, breast n=5, lung
n=5, neuroendocrine n=2 and other n=4). 12 pts were taking anti-VEGF (group 1), 26
pts tyrosine kinase inhib (group 2), 7 pts mTOR inhb (group 3) and 9 pts immune-

10.1093/ndt/gfab092 | i153
Abstracts Nephrology Dialysis Transplantation

MO136 RELATIONSHIP BETWEEN UPCR AND EGFR IN C3


GLOMERULOPATHY RESULTS: Analyses were performed using 34 one-year spans for 24 patients who met
inclusion criteria at the beginning of the 1-year span. Baseline characteristics for the 34
Carla Nester1,2, Patrick Breheny3, Monica Hall1, Alan Charney4, Martin Lefkowitz4, spans were: male, 59%; mean age, 22.7 years; mean eGFR, 83.1 ml/min/1.73m2; mean
Angelo Trapani4, Yaqin Wang4, Richard Smith1,2 UPCR, 2.86 g/g; mean plasma C3, 75.1 mg/dL.
1
Molecular Otolaryngology and Renal Research Laboratories, University of Iowa, Iowa
City, IA, United States of America, 2Stead Family Children’s Hospital, University of Iowa, eGFR / UPCR correlation analyses: Linear regression and natural cubic spline models
Iowa City, IA, United States of America, 3College of Public Health, University of Iowa, that included explanatory variables of log2 change from baseline UPCR, baseline
Iowa City, IA, United States of America and 4Novartis Pharmaceuticals Corporation, C3, baseline UPCR and baseline eGFR, were consistent in demonstrating the rela-
East Hanover, NJ, United States of America tionship between reductions in UPCR and preservation of eGFR (see Figure 1). The
linear regression model based on 34 spans indicated that a 50% reduction in UPCR
over 1 year is associated with a predicted 9% relative improvement in percent
BACKGROUND AND AIMS: Considerable knowledge gaps exist in our understanding change from baseline in eGFR (p=0.03), whereas a 30% reduction in UPCR is asso-
of the natural history of C3 glomerulopathy (C3G). Disease rarity, multiple nomenclature ciated with a predicted 4.6% relative improvement in eGFR.
changes, and the inclusion of dissimilar cases in historical cohorts have precluded Stratified analyses based on UPCR: Further analyses were performed in two sub-
retrospective studies to define the natural course of C3G and identify risks for progression to groups: (i) those with a reduction in UPCR < 50% over 1 year (N=23), and (ii) those
kidney failure (end stage renal disease/ESRD). In the present analysis, we focus on C3G with a reduction in UPCR  50% over 1 year (N=11). eGFR decreased by a mean
patients with native kidneys and examine the relationship between reductions in UPCR and value of 10.5% during 1-year spans in which there was a < 50% reduction in UPCR;
disease progression as indicated by changes in eGFR. however, for 1-year spans with a  50% decrease in UPCR, eGFR increased by
METHOD: Patients included in this study were consented and enrolled in the 8.1%. Furthermore, a categorical variable was defined such that renal progression
University of Iowa C3G ReCom Registry, which was created in 2013. Beginning in was categorized as at least a 30% or at least a 10% decline in eGFR over 1 year. For
2017, complement activity and renal function data were collected prospectively at the 23 spans with a < 50% reduction in UPCR, eGFR decreased by  10% and 
approximately 6-month intervals to define the natural history of C3G. Analyses were 30% in 10 (44%) and 5 (22%) of the spans, respectively. In contrast, for spans with a
performed across 1-year periods of time (“spans”). To be included in a span, a patient  50% reduction in UPCR, eGFR decreased by  10% in 2 (18%) spans but was not
had to meet the following criteria at the start of the 1-year period: native C3G, reduced by  30% in any spans.
eGFR 30 mL/min/1.73 m2, UPCR 1 g/g and 12 years of age. An individual
patient could be included in more than one span. Similar analyses using only the first 1-year span for each of the 24 patients produced
results that were consistent with those generated using all 1-year spans. Limitations of
this study include its small sample size and data variability due to its observational
nature.
CONCLUSION: The findings of this observational study support the premise that
reductions in proteinuria are associated with a more stable eGFR in native kidney C3G.
Regression analyses using UPCR as a continuous variable demonstrate the relationship
between reduction in UPCR and preservation of eGFR. This association was also
observed using both change in eGFR by UPCR reduction subgroup and UPCR-eGFR
categorical analyses.

MO137 DIFFERENCES IN GUT MICROBIOTA PROFILES AND


FUNCTIONS BETWEEN END-STAGE KIDNEY DISEASE AND
HEALTHY POPULATIONS

Ping-Hsun Wu1,2,3, Ting-Yun Lin4, Hsiu J. Ho5, Ching-Hung Tseng6, Yi-


Ting Lin1,3,7, Shih-Shin Liang8, Hei-Hwa Lee9, Mei-Chuan Kuo2,3,10, Szu-
Chun Hung4, Yi-Wen Chiu2,3,10, Chun-Ying Wu5,11,12,13
1
Kaohsiung Medical University, Graduate Institute of Clinical Medicine, College of
Medicine, Kaohsiung, Taiwan, R.O.C., 2Kaohsiung Medical University Hospital, Division
of Nephrology, Department of Internal Medicine, Kaohsiung, Taiwan, R.O.C.,
3
Kaohsiung Medical University, Faculty of Medicine, College of Medicine, Kaohsiung,
Taiwan, R.O.C., 4Taipei Tzu Chi Hospital, Division of Nephrology, Taipei, Taiwan, R.O.C.,
5
National Yang-Ming University, Institute of Biomedical Informatics, Taipei, Taiwan,
R.O.C., 6Germark Biotechnology, Taichung, Taiwan, R.O.C., 7Kaohsiung Medical
University Hospital, Department of Family Medicine, Kaohsiung, Taiwan, R.O.C.,
8
Kaohsiung Medical University, Department of Biotechnology, College of Life Science,
Kaohsiung, Taiwan, R.O.C., 9Kaohsiung Medical University Hospital, Department of
Laboratory Medicine, Kaohsiung, Taiwan, R.O.C., 10Kaohsiung Medical University,
Faculty of Renal Care, College of Medicine, Kaohsiung, Taiwan, R.O.C., 11Taipei Veterans
General Hospital, Division of Translational Research, Department of Medical Research,
Taipei, Taiwan, R.O.C., 12China Medical University, Department of Public Health,
Taichung, Taiwan, R.O.C. and 13National Health Research Institutes, National Institute
of Cancer Research, Miaoli, Taiwan, R.O.C.

BACKGROUND AND AIMS: Patients with end-stage kidney disease (ESKD) are
characterized by altered gut microbiota, impaired intestinal barrier function, and
experienced gut microbiota-derived metabolites related to systemic complications.
However, limited studies evaluated the microbial diversity and function in ESKD
patients previously.
METHOD: Compared to age- and gender-matched subjects without kidney disease, 82
ESKD patients in the discovery cohort and 58 ESKD patients in the validation cohort
were investigated for the microbial richness, biodiversity, gut dysbiosis, microbial
composition differences, and the functional changes by gut metabolic module analysis.
Bacterial derived free form protein-bound uremic toxins were analyzed by mass
spectrometry and their association with microbial richness in ESKD patients was
determined.
RESULTS: Compared to controls, an increased a-diversity and distinct b-diversity
were found in ESKD (Figure). The increase in a-diversity was correlated with protein-
bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index
(MDI) was found in ESKD patients with the following enriched genera:
Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina,
MO136 Figure: Linear regression and natural cubic spline models for the Akkermansia, Streptococcus, and Dysgonomonas. MDI at the genus level
relationship of change in UPCR to change in eGFR for all 1-year spans (N=34) successfully differentiated between ESKD and controls in the discovery cohort (area
included in the analysis (p<0.05). under the curve [AUC] of 81.9%) and the validation cohort (AUC of 83.2%).
Regarding functional enrichment analysis with gut metabolic modules, ESKD subjects

i154 | Abstracts
Nephrology Dialysis Transplantation Abstracts
presented with gut microbial function of increased saccharide and amino acid MO139 INDOLE-3-ACETIC ACID CORRELATES WITH MONOCYTE TO
metabolism compared with matched controls. HIGH-DENSITY LIPOPROTEIN (HDL) RATIO (MHR) IN
CHRONIC KIDNEY DISEASE (CKD) PATIENTS AND MAY BE
EFFICIENTLY REMOVED BY ACETATE-FREE
BIOFILTRATION

Valeria Cernaro1, Vincenzo Calabrese1, Saverio Loddo2, Roberta Corsaro2,


Vincenzo Macaione2, Valentina Teresa Ferlazzo2, Rosalia Maria Cigala3,
Francesco Crea3, Concetta De Stefano3, Guido Gembillo1, Adolfo Romeo1,
Elisa Longhitano1, Domenico Santoro1, Michele Buemi1, Salvatore Benvenga4,5,6
1
University of Messina, Unit of Nephrology and Dialysis, Department of Clinical and
Experimental Medicine, Messina, Italy, 2University of Messina, Department of Clinical
and Experimental Medicine, Messina, Italy, 3University of Messina, Department of
Chemical, Biological, Pharmaceutical and Environmental Sciences, Messina, Italy,
4
University of Messina, Endocrinology, Department of Clinical and Experimental
Medicine, Messina, Italy, 5University of Messina, Master Program on Childhood,
Adolescent and Women’s Endocrine Health, Messina, Italy and 6University Hospital,
Policlinico Universitario G. Martino, Interdepartmental Program of Molecular & Clinical
Endocrinology, and Women’s Endocrine Health, Messina, Italy

BACKGROUND AND AIMS: Indole-3-acetic acid (IAA, also called auxin) is a


protein-bound indolic uremic toxin deriving from tryptophan metabolism by the
intestinal bacteria. Previous studies have shown that increased IAA is associated with
enhanced tissue factor synthesis in endothelial and peripheral blood mononuclear cells,
oxidative stress and endothelial inflammation with resulting higher risk of thrombotic
events and both cardiovascular and all-cause mortality. An emerging biomarker of
cardiovascular disease is the monocyte to high-density lipoprotein (HDL) ratio
CONCLUSION: An enriched but dysbiotic gut microbiota was presented in ESKD (MHR). Its prognostic value is related to the ability of monocytes to release several
patients, in which the bacteria that were present increase amino acid metabolism cytokines involved in inflammation and atherogenesis and to the protective role of
linked to the production of protein-bound uremic toxins. HDL through removal of cholesterol from peripheral tissues and suppression of both
monocyte progenitor cell proliferation and differentiation and monocyte activation. In
this single-centre cross-sectional observational study, we investigated the potential
MO138 ASSOCIATION OF NT-PROBNP WITH OBESITY IN CKD association of IAA with MHR and other markers of cardiovascular risk in a cohort of
PATIENTS patients with CKD and evaluated the effect of a single midweek dialysis session with
AFB (Acetate-free Biofiltration) technique on IAA serum concentrations.
Ting-Yun Lin1, Szu-Chun Hung1 METHOD: We enrolled 61 non-dialysis CKD adult patients and 6 dialysis patients
1 treated with AFB technique. IAA levels were measured using an enzyme-linked
Taipei Tzu Chi Hospital, Division of Nephrology, New Taipei City, Taiwan, R.O.C.
immunosorbent assay (ELISA) kit (Cat. number abx150354; Abbexa Ltd, Cambridge,
UK). Post-dialysis IAA levels were corrected for haemoconcentration.
BACKGROUND AND AIMS: Obesity is associated with lower circulating levels of N- RESULTS: In the whole cohort of 67 patients, IAA was directly related to creatinine (q
terminal pro-BNP (NT-proBNP) both in the general population and in patients with = 0.247; P = 0.0441), potassium (r = 0.2871; P = 0.0185), Ca x P product (q = 0.256; P =
heart failure. In asymptomatic patients with CKD, NT-proBNP levels are generally 0.0365) and MHR (q = 0.321; P = 0.0082).
elevated. The prevalence of obesity is markedly increasing among patients with CKD. After adjustment for creatinine, the correlation between IAA and potassium became
However, whether obesity affects NT-proBNP levels and thresholds for increased risk not significant (r = 0.1968; P = 0.1133). Stratifying patients according to the history of
of clinical outcomes is unclear. cardiovascular disease, in the 40 patients with previous cardiovascular events IAA
METHOD: We examined the associations between NT-proBNP and obesity in 408 levels correlated significantly with uric acid (r = 0.3952; P = 0.0116) and MHR (q =
stage 3–5 CKD patients (268 men and 140 women; mean age 65613 years) free of 0.380; P = 0.0157).
heart failure at baseline, who were categorized into 3 groups according to body mass In the remaining 27 patients without history of cardiovascular disease, IAA only
index (BMI; kg/m2) as normal (<24.0), overweight (24.0–27.9), and obese (28.0). correlated with potassium (r = 0.3912; P=0.0481) and, though borderline significantly,
Multivariate Cox proportional hazards models were used to compare the risk with creatinine (q = 0.349; P = 0.0805). To assess whether IAA would independently
associations of NT-proBNP with the composite of ESKD (needing chronic dialysis or predict MHR values, we evaluated potential correlations of MHR with risk factors for
kidney transplantation) or all-cause mortality across BMI categories. cardiovascular disease. MHR was related with fibrinogen (q = 0.426; P = 0.0010),
RESULTS: NT-proBNP levels were significantly lower in obese patients than in normal arterial hypertension (q = 0.274; P = 0.0251), C-reactive protein (q = 0.332; P =
weight and overweight subjects (P <0.001). Within each CKD stage, NT-proBNP levels 0.0061), gender (q = -0.375; P = 0.0017; 0 = male, 1 = female), and CKD stage (q =
decreased with increasing BMI. In a multivariate analysis, NT-proBNP was inversely 0.260; P = 0.0337). A multiple regression analysis identified IAA as an independent
associated with obesity, as well as BMI and its fat and lean body mass components (all predictor of MHR. Lastly, IAA levels were higher in dialysis patients compared to non-
P <0.001), independent of demographics, comorbidities, and severity of CKD. During dialysis CKD patients (97.44 6 21.58 versus 65.08 6 24.38 ng/ml respectively; P =
a median follow-up of 2.2 years, 117 patients progressed to ESKD and 46 patients died. 0.0026) and it was significantly removed by a single AFB session (97.44 6 21.58 versus
Overall, higher NT-proBNP levels were independently associated with ESKD or death 54.59 6 21.74 ng/ml; P = 0.0028) with a reduction ratio of 43.80 6 17.47%.
(HR, 1.52; 95% CI, 1.22–1.89). Specifically, higher NT-proBNP levels were consistently CONCLUSION: This study shows a statistically significant association between IAA
associated with poor outcomes in all BMI categories (P for interaction = 0.096). and MHR. Based on previous experimental studies, such relationship could be
CONCLUSION: Obese CKD patients have significantly lower NT-proBNP levels. explained by the activation of the transcription factor aryl hydrocarbon receptor.
Nevertheless, BMI category did not modify the relationship between NT-proBNP and Indeed, IAA is a potent ligand of aryl hydrocarbon receptor and the latter has
clinical outcomes. Increased risk may be seen at relatively lower levels of NT-proBNP proinflammatory and proatherogenic activities and can reduce HDL levels. Moreover,
in obese CKD patients. AFB efficiently removes IAA during a single dialysis session. Prospective studies with
appropriate sample size and sufficiently long period of observation are required to
evaluate if decreasing IAA levels, through targeted therapeutic strategies in non dialysis
CKD patients or by optimization of dialysis techniques and prescriptions in patients
receiving renal replacement therapy, may reduce MHR levels and cardiovascular events
and improve clinical outcomes and survival.

10.1093/ndt/gfab092 | i155
Abstracts Nephrology Dialysis Transplantation

progenitor cells with differentiating ability is still lacking. The aim of the study is to
investigate the IS mediated cell damage on differentiating neuronal progenitor cells
METHOD: The study was divided into 2 parts: clinical investigation and in vitro study.
The clinical investigation collected 36 participants (12 health controls and 24 ESRD
patients with cognitive impairment by MMSE<=24). The in vitro study used the
human neuroblastoma cell line SH-SY5Y cells with differentiating protocol by retinoic
acid (RA, with concentration 10%). Indoxyl sulfate was given at concentration at 0, 25,
50 and 100lM at initiation of retinoic acid given and the 7 days after retinoic acid was
given. Microscopic morphology, MTT assay, annexin V-PI dual stain, and western
blotting for cleaved-caspase 3, Bax, Bcl-2 and oxidative stress (DCFCA) were
measured.
RESULTS: Among the 36 participants, the concentration of IS was higher in the ESRD
patients with cognitive impairment (43365.26624291.55 vs 5212.00614621.82 mg/dL,
p=0.00). The serum concentration of IS was negatively correlated with the total MMSE
score (r=-0.446, p=0.006) and the categories of MMSE (orientation to time: r=-0.537,
p=0.001, calculation: r=-0.541, p=0.001; recall: r=-0.402,p=0.014). In in vitro study, the
cell viability was not influenced in undifferentiated and differentiated (retinoic acid
treated for 7 days) SH-SY5Y cells. When IS during the initiation of RA treatment, the
cell viability decreased 3 hours after IS was given. The annexin-V-PI dual stain
demonstrated that the early apoptotic cells with annexin-V stained increased in IS
treated cell with dose-dependent manner. The caspase 8 and cleaved caspase 3
increased at 6 hours after IS treated when RA given. The Bax increased after IS treated
at 6 hours. The Bax/Bcl2 ratio increased at the IS concentration 50lM. The DCFCA
increased after IS treated at 1 hour with dose-dependent manner, and the cell viability
was rescued by N-acetylcystein.
CONCLUSION: The serum IS was negatively correlated the MMSE and predictive to
cognitive impairment in our cohort with 36 participants (12 health control and 24
ESRD patients with MMSE <=24). The in vitro study demonstrated that IS induced
differentiating SH-SY5Y cells apoptosis by activating caspase-dependent cell death
after generating oxidative stress.

MO140 INDOXYL SULFATE INDUCES THE APOPTOSIS OF THE


DIFFERENTIATING NEURONS BY ENHANCING OXIDATIVE
STRESS AND CLINICAL COGNITIVE IMPAIRMENT

Yi-Chou Hou1,2, Kuo-Cheng Lu3, Chuen-Lin Huang4, Yuh-Feng Lin5, Ruei-


Ming Chen6
1
Taipei Medical University, Graduate Institute of Clinical Medicine, College of Medicine ,
Taipei Medical University, Taipei City, Taiwan, R.O.C., 2Cardinal Tien Hospital,
Department of Nephrology, New Taipei City, Taiwan, R.O.C., 3Taipei Tzu Chi Hospital,
Department of Nephrology, New Taipei City, Taiwan, R.O.C., 4Cardinal Tien Hospital,
Department of Medical Research, New Taipei City, Taiwan, R.O.C., 5Taipei Medical MO140 Figure 1: The correlation between indoxyl sulfate and the MMSE scores.
University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei City,
Taiwan, R.O.C. and 6Taipei Medical University, Graduate Institute of Medical Sciences,
College of Medicine, Taipei City, Taiwan, R.O.C.

BACKGROUND AND AIMS: Indoxyl sulfate (IS) is a protein-bounded uremic toxin


involving the multi-organ dysfunction, including neurologic system. It has been
noticed that IS could induce the oxidative stress within brain by activating the
inflammation mediated by astrocyte, and its concentration was associated with
cognitive impairment. It has been noticed that the neuronal progenitor cells with
differentiating abilities could replace the damaged neuron. The damage of IS on the

i156 | Abstracts
Nephrology Dialysis Transplantation Abstracts
performed a logistic regression model to identify independent risk factors for AKI and
actuarial survival analysis to establish risk factors for mortality in this population.
RESULTS: 759 patients were included, with a median age of 64 years. 59% were men
and baseline median creatinine was 0.80 mg/dL. Most frequent malignance was lung
cancer and 56% were receiving PD1. 15.5% developed AKI during the follow-up. Age
and baseline kidney function were identified as independent risk factors for AKI
related ICI. At the end of follow-up, 52.3% patients had died. Type of cancer (not
melanoma, lung or urogenital malignance), type of CPI (not CTLA4, PD-1, PD-L1 or
their combination) and the presence of an episode of AKI were identified as risk factors
for mortality.
CONCLUSION: 15.5% of patients under immunotherapy presented AKI. A single
AKI episode was identified as an independent risk factor for mortality in these patients
and age and baseline renal function were risks factors for the development of AKI.

MO142 A SINGLE-CENTER CASE SERIES OF 150 PATIENTS WITH


RENAL FANCONI SYNDROME

Xiaoxiao Shi1, Ying Wang1, Jiaying Li1, Zhixin Chen1, Tiantian Ma1, Yubing Wen1,
Wei Ye1, Yan Qin1, Xuemei Li1, Yang Yu1, Limeng Chen1
1
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical
College Hospital, Chinese Academy of Medical Science and Peking Union Medical
College, Department of Nephrology, Beijing, P.R. China

BACKGROUND AND AIMS: Renal Fanconi syndrome (RFS) is characterized by


MO140 Figure 2: The cell viability decreased in IS treated differentiating(B and F) generalized dysfunctions of renal proximal tubular (PT) transport. The causes of FS
SH-SY5Y cells than IS treated differentiated SH-SY5Y cells. can be inherited or acquired, the latter of which mostly includes drugs, heavy metals,
monoclonal light chains (LC), and primary Sj gren’s syndrome (pSS). We intended to
observe the clinico-pathological features of RFS with different etiologies.
METHOD: From January 2012 to September 2018, all the patients diagnosed as RFS in
our hospital were enrolled. Their clinicopathological records were retrospectively
reviewed. The diagnosis of RFS was defined as existence of  3 of the following five
items alone or  2 items combined with an evidence of PT damages in kidney
pathology: (I) normoglycemic glycosuria; (II) generalized aminoaciduria; (III)
hypophosphatemia and hyperphosphaturia; (IV) hypouricemia and hyperuricosuria;
(V) proximal RTA.
RESULTS: 1.: Clinical characteristics: We identified 150 RFS patients, with an average
age of (45.9614.2) years old and male: female ratio 1.3:1. They presented with different
degrees of PT dysfunctions and the most common were hypophosphatemia (83.2%)
and aminoaciduria (80.6%). Their mean eGFR levels were 76.3 (4.5-188.6) ml/min/
1.73m2 with 73.5% had proteinuria. 2. Renal pathological features: 47 RFS patients
received kidney biopsy and the most common pathological diagnosis was interstitial
nephritis. They all presented with different degrees of proximal tubule atrophy,
defective brush border, interstitial edema and fibrosis. 3. Etiology-related
clinicopathologic features: The most common causes of our RFS were LC (14.0%),
drugs (13.3%), and pSS (9.3%). Compared to pSS associated RFS, LC associated RFS
patients showed a higher prevalence of bone involvement, more severe proteinuria and
less severe hypokalemia (P < 0.05) despite similar eGFR levels. Specific renal
pathological features were seen in different etiology groups, including crystalline
formation and increased lysosomes in PT cells under electron microscope in LC
associated RFS, and CD21 positive ectopic germinal center formation in renal
interstitum in parts of the pSS associated RFS.
CONCLUSION: We identified 150 RFS with different etiologies and they showed
etiology-specific patterns of PT dysfunctions and renal pathologic changes.

MO140 Figure 3: The cell viability was rescued in IS-treated SH-SY5Y cells by
pretreated by N-acetylcystein.
MO143 UTILITY OF SIFT-MS TO EVALUATE VOLATILE ORGANIC
COMPOUNDS IN NEPHROPATHIC PATIENTS’ BREATH

Annalisa Romani1,2, Anna Pietroboni Zaitseva3, Andrea Carretta4,


Giulia Marrone3,5, Chiara Vita2, Manuela Di Lauro3, Francesca Di Daniele3,5,
MO141 ACUTE KIDNEY INJURY AS A RISK FACTOR FOR Annalisa Noce3
MORTALITY IN ONCOLOGICAL PATIENTS RECEIVING 1
University of Florence, PHYTOLAB (Pharmaceutical, Cosmetic, Food Supplement,
CHECK-POINT INHIBITORS Technology and Analysis), DiSIA,, Sesto Fiorentino, FI, Italy, 2University of Florence,
QuMAP Laboratory, PIN Polo Universitario Citt a di Prato, Prato, Italy, 3University of
Clara Garcıa Carro1, Mo nica Bolufer2, Roxana Bury2, Zaira CAstan ~eda2, Rome Tor Vergata, UOC of Internal Medicine-Center of Hypertension and Nephrology
Eva Mun ~oz3, Enriqueta Felip3, David Lorente4, Maria Jose Carreras5, Unit, Department of Systems Medicine, Rome, Italy, 4Agilent SRA Instruments, Cernusco
Alejandra Gabaldon6, Irene Agraz2, Daniel Seron Micas2, Marıa José Soler2 sul Naviglio, MI, Italy and 5University of Rome Tor Vergata, PhD School of Applied
1
Clınico San Carlos Hospital, Nephrology, Madrid, Spain, 2Vall d’Hebron Hospital, Medical, Surgical Sciences, Rome, Italy
Nephrology, Barcelona, Spain, 3Vall d’Hebron Hospital, Oncology, Barcelona, Spain,
4
Vall d’Hebron Hospital, Urology, Barcelona, Spain, 5Vall d’Hebron Hospital, BACKGROUND AND AIMS: Breath analysis techniques allow detection and
Pharmacology, Barcelona, Spain and 6Vall d’Hebron Hospital, Pathology, Barcelona, quantification of multiple analytes present in breath to the low parts per billion volume
Spain (ppbv) level. One such technique is selected ion flow tube–mass spectrometry (SIFT-
MS), which can measure numerous volatile organic compounds (VOCs) in breath on-
BACKGROUND AND AIMS: Checkpoint inhibitors (CPI) have drastically improved line and in real-time. This technique has already been used in an innovative manner to
metastatic cancer outcomes. However, immunotherapy is associated to multiple monitor infectious, inflammatory status and metabolic conditions. However, there is
toxicities, including acute renal injury (AKI). Data about CPI related AKI are limited. no evidence on its use in ambulatory patients with chronic kidney disease (CKD). End-
Our aim was to determine risk factors for CPI related AKI, as well as its clinical stage-renal-disease patients are characterized by "uremic halitosis" caused by the
characteristics and its impact on mortality in patients undergoing immunotherapy. accumulation of uremic toxins that are detectable in breath such as ammonia and
METHOD: All patients under CPI at our center between March 2018 and May 2019, amines. The aims of this study are identifying a possible correlation between the
and with a follow up until April 2020, were included. Demographical, clinical data and detected VOCs and the presence of CKD, moreover, exploring the range of VOCs
laboratory results were collected. AKI was defined according to KDIGO guidelines. We levels in patients with different CKD stage.

10.1093/ndt/gfab092 | i157
Abstracts Nephrology Dialysis Transplantation

METHOD: In the present study, a mobile Voice200ultraV R SIFT-MS instrument was MO144 OVERLAP SYNDROME OF ANTINEUTROPHIL CYTOPLASMIC
made available by the Agilent SRA Division. The SIFT-MS allowed to quantify the ANTIBODY-ASSOCIATED VASCULITIS AND IGG4-RELATED
VOCs in CKD patients. The SIFT-MS uses a precise and controlled application of DISEASE: DISTINCT CLINICOPATHOLOGIC CLUES FOR
“soft” chemical ionization. PRECISE DIAGNOSIS
We enrolled 50 CKD patients, divided into two subgroups according to the estimated
glomerular filtration rate (eGFR): eGFR 30 mL/min/1.73m2 (A) and eGFR <30 mL/ Peifen Liang1, Qianqian Han1, Bo Liu1, Qiongqiong Yang1
min/1.73m2 (B) compared to 18 healthy subjects (C). The anamnestic data and 1
Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Department of Nephrology,
information about any comorbidities such as arterial hypertension, cardiovascular and Guangzhou, P.R. China
metabolic diseases, were collected for each patient. In order to reduce the possible
interferences in the exhaled composition induced by different lifestyles, all participants BACKGROUND AND AIMS: Both antineutrophil cytoplasmic antibody (ANCA)-
were instructed to perform hygienic procedures before the test execution. The exhaled associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are multi-system
was sampled through the use of a standard spirometry mouthpiece for single use, inflammatory disorders. The coexistent of both diseases present the possibility of a new
directly connected with the input probe to the MS detector of the instrument that was overlap syndrome which leads to different treatment and outcome. In this study, we
able to detect more than 30 VOCs. The processing of the sample was made through the aim to investigate the possibility and clinicopathologic clues to the diagnosis of this
direct use of an internal comparison library (Syft library). The SIFT-MS software overlap syndrome.
instantly calculates the absolute concentration of the target compounds by METHOD: A case of a 67-year-old man in our hospital who exhibited the
interpolating mass-to-charge ratios, reaction rate coefficients and branching ratios. clinicopathologic characteristics of both AAV and IgG4-RD was presented. The serial
RESULTS: Among all the VOCs analyzed, the most significant results are observed for alterations in serum parameters and treatment response of the case were followed up
ammonia and isoprene. In particular, the ROC curve of ammonia highlighted for the next 15 months. Then, a systematic literature review of the overlap syndrome
statistically significant differences between the three subgroups respectively A vs C was performed on PUBMED database from 1976 until January 2020.
AUC=0,756 p=0,001; B vs C AUC=0,942 p<0,001; A vs B AUC=0,797 p<0,001 RESULTS: Forty-two patients fully met both AAV and IgG4-RD criteria in the
(Figure 1). Youden index J between subgroups B and C defines the best cut-off =0,8704 literature. The median age was 60 years ranged from 31 to 73 years at diagnosis.
associated with the criterion ammonia concentration 4700 ppbv with sensitivity Twenty-eight (66.7%) patients were men. Serum IgG4 concentration increased in 41
=94,44% and specificity = 92,59%. (97.6%) patients (median:395 mg/dl; range:177-876mg/dl). Forty-one patients (97.6%)
tested positive for ANCA with 37 (90.2%) patients showing a specificity for MPO.
Kidney histology of 23 (69.7%) patients presented pauci-immune necrotizing or
crescentic glomerulonephritis and IgG4-relative tubulointerstitial nephritis.
Glucocorticoids combined with cyclophosphamide therapy was commonly prescribed
with a high remission rate within 3 months. Four common clinicopathologic features
of the overlap syndrome were identified from the case and literature.
CONCLUSION: AAV may overlap with IgG4-RD while presenting atypical
manifestations. Four common clinicopathologic characteristics could be used as
specific clues to the diagnosis of overlap syndrome.

MO143 Figure 1: Ammonia ROC curves.


Subgroups:A, CKDpatients with eGFR O mUmin/1.73m2; B, eGFR <30 mUmin/
1.73m2; C, control group.

The ROC curve of isoprene showed statistically significant differences between the
MO144 Figure 1: Pathological findings in the tubular basement membrane. A, By
three subgroups respectively B vs C AUC=0,669 p=0,050; A vs B AUC=0,691 p=0,014
immunofluorescence, granular tubular basement membrane staining for IgG is seen (
(Figure 2). These data allow us to define this a highly accurate test.
200). B, electron-dense without substructure deposits in the tubular basement
membrane ( 12000). C, electron-dense without substructure deposits and absorbs in
the tubular basement membrane ( 12000).

MO143 Figure 2: Isoprene ROC curves.


Subgroups: A, CKD patients with eGFR >30 mUminll.73m2; B, eGFR <30
m.Uminll.73m2; C, control group.

The same significant results were observed also with Anova one-way test that MO144 Figure 2: Pathological findings in the renal biopsy specimen. D, crescentic
highlighted an inversely correlation between the ammonia breath concentration and glomerulonephritis (MASSON,  200). E, CD38-positive plasma cells infiltrate in the
eGFR, and a direct correlation between isoprene and eGFR. renal interstitium ( 400). F, IgG4-positive plasma cells in the renal interstitium (
CONCLUSION: This preliminary data confirms the potential utility of SIFT-MS for 400). G, IgG-positive plasma cells in the renal interstitium ( 400).
the CKD diagnosis and the possible relation between the VOCs concentration and
CKD stage. This exam could be a new, non-invasive, fast-performing diagnostic
technique with real-time results useful for clinical management of CKD.
The study was inserted in the projects: “MioMen u: nuova filiera dell’agro-industria e
una cucina tracciata natura/benessere- Lazio Region” and “BioSynOL- Oil and
Legumes: biodynamic and synergistic crops for naturally fortified foods and innovative
products for health and sport – G.O.Tuscany Region”.

i158 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO145 CAROTID PLAQUE THICKNESS COMPARED WITH SEVERITY METHOD: This was a prospective observational study of outpatient adults referred for
OF CAROTID AND CORONARY ARTERY CALCIFICATION IN clinically indicated transthoracic echocardiograms at an academic hospital between
PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 2016 and 2018. A left ventricular ejection fraction (LVEF) below 45% was required for
inclusion (HFrEF).
Sasha Saurbrey Bjergfelt1, Ida Maria Hjelm Soerensen1, Henrik Oeder Hjortkjaer2, Mediation is the process through which an exposure causes disease. We hypothesized
Nino Emanuel Landler3, Ellen Linnea Freese Ballegaard1, Tor Biering-Sørensen3, that some of the total effect of extracellular water (ECW) to intracellular water (ICW)
Klaus F. Kofoed2, Theis Lange4, Bo Feldt-Rasmussen1, Henrik Hegaard Sillesen5, (as assessed by bioimpedance) ratio on lung congestion (as assessed by lung
Christina Christoffersen6, Susanne Bro1 ultrasonography) is mediated by C-reactive protein (CRP), left atrium volum index
1
Copenhagen University Hospital, Rigshospitalet, Nephrology, Copenhagen, Denmark, (LAVI) or estimated glomerular filtration rate (eGFR) – the mediators.
2
Copenhagen University Hospital, Rigshospitalet, Cardiology, Copenhagen, Denmark, RESULTS: Our study included 153 patients. The mean age and eGFR values of the
3
Gentofte Hospital, Cardiology, Hellerup, Denmark, 4University of Copenhagen, Public population at baseline were 67.1 years and 66.5 ml/min/1.73m2. The mean median
Health (Biostatistics), Copenhagen, Denmark, 5Copenhagen University Hospital, value for CRP was 25.6 (IQR 9.0-56.4) mg/L.
Rigshospitalet, Vascular Surgery, Copenhagen, Denmark and 6Copenhagen University Figure 1 depicts the structural equation models with the calculated magnitude of the
Hospital, Rigshospitalet, Clinical Biochemistry, Copenhagen, Denmark direct and indirect effects of ECW/ICW on the B-lines number in our population. In
this model, the fluid status has both direct and indirect effects on lung congestion.
BACKGROUND AND AIMS: Chronic kidney disease (CKD) accelerates both Specifically, it has a direct effect on LAVI and eGFR, which in turn have a direct effect
atherosclerosis and arterial calcification. The aim of the present study was to explore on the number of B-lines. Therefore, the indirect effect mediated by LAVI and eGFR
whether maximal carotid plaque thickness (cPT max) was increased in patients with accounts for a significant proportion of 27.6% of the total effect of ECW/ICW on lung
CKD stage 3 compared to controls and associated with cardiovascular disease and congestion
severity of calcification in the carotid and coronary arteries.
METHOD: The study group consisted of 200 patients with CKD stage 3 from the
Copenhagen CKD Cohort and 121 age- and sex-matched controls. cPT max was
assessed by ultrasound and arterial calcification by computed tomography scanning.
RESULTS: Carotid plaques were present in 58% of patients (n=115) compared with
40% of controls (n=48), P=0.002. Among participants with plaques, cPT max (median,
interquartile range) was significantly higher in patients compared with controls (1.9
(1.4-2.3) versus 1.5 (1.2-1.8) mm, P=0.001. Cardiovascular disease was present in 9.4%
of patients without plaques (n=85), 23.2% of patients with cPT max 1.0-1.9 mm (n=69)
and 34.8% of patients with cPT max >1.9 mm (n=46), P=0.001.
Carotid and coronary calcium scores >400 were present in 0.0% and 4.0%,
respectively, of patients with no carotid plaques, in 19.1% and 24.2% of patients with
cPT max 1.0-1.9 mm, and in 47.5% and 52.6% of patients with cPT max >1.9 mm,
P<0.001.
CONCLUSION: This is the first study showing that cPT max is increased in patients
with CKD stage 3 compared to controls and closely associated with prevalent
cardiovascular disease and severity of calcification in both the carotid and coronary
arteries.

MO146 Figure 1: Path analysis illustrated by the structural equation model with
standardized coefficients of direct effects for HFrEF patients. Dashed lines represent
non-significant pathways (tested, but not included in the model) and solid lines
represent significant pathways (included in the model).

Although ECW/ICW has a direct effect on inflammation, this doesn’t have any effect
on renal function or lung congestion.
CONCLUSION: We show that eGFR and LAVI partly mediate the effect of ECW/
ICW on lung congestion in patients with HFrEF. While the deleterious effects of fluid
overload on lung congestion have long been recognized, this study provides evidence
for a relationship of significant magnitude linking fluid overload with decreased eGFR
and increased LAVI, which in turn lead to elevations in the B-lines number.
This work was supported by a grant of the Ministery of Research and Innovation,
CNCS-UEFISCDI, project number PN-III-P1-1.1-PD-2016-0287, within PNCDI III
and by a grant of the “Grigore T. Popa” University of Medicine and Pharmacy,
contract number 27505/2018.

MO145 Figure: Association between maximal carotid plaque thickness (cPT max)
and coronary artery calcium score. MO147 ASSOCIATION OF CHA2DS2-VASC SCORE WITH CAROTID-
According to carotid ultrasound findings, patients were divided into 3 groups: No FEMORAL PULSE WAVE VELOCITY IN CHRONIC KIDNEY
carotid plaques, cPT max 1.0-1.9 mm, cPT max >1.9 mm. Based on the distribution of DISEASE PATIENTS
calcium scores from noncontrast CT scanning of the coronary arteries, patients were
divided into calcium score categories of 0, 1-100, 101-400 and >400. Nina Vodosek Hojs1, Robert Ekart2, Sebastjan Bevc1, Nejc Piko2, Radovan Hojs1
1
University Medical Centre Maribor, Clinic of Internal Medicine, Department of
Nephrology, Maribor, Slovenia and 2University Medical Centre Maribor, Clinic of
Internal Medicine, Department of Dialysis, Maribor, Slovenia

MO146 RENAL FUNCTION MEDIATES THE EFFECT OF FLUID BACKGROUND AND AIMS: Chronic kidney disease (CKD) patients suffer from
EXCESS ON LUNG CONGESTION IN PATIENTS WITH HFREF high cardiovascular morbidity and mortality. Arterial stiffness is an important
parameter for the evaluation of cardiovascular risk. Carotid-femoral pulse wave
Raluca Popa1, Radu Sascau2, Cristian Statescu2, Vlad Vasiliu3, velocity (cfPWV) is the gold standard measure for the assessment of arterial stiffness.
Andreea Neamtu3, Andreea Bucur3, Mehmet Kanbay4, Dimitrie Siriopol1 CHA2DS2-VASc score was originally used to predict cerebral infarction in patients
1
“Saint John the New” County Hospital, Nephrology, Suceava, Romania, 2“Grigore T. with atrial fibrillation (AF). However, it is also useful in predicting outcome in different
Popa” University of Medicine and Pharmacy, Iasi, Cardiology, Iasi, Romania, 3“Dr. C.I. cardiovascular conditions, independent of the presence of AF. Therefore, the aim of
Parhon” Clinical Hospital, Nephrology, Iasi, Romania and 4Koc University School of our research was to assess the association of CHA2DS2-VASc score with cfPWV in
Medicine, Division of Nephrology, Department of Medicine, Istanbul, Turkey CKD patients.
METHOD: Eighty-seven non-dialysis CKD patients from our outpatient clinic were
included. At the time of inclusion, medical history data and standard blood results
BACKGROUND AND AIMS: Despite impressive improvements in treatment
were collected, CHA2DS2-VASc score was calculated, cfPWV measurements
strategies, heart failure (HF) morbidity and mortality remain substantially high
(SphygmoCor System) were done. Correlation between CHA2DS2-VASc score and
worldwide. Pulmonary congestion is considered the leading cause for hospital
cfPWV was assessed. Multiple regression analysis with cfPWV as dependent and
admissions and death among patients with HF. The aim of this study is to investigate if
CHA2DS2-VASc score, eGFR, urinary albumin/creatinine, haemoglobin, high
the effect of fluid status, as assessed by bioimpedance spectroscopy (BIS) on lung
sensitivity CRP, serum calcium, phosphate and intact PTH as independent variables
congestion is mediated by renal function, inflammation or cardiac function.
was performed. Additionally, patients were divided into two groups according to

10.1093/ndt/gfab092 | i159
Abstracts Nephrology Dialysis Transplantation

median value of CHA2DS2-VASc score (group 1: CHA2DS2-VASc score 2, group 2: Currently, iptacopan is being evaluated in an ongoing adaptive seamless double-blind
CHA2DS2-VASc score >2). Data of both groups were compared by t-test or Mann- and placebo-controlled dose-ranging Phase 2 study (CLNP023X2203, Part 1 and Part
Whitney test. 2) in patients with biopsy-confirmed IgAN and elevated proteinuria [urine protein to
RESULTS: CHA2DS2-VASc score correlated with cfPWV (r=0.380, p=0.001). In creatinine ratio (UPCR)  0.75 g/g]. An interim analysis (IA) at 90 days of treatment
multiple regression analysis only CHA2DS2-VASc score was significantly associated in the Part 1 study showed that iptacopan administered up to 200 mg b.i.d for 90 days
with cfPWV (p=0.001). Data of both groups of patients divided according to median was safe, well tolerated and may be effective in reducing proteinuria. A further IA
value of CHA2DS2-VASc score are presented in table 1. cfPWV was significantly higher combining participants in Part 1 and Part 2 will be completed in early 2021 and the
in group 2 (13.4063.50 vs 10.4662.93, p=0.001). Groups of patients also differed pivotal phase 3 trial is to start in early 2021.
significantly in age, presence of diabetes, eGFR and serum phosphate. AIM: APPLAUSE-IgAN (NCT04578834; CLNP023A2301) is a multicenter,
CONCLUSION: CHA2DS2-VASc score is associated with cfPWV in CKD patients. randomized, double-blind, placebo-controlled parallel-group Phase 3 study which aims
Patients with a higher CHA2DS2-VASc score have stiffer arteries. to evaluate the efficacy and safety of iptacopan (LNP023) compared with placebo in
addition to supportive therapy on proteinuria reduction and slowing kidney disease
progression in primary IgAN patients.
METHOD: Adult patients diagnosed with primary IgAN (based on kidney biopsy and
MO148 A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND,
elevated proteinuria [UPCR  1 g/day]) will be recruited. A run-in period will ensure
PLACEBO CONTROLLED, PARALLEL GROUP, PHASE III
that patients have received ACEi/ARB at a maximally tolerated dose for at least 90 days
STUDY TO EVALUATE THE EFFICACY AND SAFETY OF
and receive required vaccinations at least 2 weeks prior to first dosing. Patients will be
LNP023 IN PRIMARY IGA NEPHROPATHY PATIENTS
randomized in a 1:1 ratio to either iptacopan 200 mg b.i.d or matching placebo for a
24-month treatment period.
Vlado Perkovic1, Brad Rovin2, Hong Zhang3, Naoki Kashihara4, Bart Maes5,
The trial will enroll approximately 450 participants, aiming for 430 with eGFR 30 mL
Dana Rizk6, Wenyan Wang7, Matthias Meier8, Dmitrij Kollins8,
/min/1.73m2 (main study population). About 20 participants with eGFR 20 to <30
Olympia Papachristofi8, Alan Charney7, Jonathan Barratt9,10
1
mL/min/1.73m2 (severe renal impairment population) will also be enrolled to explore
University of New South Wales, UNSW Research Grants and Contract Office, Level 3, PK and safety of iptacopan in this group, but will not be included in the efficacy
Rupert Myers Building South Wing, UNSW Kensington Campus, Kensington, Australia, analyses.
2
The Ohio State University, OSU Wexner Medical Center, Nephrology Division, Ground PRIMARY OBJECTIVES: 1) At IA (when approximately 250 patients have completed
Floor 395 W. 12th Avenue Columbus, United States of America, 3Renal Division, Peking the 9 months visit): To demonstrate superiority of iptacopan vs. placebo in
University First Hospital, Peking University, Institute of Nephrology, No.8 Xi Shi Ku Street, the reduction of proteinuria. The IA results may be submitted to support accelerated/
Xi Cheng District, Beijing , P.R. China, 4Department of Nephrology and Hypertension, conditional approval.
Kawasaki Medical School, 577 Matsushima, Kurashiki Okayama, Japan, 5Department 2) At final analysis (when approximately 430 patients have completed 24 months of
of Nephrology, AZ Delta Wilgenstraat 2, 8800 BE Roeselare, Belgium, 6Medicine/ active treatment): to demonstrate superiority of iptacopan vs. placebo in slowing
Nephrology, 703 19th Street South, 614 Zeigler Research Building, Birmingham AL kidney disease progression measured by the annualized total slope of eGFR decline
35294-0007, United Kingdom, 7Novartis Pharmaceuticals Corporation, 1 Health Plaza, over 24 months.
East Hanover, United States of America, 8Novartis Pharma AG, Lichtstrasse 35, 4056 RESULTS: Recruitment will start in Q1 2021.
Basel, Switzerland, 9University: The Mayer IgA Nephropathy Laboratories, Lab 105, 107, CONCLUSION: This trial will evaluate the efficacy of iptacopan, a promising new
125 and 10NHS: The John Walls Renal Unit, Leicester General Hospital, Gwendolen therapy for IgAN, in reducing proteinuria and slowing loss of kidney function over 2
Road, Leicester LE5 4PW, United Kingdom years.

BACKGROUND AND AIMS: IgA nephropathy (IgAN) is the most common primary
glomerulonephritis worldwide. It is an autoimmune disease characterized by deposits
of IgA1-containing immune complexes in the glomerular mesangium leading to local
inflammation and subsequent decline in kidney function. Currently, there are no
targeted therapies for IgAN. The KDIGO guidelines (2012) recommend optimized
long-term supportive care including inhibition of the RAS (ACEi or ARB) as well as
lifestyle modification for blood pressure control and proteinuria reduction. Patients
who remain at high risk of progressive CKD despite maximal supportive care might be
considered for high-dose corticosteroids or immunosuppressants.
In recent years, mounting evidence has supported an important role for complement
activation in disease onset and progression of IgAN. The alternative complement
pathway (AP) and lectin complement pathway (LP) are found to be activated in 75- MO148 Figure: Study Design
90% and 17-25% of IgAN patients, respectively (Floege et al 2014, Maillard et al 2015).
Factor B (FB) is an essential component of C3- and C5-convertases. Iptacopan
(LNP023) is an oral, first-in-class, highly potent selective inhibitor of FB and thereby
blocks the activity of AP C3 and C5 convertases, inhibiting the AP as well as the
amplification of the classic and lectin complement pathways.

MO147 Table 1. Eighty-seven CKD patients were divided into two groups according to the median value of CHA2DS2-VASc score. Data are presented as
mean6SD or as absolute number of patients with a known condition.

Group 1 (N=52) CHA2DS2-VASc score 2 Group 2 (N=35) CHA2DS2-VASc score >2 p


Age (years) 53.98610.48 69.66610.05 0.001
Sex - male/female 37/15 20/15 0.180
Arterial hypertension 50 35 0.243
Diabetes 6 16 0.001
Dyslipidaemia 22 21 0.108
Smoking - past or current 27 12 0.107
eGFR (ml/min/1.73m2) 33.24626.63 23.95612.98 0.034
Urinary albumin/creatinine (mg/g) 859.9461143.76 1048.3761778.92 0.549
Haemoglobin (g/l) 132.21619.09 125.26617.02 0.086
High sensitivity CRP (mg/l) 4.5766.71 6.30611.91 0.390
Calcium (mmol/l) 2.2360.15 2.2360.13 0.864
Phosphate (mmol/l) 1.1760.33 1.3260.38 0.046
Intact PTH (pg/ml) 135.446118.59 144.88697.95 0.704
Carotid-femoral pulse wave velocity (m/s) 10.4662.93 13.4063.50 0.001

i160 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO149 PREGNANCY AFTER LIVING KIDNEY DONATION, A Central Hospital between April 1 and May 31, 2020. Serum Na level of < 135 mEq/L
SYSTEMATIC REVIEW OF THE AVAILABLE EVIDENCE AND A was defined as hyponatremia, 135–145 mEq/L as normonatremia, and > 145 mEq/L as
REVIEW OF THE CURRENT GUIDANCE hypernatremia. Inflammation was assessed by serum C-reactive protein (CRP) levels.
Univariate logistic regression analyses were used to assess associations between
Maria Pippias1,2, Laura Skinner2,3, Anna Varberg Reisæter4,5, hyponatremia at admission and need for oxygen or death during hospitalization. A
Daniel Abramowicz6, Marlies Noordzij7, Vianda Stel8, Kitty J Jager8 comparison of serum Na levels at admission and discharge was tested using a paired t-
1
University of Bristol, Department of Health Care Evaluation, Population Health test. Cross-sectional associations between serum Na and CRP levels at admission or
Sciences, United Kingdom, 2North Bristol NHS Trust, United Kingdom, 3University of days from onset to admission were analyzed using multivariate linear regression
Bristol, Translational Health Sciences, Bristol , United Kingdom, 4Oslo universitetssykehus analyses. A restricted cubic spline (RCS) curve incorporated in one of these
Rikshospitalet, Department of Transplantation Medicine, Oslo, Norway, 5Norwegian multivariate linear regression analyses was used to identify when serum Na levels were
Renal Registry, Oslo University Hospital, Rikshospitalet, Oslo, Norway, 6Antwerp the lowest. In addition, we employed a mixed-effect model to examine the longitudinal
University Hospital, Department of Nephrology, Antwerp, Belgium, 7University Medical association between changes in serum Na and CRP levels during hospitalization.
Center Groningen, Department of Internal Medicine, Groningen, The Netherlands and
8
Amsterdam UMC, locatie AMC, European Renal Association-European Dialysis and
Transplant Association (ERA-EDTA) Registry, Department of Medical Informatics,
Amsterdam, The Netherlands

BACKGROUND AND AIMS: It was long believed that living kidney donation did not
infer a risk to the health or longevity of living kidney donors (LKD), though recently,
some studies have called this into question. The majority of LKD are women of
childbearing age, it is therefore vital that a clear picture of the risks associated with
pregnancy post-kidney donation is obtained. Furthermore, it is imperative that the
guidance pertaining to accepting an LKD of childbearing age is both comprehensive
and clear.
We performed a systematic review with the aim of identifying all original research
articles examining pregnancy outcomes, such as gestational hypertension and pre-
eclampsia in LKD, and to compare the quality and consistency of the guidelines,
consensus statements and expert opinions in this area.
METHOD: We searched Embase Ovid, MEDLINE Ovid, PubMed, society webpages
and guideline registries for English-language publications published up until 18th
December 2020. Article references and citation lists were also examined. The study was
performed in accordance with the PRISMA guidelines.
RESULTS: A total of 94 articles were screened. Nine cohort studies, two case reports,
and one congress abstract were identified. The four most recent published papers were
retrospective cohort studies, which included a combined number of 1,298 LKDs. All
four studies reported an increase in both the relative and absolute risk of pregnancy-
related complications. For example, the absolute risk of pre-eclampsia increased from
1-3% of pregnancies in LKD pre-donation to 4-6% of pregnancies in LKD post-
donation. This meant that LKDs had a lower absolute risk of pre-eclampsia pre-
donation, but after donation their risk of pre-eclampsia matched that of the general
population. None of these studies distinguished between early or late onset pre-
eclampsia. Participants were predominantly limited to Caucasian women. The lack of
an ideal ‘living donor comparator group’ hindered a full quantification (including
meta-analysis) of the pregnancy-related complications in LKD.
We identified seven clinical guidelines and consensus statements published since 2010.
These were broadly consistent in stating that the risk of pregnancy-related
complications in LKD was similar to the general population’s risk, and that potential
LKD should be informed of this risk. They were however inconsistent in their scope.
For example, only three guidelines recommended enquiring into prior pregnancy-
induced complications, and only two offered specific guidance on post-donation
pregnancy follow-up. The most striking inconsistency was the differing view as to
whether or not women who had not yet completed a family should be accepted as
LKD. For example, one guideline stated that ‘women should not be excluded from
donation solely on the basis of a desire to have children after donation’, whilst another
stated that ‘it seem(ed) advisable to have completed a planned family before donation’.
CONCLUSION: The relative risk of pregnancy-related complications in LKD
increases relative to the risk in non-LKD, though the increase in absolute risk remains
very low. Though multiple guidelines for living kidney donation were identified, their
advice for women of childbearing age was at times scant and inconsistent. The LKD of
the future is likely to differ from the LKD of yesteryear. As such more focus should be
placed on better identifying and individualising risk for LKD. Whilst the evidence
suggests that an LKD’s risk of complications in pregnancy remains low post donation,
one should keep in mind that a potential LKD’s personalised risk is unknown.

RESULTS: Ninety-eight patients were enrolled, of whom 53 (54%) were male and 39
(40%) had a smoking history. Mean (SD) or median (IQR) of age, eGFR, body mass
MO150 SERUM SODIUM DECLINE OCCURS DURING THE ACUTE
index (BMI), serum Na, and CRP at admission were 50 (17) years, 82 (20) mL/min/
PHASE OF COVID-19
1.73m2, 23.3 (5.5), 138 (3.7) mEq/L, and 1.8 (0.2–6.0) mg/dL, respectively. It took an
mean of 8.9 (3.7) days from onset to admission due to social disruption. According to
Keiko Tanoue1,2, Masamitsu Senda1, Kaku Tamura1,3, Kazuo Imai1,
government policies, during observation period, patients diagnosed with COVID-19
Mayu Nagura1, Sakiko Tabata1, Kazuyoshi Miyoshi1, Hanako Matsunobu1,
have to be hospitalized, even if they have minor or improving clinical symptoms.
Satoko Nakamura1, Toshimitsu Ito1
1
At admission, hyponatremia was observed in 11 (11.2%) patients; the rest of the
Self-Defense Forces Central Hospital, Department of Internal Medicine, Tokyo, Japan, patients had normonatremia. Twenty-seven (27.6%) patients received oxygen, and 4
2
National Defense Medical College, Department of Nephrology and Endocrinology, (4.1%) died during hospitalization. Hyponatremia at admission was significantly
Saitama, Japan and 3Self-Defense Forces Sasebo Hospital, Department of Internal associated with the need for oxygen (odds ratio: 41.2; 95% CI: 4.9–344; P=0.001) and
Medicine, Nagasaki, Japan death (odds ratio: 32.3; 95% CI: 3.0-347; P=0.004). Irrespective of hyponatremia at
admission, the serum Na levels at discharge were significantly higher than those at
BACKGROUND AND AIMS: Hyponatremia is associated with aggravation of admission (Fig. 1).
inflammation in COVID-19 patients. However, to the best of our knowledge, no study In both cross-sectional and longitudinal analyses, serum Na levels were negatively
has used longitudinal data and investigated the association between hyponatremia and associated with serum CRP levels after adjustment for age, sex, eGFR, BMI, and
COVID-19. Therefore, we analyzed COVID-19 patients’ changes in serum sodium smoking history (P<0.001), which suggests that serum Na levels may reflect the
(Na) levels from admission to discharge. activity of COVID-19. Furthermore, the serum Na levels at admission were positively
METHOD: We conducted a retrospective, single-center, observational cohort study, associated with days from onset to admission after adjustment for age, sex, eGFR, BMI,
involving adult COVID-19 patients who were admitted to Japan Self-Defense Forces smoking history, and serum CRP levels (P=0.035), and the RCS curve showed that the

10.1093/ndt/gfab092 | i161
Abstracts Nephrology Dialysis Transplantation

serum Na levels tended to be the lowest around the 7th day after onset (Fig. 2). variables and t-tests were employed for pseudo normally distributed continuous
CONCLUSION: Hyponatremia in COVID-19 may occur secondarily, and a condition variables.
called “COVID-19-induced hyponatremia” might exist. RESULTS: Of the 53 participants, the median age was 59 years (26-89). 41.5% were
women. The median time on dialysis was 1.6 years.
According to the CFS, 6 patients were categorised as non-frail, 30 patients as
intermediately frail and 17 as frail.
MO151 CLINICAL COURSE AND OUTCOMES OF COVID-19
Among frail participants, 41% were correctly perceived as frail by their nephrologist.
PATIENTS WITH BIOPSY-PROVEN GLOMERULAR AND
Among non-frail participants, 100% were correctly perceived as non-frail by their
TUBULAR KIDNEY DISEASE. LOW HEMOGLOBIN LEVELS AS
nephrologist.
A RISK FACTOR FOR MORTALITY
Among those who were frail according to the CFS, those misclassified as intermediately
n Roman1, Clara Garcıa Carro1, Irene Agraz1, Néstor Toapanta1, frail or non-frail, were younger (median age of those misclassified 49 years vs 62 years
Juan Leo
of those not mis-classified, P=0.03) but did not differ by sex (P=1), time on dialysis
Ander Vergara Arana1, Alejandra Gabaldon2, Irina Torres Rodriguez1,
(P=0.39), presence of diabetes (P=0.30) or presence of vascular disease (P=1).
Roxana Bury1, Cinthia Baldallo1, Daniel Seron Micas1, Marıa José Soler1
1
CONCLUSION: In this study of adult patients undergoing chronic haemodialysis,
Vall dHebron Hospital, Nephrology and 2Vall dHebron Hospital, Pathology, Barcelona, perceived frailty correlated with measured frailty using the CFS less than 50% of the
Spain time. This suggests that clinical perception is not an accurate surrogate for frailty status
in this population group. Additionally, this study suggests that younger patients with
BACKGROUND AND AIMS: COVID-19 infection is responsible for respiratory ESRD are less likely to be correctly perceived as frail. Such misclassification could
infection with variable clinical expression from its asymptomatic form to severe influence clinical decisions for treatment, including candidacy for kidney
pneumonia associated with acute respiratory distress syndrome and death. Risk factors transplantation.
related to higher mortality are age over 65 years, cardiovascular, pulmonary and kidney
disease, hypertension, and diabetes. There is limited scientific literature on COVID-19
infection and previous kidney disease, specifically in patients with glomerular and
MO153 RENAL FUNCTIONS OUTCOME IN METASTATIC NON SMALL
tubular kidney disease. The aim of this study was to determine general characteristics,
LUNG CARCINOMA PATIENTS: THE RISK OF AKI IN FIRST
analytical parameters and clinical evolution of patients with kidney disease who have
LINE THERAPY
undergone kidney biopsy and who presented infection or high suspicion of infection by
COVID-19. Identify mortality and associated risk factors.
Francesco Trevisani1, Federico Di Marco2, Francesco Fiorio2, Monica Cattaneo3,4,
METHOD: we studied patients with high clinical suspicion of infection or confirmed
Erika Rijavec3, Michele Ghidini3
infection by COVID-19 from March 2020 to May 15, 2020 of all patients who 1
underwent percutaneous renal biopsy at the Vall d’Hebron Hospital between January San Raffaele Scientific Institute, Urology, Milan, Italy, 2Urological Research Institute
2013 and December 2019. (URI), Division of Experimental Oncology, Milan, Italy, 3Fondazione IRCCS Ca’ Granda
RESULTS: 39 of the 553 patients have been diagnosed with COVID-19 infection since Ospedale Maggiore Policlinico, Medical Oncology Unit, Milan, Italy and 4University of
March 2020. The average age was 63615 years and 48.7% were male. Hypertension Udine, Deparment of Medicine, Udine, Italy
was present in 79.5% of patients, chronic kidney disease without renal replacement
therapy in 76.9%, and cardiovascular disease in 64.1%. Nasopharyngeal swab was BACKGROUND AND AIMS: The optimal use of immune and target therapies, the
performed in 26 patients; older patients (p=0.01), patients with hypertension optimal use of standard chemotherapy (CT) is of paramount importance, especially for
(p=0.005), immunosuppression (p=0.01), use of RAS-blocking drugs (p=0.04) and patients affected by chronic kidney disease (CKD) who require dose adjustment
gastrointestinal symptoms (p=0.02) were more likely to be tested for COVID-19. 22 according to the glomerular filtration rate (GFR) to avoid acute kidney injury (AKI)
patients required hospitalization and 15.4% died. In the bivariate analysis, mortality establishment. Immune checkpoint inhibitors (ICIs) and platinum-based
was associated with older age (p=0.03), cardiovascular disease (p=0.05), chronic chemotherapy (CT) are options for the palliative treatment of metastatic non-small cell
obstructive pulmonary disease (COPD) (p=0.05) and low hemoglobin levels (p=0.006). lung cancer (NSCLC). Recently, CT in combination with immune-checkpoint
Adjusted Cox regression showed that low hemoglobin levels (10.1261.89g/dL) at inhibitors has become the treatment of choice for this setting of patients. Therefore, it
admission had 1.81 greater risk of mortality [1.04-3.13; p=0.04]. is fundamental to investigate the potential nephrotoxic effects of both treatments and
CONCLUSION: Patients with COVID-19 infection and kidney disease confirmed by their potential additive effects on renal function.
kidney biopsy presented mortality of 15.4%. Swab test for COVID-19 was more likely Aim of our study was to compare the nephrotoxic effect of both ICIs and CT (cisplatin
to be performed in older, hypertensive, use of RAS-blocking drugs, immunosuppressed and carboplatin-based) in a consecutive cohort of patients affected by metastatic
patients and those with gastrointestinal symptoms. Low hemoglobin is a risk factor for NSCLC.
mortality. METHOD: A consecutive cohort of 126 patients treated in first-line for NSLCL was
enrolled in a single tertiary Hospital between 2018 and 2020. Inclusion criteria were:
age (> 18 years old), eGFR (> 15 ml/min/1.73), histological diagnosis of metastatic
NSCLC. Each patient underwent immunotherapy or CT according to clinical
MO152 CORRELATION OF PERCEIVED FRAILTY WITH MEASURED
conditions, comorbidities and programmed death ligand 1 (PD-L1) expression status.
FRAILTY IN AN ADULT HAEMODIALYSIS POPULATION
eGFR (using CKD-EPI formula 2009) was detected at baseline and after each cycle of
immunotherapy or CT (using cisplatin or carboplatin) in order to determine the
Ruth Fergie1, Jennifer McCaughan2, Peter Eves1, Siddesh Prabhavalkhar1,
correct renal status using the K-DIGO 2012 guidelines for AKI stages and CKD classes.
Girish Shivashankar1, Emma Cunningham3,4
1
Pts were subdivided into CKD categories G according to their eGFR values before and
Altnagelvin Hospital, Renal Unit, Altnagelvin, United Kingdom, 2Belfast City Hospital, after the treatment. AKI onset was evaluated by rise in creatine levels according to K-
Renal Unit, United Kingdom, 3Belfast Health & Social Care Trust, United Kingdom and DIGO criteria. Clinical stage according to cTNM (AJCC TNM system-2019) was
4
Queen’s University Belfast, Centre for Public Health, United Kingdom collected at baseline before the first treatment. Comorbidities (e.g., diabetes, blood
hypertension, overweight and obesity) were also included. Comparison between
BACKGROUND AND AIMS: Frailty is a measure of physiological reserve and the numerical variables was performed using linear regressions; between groups using
ability to respond to physiological stress. Increasing frailty predicts adverse health Kruskal-Wallis rank sum test for numerical variables and Pearson’s Chi square test for
outcomes in patients with end stage renal disease (ESRD) Despite this, frailty is not categorical variables. Log rank test was used to test differences between groups in terms
routinely measured in clinical practice where clinician perception of frailty is used to of AKI onset during the therapy.
inform decision making. RESULTS: Clinical and pathological characteristics are reported in table 1. From the
The Clinical Frailty Scale (CFS) is a clinical judgement-based score that is a useful analysis, no significative differences were detected between Immunotherapy and CT
screening tool for frailty. Increasing frailty measured by CFS is predictive of adverse group for age, gender, basal serum creatinine, basal eGFR, basal BMI, diagnosis of
outcomes in patients with advanced chronic kidney disease (CKD) including falls, diabetes, hypertension, basal CKD G group or overall AKI onset. Treatment cycles
worsening disability, care home admissions, hospitalizations and ultimately mortality. were significantly different between the two groups (p<0.001) with a short median
It has been widely used in the assessment of patients with COVID-19 to help inform number of cycles for the CT group. No significative difference in terms of decay of
decisions regarding ceiling of care. eGFR calculated as final-basal values was detected (p=0.8). AKI onset over cycles was
This study aimed to assess the correlation between clinician perception of frailty and significantly different between the two groups (p=0.02), observing a higher risk of
frailty as measured using the CFS. developing earlier AKI for CT group (cisplatin or carboplatin) (13,9%) with respect to
METHOD: Frailty was assessed for all patients undergoing in centre hospital immunotherapy (7,4%) (figure 1 and 2).
haemodialysis (n=53) in a single dialysis unit in Northern Ireland. A CFS score was
calculated for all patients by a clinician who routinely uses the CFS in clinical practice.
Patients with a score of 1-3 were classified as not frail, 4-5 as intermediately frail and 6-
9 as frail.
Nephrologists received basic education about frailty. They were then asked to
categorize their patients as non-frail, intermediately frail or frail.
The relationship between measured and perceived frailty was assessed using percent
agreement. Participant characteristics of frail patients who were misclassified as
intermediately frail or non-frail by clinicians were compared to those patients correctly
classified as non-frail by clinicians. Fisher’s exact test was employed for categorical

i162 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO154 ASSESSMENT OF MILD COGNITIVE IMPAIRMENT IN PRE-
DIALYSIS CHRONIC KIDNEY DISEASE AND ITS
ASSOCIATION WITH INFLAMMATION AND CHANGES IN MRI:
WHAT THE EYES DONT SEE

Leopoldo Antônio Pires1, Ana Laura Maciel de Almeida1, Marilise Paraizo1,


Debora Dias2, José Ot avio Correa2, Danielle Ezequiel1, Rogerio De Paula1,
Natalia Maria Da Silva Fernandes1
1
Universidade Federal de Juiz de Fora, Medicine, Juiz de Fora, Brazil and 2Universidade
Federal de Juiz de Fora, Biochemistry, Juiz de Fora, Brazil

BACKGROUND AND AIMS: Mild cognitive impairment (MCI) consists of a decline


of one or more cognitive domains, independent of functional impairment. There are
common pathophysiological factors between chronic kidney disease (CKD) and MCI.
The aim of this study was to evaluate the association of MCI in pre-dialysis CKD with
inflammation markers and alterations of image exams (Nuclear Magnetic Resonance-
MRI).
METHOD: Cross-sectional study, were evaluated non-dialysis CKD patients in
categories 1 to 5 in a secondary care clinic, from 2013 to 2015. Inclusion Criteria: age 
21 and  65 years and having signed the informed consent form. Non-inclusion
criteria: previous history of stroke, degenerative and infectious diseases of the CNS,
presence of delirium and / or psychotic disorders, previous history of mental
retardation and cranioencephalic trauma, visual and auditory disorders that prevented
the tests, HIV and / or AIDS, contraindication or intolerance to MRI. The project was
approved by the Research Ethics Committee. MCI was assessed using the Montreal
Cognitive Assessment (MoCA) and the estimated glomerular filtration rate (eGFR),
using the CKDEPI formula. Socio-demographic and clinical data were collected from
medical records. Laboratory data were collected a maximum of 3 months after the
MoCA evaluation, as well as the measurement of IL4, IL6, IL17, TNF alpha and hs-
CRP. The brain MRI scans were performed in a Siemens Avanto high-field device (1.5
Tesla), without the use of paramagnetic contrast. Fazekas scales were used to quantify
white matter lesions, MTA scale to quantify hippocampal involvement, ACG scale for
global cortical atrophy. Statistical analysis: a descriptive analysis was performed,
followed by a comparison of abnormal vs normal MoCA among all variables with the
relevant tests; MoCA and eGFR were also correlated with all variables. Finally, we
performed a linear regression using MoCA as a dependent variable, adjusting for
MO153 Figure: Kruskal-Wallis rank sum test
relevant confounding variables.
RESULTS: 111 patients were invited, 80 were included in the neuropsychological
Pearson’s Chi-squared test assessment and 56 patients performed all stages of the study. The mean age was 56.3 6
Loess regression of eGFR decay overt time for Immunotherapy and Chemo patients. 8.3 years, 51.8% had an altered MoCA. Comparing those with altered vs normal
Numbers indicate the patients present at a specific cycle time point. MoCA, we observed that there were fewer years of schooling (p = 0.04), greater use of
Kaplan-Meier curve for AKI onset for Immunotherapy and Chemo patients over diuretics (p = 0.04) and AAS (p = 0.002); in addition to higher levels of IL6 (p = 0.02)
treatment cycles. Vertical small ticks represent right censored data. and IL17 (p = 0.05) among those with altered MoCA. There was no correlation
between MoCA and eGFR. MoCA correlated with IL6 (R-0.201, p = 0.04). There was a
correlation between eGFR (IL4 (R- -0.467, p = 0.005; IL6 (R- -0.652, p <0.001); IL17
(R- -0.554, p = 0.001), TNF alpha (R- -0.684, p <0,001). There was no correlation
between the findings in MRI and eGFR or MoCA. In a linear regression model, the
variables IL17 and IL6 were independent predictors of lower values of MoCA (CI -
0.031 to -0.002, p = 0.002; CI-0.012 to -0.001, p = 0.002).
CONCLUSION: The prevalence of changes in MoCA in this population was 51.8%,
the eGFR was correlated with inflammation, MoCA was negatively correlated with IL6.
There was no association between MRI findings and eGFR or inflammatory variables,
and eGFR was not a predictor of MoCA values, while IL17 and IL6 were.

MO155 RENAL DAMAGE IN COVID-19: RESULTS FROM A COHORT


STUDY IN 1,280 PATIENTS

Natalia Chebotareva1, Svetlana Berns 2 , Angelina Berns3, Tatyana Androsova 2 ,


Sergey Moiseev 2
1
Sechenov First Moscow State Medical University, Nephrology, Moscow, Russia and
3
Sechenov First Moscow State Medical University, Nephrology, Moskva, Russia

BACKGROUND AND AIMS: The development of acute kidney injury in COVID-19


patients is associated with a high risk of death. Published data demonstrate the
possibility of severe kidney injury in patients suffering from COVID-19; however, these
data are still controversial.
METHOD: A total of 1,280 patients with a proven diagnosis of COVID-19 were
included in our study. COVID-19 disease was confirmed by RT-PCR through a
nasopharyngeal swab and typical images from a computed tomography scan in all
CONCLUSION: Our study highlights that both cisplatin and carboplatin-based CT
patients. Demographic data, underlying comorbidities, and laboratory blood tests were
displays an augmented incidence of AKI development after a lower number of therapy
assessed. We finally assessed the acute kidney injury (AKI) incidence and mortality
cycles in respect of immunotherapy. The nephrotoxic effects of combined therapy for
defined by the survival status at discharge.
NSLCL should be always evaluated by nephrologist during the treatment of NSLCL
RESULTS: In 648 (50.6%) of the patients with COVID-19, proteinuria was evidenced.
patients to avoid an augmented risk of AKI derived from the combination of
Haematuria was detected in 77 (6%) patients, and leukocyturia was detected in 282
immunotherapy and CT in first line.
(22%) hospitalized patients. AKI was determined in 371 (29%) patients, and 10 (2.7%)
of them required dialysis. Independent AKI risk factors were age >65 years,
augmentation of CRP, ferritin and increase in aPTT values as a result of consumption
coagulopathy. A total of 162 (12.7%) of the 1,280 hospitalized patients and 111 (30%)
of the 371 patients with AKI did not survive. The hazard ratio for mortality 3.96 [CI
95% 2.828 – 5.542] for patients with AKI vs. No-AKI.
CONCLUSION: AKI was determined in 29% patients, in 2.7% of them severe kidney
injury required dialysis. Risk factors for AKI in COVID-19 patients are old age, the

10.1093/ndt/gfab092 | i163
Abstracts Nephrology Dialysis Transplantation

inflammatory response, the severity of lung involvement and DIC. The same factors
and arterial hypertension were found to increase risk of mortality.

MO156 THE ‘WITHIN-DAY’ VARIABILITY OF ALBUMINURIA


INFLUENCES THE MONITORING OF NEPHROPROTECTIVE
TREATMENT EFFECT

Michele Provenzano1, Raffaele Serra2, Ashour Michael3, Giuseppina Crugliano3,


Alessandra Urso3, Roberta Arena3, Ida Gagliardi3, Teresa Faga3,
Michele Andreucci3
1
University Magna Graecia of Catanzaro, Medical and Surgical Sciences, Catanzaro,
Italy, 2University Magna Graecia of Catanzaro, Medical and Surgical Sciences,
Catanzaro, Italy and 3University Magna Graecia of Catanzaro, Department of Health
Sciences, Catanzaro, Italy

BACKGROUND AND AIMS: Measurement of urine proteins, mainly through the


24-hour excretion or the albumin-to-creatinine ratio (ACR) has become crucial in
current clinical practice in Nephrology. Besides being a biomarker of injury,
albuminuria also exerts direct pro-inflammatory and pro-fibrotic effects on renal
tubules. Hence, a large number of intervention studies have been aimed at lowering
albuminuria levels in patients with Chronic Kidney Disease (CKD). However,
albuminuria is a measure characterized by a random variability that has been evaluated
in several mechanistic and experimental studies and may be influenced by several
factors, such as posture, exercise and dietary factors. The aim of the present study was
to evaluate the within-day variability, specifically in a cohort of CKD outpatients who
were on Renin-Angiotensin-Aldosterone-System inhibitors (RAASi) therapy.
METHOD: We enrolled consecutive CKD patients referred to the Nephrology Unit at
Magna Graecia University Hospital of Catanzaro between January 1st and March 30th
2020. Inclusion criteria were: age > 18 years, diagnosis of CKD from any cause,
presence of albuminuria in the range 150-3500 mg/g at screening. Patients already
treated with RAASi, patients with active malignancy/signs of glomerulonephritis
requiring immunosuppressive therapies, were excluded. At screening visit, patients
with increased albuminuria were started with an Angiotensin Converting Enzyme
inhibitor (ACEi) or an Angiotensin II Receptor Blocker (ARB). A second ambulatory
visit was scheduled 1 month after start of RAASi therapy. During this visit, patients
CONCLUSION: The present analysis showed a significant individual within-day
were asked to stay in the Renal Unit for 12 hours. They collected urine void for ACR,
variability of albuminuria, measured as both ACR and PCR, suggesting that another
protein-to-creatinine ratio (PCR) and urine creatinine (Ucreat) assessment at
parameter, in addition to those already known, may be responsible for the day-by-
8am,1pm and 6pm. For each patient, comparisons between ACR, PCR and Ucreat
day albuminuria variation. Moreover, the absence of variability in Ucreat, namely the
were assessed by Kruskal-Wallis test and Friedman post-hoc, using the Benjamini-
denominator of the ACR/PCR formula, suggests that the true variation is likely
Hochberg as adjustment method. Coefficients of variation (CV,standard deviation/
dependent on the urine protein values. Thus, albuminuria reduction in response to
mean) were also computed.
RAASi treatment should be carefully evaluated by measuring ACR/PCR preferentially
RESULTS: Final analysis included 43 patients (46.5% of males). Mean age was
at a similar time of the day for each patient. This would allow to avoid under- or
59.6616.7 years and median eGFR 41 [21-74] mL/min/1.73m2. A high cardiovascular
overestimation of the actual treatment effect.
(CV) risk profile was testified by the prevalence of type 2 diabetes (30.2%) and previous
CV disease (34.8%). When patient characteristics were compared across ACR
categories (<30, 30-300, >300 mg/g), systolic blood pressure was increased (p=0.020)
and mean age decreased from 68.0 to 54.8 years on average (p=0.038). ACR values MO157 HYPONATREMIA AND DISEASE SEVERITY IN
collected were 189 [38-759], 252 [51-1685] and 229 [56-1185] mg/g at 8am, 1pm and LEPTOSPIROSIS
6pm, respectively, with a CV of 24.6% (95%CI 12.4-39.1). 8am ACR was significantly
different from 1pm ACR (p<0.001) and from 6pm ACR (p<0.001). 1 pm ACR was Gdayllon Cavalcante Meneses1, Pedro Eduardo Andrade de Carvalho Gomes1,
significantly different from 6pm ACR (p=0.002). Median PCR were 335 [115-932], 429 Gabriela Studart Galdino1, Geraldo Bezerra da Silva Junior2, Nicole Coelho
[146-1811] and 447 [151-1465] mg/g respectively at 8am, 1pm and 6pm, with CV Lopes1, Alice Maria Costa Martins3, Luis Arthur Brasil Gadelha Farias4,
being 17.8% (95%CI 9.0-26.6). 8am PCR differed significantly from 1pm and 6pm PCR Elizabeth De Francesco Daher1
(p<0.001 for both), while 1pm ACR was lower than 6pm ACR (p<0.001). Ucreat was 1
Federal University of Ceara, Medical Sciences Post-Graduate Program, Fortaleza, Brazil,
66 [53-103], 63 [47-96] and 69 [50-90] mg/dL respectively at 8am, 1pm and 6pm with 2
University of Fortaleza, School of Medicine, Post-Graduation Programs in Public Health
no significant variation trend. Individual within-day ACR and PCR trends are depicted and Medical Sciences, Fortaleza, Brazil, 3Federal University of Ceara, Pharmacology
in the Figure. Post-Graduate Program, Fortaleza, Brazil and 4Hospital S~ ao José de Doenças
Infecciosas, Fortaleza, Brazil

BACKGROUND AND AIMS: Hyponatremia is associated with severe complication


in tropical diseases and may be associated with higher mortality. The aim of this study
was to investigate the association between hyponatremia and disease severity in

i164 | Abstracts
Nephrology Dialysis Transplantation Abstracts
patients with leptospirosis. MO159 CHA2DS2-VASC SCORE AS A PREDICTOR OF
METHOD: This is a retrospective study including patients with confirmed diagnosis of CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY
leptospirosis admitted to three reference hospitals in Fortaleza, northeast Brazil, in the DISEASE PATIENTS
period from 1985 to 2018. Demographic, clinical and laboratory data were analyzed,
and the incidence of unfavorable outcomes were investigated: acute kidney injury Nina Vodosek Hojs1, Robert Ekart2, Sebastjan Bevc1, Nejc Piko2, Radovan Hojs1
1
(AKI) – defined according to KDIGO criteria, hemodialysis need and death. Patients University Medical Centre Maribor, Clinic of Internal Medicine, Department of
were divided in groups according to the levels of sodium at hospital admission (< or Nephrology, Maribor, Slovenia and 2University Medical Centre Maribor, Clinic of
135mEq/L). Statistical analysis was done with the SPSS program version 23.0. Internal Medicine, Department of Dialysis, Maribor, Slovenia
RESULTS: A total of 319 patients were included. Hyponatremia was found in 163
cases (51%) at hospital admission. Patients’ mean age was 37615 years, and 84% were BACKGROUND AND AIMS: Cardiovascular mortality is high in chronic kidney
male. The group with hyponatremia had higher frequency of some symptoms and disease (CKD) patients. Recognizing patients with higher cardiovascular risk might
signs, such as disorientation (8.1% vs 1.3%, p=0.047) and jaundice (76% vs 54%, help in their treatment. CHA2DS2-VASc score was originally used to predict cerebral
p<0.001). Higher levels of urea (130680 vs 94634mg/dL, p<0.001) and creatinine infarction in patients with atrial fibrillation (AF). However, it is also useful in
(4.362.7 vs 3.062.6mg/dL, p<0.001) were observed at hospital admission, as well as predicting outcome in different cardiovascular conditions, independent of the presence
maximum levels of bilirubins, in the group with hyponatremia (p<0,05). Median lower of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc
levels of platelets during hospital stay were observed in the group of hyponatremia (45 score in cardiovascular mortality in CKD patients.
[26 – 110] vs 73 [42 – 157] x103/mL p=0.001). A higher frequency of complications was METHOD: Eighty-seven non-dialysis CKD patients from our outpatient clinic were
also observed in the group with hyponatremia: hemodialysis need (38% vs 20%, included. At the time of inclusion, medical history data and standard blood results
p<0.001) and AKI stage 3 (71% vs 46%, p=0.002). There was no difference regarding were collected and CHA2DS2-VASc score was calculated. Patients were followed for
mortality rate between the two groups (14.1% vs 10.1%, p=0.281). assigned time or until their death. Mean follow-up time was 1696.456564.60 days.
CONCLUSION: Hyponatremia in patients with leptospirosis, at hospital admission, is RESULTS: Descriptive statistics of our patients are presented in table 1. During follow-
associated with worse prognosis and can be an important parameter to guide clinical up 11 patients suffered from cardiovascular death. Univariate Cox regression analysis
care in this group of patients. showed that CHA2DS2-VASc score is a significant predictor of cardiovascular
mortality (HR: 2.19, CI: 1.42-3.37, p=0.001). In multivariate Cox regression analysis in
which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine,
MO158 CLINICOPATHOLOGICAL FEATURES OF COEXISTENT LIGHT haemoglobin, high sensitivity CRP and intact PTH were included, CHA2DS2-VASc
CHAIN CASE NEPHROPATHY AND LIGHT CHAIN score was an independent predictor of cardiovascular mortality (HR: 2.04, CI: 1.20-
DEPOSITION DISEASE IN PATIENTS WITH NEWLY 3.45, p=0.008) (table 2).
DIAGNOSED MULTIPLE MYELOMA
MO159 Table 1. Descriptive statistics of 87 CKD patients presented as
Zishan Lin1, Xu Zhang1, Dan-Yang Li1, Xiaojuan Yu1,2, Xinan Cen3, Fude Zhou1, mean6SD or as absolute number of patients with a known condition.
Suxia Wang1, Minghui Zhao1,4
1
Peking University First Hospital, Nephrology, Beijing, P.R. China, 2, 3Peking University CKD patients
First Hospital, Hematology, Beijing, P.R. China and 4Peking University First Hospital,
Nephrology, Beijing, (N=87)
Age (years) 60.29612.84
BACKGROUND AND AIMS: Several patients with multiple myeloma suffered from Sex - male/female 57/30
more than one type of kidney disease simultaneously, of which the most common
Arterial hypertension 85
pattern is coexistent light chain cast nephropathy and light chain deposition disease
(LCCNþLCDD). We investigated clinicopathological characteristics of LCCNþLCDD Diabetes 22
in comparison with pure LCCN and pure LCDD. Dyslipidaemia 43
METHOD: Forty-seven percent of the renal biopsies revealed a monoclonal j light
chain restriction, ranging from 31% in the pure LCCN group to 90% in the pure LCDD Smoking - past or current 39
group. Of note, more than half of the patients with LCCNþLCDD showed k light CHA2DS2-VASc score 2.4961.40
chain isotype, which was significantly different from patients with pure LCDD (56% vs. Serum creatinine (mmol/l) 260.406134.69
10%, p = 0.033). Compared with patients with pure LCDD, patients with
LCCNþLCDD usually presented atypical features of LCDD with less nodular eGFR (ml/min/1.73m2) 29.50622.54
glomerulosclerosis (p = 0.003) and less diffuse deposit distribution (p = 0.027). Urinary albumin/creatinine (mg/g) 935.7561426.71
Compared to patients with pure LCDD, patients with LCCNþLCDD had lower
hemoglobin (126.5 g/L vs. 82.0 g/L, p = 0.008), higher incidence of AKI (20% vs. 89%, p
Haemoglobin (g/l) 129.41618.50
= 0.003), lower percentage of urinary albumin excretion (%UAE) (68.9% vs. 5.1%, p = High sensitivity CRP (mg/l) 5.2769.14
0.003). There was no significant clinical difference between patients with Calcium (mmol/l) 2.2360.14
LCCNþLCDD and patients with pure LCCN.
Compared to patients with pure LCDD, patients with pure LCCN had lower Phosphate (mmol/l) 1.2360.35
hemoglobin (126.5 g/L vs. 87.0 g/L, p = 0.001), higher incidence of AKI (20% vs. 85%, p Intact PTH (pg/ml) 139.106110.52
< 0.001), higher incidence of hemodialysis at diagnosis (10% vs. 65%, p = 0.003),
higher serum creatinine (165.8 lmol/L vs. 627.0 lmol/L, p = 0.02) and lower incidence
of hematuria (6/10 vs. 4/26, p = 0.035).
RESULTS: Forty-seven percent of the renal biopsies revealed a monoclonal j light MO159 Table 2. Multivariate Cox regression analysis of factors related to
chain restriction, ranging from 31% in the pure LCCN group to 90% in the pure LCDD cardiovascular death in CKD patients.
group. Of note, more than half of the patients with LCCNþLCDD showed k light
chain isotype, which was significantly different from patients with pure LCDD (56% vs. Hazard ratio 95% confidence interval p
10%, p = 0.033). Compared with patients with pure LCDD, patients with
LCCNþLCDD usually presented atypical features of LCDD with less nodular CHA2DS2-VASc score 2.04 1.20-3.45 0.008
glomerulosclerosis (p = 0.003) and less diffuse deposit distribution (p = 0.027). Serum creatinine 1.00 0.99-1.01 0.384
Compared to patients with pure LCDD, patients with LCCNþLCDD had lower
hemoglobin (126.5 g/L vs. 82.0 g/L, p = 0.008), higher incidence of AKI (20% vs. 89%, p
Urinary albumin/creatinine 1.04 0.63-1.71 0.891
= 0.003), lower percentage of urinary albumin excretion (%UAE) (68.9% vs. 5.1%, p = Haemoglobin 0.95 0.90-1.00 0.051
0.003). There was no significant clinical difference between patients with High sensitivity CRP 0.90 0.74-5.27 0.245
LCCNþLCDD and patients with pure LCCN.
Compared to patients with pure LCDD, patients with pure LCCN had lower Intact PTH 1.00 0.99-1.01 0.639
hemoglobin (126.5 g/L vs. 87.0 g/L, p = 0.001), higher incidence of AKI (20% vs. 85%, p
< 0.001), higher incidence of hemodialysis at diagnosis (10% vs. 65%, p = 0.003), CONCLUSION: CHA2DS2-VASc score is a simple and quick way to identify
higher serum creatinine (165.8 lmol/L vs. 627.0 lmol/L, p = 0.02) and lower incidence cardiovascular risk in CKD patients.
of hematuria (6/10 vs. 4/26, p = 0.035).
CONCLUSION: Pathologically, patients with LCCNþLCDD were more likely to have
k light chain isotype and presented atypical features of LCDD including less nodular
glomerulosclerosis and less deposit distribution than patients with pure LCDD. In
clinical characteristics, patients with LCCNþLCDD and patients with pure LCCN
shared similar features. For patients with LCCD, especially those with k restriction,
nephrologists should carefully evaluate the kidney specimens to exclude the possibility
of combined LCCN.

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MO160 COVID-19 INFECTION AND ACUTE TUBULOINTERSTITIAL However, our knowledge about alterations of specific T cell subpopulations, as well as
NEPHRITIS the further modifications occurring after dialysis initiation, is limited. The present
study aimed to investigate the changes of T lymphocyte subtypes in CKD patients due
Juan Carlos Leo n1, Irene Agraz1, Ander Vergara Arana1, Natalia Ramos Terrada1,
to Diabetic Nephropathy (DN-CKD) and compare to nonDN-CKD patients.
Clara Garcıa Carro1, Alejandra Gabaldon2, Roxana Bury1, Sheila Bermejo Garcia1, Furthermore, the effect of dialysis, was also estimated in both groups.
Daniel Seron Micas1, Marıa José Soler1 METHOD: In 30 DN-CKD, 30 nonDN-CKD patients and 25 healthy individuals,
1
Vall dHebron Hospital, Nephrology, Barcelona, Spain and 2Vall dHebron Hospital, cytometric analysis of T cell subpopulations was performed, including CD4þ, CD8þ,
Pathology, Barcelona, Spain CD4þCD28null, CD8þCD28null, Natural Killer cells and Tregs. Measurements were
performed at the day started (T0) on either hemodialysis (HD) or continuous
BACKGROUND: COVID-19 infection manifests as pneumonia associated with ambulatory peritoneal dialysis (CAPD) and repeated six months later (T6).
multiple organ failure, and death. Acute kidney injury is a risk factor for mortality. RESULTS: At time T0, CD4þ, NK cells and Tregs were significantly reduced (p=0.001,
There is limited scientific literature on COVID-19 infection and allergic p=0.01, p<0.0001, respectively), while CD28null cells were increased (p=0.005) in
tubulointerstitial nephritis, its clinical course and short- and long-term prognosis. CKD patients compared to controls. CD4CD28null and CD8CD28null (%) cells were
METHOD: We performed a retrospective study where medical records of 60 patients increased in DN-CKD compared to nonDN-CKD (p=0.03, p=0.02, respectively). At
with histological diagnosis of allergic tubulointerstitial nephritis from January 2009 to time T6, a significant increase in total CD28null cells were noticed in DN patients
November 2020. In these patients, we studied the incidence of COVID-19 infection, (p=0.05) but not in nonDN patients. More interestingly, DN-CKD patients who started
clinical characteristics and prognosis from March to the actual date. on HD showed a significant increase in CD4CD28null cells [from 30(14-100) to
RESULTS: Of 60 patients with allergic tubulointerstitial nephritis, 6 (10%) patients 52.7(15-203), p=0.02], CD8CD28null cells [from 130(47-400) to 212(25-1192), p=0.02]
were diagnosed with COVID-19. The first case, an 85-year-old woman with a history and NK cells [from 137(56-275) to 266(103-456), p=0.01], while those DN-CKD
of metastatic melanoma treated with nivolumab and allergic tubulointerstitial nephritis started on CAPD showed a significant reduction in the percentage of CD4CD28null
by immunobiological agents in 2018, diagnosed with mild COVID-19 infection in cells [from 9.8(2.9-19.8) to 6.9(1.3-þ18), p=0.05].
April 2020 without deterioration of renal function in controls at 3 and 6 months of CONCLUSION: Patients with CKD due to DN are more likely to have impaired T cell
follow-up. The second case, a 51-year-old woman with a history of large B-cell immunity, mainly regarding CD28null cells, which further deteriorates after initiation
lymphoma with plasmacytic differentiation and progression to multiple myeloma of of HD. Instead, CAPD method seems to ameliorate those changes.
lambda light chains and allergic tubulointerstitial nephritis due to chemotherapy since
2019, admitted for acute pyelonephritis and PRES syndrome secondary to first dose of
bortezomib complicated with COVID-19 nosocomial pneumonia and acute MO162 IMPACT OF THE IMMUNOSUPPRESSIVE TREATMENT, X-
pancreatitis treated with corticosteroids and broad spectrum antibiotic therapy; she RAY EXPOSITION AND RENAL PATHOLOGY ON OVARIAN
died of abdominal refractory septic shock. The third patient, a 64-year-old man RESERVE IN YOUNG WOMEN
without prior renal impairment, was admitted for severe COVID-19 pneumonia and
acute kidney injury secondary to acute tubulointerstitial nephritis of uncertain etiology Rasała Julia1, Ciszewska Anna1, Małgorzata Kro l1, Mariusz Kusztal1, Koscielska-
that required orotracheal intubation and continuous veno-venous hemodiafiltration Kasprzak Katarzyna1, Andrzej Tukiendorf2, Maciej Kanafa1, Augustyniak-
for a week who received methylprednisolone in bolus for 3 days and continued Bartosik Hanna1, Oktawia Mazanowska1, Krajewska Magdalena1
treatment with corticosteroid therapy with complete recovery of renal function and 1
improvement in proteinuria at 3 months of follow-up. The fourth patient, an 82-year- Wroclaw Medical University, Department of Nephrology and Transplantation
old woman with acute kidney injury AKIN 3 secondary to acute allergic Medicine, Wrocław, Poland and 2Wroclaw Medical University, Department of Public
tubulointerstitial nephritis related to ciprofloxacin complicated with severe COVID-19 Health, Wrocław, Poland
nosocomial pneumonia, who died despite ventilatory support and high-dose steroids
therapy and tocilizumab. The fifth patient, a 75-year-old with a history of metastatic BACKGROUND AND AIMS: Cyclophosphamide treatment and X-ray exposition in the
lung adenocarcinoma treated with immunobiological agents and allergic area of the ovaries are proven to be the gonadotoxic factors in childbearing age women.
tubulointerstitial nephritis in 2018, admitted in march 2020 for mild COVID-19 Anti-Müllerian hormone (AMH) is regarded as a biomarker for ovarian reserve.
pneumonia treated with steroids and hydroxychloroquine without deterioration of METHOD: The study included 167 consecutive premenopausal women attending
respiratory and kidney function. The sixth patient, an 86-years-old man with acute Nephrology Clinic who gave informed consent and met exclusion criteria (past ovarian
kidney injury AKIN 3 due to acute allergic tubulointerstitial nephritis secondary to surgical procedure, PCOS, eGFR <30ml/min, irregular menstrual cycles). Clinical
proton-binding inhibitors and nosocomial COVID-19 infeccion with improvement of (renal pathology, smoking, X-rays exposition, eGFR standardized MDRD4,
kidney function with steroids therapy only. contraceptives) and demographic characteristics, as well as previous and current
CONCLUSION: Our 6 patients with allergic tubulointerstitial nephritis and COVID-19 immunosuppressive therapies were recorded. Serum AMH levels were measured by
infection presented different spectrum of the disease. It seems that nosocomial COVID-19 Beckman Coulter’s Gen II enzyme linked immunosorbent assay (ELISA) kit; AMH
infection in patients admitted with recent diagnosis of acute allergic tubulointerstitial levels were classified as low or normal/above age-adjusted reference levels (published
nephritis presented a worse clinical prognosis compared with long-term diagnosed acute norms).
tubulointerstitial nephritis. Further studies with a larger sample size are needed. Statistical analysis included both regressive and non-regressive relationships between
the studied clinical features. Due to the presumption of the remaining non-regression
relationships between clinical factors, an original taxonomic method by Marczewski &
Steinhaus was used instead of general linear modeling. Based on patient age, eGFR,
renal pathology an ‘optimal’ segregation of patients was performed following the
created classification tree (dendrogram).
RESULTS: Median age of the patients was 33 (range 18-44). Median AMH
concentration was 2,66 ng/ml; AMH levels were classified in 64 females as low
(median 1,015) and in 103 as normal/above age-adjusted reference (median 4,04). Sixty
one patients were treated with cyclophosphamide in the past and 45 underwent kidney
transplantation. 92 women suffered from glomerulonephritis, 44 from lupus nephritis,
12 from interstitial kidney disease, 5 from ADPKD and 14 from other kidney diseases.
Age, eGFR, pregnancies in the past as well as being the kidney transplant recipient were
the coefficients strongly correlated with AMH level. Presence of lupus nephritis was
correlated with lower levels of AMH in comparison to other renal diseases and in
contrast to cyclophosphamide. X-ray exposition measured in cumulative lifetime dose
was not correlated with AMH levels.
CONCLUSION: Although previous researchers suggested cyclophosphamide to be the
strong gonadotoxic factor, our statistical analysis approach shows that lupus as the
disease often treated with cyclophosphamide may be the lowering ovarian reserve
factor itself. Further studies on this subject are still necessary.
MO161 DIABETIC NEPHROPATHY AS AN ADDITIONAL FACTOR
CAUSES DISTURBANCES IN T CELL IMMUNITY IN CHRONIC
KIDNEY DISEASE PATIENTS

Erasmia Sampani1, Georgios Lioulios2, Chrysostomos Dimitriadis2,


Zoi Mitsoglou2, Dimitra Vasileia Daikidou 3 , Ioannis Tsouchnikas 3 ,
Despoina Asouchidou 3 , Asimina Fylaktou 3 , Aikaterini Papagianni 3 ,
Maria Stangou 3
1
Ippokrateio - General Hospital of Thessaloniki, Nephrology, Thessaloniki, Greece and
2
Ippokrateio - General Hospital of Thessaloniki, Nephrology
MO162 Figure: Classification tree (dendrogram) of patients with clusters
BACKGROUND AND AIMS: Chronic kidney disease (CKD) and Diabetes Mellitus
(DM), are chronic inflammatory conditions, and may both affect T-cell immunity.

i166 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO162 Table. Characteristics of patients in clusters (mean6st. dev. and %) with
p-values (<0.05)

Clinical factor Cluster1 Cluster2 Cluster3


p- Cluster4
value
Age 30.662.5 37.863.9 33.966.6 23.263.8 0.0000
Kidney transplant 71% 39% 45% 19% 0.0012
eGFR (MDRD4) 38.4610.1 66.7621.8 9.063.3 91.8623.7 0.0000
Renal pathology 12% 38% 9% 15% 0.0051
(lupus vs. other)
Born children 0.260.4 0.860.8 0.861.4 0.360.7 0.0010
AMH 3.2262.16 2.3761.95 3.5163.37 4.6663.16 0.0000

MO163 Figure 1: Comparison of survival probability according to treatment

MO163 FIFTY-NINE CASES OF CANCER-ASSOCIATED


THROMBOTIC MICROANGIOPATHY: TYPICAL
PRESENTATION AND TREATMENT

Antoine Decaestecker1, Aghiles Hamroun2, François Provôt2, Eric Rondeau3,


Stanislas Faguer4, Clément Deltombe5, Marion Sallee6, Steven Grange7,
Raymond Azar8, Titeca Dimitri9, Alexandra Forestier1, Jean-michel Rebibou10,
Claire Cartery1
1
Valenciennes, Valenciennes, France, 2Lille, Lille, France, 3Paris, Paris, France, 4Toulouse,
Toulouse, France, 5Nantes, Nantes, France, 6Marseille, Marseille, France, 7Rouen, Rouen,
France, 8Dunkirk, Dunkirk, France, 9Amiens, Amiens, France and 10Dijon, Dijon, France

BACKGROUND AND AIMS: Thrombotic microangiopathy (TMA) are a


heterogeneous group of diseases characterized by mechanical hemolytic anemia,
peripheral thrombocytopenia, and organ failure of variable severity. In patients with
cancer, TMAs are frequently induced by antineoplastic drugs but may be related to the
malignant disease itself. Small series have reported poor prognosis. Only chemotherapy MO163 Figure 2: Comparison of renal remission according to treatment
succeeded in lengthening life expectancy, even if few reports have described efficacy of
therapeutic plasma exchange (TPE) or Eculizumab. Complement regulation was not
studied in these publications, as the pathophysiology was rarely explored. In this study,
we investigated retrospectively 59 cases of cancer-associated TMAs, to describe
characteristics at diagnosis and efficacy of treatment.
METHOD: We conducted a retrospective multicentric observational study including MO164 NOVEL PARAMETERS TO ASSESS ENDOTHELIAL
all patients with a diagnosis of cancer-associated TMA, hospitalized in nephrological DYSFUNCTION BY PULSE WAVE ANALYSIS
intensive care units (members of the French Intensive Care Network), between 2008
and 2019. We excluded patients receiving chemotherapy known to cause TMAs. We Niklas Mueller1, Sandra Müller2, Joachim Streis3, Stefan Reuter4, Hermann
analyzed clinical and biological characteristics at diagnosis. We reported complement Josef Pavensta €dt4, Thomas Felderhoff3, Veit Busch3,4,5
analysis when available. We defined four distinct treatment groups: No treatment (N), 1
Hospital of the Ludwig-Maximilians-University Munich, Oncology , Munich, Germany,
Plasmapheresis (P), Chemotherapy with or without chemotherapy (CþP), Eculizumab 2
University of Vienna, Kurt Gödel Research Center, Faculty of Mathematics, Vienna,
with or without Chemotherapy or Plasmapheresis (EþCþP). Renal remission and Austria, 3University of Applied Sciences and Arts, Research Center for BioMedical
global survival were compared according to treatment group. Technology, Dortmund, Germany, 4University hospital of Muenster, Nephrology,
RESULTS: We included 59 patients admitted to intensive care units for cancer- Muenster, Germany and 5Diavital, Dialysis, Kamen
associated TMA. Twenty patients had a past history of cancer. Fifty percent was female,
and mean age was 62.8 years. The primary cancer was breast (23.7%), lung (18.6%), BACKGROUND AND AIMS: Pulse wave morphology changes under the high flow
stomach (10.2%), and prostate (10.2%). Adenocarcinoma was the most frequent condition of reactive hyperaemia. We hypothesized, that those alterations may be able
histologic subtype (47.5%). The cancer was metastatic in almost cases (89.8%). At to indicate endothelial dysfunction.
presentation, TMA manifestations were pulmonary (57.6%), neurologic (49.2%), bone METHOD: We recorded digitized pulse waves measured tonometrically with the
pain (30.5%), and disseminated intravascular coagulopathy (DIVC) (55.9%). Forty-one SphygmoCorV R device of 64 persons, 41 kidney transplant recipients and 23 healthy
patients had a bone marrow aspiration and/or biopsy. Among them, medullar individuals, under normal conditions (NC) and under reactive hyperaemia (RH).
metastases were found in 20 patients (48.7%). We observed low C3 in 14.7% of cases Using matlabV R , we calculated novel parameters, which had a temporal relationship
suggesting an activation of the alternative pathway. No genetic analysis was performed. with 3 charactereristic points (PO) of the normalized pulse wave, namely the
Only one patient had an undetectable ADAMTS13 <5% without inhibitory maximum of the antegrade wave (1), the diacrotic notch (2) and the first diastolic
ADAMTS13 antibodies. Renal failure was seen in 28 patients whom 63.7% had severe inflection point (3). The following parameters were calculated: Mean slope between PO
grade 3 acute kidney injury. Renal biopsy was performed in 6 patients with severe 1 and 2 (k2), area under the curve (AUC) in the systole (Asys), AUC between PO 1 and
arteriolar TMA lesions. Seventeen patients had no treatment (N), fifteen patients were 3 (A13), AUC between PO 1 and 2 (A12) and AUC between PO 2 and 3 (A23).
treated with TPE (P), twenty patients received chemotherapy with TPE (CþP), and Parameters were analyzed as their difference under reactive hyperaemia and under
seven patients received Eculizumab with TPE (E). Hematological and renal remission normal conditions. Also the maximum of the instantaneous difference of normalized
was not significantly different between treatment groups (p=0.74 and p=0.10 pulse waves under NC und RH (Dmax) was analyzed. Endothelial function was
respectively). Mortality was high, 52.5% at one month, 90% after one year of follow-up. evaluated by duplex sonography using ROC-analysis of peak systolic and end-diastolic
The median duration of survival was 27 days [8.5;95.5] in patients who received flow difference under NC and RH.
treatment. Survival was improved in (CþP) and (EþCþP) groups, significantly RESULTS: ROC-assessment of endothelial dysfunction as indicated by systolic peak
(p<0.0001). flows demonstrated AUCs of 0.733 for k2 (p=0.002), 0.751 for Dmax (p< 0.001), 0.698
CONCLUSION: We report the largest series of cancer-associated TMAS since the for Asys (p=0.006), 0.648 for A13 (p=0.077), 0.678 for A12 (p=0.027) and 0.732 for
advent of Eculizumab for the treatment of HUS. Typical presentation included old age, A23 (p=0.001). For the diastole the values were 0.753 for k2 (p=0.003), 0.733 for
bone pain, dyspnea, and DIVC. These symptoms, when associated with TMA, should Dmax (p=0.002) 0.670 for Asys (p=0.038), 0.566 for A13 (p=0.495), 0.664 for A12
therefore suggest a diagnosis of cancer. Bone marrow aspiration or biopsy led to (p=0.091) and 0.722 for A23 (p=0.015) respectively.
diagnosis of cancer in half of cases, and should be systematically performed to rapidly CONCLUSION: Pulse wave analysis under the condition of reactive hyperaemia
confirm diagnosis. The overall prognosis remained dramatically poor, with a mortality probably is useful to assess endothelial function in kidney transplant recipients.
rate of 90% in the first year. Chemotherapy is probably the most efficient therapy to
delay the death. C3 serum level was decreased in only 7 patients, suggesting that the
pathophysiology of cancer-associated TMA is not linked to complement activation. As
a result, neither TPE nor Eculizumab improved survival rate.

10.1093/ndt/gfab092 | i167
Abstracts Nephrology Dialysis Transplantation

body cell mass index (BCMI), extracellular:intracellular water ratio (ECW/ICW), waist
circumference (WC), lab test exams and clinical variables were examined at baseline
and after 6 months. Statistical analysis: Kruskal-Wallis rank sum test; Data analysis: R
programming language and RStudio integrated development environment.
RESULTS: Population divided as follows: average age: 69.8 (þ/- 10.3); # : $ ratio: 2.4;
Hypertension: 57.28%; Diabetes: 19,41%; CKD classification: 3,88% stage 2, 87,37%
above stage 3. At time zero no pts were underweight and 51 % were overweight or
obese with difference condition of FM percentage (FM % average: 24.3 % $ and 18.1 %
#for CS pts vs 31.6 % $ and 18.2 % #for CT pts). Only 2.1% of pts had a PA of less
than 4 , considered a negative prognostic index (PA average: 5.6 for CS pts vs 5.5 for
CT pts) and 6.3 % of pts had a value of cell mass less than 8 kg/m2 indicative of reduced
lean mass (BCMI average: 10.4 kg / m2 for CS pts vs 11 kg / m2 for CT pts). An
increase in ECW/ICW ratio greater than 1 was more present in CT pts in respect to CS
pts (41.6 % vs 22.8 % and ECW/ICW average: 1.01 for CT pts vs 0.93 for CS pts) as
well as WC measurement associated with increased cardiovascular risk (WC average:
87 cm $ and 99 cm # for CS pts vs 97 cm $ and 104 cm # for CT pts).
After 6 months of diet, we observed a similar behavior between the CS and the CT
cohorts in terms of renal metabolites and eGFR profile. In fact, the 65% of onco-
nephrological and the 55% of nephrological pts displayed a significative decrease in
urea plasmatic levels (- 27,76 mg/dl) and eGFR improvement (þ 6,27 ml/min/1,73).
The nutritional status, as assessed by the MST, was preserved in both groups during the
study. In addition, all pts had an improvement in BMI (CS: 2.8 kg/m2; CT :1.3 kg/m2)
PA (CS: 2.8 ; CT: 1.3 ), BCMI (CS: 1.31 kg / m2; CT :0.38 kg / m2) and FFMI (CS; 0.1
$ and 0.1 #; CT; 2.9 $ and 1.1 #) and a decrease of WC (CS: - 1.3 cm; CT– 1,65), FM
percentage (CS: 0 %; CT – 2.7) and ECW/ICW (CS: 0.02; CT 0.03).
CONCLUSION: Our study suggests that LNP high calorie diet ameliorates the
nephrological scenarios, the metabolic complications, and the nutritional perspective
in uro-oncological pts with stage 2-5 CKD. A larger prospective study to validate these
results is on-going.

MO166 AUTOPTIC KIDNEY FINDINGS IN HOSPITALIZED PATIENTS


WITH COVID-19

Giulio Nobile1, Simone Nicoletti1, Marisa Santostefano1


1
Ospedale Sant’Orsola - Malpighi, Padiglione 1, Nephrology, Bologna, Italy

BACKGROUND AND AIMS: SARS-CoV-2, isolated for the first time at the end of
2019, is the third human infecting Coronavirus found so far. Acute kidney injury (AKI)
is the most common presentation when kidney is involved. There is evidence that
kidney damage is determined through different pathological mechanisms. Has been
observed that pathological kidney lesions can be due to the direct cytopathic effect of
the virus on tubular cells or by pro-inflammatory cytokine storm. Aim of this
observation is to evaluate the clinical and pathological patterns of kidney damage
mediated by Coronavirus.
METHOD: We analysed kidney autopsies of 4 patients with COVID-19 infection,
hospitalized between March and April 2020, admitted to the Intensive Care Unit. The
tissue samples have been observed by light microscopy and immunofluorescence. RT-
PCR SARS-CoV-2 was performed in all cases.
RESULTS:
CASE 1: female, 69 y; affected by obesity, previous ictus; smoking habit. Admitted for
MO165 CANCER, KIDNEY AND DIET: THE NUTRITIONAL COVID-related pneumonia. At onset creatinine 0.45 mg/dl. Progression of lung failure
MANAGEMENT IN ONCO-NEPHROLOGICAL PATIENTS. A and exitus after 3 days. Autopsy: diffuse alveolar damage. Renal autopsy: acute tubular
SINGLE CENTER EXPERIENCE necrosis; mild glomerular ischemia, lymphocyte T CD4þ parenchyma infiltration.
CASE2: male, 66 y; affected by hypertension with cardiac involvement. Admitted for
Arianna Bettiga1, Federico Di Marco1, Francesco Fiorio1, Riccardo Vago1, persistent fever. At onset creatinine 0.98 mg/dl. Nasopharingeal swab COVID-19
Umberto Capitanio1,2, Andrea Salonia1,2, Francesco Montorsi2, positive. Progression of lung failure and oligoanuric AKIn 3 (creatinine 4.5 mg/dl, urea
Francesco Trevisani2 239 mg/dl), dialysis dependent. Exitus after one week for diffuse alveolar damage and
1 sepsis.
Urological Research Institute (URI), Division of Experimental Oncology, Milan, Italy and
2 Renal autopsy: proximal and distal acute tubular moderate injury, mild diffuse
San Raffaele Scientific Institute, Urology, Milan, Italy
glomerular ischemia, glomerular capillaritis, overlap chronic nephropathy.
BACKGROUND AND AIMS: Controlled low-normal protein (LNP) diet in CKD CASE 3: male 45 y; affected by obesity and diabetes. Admitted for COVID-related
patient is effective in controlling the progression of renal impairment. Oncological pneumonia with acute lung failure requiring ECMO. After one week developed AKIn 3
guidelines explain how a high protein level should be always required in patients (pts) dialysis dependent. Exitus for cardio-respiratory arrest. Renal autopsy: diffuse acute
affected by malignancies in order to compensate the cancer derived metabolism and tubular necrosis, glomerular capillaritis, overlap chronic diabetic nephropathy.
avoid catabolism. But what about the onco-nephrological pts? Aim of our study is to CASE 4: male, 51 y; affected by CKD grade IV, hypertension, previous ictus; drug
investigate the metabolic impact of a low-normal protein diet in a consecutive cohort abuser. Admitted for AKIn 2 and COVID-related pneumonia. After 3 days progression
of 103 nephrological pts affected or not by urological non-metastatic malignancies. of lung and renal failure requiring intubation and dialysis treatment. Exitus the day
METHOD: A consecutive cohort of 103 pts was enrolled in the Urological Department after for diffusive alveolar damage and lymphocytic myocarditis. Renal autopsy:
at San Raffaele Scientific Institute between 2018-2020. Inclusion criteria were: Age diffused acute tubular necrosis, glomerular ischemia with mild tuft collapsing, diffuse
(>18 years old), eGFR (< 90 ml/min/1.73), Malnutritional Screening Tool (MTS<2), infiltration of lymphocytes CD4þ.
Urological Cancer aggressiveness (no metastatic process), Informed consent (signed). In all cases light microscopy examination showed diffuse proximal tubular injury, with
We divided the total cohort in 2 matched subgroups; case (CS: onco-nephrological pts isomeric and non-isomeric vacuolar degeneration; collapsing tuft, and interstitial
with urological malignancies) and control (CT: nephrological pts) with a 2.1 ratio. Each inflammation. Virus RNA performed by RT-PCR on kidney tissue was positive in all
patient underwent an initial nephrological and nutritional evaluation and was patients. Moreover in some cases our patients showed multi-systemic organ
subsequently subjected to a conventional CKD LNP-diet (0,7-1 g/Kg/die: calories: 30- involvement: lung in 4 cases, heart in 1, liver in 1.
35 kcal per kg body weight/die) for a period of 6 months (þ/- 2 moths). The diet was CONCLUSION: Our observations show that the main pathological effect caused by
based on the estimated Glomerular Filtration Rate (CKD-EPI 2012 formula), Coronavirus is a direct cytopathic effect on the proximal tubules with variable degree of
comorbidities, nutritional status and hypermetabolic conditions. LNP-diets were damage until acute tubular necrosis (ATN). In addition to this pathway, other factors
integrated with aproteic food to maintain a relevant amount of high–biological value contributing to kidney damage include systemic hypoxia, microvascular capillaritis.
proteins, especially for oncological and advanced CKD pts. MTS, Body Mass Index Associated sepsis can worse overall and renal survival. Previous comorbidities,
(BMI), Phase Angle (PA), Fat Mass percentage (FM%), Fat-Free Mass Index (FFMI), especially obesity, diabetes, systemic hypertension and preexisting chronic renal
failure, are significant negative prognostic factors.

i168 | Abstracts
Nephrology Dialysis Transplantation Abstracts
mg/dl and severe metabolic encephalopathy. He received 4 sessions of hemodialysis
followed by an improvement in his kidney function with a creatinine level down to 3.2
mg/dl a month after his discharge and he remains off dialysis until now.
CONCLUSION: Around 400 cases are currently recognized worldwide, emphasizing
the under recognition of this autosomal recessive disease. Considering that the
homozygoty causing a complete APRT deficiency should range between 1/50 000 and
1/100 000 cases, this would translate in at least 80 000 cases worldwide. The variant
found in our patient has previously been described as disease causing for APRT
deficiency in four cases. Reviewing the phenotype of these cases we find differences in
terms of presentation and evolution, highlighting the variability in the APRT deficiency
phenotype and underlining the fact that no correlation between phenotype and
genotype was reported to date even for the same type of mutation. This case report
shows us that the initiation of an adequate therapy is necessary even at advanced stages
of the disease since it can improve our kidney outcome.

MO167 AN UNUSUAL COURSE OF A 2,8 DHA CRYSTAL INDUCED


NEPHROPATHY MO167 Figure: A, B, C. Acute tubular necrosis, interstitial inflammation, tubular
atrophy and, fibrosis. Brown-green rod, rhomboid, annular, and fan-like (C –
Nicole Nourié1, Hussein Nassereddine2, Micheline Mia Kotait1, Sarah Mouawad1, arrowhead) crystals within tubular lumen, tubular epithelial cells, interstitium, and
Hiba Azar1 macrophages (C – asterisk). D. The crystals are argyrophilic with silver stain (arrow).
1
Hotel Dieu de France University Hospital, Nephrology department, Beirut, Lebanon E, F. Crystals are birefringent under polarized light. Characteristic “maltese crosses”
and 2Hotel Dieu de France University Hospital, Pathology department, Beirut, Lebanon under polarized light are shown (F – in frame).

BACKGROUND AND AIMS: 2, 8 dihydroxyadenine (DHA) deposition is a less


known etiology of crystal-induced nephropathy, caused by a deficiency in a purine
salvage enzyme, the adenine phosphoribosyl transferase (APRT). DHA is an insoluble
molecule in urine leading to crystal formation, tubular obstruction or stone formation. MO168 MANAGEMENT OF ANTICOAGULANT RELATED
The disease manifests as a history of urolithiasis, chronic kidney disease and even loss NEPHROPATHY: SLOVENIAN CASE SERIES AND REVIEW OF
of renal allograft when the disease is undiagnosed in native kidneys. The cornerstone of CURRENT KNOWLEDGE
treatment is the inhibition of xanthine dehydrogenase reducing thus the formation of
2,8-DHA and its renal excretion. 
Zeljka Ve c-Haler1, Tanja Bel
ceri ci 1, Nika Kojc2, Maja Frelih2,
c Mikic
METHOD: A 59-year-old obese Lebanese male patient, born to a consanguineously Andreja Ales Rigler1
married couple, was admitted to another hospital with desaturation, a history of 1
progressive shortness of breath and a creatinine level of 2,8 mg/dl. He had no University Medical Center Ljubljana, Department of Nephrology, Ljubljana, Slovenia
hypertension nor diabetes. His family history was positive for a sister with ESRD of and 2Institute of Pathology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
unknown etiology. He was discharged on oxygen and continuous airway positive
pressure therapy for severe obstructive sleep apnea. His renal function deteriorated BACKGROUND AND AIMS: Anticoagulant-related nephropathy is a recently
leading to a creatinine level of 9.8 mg/dl three months later. There were no signs of recognized form of acute kidney injury associated with previously underdiagnosed
systemic disease, no gross hematuria, no fluid overload. His blood pressure was kidney damage in addition to (usually) excessive anticoagulation. It occurs in patients
normal. Laboratory work up showed anemia, low grade proteinuria, intermittent receiving warfarin as well as those receiving direct oral anticoagulants.
microscopic hematuria and negative serological and immunological workup. Kidney METHOD: We collected and analyzed cases of Slovenian patients with
ultrasound showed normal size kidneys with no evidence of collecting system pathohistologically documented anticoagulant-related nephropathy associated with all
dilatation or urolithiasis. Due to this atypical presentation, the patient was admitted for types of anticoagulant treatment from the first case in 2014 to 2020. We also performed
a renal biopsy with a creatinine level of 11 mg/dl upon admission. an analysis of previously documented cases of anticoagulant-related nephropathy in
RESULTS: The renal biopsy showed tubulo-interstitial nephritis associated with the global literature (PubMed) in the period from their first mention until recently.
numerous brown-green crystals by Haematoxylin and eosin of various shapes RESULTS: In Slovenia, 13 patients with anticoagulant-related nephropathy have been
birefringent under polarized light with the characteristic “maltese cross”. Crystals were histologically verified so far. All patients were diagnosed with concomitant underlying
found within tubular lumens and cytoplasm, interstitium, and macrophages. These renal disease, and 80% had IgA nephropathy, which was disproportionately mild
findings were characteristic of 2,8 DHA crystals deposition in the kidney. The patient according to the degree of renal function impairment. After supportive measures and
was started on 120 mg of Febuxostat with a low purine and high fluid diet. A genetic reversal of excessive anticoagulation, 8 of 13 patients were further treated with
testing showed a pathogenic homozygous variant in the APRT gene which causes an corticosteroids, resulting in significant improvement in renal function. During the
amino acid change from Glycine to Aspartate at position 63. Two weeks later the follow-up period, a total of one steroid-treated patient died due to infectious
patient was admitted to the ICU with pneumonia, respiratory failure, a creatinine of 9 complications and one patient progressed to end-stage renal failure. In the worldwide
literature, we found 46 case reports or case series of patients with anticoagulant-related

10.1093/ndt/gfab092 | i169
Abstracts Nephrology Dialysis Transplantation

nephropathy. Failure of restitution of renal function with the need for maintenance discharged home on Azithromycin 500 mg daily x 3 days and Cefdinir 300 mg BID x 5
dialysis was reported much more frequently compared to the results of our cohort (up days.
to 67% vs. 8.3%)
CONCLUSION: To our knowledge, the Slovenian cohort of patients with
histologically established anticoagulant-related nephropathy is the largest reported
series to date that received corticosteroid therapy in addition to conservative measures.
Our results indicate that steroids have a beneficial effect, likely exerted via suppression
of hemoglobin-associated oxidative stress and inflammation. However, considering the
polimorbidity of these patients, the benefit of additional steroid therapy must be
weighed against the potential risks of side effects, especially life-threatening infections.

MO169 FUNCTIONAL STATE OF THE KIDNEYS IN PATIENT AFTER


CORONARY REVASCULARIZATION

Shavkat Muminov1, Durdona Saipova1


1
Tashkent Medical Pediatric Institute, Internal disease, Tashkent, Uzbekistan

BACKGROUND AND AIMS: The aim of the study was to study the functional state
of the kidneys in patients with coronary artery disease in the long-term period after
coronary revascularization.
METHOD: There were 160 patients with coronary artery disease under observation
who underwent re-endovascular procedures (RE). The average age of the patients was
56.6 6 1.27 years. The study included patients with an eGFR of at least 60 ml / min,
determined by the serum creatinine concentration. A dynamic determination of the
serum creatinine concentration was carried out to isolate patients in whom the
postoperative REB was complicated by contrast-induced nephropathy (CIN). In the
present study, CIN was defined as an increase in serum creatinine concentration by
25% 24 or more hours after REB. In the future, all patients underwent dynamic
determination of serum creatinine concentration in terms of 3 months - 1 year -2
years. Patients received standard therapy for coronary artery disease: antiplatelet
therapy (in the case of stenting of coronary arteries - double therapy), bisoprolol,
valsartan, atorvastatin.
RESULTS: The results of the study showed that during 2 years of follow-up after
coronary revascularization, a progressive decrease in eGFR was observed. So, by the MO170 Figure 1: Sequence of chest radiographs, normal in November 2019 (A),
3rd month, eGFR decreased by -17.39 6 1.17%, by the end of the 1st year - by -43.62 6 before initial hospital admission - March 20, 2020 @ 02:10:10 (B), and just before
1.28%, by the end of the second year of observation - by -46.50 6 1.79%. At the same intubation in the Emergency Department following the second .admission - March 22,
time, the decrease in eGFR was significantly more pronounced in the group of patients 2020 @ 03:32:01 (C).
who had CIN in the early period after endovascular intervention (37 patients): (-39.82
6 2.02% by the end of the 3rd month, -54.61 6 2.94% by the end of the 1st year and - He cheerfully went home. Later that night he quickly developed worsening dyspnea.
60.10 6 3.99% by the end of the 2nd year of observation versus -10.65 6 0.57%, -40.32 He was readmitted about 18 hours post-discharge. Temperature 99.40F, blood pressure
6 1, 27% and -42.41 6 1.85% in patients with CIN-, respectively, p <0.001 for 161/101, pulse 100/min. He was tachypneic and pulse oximetry was 82% on room air.
intergroup comparisons of the relative dynamics of eGFR at all three time points). This improved to 93% on 4.5 LPM nasal cannula oxygen. Initial EKG was normal. New
CONCLUSION: Thus, the present study has demonstrated that in patients with pertinent laboratory data: Bicarbonate 17 mmol/L, phosphorus 5.5 mg/dL, calcium 7.2
coronary artery disease after revascularization, there is a significant decrease in the mg/dL, creatinine 1.1 mg/dL, BNP 31 pg/mL and lactic acid 1.2 mmol/L. PTT was 28.3
glomerular filtration function of the kidneys as early as 3 months after the sec. HIV-1 p24 AG, HIV-1 AB, HIV-2 AB, HbSAG and Hepatitis C AB were negative.
endovascular procedure. CKD progression continues for at least 2 years after Chest radiograph showed worsening bilateral infiltrates (Figure 1C). He very quickly
revascularization. One of the predictors of CKD progression is the development of CIN desaturated in the ED down to 81% despite high flow oxygen therapy. He was
in the early period after endovascular intervention. promptly intubated (Figure 2A). Oxygenation immediately improved. He was
transferred to the ICU on IV Vancomycin and IV Cefepime. He developed septic shock
and required IV Norepinephrine. With worsening chest radiographs, (Figures 2B &
MO170 “SWEET HYPOXIA” WITH ACUTE KIDNEY INJURY: THE 2C), he was transferred to a tertiary medical center. On transfer, pertinent new data:
UNPREDICTABILITY OF ACUTE HYPOXIC RESPIRATORY creatinine 1.38 mg/dL, albumin 2.8 g/dL, Ferritin 2,573 ng/mL, LDH 534 u/L, CRP 6.0
FAILURE IN COVID-19 INFECTION - A COMMUNITY mg/L, INR 1.2, D-Dimer 1.04, procalcitonin 0.38 ng/mL, WBC 13.3 x 109/L. EKG
HOSPITAL EXPERIENCE showed sinus bradycardia. Urine Legionnaire AG and Strep. Pneumonia AG were
negative. IV Azithromycin 500 mg daily and IV Ceftriaxone 2 gm daily were
Macaulay Onuigbo1, Kolade Olabode1, Mohan Sengodan2 administered for 8 days. Chloroquine phosphate 500 mg 2x daily was added. IV
1 Norepinephrine was continued. IV fluids were withheld. The head of the bed was
The Robert Larner, M.D. College of Medicine at The University of Vermont, MEDICINE,
elevated to >300. DVT prophylaxis with SQ Enoxaparin and Vitamin C were
Burlington, United States of America and 2Aspirus Divine Savior Hospital, HOSPITAL
administered. New blood cultures remained negative. COVID-19 RT-PCR after 3 days
MEDICINE, Portage, United States of America
remained positive. He was extubated after 4 days and discharged home after 9 days
with normalized creatinine of 1.03 mg/dL.
BACKGROUND AND AIMS: Severe COVID-19 infection may result in hypoxemic CONCLUSION: We have for the first time demonstrated the sequential chest radiographic
respiratory failure necessitating invasive mechanical ventilation. We revisit the images of the progressive radiological trajectory of COVID-19 pneumonia. The place of
phenomenon of asymptomatic patients despite very low pulse oximetry readings, the non-invasive ventilation demands further study. The so-called “sweet hypoxia” or “happy
so-called “sweet hypoxia” or “happy hypoxia” or “silent hypoxemia”. We describe for hypoxia” or “silent hypoxemia” in COVID-19 is revisited – indeed, it is not exactly limited
the first time, the sequential chest radiographic images of the progressive radiological to COVID-19 patients. The need to mitigate lung barotrauma is mandatory. Finally,
trajectory of COVID-19 pneumonia. prognostication of pneumonia in COVID-19 is unpredictable. Too early premature
METHOD: Case Report. discharge from the hospital is strongly discouraged.
RESULTS: A 62-year old hypertensive obese Caucasian male, an ex-smoker, was
diagnosed with mild community-acquired pneumonia in mid-March 2020, following
evaluation for low grade fever. He had traveled to Florida and Texas in the previous
month. He tested positive for COVID-19 by RT-PCR. A week later, he was admitted to MO171 BARRIERS TO RENAL SUPPORTIVE CARE IN SINGAPORE: A
a Community Hospital with one day history of new shortness of breath and loose SURVEY BASED STUDY OF NEPHROLOGISTS,
stools. Vital signs were stable. Pulse oximeter was 96% on room air. He was fatigued GERIATRICIANS AND PALLIATIVE PHYSICIANS
with few bibasilar lung crackles. CBC was normal. Creatinine was 1.0 mg/dL.
Abnormal laboratory: sodium 131 mmol/L, AST 50 iu/L, ALT 96 iu/L. Chest Yan Ting Chua1, Santhosh Seetharaman2, Priyanka Khatri1
1
radiograph revealed new patchy left lower lobe airspace infiltrate (Figure 1B). EKG National University Hospital, Department of Medicine, Division of Nephrology,
showed regular sinus rhythm of 96/min, QT interval 445 msec and PVCs. Treatment Singapore, Singapore and 2Alexandra Hospital, Healthy Ageing Programme, Singapore,
included nasal cannula oxygen, IV fluids, IV Azithromycin and IV Ceftriaxone. He Singapore
improved the next day, requested discharge home, vital signs were stable, pulse
oximetry was 91% on room air, sodium had normalized at 137 mmol/L and he was BACKGROUND AND AIMS: Renal supportive care is a patient-centred approach to
management of advanced chronic kidney disease, especially in elderly patients.

i170 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Adoption of renal supportive care in Asian countries has been slow. This study aims to Hyponatremia was associated with dyspnea at admission and with higher levels of
investigate the barriers towards renal supportive care as perceived by physicians in LDH, neutrophil cells account and C reactive protein. However, no worse prognostic
Singapore. was associated with lower serum sodium. All patients recover sodium levels at
METHOD: An online survey was sent out to all practising and training nephrologists, discharge treated with salt supplementation and free water intake.
geriatricians and palliative physicians in Singapore public hospitals between October CONCLUSION: mild hyponatremia is a common electrolyte disorder associated with
1st and October 30th 2020. Responses were compiled and analysed. COVID19. Sing as low urine sodium and recover with water and salt ingestion, point
RESULTS: Out of 365 surveys sent, 75 nephrologists, 43 geriatricians and 28 palliative toward hydrosaline dehydration instead of SIADH as most common origin of
care physicians responded, accounting for a 40% response rate. Most of the hyponatremia.
participants managed 16 to 30 chronic kidney disease patients in a week. Older patients
aged >75 years accounted for at least 30% of the chronic kidney disease cohort
managed by 72% of respondents. Most agreed that renal supportive care aims to
MO173 SPONTANEOUS RENAL ARTERY DISSECTION (SRAD): IS IT
improve quality of life in chronic kidney disease (97.9%) and can be implemented
REALLY SO RARE?
alongside life-prolonging treatments such as dialysis (83.6%). However, only 51.4%
recognised a distinction between renal supportive care and palliative care. Fewer
Fausta Catapano1, Maria Cristina Galaverni2, Simone NIcoletti1,
nephrologists compared to geriatricians received prior palliative care training (54.7% vs
Elena Mancini1
93.0%) or were certified advanced care planning facilitators (33.3% vs 67.4%). All 1
respondents agreed that nephrologists should be aware of basic principles of palliative Nephrology, Dialysis and Hypertension Unit, Policlinico S. Orsola, Bologna, Italy and
2
care, and 89.7% felt that palliative care should be incorporated into nephrology Radiology Unit, Policlinico S. Orsola, Bologna, Italy
training. Most were comfortable holding discussions regarding dialysis withholding
and withdrawal (93.8% and 87.7% respectively), and managing symptoms of pain INTRODUCTION.: Spontaneous Renal Artery Dissection (SRAD) is a rare and often
(74.7%), breathlessness (87.0%) and anticipated symptoms after dialysis withdrawal unrecognized clinical entity, which only accounts for 1-2% of all arterial dissections.
(78.8%). Fewer physicians were comfortable with managing symptoms of pruritus Due to its rarity, it may be difficult to diagnose and treat.
(65.1%) and restless legs syndrome (56.2%). Majority (60%) did not feel confident in METHODS.: All patients affected by SRAD and admitted in our Unit in the last year
providing spiritual support as part of end-of-life care. Main barriers to renal supportive were included.
care included inadequate time during clinic consults to address the patients’ needs RESULTS.: Five patients presented with renal infarction due to SRAD were admitted
(87%), reliance on family members to make decisions (69.2%), inadequate palliative in our Unit in 2020. Patient Characheristics are shown in Table 1. At onset, all suffered
training during fellowship (67.1%) and inadequate community support services from abdominal pain and high blood pressure. In all patients renal function was
(55.5%). Some cited lack of awareness and acceptability of renal supportive care normal. Abdomen computed tomography angiography (CTA) was diagnostic in all
amongst patients and relatives in Singapore’s Asian cultural context. Most felt that patients (Figure 1). They were treated with antihypertensive drugs and systemic
encouraging advanced care planning discussions earlier in the course of chronic kidney anticoagulation followed by oral anticoagulants. At 3 month-follow-up, all patients
disease (80.8%), having dedicated renal supportive care services in hospital (78.1%) and became normotensive and partial or total renal artery recanalization were found
including palliative care rotation as part of training (69.2%) could potentially increase (Figure 2).
uptake of renal supportive care in Singapore.
CONCLUSION: Nephrologists, geriatricians and palliative physicians in Singapore
recognise the value of renal supportive care, but are faced with barriers such as patients’
and family’s resistance toward renal supportive care as well as inadequate palliative
training. A unique model of renal supportive care with the patient as well as family’s
involvement early in the decision-making process is likely to be better perceived in
Asian countries. Incorporation of palliative care training in the nephrology fellowship
curriculum should be considered.

MO172 HYPONATREMIA IN PATIENTS WITH COVID19


Esmeralda Castillo-Rodrıguez1, Daniel Villa2, Marta Alvarez Nadal1,
Paula Regueiro Toribio2, Milagros Fernandez Lucas1
1
Hospital Ramon y Cajal, Nephrology, Madrid, Spain and 2Hospital Ram
on y Cajal,
General physician, Madrid, Spain

BACKGROUND: Among laboratory abnormalities described in the context of SARS-


COV-2 infection, hyponatremia seem to be the most common. The mechanism of this
sodium disbalance is not well known.
AIMS: Characterize the incidence, etiology and prognostic value of sodium disbalance MO173 Figure 1: Abdominal CTA of 4 patients with SRAD at onset
in patients with COVID19.
METHOD: Observational pilot study with 37 patients admitted to Hospital Ramon y
Cajal in Madrid, Spain, between March and April 2020, with a confirmed diagnosis of
COVID19. Patients were followed until discharge or death. Clinical and laboratory
data were collected at admission and before the clinical outcome. Variables were
analyzed comparing hyponatremic vs eunatremic patients.

RESULTS: Distribution of patients according to their serum sodium was as follows: 16


patients with hyponatremia (44%), 19 with normal serum sodium (51%) and 2 with MO173 Figure 2: Abdominal CTA of 4 patients with SRAD after therapy
hypernatremia (5%). The average sodium level in hyponatremic patients was 130 63.2
mmol/l, median urine sodium was 36 63.2 mmol/l (only 6 urine sample available).

10.1093/ndt/gfab092 | i171
Abstracts Nephrology Dialysis Transplantation

MO173 Table 1. Patient Characteristics at onset.

Patient Sex Age (years) Blood Pressure SRAD Comobidities Cerebral MRI/CT
(mmHg)
1 F 61 150/100 Left segmental branch ante- Kidney stones negative
rior inferior and
Right renal artery
2 M 49 150/90 Right renal artery Severe cardiovascular familiarity, GIST negative
3 M 39 140/90 Left segmental antero-inferior Severe cardiovascular familiarity, negative
renal artery OFP ostium II
4 F 51 145/85 Left renal artery Dolicocolon Carotid-oftalmic aneurism
5 M 50 150/100 Right and left renal artery Family history for tumors negative

CONCLUSIONS.: In our experience, SRAD seems to be not very rare in young and MO174 Table 1: Demographic Data of SLE Patients and Healthy Controls
healthy patients with minimal comorbidities. Abdomen CTA is one of the “gold
standard” non invasive diagnostic method. In patient treated with conservative medical
Parameter SLE (n=60) Control (n=30) p
therapy renal outcome is favourable. More studies are necessary to find underlying
causes. value
Female/Male (n) 51 / 9 25 / 5
Age (years) 35 (18-65) 36 (23-52) 0.966
MO174 FIBROSCAN DETECTION OF FATTY LIVER AND LIVER
Body mass index (kg/m2) 26.8 (15.1-45.9) 24.5 (18.1-34.0) 0.376
FIBROSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Waist circumference (cm) 89 (62-120) 81 (63-104) 0.098
Ozge Yetginoglu1, Dilek Barutcu Atas2, Arzu Velioglu2, _Izzet Hakkı Arıkan2, Hip Circumference (cm) 106 (83-141) 102 (86-124) 0.344
Yusuf Yilmaz3, Fatma Alibaz Oner4, Haner Direskeneli4, Z. Serhan Tuglular2,
Ebru Asicioglu2 Waist/Hip circumference ratio 0.82 (0.71-0.97) 0.81 (0.64-0.96) 0.155
1
Marmara University, School of Medicine, Department of Internal Medicine, Istanbul, Duration of disease (years) 11 (0.3-40.0)
Turkey, Turkey, 2Marmara University, School of Medicine, Department of Internal Age at Diagnosis (years) 25 (12-52)
Medicine, Division of Nephrology, Istanbul, Turkey, Turkey, 3Marmara University, School
of Medicine, Department of Internal Medicine, Division of Gastroenterology, Istanbul,
Turkey, Turkey and 4Marmara University, School of Medicine, Department of Internal
Medicine, Division of Rheumatology, Istanbul, Turkey, Turkey
MO175 TROPONIN CUT-OFFS FOR ACUTE MYOCARDIAL
INFARCTION IN PATIENTS WITH IMPAIRED RENAL
BACKGROUND AND AIMS: Systemic Lupus Erythematosus (SLE) is a chronic, FUNCTION - A SYSTEMATIC REVIEW AND META-ANALYSIS
multi-organ, systemic autoimmune disease that is more common in women than men
and is typically diagnosed during the reproductive age. Although liver dysfunction is Jan Kampmann1, Jeff Granhøj1, Frans Brandt Kristensen1, Andreas Pedersen2,
not considered the main organ pathology in SLE, the frequency of liver dysfunction or Christian Backer Mogensen2, James G. Heaf3, Hans Mickley4
abnormal liver enzyme values may be observed in 50-60% of patients. Liver-related 1
Sygehus Sønderjylland, Sønderborg, Sønderborg, Denmark, 2Sygehus Sønderjylland,
complications may present as asymptomatic hepatomegaly, subclinical steatosis and
Aabenraa, Denmark, 3Roskilde Sygehus, Roskilde, Denmark and 4Odense University
abnormal liver enzymes. The most common causes are drug-associated liver injury,
Hospital, Odense, Denmark
lupus-associated hepatitis, and fatty liver disease. The aim of this study was to assess
fatty liver and liver fibrosis in SLE patients using the FibroScan method as well as
associated factors such as immunosuppressive medications. BACKGROUND AND AIMS:
METHOD: Sixty SLE patients and 30 healthy controls were included. Patients with BACKGROUND: Identifying acute myocardial infarction in patients with renal disease is
HBV, HCV or cirrhosis, malignancy, cardiac disease, or patients on dialysis were notoriously difficult due to atypical presentation and chronically elevated troponin.
excluded. All participants underwent FibroScan measurements. Demographic data and AIM: To generate an optimized troponin cut-off value for patients with impaired renal
cumulative doses of immunosuppressive medications were extracted from patient function and acute myocardial infarction via meta-analysis.
charts. Fasting blood was collected for analysis METHOD: Two investigators screened 2,580 publications from Medline, Embase,
RESULTS: Demographic and clinical characteristics of the study groups are shown in Pubmed, Web of Science and Cochrane library. Only studies that investigated
Tables 1. The prevalence of fatty liver disease was similar between SLE patients and alternative cut-offs according to renal impairment were included.
healthy controls (21.7% vs 26.7%, p= 0.597) and was associated with body mass index 15 articles fulfilled the inclusion criteria and results were included in a meta-analysis.
(BMI) (p= 0.026) and C-reactive protein (CRP) (p= 0.046) in multivariate analysis. Study characteristics and cut-off values were extracted. Study quality and risk of bias
Liver fibrosis was also similar between the two groups (26.7% vs 10.0%, p= 0.069). were assessed by using QUADAS-2 score. Six studies were included in the meta-
There was no relationship between cumulative drug doses including glucocorticoids analysis. To calculate the optimal cut off value in accordance to AUC for troponin T
with either fatty liver disease or liver fibrosis. Since the majority of SLE patients were and troponin I in patients with renal impairment a bivariat mixed effect model on the
female, we performed a subgroup analysis in female patients (n=51) and healthy sensitivity and specificity transformed by way of the inverse probit function similar to
controls (n=25). Fatty liver disease was similar between female SLE patients and the model implemented in the R-package diagmeta was employed.
healthy controls (23.5% vs 24.0%, p= 0.964). However, liver fibrosis in female patients RESULTS: Review: There was a considerable diversity in study design, study
with SLE was increased compared to the female healthy population (29.4% vs 4.0%, p= population and endpoint definition. The cut-off value for patients on peritoneal
0.011) and was associated with age (p= 0.034) and low-dose cumulative glucocorticoid dialyses was twice as high (144 ng/L) when compared to patients on hemodialysis (75
use (p = 0.034). Low-dose cumulative glucocorticoid use was defined as less than 17.45 ng/l). Asian studies suggested a substantially higher troponin cut-off when compared
g, which was the 75th percentile value. Only 1 out of 15 female patients with fibrosis to European and American studies. The risk of bias was low in the analyzed studies, yet
had high-dose cumulative glucocorticoid use (>17.45 g), while the remaining 14 several studies were considered to have a low applicability.
patients had used lower doses (<17.45 g). META-ANALYSIS: Cut-off value for troponin T in patients not in dialysis with eGFR <60
CONCLUSION: The prevalence of fatty liver was similar between SLE patients and ml/min/1.73m2, a troponin T value of 47.89 ng (23.95; 71.83) was found. In patients on
healthy controls, while liver fibrosis was increased in the female patient group as dialysis a troponin T value of 239.75 ng/l ( 69.27 ; 410.23) was demonstrated. The 99th
compared to controls. Furthermore, liver fibrosis was associated with age and low dose percentile of the upper reference limit for troponin T was 14 ng/l. Cut-off value for
cumulative glucocorticoid use. Interestingly, fatty liver did not precede liver fibrosis in troponin I: In patients not in dialysis with eGFR < 60 ml/min/1.73m2 a troponin I value of
the majority of cases, contrary to what is observed in the general population. We 42.45 ng/l ( 33.83 ; 51.08 ) was demonstrated. The 99th percentile of the upper reference limit
hypothesized that liver fibrosis may be the result of subclinical inflammation and for troponin I ranged from 9-42 ng/l depending on the assays used. Troponin I cut-off for
autoimmunity associated with SLE itself and the use of steroids may prevent or prolong patients in dialysis could not be calculated due to limited data.
fibrosis formation in the liver. CONCLUSION: The new cut-off values could help to identify patients whose troponin
suggests acute myocardial infarction rather than renal function related troponin
elevation. The meta-analysis is based on only six studies in total. Further subdivision
according to eGFR would be desirable in order to optimize troponin cut-off values

i172 | Abstracts
Nephrology Dialysis Transplantation Abstracts
especially for dialysis patients. A differentiation on troponin cut-offs for HD and PD
patients may yield further benefits. Asian studies suggested a substantially higher Age Season n Mean (SD) SD Sig
troponin cut-off when compared to European and American studies. The factors
p
behind these findings may be worth investigating.
18-65 years Summer 8.823 288,9 (4,3) 0,000
Autumn 8.154 287,8 3,8
Winter 6.518 288,1 4,1
65-75 years Summer 3.889 290,5 4,4 0,000
Autumn 4.541 289,5 3,9
Winter 3.130 289,8 4,1
75-85 years Summer 2.702 290,5 5,2 0,000
Autumn 3.002 289,4 4,7
Winter 2.293 289,7 4,8
>85 years Summer 801 289,6 6,8 0,275
Autumn 754 289,1 6,2
Winter 629 289,5 6,4

*Summer (July, August, September), Autumn (Otober, November),


Winter (December, January)

MO177 RENAL PROXIMAL TUBULAR DISORDER AND RENAL


FUNCTION LOSS IN HIV-INFECTED PATIENTS TREATED
MO176 IS IT REALLY INDICATED TO INCREASE FLUID INTAKE IN
WITH TENOFOVIR DISOPROXIL FUMARATE
ELDERLY PATIENTS DURING SUMMER MONTHS?
Bingbin Zhao1, Xiaoxiao Shi1, Tiantian Ma1, Jiaying Li1, Peng Xia1, Yang Yu1,
Clara Maria Cases Corona1, Adrian Arroyo Santayana1, Juan Manuel Acedo2,
Wei Lv2, Limeng Chen1
Maria Luisa Casas2, Patricia Dominguez Torres1, Yunayka Diaz Enamorado1, 1
Eugenia Landaluce-Triska1, Ana Tato Ribera1, Gema Maria Fernandez Juarez1 State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of
1 Medical Sciences & Peking Union Medical College Hospital, Department of Nephrology,
Hospital Universitario Fundaci on, Nephrology , Spain and 2Hospital
on Alcorc
Beijing, P.R. China and 2Chinese Academy of Medical Sciences & Peking Union Medical
Universitario Fundacion Alcorc
on, Laboratory, Spain
College Hospital, Department of Infectious Diseases, Beijing, P.R. China
BACKGROUND AND AIMS: Thirst mechanism is essential to maintain an adequate
BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF), as the most
osmolarity and homeostasis. During summer heat waves, there is an increased
common antiviral drug, can cause both proximal tubular transportation dysfunctions
morbidity and mortality in elderly patients that has led to generally recommend an
and eGFR decline. The relationship between them is not clear due to lack of clinical
increase in fluid intake in all elderly patients beyond thirst stimulation, even in those
data from large cohorts, especially in the Chinese population. In this study, we
independent patients with free access to water.
summarized the characteristics of proximal tubular injuries and eGFR decline in the
The aim of this study was to observe the differences in calculated serum osmolarity
cohort of HIV-infected patients treated with TDF, and explore the the impact of
(cOsm) between young, elderly and very elderly patients who were neither
tenofovir on tubular transporters in vitro.
institutionalized nor hospitalized, in different seasons throughout the year.
METHOD: We enrolled HIV-infected patients treated with TDF, who were regularly
METHOD: We conducted a retrospective cross-sectional study in outpatients between
followed up in our hospital from Sep 1, 2001 to August 31, 2019. Their baseline and
18-104 years old that had undergone a blood test between July 2019 and January 2020,
follow-up clinical data were collected. Proximal tubular dysfunction was defined as
in which serum osmolarity could be calculated. Patients with serum creatinine above
meeting two or more of the following criteria: hypophosphatemia, hypouricemia, low
1.5 mg/dl were excluded.
carbon dioxide binding capacity, positive urine glucose with normal plasma glucose
RESULTS: The study included 45236 blood samples from 41132 patients, 56.1% were
level, and positive urine protein. Rapid deterioration of renal function was defined as
female. 50% of patients were between 18 and 65 years old, 45.4% were between 65 and
the annual decline rate of eGFR exceeding 5ml/min/1.73m2. We also used human renal
85 years old and 4.6% were >85 years old. The mean cOsm in patients between 18-65
proximal tubular epithelial cell line (HK2) to further investigate the impact of tenofovir
years was 288.3 mOsm/kg, compared to 289.8 mOsm/kg in those between 65- 85 years
on transporters including SGLT2, NaPi-IIa, and URAT1 through
old (p<0.0001). In patients >85 years, mean cOsm was 289.4 mOsm/kg.
immunofluorescence.
When comparing cOsm between different seasons of the year, cOsm in summer
RESULTS: A total of 375 HIV-infected patients receiving TDF were enrolled, mainly
months was about 1 mOsm/kg higher than in autumn-winter (288.9 mOsm/kg vs
males (90.1%), with a median follow-up duration of 34(17, 58) months. The most
287.8 mOsm/kg in young patients, p=0.0001; 290.5 mOsm/kg vs 289.4 mOsm/kg in
common clinical manifestations were proteinuria (20.3%) and hypophosphatemia
elderly patients, p=0.0001). In the very elderly (>85 years) the difference was smaller
(12.3%). The prevalence of proximal tubular injury was 6.7%, which was significantly
and non-significant (289.6mOsm/kg vs 289.1mOsm/kg).
associated with low body weight, but was not associated with age, TDF course, baseline
CONCLUSION: Under physiologic conditions, patients >65 years have a slightly
viral load, or baseline CD4þ T lymphocyte count. Their eGFR levels at the end of the
higher calculated serum osmolarity than younger patients, nevertheless staying within
follow-up were significantly lower than the baseline levels (104.6615.2 vs. 110.6614.2
normal range. These differences only increase in 1 mOsm/kg during the summer
ml/min/1.73m2, P<0.001). The average annual decline rate of eGFR was 5.06 22.7 ml/
months. Therefore, it is not indicated to force an increase in fluid intake in the elderly
min/1.73m2, and 23.6% of our patients had an annual decline rate of eGFR exceeding 5
or very elderly population under physiologic conditions.
ml/min/1.73m2. Rapid deterioration of renal function ( 5 ml/min/1.73m2 per year)
was significantly associated with female but not related to proximal tubular
dysfunction in multivariate logistic regression analysis. In vitro, the survival rate of
HK2 cells was more than 95% when treated with tenofovir with a concentration of
1lmol/L for 48h. The expression levels of transporters (SGLT2, URAT1, and NaPi-IIa)
were declined under the condition.
CONCLUSION: Among the HIV-infected Chinese patients treated with TDF, 6.7%
had proximal tubular dysfunction and 23.6% showed accelerated annual decline rate of
eGFR ( 5 ml/min/1.73m2 per year).

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Abstracts Nephrology Dialysis Transplantation

MO178 DOES OBTAINING AN EXTRA CORE KIDNEY BIOPSY FOR significant difference in survival time, depending on the presence of heart disease as a
RESEARCH PURPOSES INCREASE THE RISK OF comorbidity (p =0.037). Conducted Cox regression analysis showed that HR - for heart
COMPLICATIONS? A SINGLE CENTER EXPERIENCE disease, as a comorbidity, is 1.837 95% CI (1.020 - 3.306) and p = 0.043. The death rate
for patients with heart disease is about 2 times higher than patients without heart
Sheila Bermejo Garcia1, Clara Garcıa Carro1, Irene Agraz1, Richard Mast2, disease. Cumulative survival was higher in the group of patients without
Ander Vergara1, Juan Carlos Leo n1, Mo nica Bolufer1, Daniel Seron Micas1, Maria
cardiomyopathy - 64.2% (0.07) compared to the group of patients with
Jose Soler Romeo1 cardiomyopathy- 43.8% (0.07). Multivariate Cox regression analysis as significant
1
Hospital Vall d’Hebron, Nephrology, Barcelona, Spain and 2Hospital Vall d’Hebron, independent predictors of survival in patients with ABO confirmed the diuresis (p =
Radiology, Barcelona, Spain 0.029) and albumin (p = 0.006).
CONCLUSION: AKI survivors with high burden of comorbidities are at high risk for
BACKGROUND AND AIMS: Kidney biopsy (KB) is the “gold standard” to diagnose postdischarge death. Cardiomyopathy, as a risk factor, for two times increases the risk
nephropathies in our renal patients and it is a procedure with a low rate of of death. CCI score is significant independent high-risk prognostic factors for poor
complications. Obtaining material for kidney biopsy biobank requires the extraction of outcome in elderly patients with AKI. Remain the recommendation for individual
one more renal cylinder. The main objective of our study is to analyze the clinical approach, assessment and selection for the application of treatment taking into
characteristics of a cohort of patients with KB, the safety of the establishment of a renal account the overall condition in adult patients with acute renal injury.
biopsy biobank with the objective to obtain at least one core of kidney biopsy for
research purposes.
METHOD: Observational and prospective study of kidney biopsies performed in our MO180 CHRONIC KIDNEY DISEASE IN PATIENT WITH CHRONIC
center from January 2019 and 2020. We started a collection of kidney biopsy samples CORONARY DISEASE AFTER CORONARY
to obtain a biobank at January 2019. Therefore, in patients who accepted, instead of REVASCULARIZATION
two cylinders, three cylinders were obtained during the procedure when possible.
Clinical and laboratory data of the patients were reviewed and we looked for risk Shavkat Muminov1, Durdona Saipova1
factors for complications, including the number of cylinders obtained in the procedure. 1
RESULTS: We reviewed a cohort of 221 patients in whom we performed a kidney Tashkent Medical Pediatric Institute, Internal disease, Tashkent, Uzbekistan
biopsy at our hospital. Eight patients (3.6%) underwent trans-jugular renal biopsy,
which we have eliminated from the analysis. Of the remaining 213, 126 (59.2%) were BACKGROUND AND AIMS: to study of renal function in patients with coronary
men, the mean age was 56.8 (6 16.9) years, 122 (57.3%) patients had hypertension, 46 artery disease, depending on the method of revascularization and the initial state of the
(23%) were diabetics, 14 (6.5%) were under anticoagulant treatment and 35 (16.4%) kidneys.
were under antiplatelet treatment. Regarding the analytical values, the mean creatinine METHOD: There were 160 patients with coronary artery disease under observation
was 2.22 (6 1.9) mg / dl, protein / creatinine urine ratio 1119.6 [448.3-2957.9] mg / gr, who underwent re-endovascular procedures (RE). The average age of the patients was
44.6% (n = 95) had microhematuria, the median hemoglobin pre-KB was 12.1 (6 2.3) 56.6 6 1.27 years. Coronary artery bypass grafting (CABG group) was performed in 21
g / dL, 254380 (6 8873) platelets, INR 0.98 (6 0.09), prothrombin time of 11.8 (6 patients with coronary artery disease and percutaneous coronary intervention (PCI
1.16) seconds, systolic blood pressure was 135 (6 24.3) mmHg, diastolic blood group) - in 139 patients. The study included patients with an eGFR of at least 60 ml /
pressure was 76 (6 15.5) mmHg. The median kidney size was 11 (6 1.23) cm and min, determined by the serum creatinine concentration. Patients received standard
cortical size was 1.7 (6 0.65) cm. In 113 (53.1%) patients the right kidney was biopsied. therapy: antiplatelet therapy (double therapy), bisoprolol, valsartan, atorvastatin. All
69.5% (n = 148) of the patients 3 renal sample cylinders were obtained, 27.2% (n = 58) patients underwent dynamic determination of serum creatinine concentration in terms
2 cylinders and in 3.3% (n = 7) one cylinder. We did not found differences regarding of of 3 months - 1 year -2 years.
renal and cortical size in the patients according to the number of cylinders obtained. RESULTS: The CABG groups (21 patients) and the PTCA group (139 patients) who
We observed that patients in whom 3 cylinders were had a higher percentage of renal received standard therapy for coronary artery disease (group B). In the CABG and PCI
biopsy in the left kidney (p = 0.028). We evidenced minor complications in 13.6% (n = groups, the eGFR was 105.66 6 3.74 ml / min and 102.71 6 1.59 ml / min,
29) and 3.3% (n = 7) major complications. Patients with complications in KB were respectively. By the 3rd month of follow-up, the dynamics of eGFR in the groups, did
older (p = 0.039) and had a higher INR (p = 0.031). Patients with one renal cylinder Jin not differ (-16.36 6 3.30% and -17.55 6 1.25%, respectively), by the 3rd month eGFR
KB, presented a higher percentage of complications with 57.1% vs 17.2% two cylinders observation in the CABG and PTCA groups was also comparable, although it also
and 14.9% with three cylinder (p =0.014). We did not find differences in terms of differed in the baseline data (90.14 6 6.05 ml / min and 86.46 6 2.37 ml / min,
complications according to the laterality of kidney biopsy (right vs left). respectively, the differences with the baseline data in both groups - p < 0.001. By the
CONCLUSION: Kidney biopsy is a procedure with a low complication rate. Obtaining end the 1st year the following pattern emerged: in patients who underwent surgical
three renal biopsy cylinders for biobank has not shown an increase in the rate of revascularization, the decrease in eGFR was more pronounced than in patients who
complications, which remains similar than previously published reports. Our results underwent stenting of the coronary arteries (-51.80 6 3.51% versus -42, 39 6 1.35%, p
suggest that the complications are observed mainly in the first and/or second cylinder, <0.05), and the differences increased even more during the second year of observation
and in that case the third core is not performed. (-57.99 6 4.75% versus -44.76 6 1.89%, p <0.05). The second year of observation,
eGFR in the CABG group was lower than in the PTCA group (44.63 6 5.37 ml / min
versus 56.54 6 2.01 ml / min, p <0.05). This pattern can be explained that fact in the
CABG group were more patients with diabetes - 80.95% (17 patients out of 21)
MO179 ACUTE KIDNEY INJURY IN ELDERLY- PROGNOSTIC VALUES compared with PTCA patients - 12.23% (17 patients out of 139, chi square 49.83, p <
OF COMORBIDITY AND THE AGE FOR THE SHORT AND THE 0.001). All patients divided into 2 subgroups depending on the degree of eGFR by the
LONG TERM OUTCOME 3rd month of observation: patients with eGFR by the 3rd month of observation more
than 20% (31 patients, group 1) and less than 20% (group 2 - 129 sick). Initially, eGFR
Zvezdana Petronijevikj1, Gjulsen Selim2, Biljana Gerasimovska2, Lada Trajceska2 in group 1 was lower than in group 2. The relative dynamics of eGFR during the
1
Clinic of nephrology, Intensive care unit, Skopje, Republic Of North Macedonia and entire observation period was greater in patients of group 1 compared with group
2
Clinic of nephrology, Intensive care unit, Skopje, Republic Of North Macedonia 2 (-43.58 6 1.72% versus -11.10 6 0.58% by the end 3rd month of observation, -61.30
6 1.44% versus -39.38 6 1.29% by the end of the first year and -68.78 6 2.56% versus -
BACKGROUND AND AIMS: Acute kidney injury (AKI) is defined by a rapid decline 41.14 6 1.85% by the end of the second year of observation, the reliability of the
in glomerular filtration rate (GFR), resulting in disturbance of renal physiological difference in the relative dynamics between the groups at all three observation points is
functions including impairment of nitrogenous waste product excretion, loss of water p <0.001).
and electrolyte regulation and loss of acid-base regulation. Coexisting disease and the CONCLUSION.: In patients with coronary artery disease who underwent coronary
structural and functional changes that occur during the aging process are disposing revascularization, there is a decrease in renal function after revascularization. The most
factors that increase the risk of AKI in elderly population. significant decrease was observed in patients undergoing coronary artery bypass
METHOD: 101 elderly patients ( 65) who filling out one of the criteria of definition grafting, as well as in patients with initially low filtration function of the kidneys.
of AKI according to Kidney Disease Improving Global Outcome (KDIGO), were
included in the study. Patients were divided into 2 groups by age, group <75 and
group> 75 years old. In terms of outcome they were divided in group with short and MO181 ULTRASOUND ASSESSMENT OF KIDNEY SIZE AND ITS
90-day survival. The burden of the simultaneous presence of comorbid conditions was CORRELATION WITH BODY MASS INDEX IN HEALTHY
estimated through the Charles Comorbid Index. (CHI) VOLUNTEERS WITHOUT RENAL DISEASE
RESULTS: The mortality rate for the 90-day follow-up period after the AKI event was
45.5%. The intra-hospital mortality rate in adult patients with AKI was 22.8%.In our Nazma Mohammed1, Muzamil Latief2, Manzoor Parry3, Manjusha Yadla1
study the age was not confirmed as a risk factor for intra-hospital and 3-month 1
outcome in elderly patients with AKI. The presence of comorbid conditions estimated Government medical college and hospital, Secunderabad, Nephrology, Hyderabad,
through the Charles Comorbid Index (CHI), differed un-significantly between India, 2Government medical college Srinagar, Nephrology, Srinagar, India and 3Sheri
survivors and deceased patients with AKI (p = 0.39, p = 0.28 consecutive). Cox Kashmir institute of medical sciences, Nephrology, Srinagar, India
regression analysis confirmed the CCI score as a significant factor in survival in
patients with ABO. (p = 0.036).The risk of letal outcome increases by 16.3% with each BACKGROUND AND AIMS: Renal length as well as renal cortical thickness has been
increase in this unit score. Cox regression analysis confirmed heart diseases as a closely related to creatinine clearance in patients with chronic kidney disease. Our
significant prognostic factor for survival, increasing the risk of fatal outcome by about 2 primary aim was to establish a normal range of values for kidney length in our adult
times higher than patients without heart disease. Statistical analysis showed a population with normal renal function.

i174 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: This was a prospective observational study. Ultrasonographic assessment RESULTS: The cohort of crystalline light chain cast nephropathy consisted of 6 men
of renal parameters in 499 healthy volunteers between 18 to 80 years of age was done. and 2 women with a median age of 59.5 (range, 41-73) years. All patients suffered from
Volunteers with any known renal condition or any co-morbidity were excluded from advanced multiple myeloma (1 with ISS staging II, 7 with ISS staging III) and acute
the study population. Correlation between body mass index (BMI) and renal kidney injury with a median eGFR of 5.59 (range, 2.27-26.04) mL/min/1.73m2. All
parameters was assessed. patients except 1 required emergency dialysis at admission. Microhematuria was
RESULTS: Out of 499 volunteers 327 (65%) were males and 172(35%) were females. presented in 3 patients. Median proteinuria was 2.13 (rang, 0.83-3.59) g/24h and
17.8% volunteers were less than 30 years of age, 51.5% volunteers were in the age group median serum albumin was 38.2 (30.7-46.7) g/L. No one presented with nephrotic
of 30-60 years and 30.7 % were above 60 years of age. Mean BMI in males was 25.20 6 syndrome. Monoclonal immunoglobulin, detected in all patients on serum protein
3.96 kg/m2 whereas mean BMI in females was 24.08 6 3.28 kg/m2. In males the mean immunofixation electrophoresis, was k alone in 5 patients, j alone in 1 patient, IgG k
cortical thickness in right kidney was 13.68þ/- 2.47 mm and in left kidney cortical in 1 patient, IgA k in 1 patient.
thickness was 13.94 6 2.6 mm. In females right kidney cortical thickness was 12.63 6 The 8 patients were followed up with a median time of 8 (range, 2-24) months. Three
1.91 mm and left kidney cortical thickness was 13.40 6 2.37 mm. In the present study patients received VAD chemotherapy and 5 patients received bortezomib based
the right mean renal length was 9.9 6 40cm and left renal length was 10.19 6 0.97cm. regimens. At the time of last follow-up, 2 of 7 patients who needed emergency dialysis
In our study, there was positive correlation BMI with renal length. got rid of dialysis and the rest remained dialysis-dependent. Five patients died with a
CONCLUSION: Size of kidney has significant ethnic and geographic basis and there is median time of 5 (range, 2-19) months, 2 patients achieved partial remission and 1
a positive correlation between BMI and kidney size in our study population. patient achieved complete remission.
There was no significant difference in clinical features, treatments and main outcomes
between crystalline light chain cast nephropathy patients and ordinary light chain cast
nephropathy patients (Table 1). However, crystalline light chain cast nephropathy
MO182 CRYSTALLINE LIGHT CHAIN CAST NEPHROPATHY IS
patients had higher early mortality than ordinary light chain cast nephropathy patients
ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH
(50.0% vs 11.1%, p = 0.03).
MULTIPLE MYELOMA
CONCLUSION: Crystalline light chain cast nephropathy patients usually presented
with acute kidney injury requiring emergency dialysis. Although various types of
Zishan Lin1, Xu Zhang1, Xiaojuan Yu1, Suxia Wang1, Xinan Cen3, Fude Zhou1,
monoclonal immunoglobulin were detected, there was a dominance of the k isotype.
Minghui Zhao1
1
Compared to ordinary light chain cast nephropathy patients, crystalline light chain cast
Peking University First Hospital, Nephrology, Beijing, P.R. China and 3Peking University nephropathy patients had higher early mortality.
First Hospital, Hematology, Beijing, P.R. China

BACKGROUND AND AIMS: Light chain cast nephropathy is the most common
MO183 TELEMEDICINE AS A MODALITY OF HEALTH CARE
paraprotein-associated kidney lesion in patients with multiple myeloma (MM). Rarely,
DELIVERY FOR PATIENTS WITH SEVERE CHRONIC KIDNEY
light chain cast nephropathy could show crystalline appearance in patients with
DISEASE DURING COVID-19 PANDEMIC
multiple myeloma, also known as crystalline light chain cast nephropathy. We here
report the first retrospective study of crystalline light chain cast from a single centre.
Gaetano Alfano1, Francesco Fontana1, Cristina Bosica2, Annachiara Ferrari3,
METHOD: All native kidney biopsies were retrospectively studied in the Peking
Giacomo Mori2, Riccardo Magistroni1, Gianni Cappelli1
University First Hospital from 2000 to 2020. Newly diagnosed MM patients with were 1
enrolled. Patients with light chain cast nephropathy at least one cast with crystalline Policlinico di Modena Azienda Ospedaliero-Universitaria di Modena, Nefrologia,
appearance were identified as crystalline light chain cast nephropathy (Figure 1, n = 8), Modena, Italy, 2Policlinico di Modena Azienda Ospedaliero-Universitaria di Modena,
others were identified as ordinary light chain cast nephropathy (n = 18). Modena, Italy and 3Arcispedale Santa Maria Nuova, Nefrologia, Reggio Emilia, Italy

BACKGROUND AND AIMS: Telemedicine is a new modality of care delivery. Over


the last months, it has been used to deliver health care to outpatients with chronic
kidney disease (CKD) during COVID-19 pandemic. However, experience of
telemedicine in patients with severe CKD is scarce and there are not reassuring data
about its efficacy in improving patients’ outcome. To evaluate the efficacy and the
outcome profile of telemedicine in people with severe CKD, we reviewed all data of
outpatients with severe kidney impairment who underwent nephrological evaluation
during the first wave of this pandemic. In particular, outcomes of the ambulatory
activity (urgent-start dialysis, late referral and modalities of dialysis initiation) were
compared to 2019 ambulatory activity.
METHOD: Outpatients with severe chronic kidney disease included in the ambulatory
program called “Pre-Dialysis Program were enrolled in a retrospective study. We
reviewed all electronic charts of patients who underwent nephrological follow-up from
9th March to June 21st, 2020 (15 weeks in total) at the University Hospital of Modena,

MO182 Table 1. Comparing crystalline light chain cast nephropathy patients and ordinary light chain cast nephropathy

Features Crystalline light chain cast nephropathy (n = 8) Ordinary light chain cast nephropathy (n =18) p
Age (years) 59.5 (41.0, 73.0) 57.5 (43.0, 75.0) > 0.5
Male (%) 6 (75.0%) 10 (55.6%) 0.347
Hemoglobin (g/L) 89.5 (76.0, 118.0) 87.5 (72.0, 117.0) > 0.5
Proteinuria (g/24 h) 2.13 (0.83, 3.59) 1.8 (0, 23.5) > 0.5
Serum creatine (lmol/L) 218.0 (675.5, 1600.0) 441.6 (53.0, 1294.1) 0.196
eGFR (mL/min/1.73m2) 5.59 (2.27, 26.04) 9.62 (2.53, 61.98) 0.192
Emergency dialysis 7 (87.5%) 10 (55.6%) 0.114
Serum albumin (g/L) 38.2 (30.7, 46.7) 42.7 (35.6, 54.0) 0.177
Serum b2-microglobulin (mg/L) 8.45 (4.2, 16.2) 8.1 (2.9, 31.5) > 0.5
j/k 1/7 7/11 0.178
International Staging System staging (I/II/III) 0/1/7 3/4/11 0.339
Duration of follow up (months) 8 (2-24) 18 (3-120) 0.055
Bortezomib based chemotherapy 5 (62.5%) 16 (88.9%) 0.115
Independence from dialysis 2/7 2/10 0.771
ESRD 5 (62.5%) 11 (61.1%) > 0.5
Early mortality 4 (50%) 2 (11.1%) 0.03
Death 5 (62.5%) 12 (66.7%) > 0.5

10.1093/ndt/gfab092 | i175
Abstracts Nephrology Dialysis Transplantation

Italy. Extension of the observation period to 30th September 2020 allowed us to maintaining a balance between the effectiveness and safety of ACTs is extremely
determine the long-term effects of telemedicine on the rate of urgent-star dialysis, late important.
referral, and modalities of dialysis initiation. Aim is evaluation of the efficacy and safety of the use of direct oral anticoagulants
RESULTS: During 15 weeks of follow-up, 186 nephrological visits were performed (OAC) in CKD stages 1-3 in combination with AF.
(Table) They were subdivided into telemedicine visits (56.5%) and in-person visits METHOD: The study included 93 patients (38 men and 55 women) aged 41 to 86
(43.5%). Overall, mean age of patients was 71.7613.1 years with a prevalence of male years with CKD stages 1-3 and AF receiving therapy with OAC (rivaroxaban) and
(60.2%). Patients who received telemedicine visits had a statistically significant lower vitamin K antagonists (warfarin). The observation period was 12 months.
sCr (3.761.2 vs 4.561.5 mg/dl; P=0.0001) and higher eGFR level (14.766.02 vs RESULTS: An analysis of 75 patients with CKD of various stages and AF receiving
12.1665.8 ml/min; P=0.002) than patients followed in the ambulatory setting. A high rivaroxaban was performed, the control group consisted of 18 patients taking warfarin.
prevalence of patients with CKD stage 5 was monitored by in-person visits (P=0.0001). The average CHA2 DS2-VASc score in the OAC group was 4.161.8 points, in the
Patients followed by telemedicine had a clinical profile including a lower weight warfarin group - 4.261.3 points. There were also no significant differences between the
(P=0.007) and better control of metabolic acidosis (P=0.039) than the counterpart. groups in terms of the average score on the HAS-BLED scale (risk of developing
Changes in domiciliary therapy occurred more frequently in patients monitored in the hemorrhagic complications): 2.360.94 points in the OAC group, 2.560.6 points in the
ambulatory setting (P=0.036). Statistically significant differences were encountered in warfarin group. Among the comorbidities in the OAC group, 93.2% of patients had
the prescription of diuretics (P=0.002), sodium bicarbonate (P=0.043), arterial hypertension (AH), 24.5% had type 2 diabetes mellitus (DM); in the warfarin
antihypertensive drugs (P=0.001) and uric acid-lowering agents (P=0.046). During the group, 94.3% of patients had hypertension and 16.8% had type 2 diabetes. In 23.9% of
15-week period in 2019, 214 visits were performed (þ13% compared to 2020). The patients in the OAC group, minor bleeding was recorded. The largest number of
vast majority of these visits were conducted in the hospital setting (210 out of 214; hemorrhagic complications occurred in patients with stage 3 CKD: 18.9% of bleeding,
98.2%). The severity of CKD was similar between patients, without statistically which significantly (p<0.05) exceeds the number of bleeding in patients with a more
significant difference in the rate of patients in CKD stage III (P=0.7), stage IV (0.388) pronounced decrease in renal function. In 33.3% of patients with diabetes,
and stage V (P=0.593). hemorrhagic complications were recorded, which is significantly (p<0.05) more than
Implementation of telemedicine to in-person visits during COVID-19 pandemic did in the group of patients without diabetes - 21.4%. The greater number of hemorrhagic
not change the outcomes of patients. Short-term follow-up showed a similar rate in complications is most likely due to a more pronounced progression of the decline in
urgent-start dialysis (P=0.361), late referral (P=1), and HD (P=0.875) or PD initiation renal function compared with patients without diabetes: 71.4% of patients with
(P=0.661). Similar results were seen also at the end of the extended follow-up. diabetes showed a decrease in GFR by an average of 16.6 ml/min/1.73 m2 for 12
CONCLUSION: Implementation of telemedicine has been fundamental to maintain a months, which is significantly more (p<0.05) than in patients without diabetes (an
high level of care in CKD patients during the COVID-19 pandemic. Telemedicine average of 5.7 ml/min/1.73 m2).
services in combination with in-person visits have contributed to the delivery of CONCLUSION: In patients with CKD stages 1-3 with non-valvular AF, the use of
clinical monitoring in a group of patients with severe and progressive CKD. No OAC is most effective and safe in preventing thromboembolic complications. At the
differences have been identified in terms of rate of unplanned dialysis, late referral, and same time, the progression of CKD against the background of diabetes when taking
modality of dialysis initiation. anticoagulants occurs faster than in its absence, regardless of the specific anticoagulant.
Patients with AF, DM and CKD are more likely to have hemorrhagic complications,
which requires more frequent monitoring and monitoring of the functional state of the
kidneys.

MO185 THE GUT MICROBIOME-DERIVED METABOLITE


TRIMETHYLAMINE N-OXIDE AS A POTENTIAL BIOMARKER
IN LUPUS NEPHRITIS PATIENTS

Mohamed Salah1, . Rasha Samir Shemies1, Mona Elsherbeny1, Asmaa Enein1


1
Mansoura University, Mansoura Nephrology and dialysis unit, Mansoura, Egypt

BACKGROUND AND AIMS: Both human and animal studies suggest that the gut
microbe-derived metabolite Trimethylamine N-oxide (TMAO) is strongly associated
with several autoimmune disease including Rheumatoid arthritis and psoriatic
arthropathy. TMAO has been previously studied as a discriminator between SLE
patients and healthy volunteers with higher reported TMAO levels in the SLE group;
this suggests that gut microbiota may enhance TMAO generation in response to
disease severity. The aim of this study was to investigate the diagnostic and prognostic
validity of TMAO as a potential biomarker in lupus nephritis patients. To the best of
our knowledge this is the first study to investigate the gut microbe-derived metabolite
Trimethylamine N-oxide (TMAO) in patients with lupus nephritis correlating to the
criteria of disease severity.
METHOD: A total of 90 subjects were included in this cross-sectional study and
divided into 3 equivalent groups; group I (lupus nephritis patients (LN)), group II (SLE
patients without nephritis (NN)), and group III (healthy controls). Serum
Trimethylamine Levels were assessed, compared between the study groups and
correlated to the clinical, laboratory and Histo-pathological criteria obtained from
kidney biopsies of the included patients.
RESULTS: Unpredictably, TMAO levels were found to be significantly higher in
healthy controls compared to the total SLE population (p=0.003), and to LN, and NN
groups individually (p=0.01). There was no significant statistical difference of TMAO
levels between (NN) and (LN) patients (p=0.62). TMAO levels correlated to Anti-
dsDNA titres (p=0.02) and Red Blood Cells count (p=0.02) among LN patients while
they haven’t shown any correlations to the other studied clinical-laboratory and
histopathological factors.
CONCLUSION: Contrary to the results of the previous studies, TMAO levels were
found to be higher in healthy controls rather than SLE patients and did not
discriminate between LN and NN patients as well as did not show significant
correlation to most studied criteria of disease severity. The possible confounding effect
MO184 ANTICOAGULANT THERAPY IN PATIENTS WITH CHRONIC
of the dietary pattern and ingested drugs on the gut microbiome underestimate the
KIDNEY DISEASE AND ATRIAL FIBRILLATION
diagnostic and prognostic utility of TMAO as a potential marker in different diseases.
Further studies considering the dietary pattern of the included patients are still
Sherzod Abdullaev1, Rano Igamberdieva1, Olimkhon Sharapov1
1
warranted.
Tashkent pediatric medical institute, Internal medicine, Tashkent, Uzbekistan

BACKGROUND AND AIMS: Chronic kidney disease (CKD) significantly alters the
pharmacokinetics of drugs, which in practice complicates the selection of adequate
anticoagulant therapy (ACT) in patients with atrial fibrillation (AF) and CKD. At the
same time, in the vast majority of patients with AF and CKD, ACT is required to
prevent life-threatening thromboembolic complications. In such an environment,

i176 | Abstracts
Nephrology Dialysis Transplantation Abstracts
hemodyalisis (HD), group 2 (G2) represents deceased patients in HD and group 3 (G3)
represents deceased patients treated with a conservative approach.
The comorbidities were stratified according with modified Charlson comorbidity index
(mCCI)  5; the frailty according to Clinical Frailty Scale (CFS)  5). The eGFR was
calculated through Chronic Kidney Disease Epidemiology Collaboration formula
(CKD-EPI) at the time of admission. The nutritional status (based in Body Mass Index
and seric albumin), ferritine value as a marker of inflammation and the number of
hospitalizations during 2014-2020 were analyzed. Quantitative variables are described
with their mean and compared with Students T-test. A p-value <0.05 was considered
statistically significant. SPSS Statistics version 23 (Chicago, IL) was used for all
statistical analyses.
RESULTS: A total of 398 patients with CKD stage 4 and 5 presented with dyalitic
indication or conservative approach (CA) at time of admission were included: 72
(18.1%) were in CA group. Clinical characteristics are presented in Table 1.
MO185 Figure: Serum TMAO concentration in non-nephritis, nephritis, and
healthy controls.

MO185 Table 1: Spearman’s correlation between TMAO and other parameters G1 (n=159) G2 (n=159) G3
in nephritis and non-nephritis groups. (n=159)
Gender male (n) 86 99 35
Items TMAO in TMAO in Gender female (n) 73 68 37
Non-nephritis Nephritis Frailty 2,5 5,2 5,7
r P r P Charlson Index 3 4,3 5,7
Age - 0.17 0.28 0.03 0.88 Body Mass Index (Kg/m2) 25,7 22,8 23,2
Hb (gm/dL) - 0.11 0.48 0.20 0.24 Albumin (mg/dl) 258 436 386
RBC (106/mm3) - 0.13 0.41 - 0.38 0.02*
WBC(103/mm3) - 0.09 0.56 - 0.03 0.85 We analyzed the difference between patients who were still alive (G1) versus patients
who died during this observational period of seven years, accordingly with which
Lymphocytes (103/mm3) 0.25 0.11 - 0.08 0.65
treatment modality (CA or HD).
Platelet count (103/mm3) 0.26 0.09 0.09 0.59 We found no significant differences regarding gender and CKD etiology between
Serum Creatinine level (mg/dL) 0.05 0.75 0.07 0.66 groups. There were significant differences in age (G1: median age 77 vs G2:median age
76, p value < 0,001; G1: median age 77 vs G3:median age 82, p value <0,001).
Serum Na level 0.16 0.30 - 0.10 0.56 In our study, deceased population had a higher degree of frailty (G1: 2,5 vs G2:5,2, p
Serum K level - 0.05 0.77 0.10 0.55 value < 0,001; G1: 2,5 vs G3:5,7, p value 0,015), a higher Charlson comorbidity score
ANA 0.02 0.89 - 0.01 0.95 (G1:3 vs G2: 4,3, p value 0,000018; G1: 3 vs G3:5,7, p value <0,001), a poorer
nutritional status (Body Mass Index: G1:25,7 vs G2:22,8, p value < 0,001; G1:25,7 vs
Anti-ds DNA 0.20 0.20 0.29 0.02* G3:23,2, p value <0,001 and lower albumin levels: G1: 3,86 vs G2:3,23, p value 0,00001;
C3 0.06 0.69 0.04 0.80 G1: 3,83 vs G3:3,23, p value <0,001 ), higher ferritine levels (G1:258 vs G2:436, p value
<0,001; G1: 258 vs G3:386, p value < 0,001).
C4 0.15 0.33 0.01 0.94
The number of emergency admissions were higher in deceased groups (G1:0,3 vs
Urinary protein (mg/day) - 0.24 0.13 - 0.007 0.97 G2:1,2, p value < 0,001; G1:0,3 vs G3:0,8, p value < 0,001).
Count of WBCs or pus cells in urine - 0.05 0.78 - 0.06 0.74 CONCLUSION: We concluded that G2 and G3 had more comorbidities and more
frailty, as we expected.
Count of RBCs in urine - 0.26 0.09 -0.23 0.17 Knowledge of the factors associated with mortality could be of value in shared
SLEDAI-2K score - 0.15 0.36 - 0.02 0.89 decision-making and useful to help improve outcomes in CKD population.
Class of renal biopsy _ _ 0.12 0.48 In the absence of a model completely capable of predicting mortality among patients
who initiate hemodialysis versus patients undergoing conservative treatment, the
Number of glomeruli _ _ 0.09 0.59 analysis of these variables can contribute to a better selection of patients who will really
Activity index _ _ - 0.15 0.40 benefit from a conservative treatment approach. Further studies are needed to validate
a prognostic tool to choose the better treatment for elderly frail patients.
Chronicity index _ _ - 0.03 0.89

*: significant p  0.05. MO187 NON-STEROIDAL ANTI-INFLAMMATORY DRUG


r PRESCRIPTION IN THE YOUNG-OLD AND VERY- OLD: TYPE,
: correlation coefficient
ROUTE AND BURDEN OF CARDIOVASCULAR RISK FACTORS

Cynthia Lim1, Jason Choo1, Jia Liang Kwek1, Hanis Abdul Kadir1, Ngiap
Chuan Tan2
1
Singapore General Hospital and 2SingHealth Polyclinics
MO186 MORTALITY IN FRAIL ELDERLY WITH CHRONIC KIDNEY
DISEASE – WHAT CAN MAKE US CHOOSE BETWEEN
BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are
HEMODIALYSIS AND A CONSERVATIVE APPROACH?
associated with cardiovascular and kidney adverse effects, especially in older adults.
However, NSAIDs are still frequently prescribed to some at-risk groups. We aimed to
Joana Freitas1
1
evaluate the burden of traditional cardiovascular risk factors and pattern of NSAID
Centro Hospitalar Universit
ario do Porto, Nefrologia, Porto, Portugal prescription in the very-old and young-old.
METHOD: Cross-sectional study of older adults who received prescriptions over 3
BACKGROUND AND AIMS: The prevalence of Chronic Kidney Disease (CKD) is years from a large healthcare cluster in Singapore. Individuals aged 65-79 years were
increasing worldwide including a significant number of frail elderly patients. This the “young-old” and those 80 years were the “very-old”. Prescriptions and traditional
reflects the need to create tools that could help the nephrologists to choose between the cardiovascular risk factors were retrieved from electronic records.
best renal replacement treatment and a conservative approach. The identification of RESULTS: Among 197,932 older adults (including 41,079 very-old), 49.9% received at
prognostic factors and their correlation with mortality could be crucial. least 1 NSAID prescription. Topical NSAIDs were more frequently prescribed among
The aim of this study was to identify and compare some variables that could be the 19,979 very-old with NSAID prescriptions (91.5% versus 82.9% of the young-old),
associated with mortality in CKD patients whether receiving hemodialysis or in a while oral non-selective (22.1% versus 38.5%) and selective NSAID (15.1% versus
conservative approach. 24.9%) were less frequently prescribed compared to the young-old (all p<0.001). The
METHOD: The authors realized a single center retrospective study in older ( very-old with NSAID prescriptions were more likely to have diabetes (38.2% vs.
75years) and frail patients admitted in Nephrology department between in the last 32.8%), hypertension (19.3% vs. 14.0%), chronic kidney disease (51.4% vs. 23.6%) and
seven years. Baseline characteristics were collected from electronic medical records. cardiovascular disease (7.0% vs. 3.8%) than the young-old with NSAID prescriptions
Three groups were characterized: group 1 (G1) represents non deceased patients in (all p<0.001).

10.1093/ndt/gfab092 | i177
Abstracts Nephrology Dialysis Transplantation

Table 1 shows that among the very-old, the odds of receiving oral non-selective content, the Edelman equation seems to adequately predict the course of serum [Naþ].
NSAIDs was significantly lower in those with cardiovascular disease, while the odds of However, the clinical use of the Edelman-based formulas may be hampered in subjects
receiving oral COX II inhibitors was significantly higher in female and hypertension. with higher weight and higher total body cation content, which may reflect increased
Among the young-old, the odds of receiving oral non-selective NSAID was lower in tissue Naþ storage. Our analysis underlines the importance of further research into the
those with cardiovascular disease, diabetes and chronic kidney disease, while the odds role of osmotically inactive Naþ storage in osmoregulation.
of receiving oral COX II inhibitors was higher in female, hypertension, cardiovascular
disease and lower in diabetes and chronic kidney disease.
CONCLUSION: This study highlights that NSAIDs were frequently prescribed among
MO189 OUTCOMES OF AN ACCELERATED CITRATE
older adults with comorbidities that may predispose to NSAID-associated adverse
ANTIGOAGULATED MEMBRANE SEPARATION PLASMA
events. Physician education and policies are required to avoid potentially inappropriate
EXCHANGE ALGORITHM
prescriptions.
Michael Halpin1, Bonny Chen2, Richard Singer1,2
1
The Australian National University, School of Medicine, Acton, Australia and 2Canberra
MO188 RECONSIDERING THE EDELMAN EQUATION: IMPACT OF Hospital, Garran, Australia
INDIVIDUAL TOTAL BODY CATION CONTENT AND BODY
WEIGHT
BACKGROUND AND AIMS: Plasma exchange is a standard therapy for some anti
glomerular basement membrane disease and some types of renal transplant rejection.
Marjet Oppelaar1, Mart Vuurboom1, Eliane Wenstedt1, Liffert Vogt1, Rik Olde
As with other extracorporeal therapies, anticoagulation is usually required. This study
Engberink1
1
assessed the safety, efficacy and Calcium flux of an accelerated algorithm for regional
Amsterdam UMC, locatie AMC, Nephrology, Amsterdam, The Netherlands citrate anticoagulation in membrane-based plasma exchange.
METHOD: This was an observational study in patients receiving citrate
BACKGROUND AND AIMS: Treatment of dysnatremias is guided by formulas that anticoagulated, membrane-based, plasma exchange at the Canberra Hospital between
are based on the Edelman equation, including Adrogue-Madias’ and others. Edelman’s July 2017 and May 2020. Data was collected prospectively using an electronic medical
equation is the result of a unique study in which serum sodium concentration ([Naþ]), record and compared to data from our previously published algorithm which had used
total body exchangeable sodium (Naeþ) and potassium (Keþ) and total body water a slower blood pump speed.
(TBW) were measured in a highly heterogeneous population. Because these RESULTS: There were 134 plasma exchange sessions performed during the
observations resulted from steady state observations, the equation might not account observational period. Circuit clotting occurred in 4 sessions and 1 session was affected
for the recently uncovered highly dynamic Naþ body compartment where Naþ is by symptomatic hypocalcaemia. A systemic ionised calcium <0.96 mmol/L was seen
temporarily stored and released without affecting TBW. Various factors that influence in 19.4% of sessions, which was a similar frequency to that seen in our previous
this Naþ body compartment have been identified and we questioned as to what extent algorithm. A systemic ionised Ca <0.81 mmol/L occurred in 4 sessions (all
these factors affect associations between serum [Naþ] and [NaeþKe]/TBW. asymptomatic). This hypocalcaemia occurred towards the end of the sessions, after
METHOD: We performed a post-hoc analysis of original data published by Edelman. switching from albumin to fresh frozen plasma replacement fluid. Median treatment
In the linear regression model, effects of sex, edema (y/n), age and body weight (>/< time was 135 minutes, compared to 219 minutes in our previously published
median split) were examined. Serum [Naþ] was calculated by multiplying serum water algorithm. Mean net Ca gain/session was 7.7 6 2.3 mmol.
[Naþ] of the original data set by 0.93. Using piecewise regression, we analyzed CONCLUSION: An accelerated algorithm for regional citrate anticoagulation achieves
differences in slope and y-intercept for the regression between serum [Naþ] and substantial time savings while maintaining efficacy and safety. The 4 episodes of
increasing values of (NaeþKe)/TBW, in which the clinical characteristics from the systemic ionised calcium <0.81 mmol/L may have been due to recirculation of infused
subgroups were included as interaction factors . citrate but, probably more likely, are due to the additional citrate load imposed by use
RESULTS: Data was available for 85 measurements in 82 patients; 57 males and 25 of fresh frozen plasma in these sessions. Future algorithms need to better account for
females. The median age (range) age was 58 (27-90) years and median weight (range) the citrate load present in fresh frozen plasma.
was 59.6 (36.4 – 168.2) kilograms. Median serum [Naþ] (range) was 131.4 (103.4 –
150.2) mmol/L. The association between serum [Naþ] and (NaeþKe)/TBW was
different for high and low weight categories (figure 1A). Sex, age or presence of edema
did not alter the relationship. Piecewise regression showed a significant decrease in
slope in the regression between serum [Naþ] and (NaeþKe)/TBW above 149 mmol/L
(NaeþKe)/TBW (figure 1B).

MO188 Figure 1: A. Different association between serum [Naþ] and (NaeþKe)/


TBW for weight </> 59.8 kilograms (slope (SE) 1.05 (0.008) vs 0.69 (0.009), p=0.004
and intercept (SE) -26 (12) versus 28 (13.6), p=0.003) B. Adjusted relation between
serum [Naþ] and (Nae þ Ke)/TBW. Piecewise regression shows a significant decrease
in slope at 149 mmol/L (NaeþKe)/TBW (slope of 1.12 vs 0.56, p = 0.01)

CONCLUSION: Edelman equation’s coefficients are significantly affected by weight


and total body cation content. In subjects with a low weight and low total body cation

i178 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO190 NORMATIVE DATA FOR GLOMERULAR FILTRATION RATE IN monitoring and alteration of RAASi therapy. However, less than half of the patients
HEALTHY KIDNEY DONOR POPULATION benefitted from an increase in RAASi therapy after normalisation of serum potassium,
and there was definitely scope for improving this component of the care pathway via
Ashish Bhoyar1, Vinant Bhargava1, Ashwani Gupta1, Anurag Gupta1, more direct multi-disciplinary interaction with the heart failure teams.
Vaibhav Tiwari1, A K Bhalla1, Manish Malik1, Devinder Singh Rana1
1
Sir Ganga Ram Hospital, Institute of Nephrology, New Delhi, India
MO192 ASYMPTOMATIC HYPERURICEMIA AS A RISK FACTOR OF
BACKGROUND AND AIMS: Glomerular filtration rate (GFR) is estimated OUTCOME IN CARDIORENAL PATIENTS
traditionally from 24-hour urinary creatinine clearance. Creatinine is mainly filtered by
glomerulus. The collection of 24-hour urinary sample is a difficult task with many Suela Mumajesi1, Alma Idrizi1, Matilda Imeraj1, Vilma Cadri1, Nevi Pasko1,
patients fail to collect all the urine samples. As measuring GFR is cumbersome, Ariana Strakosha1, Nestor Thereska2, Myftar Barbullushi1
expensive, and not easily available in all centers, various equations are developed for 1
estimating GFR from creatinine like MDRD, CKD EPI creatinine. GFR obtained from Mother Teresa Hospital, Tirane, Albania and 2Amirica Hospital, Tirana, Albania
serum creatinine shows wide variation as muscle mass and dietary protein intake are
important determinants of serum creatinine concentration. Literature shows very few OBJECTIVE: The purpose of the study was to evaluate the impact of asymptomatic
studies with GFR estimation with reference to age in Indian population. Hence, this hyperuricemia on long-term outcome including death, rehospitalization in cardiorenal
study is planned to develop age specific nomogram for GFR in healthy kidney donor patients.
population as well as to study agreement between GFR obtained by 99m Tc DTPA INTRODUCTION: Hyperuricemia is associated with progression of kidney failure,
three sample method and GFR estimated by 24-hour urinary creatinine. The aim of cardiovascular diseases and cardiorenal syndrome, which represents a significant
this stidy was to develop age-specific nomogram GFR in healthy kidney donor health burden. There is a growing interes on evaluation of serum acid levels(SUA) as a
population and to study the agreement between the GFR measured by Technetium- risk factor in cardiorenal syndrome, because of the evidences that xanthine oxidase
99m diethylene triamine pentaacetic acid (99m Tc DTPA) and 24-hour urinary inhibitors are satisfactorily useful on cardio and renal protection.
creatinine method. MATERIALS AND METHODS: This was a descriptive cross–sectional study. A two-
METHOD: This study was conducted at Sir Ganga Ram hospital, New Delhi. All years follow up was conducted to determine the outcome in cardiorenal patients. Each
healthy individuals aged more than 20 years and less than 65 years, undergoing patient went through clinical examination with a standard valuation including the
evaluation as prospective kidney donor at our hospital were the part of this study. GFR determination of uric acid levels. 139 patients (pts) with chronic kidney disease stage 3
was measured by 99m Tc DTPA clearance using 3 sample method. GFR measured by from whom 119 had cardiorenal syndrome were included in the study. Statistical
DTPA method was used to develop nomogram. Creatinine Clearance was calculated analysis was performed by v2 test, Fisher’s exact test and binary logistic regression.
from 24-hour urinary creatinine by formula U x V/P where, U is urinary creatinine RESULTS: Hyperuricemia was founded in 65.5% of pts determined by acid uric levels
level, P is plasma creatinine level and V is total volume of urine. Nomogram was higher then 7.2 mg/dl and had a strong assosiation with cardiorenal
developed with respect to these 3 Age groups; namely, 20 to 40 years, 40 to 50 years syndrome,p=0.03.The average age was 56.7 6 12.5 years. Males were 62.2%% pts,
and 50 to 65 years p=0.031. Bivariate analysis revealed a strong relationship between hyperurcemia and
RESULTS: Total 100 kidney donors were included in this study. Enrolled subjects were cardiovascular components: hypertension p=0.047, diabetes mellitus p=0.021, sex
divided into 3 age groups; 20 to 40 years (n=28), 40 to 50 years (n=46) and 50 to 65 p=0.03, death p=0.051 and rehospitalization in 18 pts, p=0.02. Subsequently binary
years (n=26). Majority of the donors were females (n=80). The agreement between logistic regression showed that higher acid uric levels even there were not statistically
GFR obtained by 99m Tc DTPA and 24-hour urinary creatinine clearance methods correlated with mortality, were a significant predictor for all-cause death (Odds Ratio
was 92.6 vs. 94 ml/min, 80.4 vs. 76 ml/min and 76.3 vs. 70 ml/min in respective age [OR] 4.2, 95% confidence interval [CI] 0.87–20.35, p = 0.073).
groups. CONCLUSIONS: Asymptomatic hyperuricemia was common and had a powerfull
CONCLUSION: In the younger age group (20 to 40 years), there is better agreement in significant association with cardiorenal syndrome.Higher SUA was unconventionally
GFR measured by 99m Tc DTPA method and 24-hour urinary creatinine clearance associated with long-term adverse outcomes in these patients, so our efforts should be
methods. focused in immediate identification and treatment of this old forbidden marker.
KEY WORDS: chromic kidney disease, cardiovascular disease, etc

MO191 MANAGEMENT OF HYPERKALAEMIA TO FACILITATE RAASI


THERAPY IN PATIENTS WITH HEART FAILURE IN A
BESPOKE UK CLINIC MO193 EFFICACY AND SAFETY OF SINGLE DOSE RITUXIMAB IN
STEROID-DEPENDENT OR FREQUENTLY RELAPSING
1
Ibrahim Ali , Philip A. Kalra1 MINIMAL CHANGE DISEASE IN A CHINESE MEDICAL
1 CENTER
Salford Royal NHS Foundation Trust, Renal medicine, United Kingdom
Chao Li1, Peng Xia1, Hang Li1, Yan Qin1, Limeng Chen1, Xuemei Li1, Xuewang Li1
BACKGROUND AND AIMS: Best practice for treatment of patients with chronic 1
Peking Union Medical College Hospital, Nephrology, Bejing, P.R. China
heart failure involves beta-blockers and renin-angiotensin-aldosterone system
inhibitors (RAASi) such as ACE inhibitors (ACE-i), angiotensin receptor blockers
(ARB), mineralocorticoid antagonists (MRA) and neprolysin inhibitor/ARB. However, BACKGROUND AND AIMS: The purpose of our study was to evaluate efficacy and
use of these agents, and optimisation of their dosage, is frequently limited by safety of single dose rituximab in steroid-dependent or frequently relapsing minimal
hyperkalaemia, the incidence of which is increased by the co-prevalence of chronic change disease during one-year follow-up.
kidney disease (CKD). Management of patients in a bespoke Hyperkalaemia Clinic can METHOD: Twenty patients with corticosteroid-dependent (n=12) or frequently
be advantageous in facilitating optimal use of RAASi. relapsing (n=8) idiopathic minimal-change diseases were hospitalized between August
METHOD: A Hyperkalaemia Clinic was opened in July 2019 in this tertiary renal 2018 and July 2019 in the tertiary hospital. They received a single-dose rituximab (1g)
centre within an NHS trust that hosts 4 district hospital heart failure services. Referrals concomitantly with their corticosteroid and immunosuppressors. The side effects of
of patients with left ventricular systolic dysfunction whose RAASi could not be RTX were also recorded.
optimised because of hyperkalaemia were encouraged from heart failure specialist RESULTS: We included 20 patients (15 males and 5 females). The mean age of onset
nurses and cardiologists. Management of the patients incorporated commencement of renal disease was 2169 years old. The included patients were steroid dependent, of
patiromer at 8.4g daily and increases in RAASi was usually devolved to the referring whom 8 patients were frequently relapse. All patients had been received steroid in the
team. This report describes the activity and short-term outcomes of the first 17 months past. 14 patients had been treated with calcineurin inhibitors (n=13, 65%) or
after opening of the clinic (follow up until 1st January 2021). mycophenolate mofetil (n=1, 5%). The baseline serum albumin was 33610g/L, and
RESULTS: 34 patients with systolic heart failure and problems with RAASi-associated serum creatinine was 76638lmol/L, and 24-hour urine protein was 0.22 (0.06, 6.07) g/
hyperkalaemia were referred to the clinic. Mean age was 74 (range 44-88) years, 28% d. B-cell depletion (CD19þB cell<5/lL) was achieved after RTX infusion within one
had stage 3a, 28% 3b and 8% stage 4 CKD. ACE-I or ARB were being used in 73% of week. The average frequency of administered RTX was 1.47 times per person per year.
patients at referral, 73% were using beta blockers and 50% MRA with loop diuretic use We observed B cell reconstitution (CD19þB cell>20/lL) in 8 cases (35%) after the first
in 70%. At first visit 64% had normokalaemia, and 36% serum potassium 5.4-6.0 dose of RTX. During follow-up (15.567.0 months), 19 patients achieved complete
mmol/L. During follow-up, 6 (18%) patients discontinued patiromer due to remission, while one patient was resistant to treatment. However, five relapse episodes
gastrointestinal side effects, 3 no longer required the binder because of decrease in were recorded during tapering steroids or after stopping steroids. Compared with the
RAASi use and 2 patients died (one each from stroke and sepsis). One patient was year before rituximab treatment, the per-patient average number of relapses decreased
switched to an alternative potassium binder. As of 1st January 2021, patiromer was still from 1.460.6 to 0.460.7 during 1 year of follow-up. After rituximab, the per-patient
being administered to 22 (65%) patients, 8 of which had received this for >12 months; prednisone maintenance median dose decreased from 0.28 mg/kg (0.17, 0.46) to 0mg/
all patients remained normokalaemic and none of them required magnesium kg (0, 0.07) (P<0.001). Furthermore, the mean estimated GFR was stable (from
supplementation. An increase in RAASi therapy had occurred in only 12 (35%) 117626 to 120617 ml/min per 1.73m2, P>0.05). There were three cases of mild
patients. infusion reaction (manifested as skin itching and rash) and two cases of infection (one
CONCLUSION: Our experience demonstrates the relative simplicity of managing case each of pneumocystis pneumonia and skin infection caused by actinomycetes).
hyperkalaemia via a bespoke clinic in cardio-renal patients. As this was nephrology- CONCLUSION: Single-dose of RTX effectively prevented relapse and reduced the
led, optimised management was dependent upon the assertive and collaborative need for steroid in steroid-dependent or frequently relapsing minimal change disease.
involvement of the referring heart failure teams who helped with biochemical

10.1093/ndt/gfab092 | i179
Abstracts Nephrology Dialysis Transplantation

MO194 COVID-19 INFECTION IN PATIENTS RECEIVING CONCLUSION: AHUS is a critical complication in lung transplantation, shortly
IMMUNPSUPPRESSIVE THERAPY: EXPERIENCE OF A related with immunosuppressive therapy. Patients are at risk of end stage renal disease.
NORTH AFRICAN NEPHROLOGY CENTER Eculizumab treatment appears promising.

Rawnak Houli1, Samia Barbouch1, Cherni Nadia1, Hajji Mariem1, Amira Sakay1,
Fethi Ben hamida1, Harzallah Amel1, Taieb Ben abdallah1
1 MO196 KIDNEY INVOLVEMENT IN WALDENSTROM
charles nicolle teaching hospital, nephrology, tunis, Tunisia
MACROGLOBULINEMIA AND IGM MONOCLONAL
GAMMOPATHY
BACKGROUND AND AIMS: Since its outbreak in December 2019,novel coronavirus
disease 2019 (COVID-19) has become one of physicians top concerns worldwide. Sara Cardoso Fernandes1, Ricardo Gomes2, Ana Messias3, Bernardo Do
Special attention is payed to immunocompromised patients with whom the virus is Sacramento Marques Da Costa1, Ma is1,4, Helena Viana1,4, Ana
rio Go
feared to be more aggressive . Our aim was to assess outcomes in patients receiving Carina Ferreira1,5, Fernando Nolasco1,5
immunosuppressive therapy who presented with severe acute respiratory syndrome 1
Centro Hospitalar Universitario Lisboa Central, Nephrology, 2Centro Hospitalar
coronavirus-2 (SARS- CoV-2) infection.
ario Cova da Beira, 3Hospital Garcia de Orta, Nephrology , 4Centro Hospitalar
Universit
METHOD: we monitored patients undergoing immunosuppressive regimens who
ario Lisboa Central, Laboratory of Renal Morphology and 5Nova Medical
Universit
presented with SARS- CoV-2 infection during a four months period from September to
School
December 2020 in the Nephrology department of Charles Nicolle’s Teaching Hospital.
The diagnosis was made through nasopharyngygeal swabs. Kidney transplant patients
were not included. BACKGROUND AND AIMS: Renal manifestations of IgM gammopathy are less
RESULTS: we identified 9 patients who presented a confirmed SARS-CoV-2 infection common than those seen in patients with multiple myeloma. However, a wide
(details are shown in figure 1). Age varied from 32 to 67 years. Gender ratio was 0,8. Six spectrum of kidney diseases has been described in previous publications. We aim to
patients had hypertension and one patient had diabetes. Seven patients suffered from characterize kidney involvement in patients with Waldenström Macroglobulinemia
chronic kidney disease stage 4 (2 patients) and stage 5 (5 patients). Active smoking was and IgM-secreting B cell lymphoproliferative disorders.
noted in 4 patients. Indications for immunosuppressive therapy were vasculitis METHOD: We retrospectively studied 7 patients with a circulating monoclonal IgM
(5patients) , lupus nephritis (1 patient) , scleroderma (1patient), cryoglubulinemia (1 and renal histology showing evidence of monoclonal immunoglobulin deposits or
patient) and multiple myeloma (1 patient). Therapies used included corticosteroids lymphomatous infiltration. Demographic, clinical and laboratory data were collected.
alone (2 patients) or in association with cyclophosphamide (6 patients) and in one case RESULTS: Of the 7 patients studied, four (57%) were male and the median age was 68
bortezomib.COVID-19 symptoms included fever (6 patients), fatigue (7 patients), joint years old (range 41-79). Among the 7 patients, 5 met criteria for Waldenström
pain (3 patients), dry cough (all patients)and diarrhea ( one patient). Medium duration Macroglobulinemia after bone marrow biopsy; none of them had hyperviscosity
under immunosuppressive treatment was of 42,1 days when COVID-19 diagnosis syndrome. Four patients presented with nephrotic syndrome and all had impaired
was made Among the patients, six had a mild COVID-19 presentation and displayed renal function and hypertension. Four patients had microscopic hematuria and only
favorable outcomes; whereas the remaining three had severe symptoms requiring high one patient showed no proteinuria. Mean serum creatinine levels were 2.9mg/dL. Renal
dose oxygen and died. As for the renal outcomes, we observed no detioration of kidney biopsy showed different patterns of renal injury, including typical intracapillary
function following the COVID-19 infection in any of the patients .All of the patients monoclonal deposits disease (5 patients), membranoproliferative glomerulonephritis
were treated with antibiotics, heparin and vitamins. with cryoglobulinemia (1 patient), AL-amyloidosis (1 patient) and interstitial
CONCLUSION: SARS- CoV-2 infection is a serious condition that can threaten lymphoplasmacytic infiltration with CD20þ lymphocytes associated with minimal
prognosis especially in patients receiving immunosuppressive drugs responsible for a change disease. Follow-up data were obtained in 4 patients: 3 underwent chemotherapy
weaker immune response. Further work on a larger group of patients is necessary to but only one achieved complete remission and 2 progressed to end-stage renal disease.
establish whether this group is more prone to contract the COVID-19 infection and CONCLUSION: Although rare, Waldenström Macroglobulinemia and IgM
have poorer outcomes. gammopathy are responsible for diverse manifestations of renal disease. A prompt
diagnosis is of utmost importance in order to ensure early start of therapy, which
should be directed at the underlying hematologic disorder, to improve renal survival.

MO195 ATYPICAL HEMOLYTIC UREMIC SYNDROME IN LUNG


TRANSPLANTATION: TREATMENT WITH ECULIZUMAB, OUR
EXPERIENCE MO197 KIDNEY FUNCTION AT THE EARLY ON ADMISSION HAS NO
CORRELATED WITH DISEASE SEVERITY AND MORTALITY IN
Raquel Berzal Rico1, Teresa Cavero Escribano1, Pilar Aunon1, Aida Frıas COVID-19 PATIENTS WHO ARE TREATED IN ISOLATION
Gonzalez1, Lucia Aubert1, Justo Sandino Pérez1, Lucıa Cordero Garcıa-Gal
an1, ROOM OF MUHAMMADIYAH HOSPITAL PALANGKARAYA
Marta Rivero Martınez1, Amado Andrés Belmonte1, Manuel Praga1 INDONESIA
1
Hospital Universitario 12 de Octubre, Nephrology
Darryl Virgiawan Tanod1
1
PKU Muhammadiyah Islamic Hospital, Internal Medicine, Palangkaraya, Indonesia
BACKGROUND AND AIMS: Atypical haemolytic uremic syndrome (aHUS) is a
clinical entity characterized by acute kidney injury, thrombocytopenia and
microangiopathic hemolytic anemia. There are several cases of AHUS in non-renal BACKGROUND AND AIMS: Covid-19 easily to infected and spread between person
solid organ transplants described in the literature, included lung transplant. Kidney to person with different mortality rates. Affected by several factors, including the
and patient survival are compromised by this complication because of the lack of an comorbid factors that are different in each patients . One of the comorbid factors
effective treatment. Eculizumab is C5 complement factor specific blocker already currently being discussed is the function of the kidneys which can affect the severity of
administered in another kind of secondary aHUS with encouraging results disease and mortality in people with Covid-19. The purpose of this study was to
METHOD: We analys six lung transplants in a retrospective single-center study determine whether early kidney function in Covid-19 patients who were treated in
between 2018-2020 who developed an aHUS and were treated with eculizumab. hospital isolation rooms Muhammadiyah Palangkaraya has an effect on degrees of
Clinical and analytical data were collected along the follow-up. Principal outcome was severity and mortality.
to explore haematologycal and renal response after treatment with eculizumab. METHOD: This study was a retrospective observational study conducted at a Covid-
RESULTS: We included a total of six patients (83% were female) with a median age of 19 referral hospital. The data were taken from the electronic health records of the
57 years at the time of transplantation. Aetiologies of lung transplantation were hospital from July – December 2020. A 38 male and female patients, with mild and
chronic obstructive pulmonary disease in 2 patients, interstitial lung disease in another severe disease. Kidney function is known by calculating the eGFR value at the time of
2, and cystic fibrosis in the remaining two. Induction and maintenance patients initial admission using serum creatinin through venous blood test then
immunosuppressive therapy were based on tacrolimus, mycophenolate and prednisone calculated using the formula CKD-EPI calculator. Independent Sample T-test
in all cases. Baseline serum creatinine after lung transplantation was 1.1 mg/dl (0.9- statistical was perform to see the correlation between eGFR and the degree of severity
2.4). Two patients developed an aHUS in the immediate post-transplant, one of them and mortality of Covid-19 patients.
died because of surgical complications. Another four patients developed an aHUS 59 RESULTS: In this study, a total of 38 patients consist of 15 (39.47%) men and 23
months (33-95) after transplantation. Previously of thrombotic microangiopathy, three (60.52%) women who suffered from mild Covid-19 were 11 (28.94%) people, and
patients were on treatment with everolimus instead of mycophenolate and two lung severe 27 (71.05%) people. There were 5 patients who died (13.15%) and 33 (86.84%)
transplants have cytomegalovirus reactivation. At the aHUS onset, median serum who were alive. It was found that there was no correlation between the patient’s
creatinine was 4mg/dl (2.4-5-7) and acute dialysis was performed in 50% of patients. baseline eGFR and the patient’s mortality rate (p = 0.98), while the eGFR with the
Median hemoglobin was 7.2g/dl (6.9-7.7), platelet count was 32x1000/mL (17-58), and degree of severity was also not correlated (p = 0.89).
DHL was 1343 U/L (581-1597) at the start of eculizumab despite having treated the CONCLUSION: In this study, there was no correlation between initial kidney function
trigger. After a median of 6 doses of eculizumab, the five surviving patients had in admission Covid-19 patients with the severity of Covid-19 and mortality rates.
haematologycal and renal response. No patients underwent chronic dialysis. Serum Other comorbid factors apart from renal function, early management and optimal
creatinine was 2.2 mg/dl (1.7-2.3), hemoglobin 9.8 g/dl and platelet count 159x1000/mL treatment are thought to affect severity and mortality of these patients regardless of
at the end of follow-up. initial renal function at the time the patient was treated.

i180 | Abstracts
Nephrology Dialysis Transplantation Abstracts
model adjusted for age and Charlson index, presenting an eGFR lower than 60 ml/min/
1.73m2 was an independent predictor for the combined event (HR 6.7 [95% CI 1.7-
26.7], p = 0.007) (Figure 2)

MO197 Figure: KIDNEY FUNCTION (eGFR)


&cenveo_unknown_entity_wingdings_F0E0; Severity and Mortality Covid-19
STUDY RESULT :
Kidney Function early admission and Severity (p=0.89)
Kidney Function early admission and Mortality (p=0.98)

MO198 IMPACT OF KIDNEY FUNCTION ON THE EVOLUTION OF


MONOCLONAL GAMMOPATHIES OF UNCERTAIN
SIGNIFICANCE

Yohana Gil Giraldo1, Patricia Mun ~oz Ramos1, Ana Sanchez1, Alicia Cabrera1,
Borja Quiroga1
1
Hospital Universitario de La Princesa, Nephrology , Madrid, Spain
CONCLUSION: Among patients with MGUS, the presence of eGFR lower than 60 ml/
BACKGROUND AND AIMS: Monoclonal gammopathies of uncertain significance
min/1.73m2 is independently associated with a higher incidence of RRT and/or
(MGUS) are very prevalent, but neoplastic transformation barely reaches 1% per year.
mortality.
Renal involvement in the course of a MGUS is a risk factor for complications. The
objective of our study is to determine the prognosis of MGUS that present renal
deterioration during their evolution.
METHOD: In the present retrospective cohort study, MGUS cases from our center MO199 DENOSUMAB: NOVEL APPROACH TO TREATMENT OF
were included. Baseline epidemiological and comorbidity data were collected OSTEOPOROSIS IN RENAL DISEASE
(including renal function and hematological parameters). At 6 and 12 months, data on
renal function and proteinuria were collected. During the follow-up, fatal events and Rosita Greco1, Agata Mollica1, Francesco Zincone1, Teresa Papalia1
the need for renal replacement therapy (RRT) were recorded as a combined endopoint. 1
Annunziata Hospital, Nephrology Dialysis And Transplantation, Cosenza, Italy
Associated factors to this combined endpoint were evaluated.
RESULTS: One hundred twenty patients (47% women, age 8169 years.) with
BACKGROUND AND AIMS: Denosumab is a fully human monoclonal antibody to
diagnosis of MGUS were included. Of these, 61 (51%) had renal involvement at the
the receptor activator of nuclear factor kappa-B ligand (RANKL), an osteoclast
time of diagnosis and 16 (13%) had an estimated glomerular filtration rate (eGFR) of
differentiating factor. It inhibits osteoclast formation, decrease bone resorption,
less than 60 ml/min/1.73m2 during follow up.
increase bone mineral density (BMD), and reduce the risk of fracture. There is no
Associated factors with presenting eGFR less than 60 ml/min/1.73m2 were
restriction of its use in patients with renal disease, for whom biphosphonates are
hypertension (p=0.001), peripheral vascular disease (p=0.05), age (p=0.05), Charlson
considered controindicated. The aim of our study was to evaluate the effectiveness in
comorbidity index (p<0.001), b2microglobulin (p = 0.002), baseline proteinuria (p
reducing facture risk and safety of Denosumab in patients with Osteoporosis and renal
<0.001) and baseline renal function (p <0.001).
disease.
METHOD: This is a prospective analysis of 17 patients with Osteoporosis (average T-
score below -2.5) admitted to our Nephrology Department for CKD in the last four
years. in Vasculitis, Renal Allograft Recipients. Patients with severe
Hyperparatiroidism were excluded. We estimated creatinine clearance (eGFR) using
Cockcroft-Gault and classified levels of kidney function using the modified National
Kidney Foundation classification of CKD. All patients were adequately supplemented
with calcium and vitamin D before and while taking Denosumab 60 mg every 6
months. The primary endpoint is the change in bone mineral density (BMD) at one
and two years. Secondary endpoints include changes in bone mineral metabolism
parameters (Ca, P, PTHi, 25-OH VitD), incidence of fractures, and renal/allograft
fuction at one and two years.
RESULTS: The mean age was 52.564 years and 8/17 (47%) were females. N.13
patients (76.5%) were renal transplant recipients (RTR) on standard triple
immunosoppression including steroids (prednisone 5 mg/day), CNI and MMF, with
average eGFR 65.7612.5 ml/min. N.2 patients (11.75%) were in hemodialysis. N.2
patients (11.75%) with Anca Vasculitis on steroid therapy and average eGFR 35.667.2
ml/min. All patients enrolled were with a BMD T-score of greater than -4.0 and less
than -2.5. Only 2 patients had a history of fractures confirmed by a radiology report.
Baseline parameters: calcium 9.860.32 mg/dl, phosphate 3.960.8 mg/dl, PTHi
137691.0 ng/L, 25-OH VitD 18.368.9 ng/mL. From baseline at 1 month there were an
increase in PTH and a decrease in calcemia in only 2 transplant recipients (CKD II and
IV), that improved with an increased dose of Vit D. There were no significant
difference in baseline bone mineral metabolism parameters to year 1 and 2 in all other
patients. We found no difference in eGFR and proteinuria from baseline to 1 and 2
years in RTR and ANCA vasculitis. Significant improvement in T-score was observed
at 1 year and 2 years (< -1) in all patients. No one discontinued therapy for adverse
During follow-up (median 41 [20-60] months), 34 patients (28%) presented the events.
combined event (8 required RRT and 28 died). The presence of an eGFR less than 60 CONCLUSION: Denosumab may have advantages in patients with kidney
ml /min/1.73m2 during the first year of follow-up was associated with the combined dysfunction, because not excreted by the kidney and there is no need for dose
event (p = 0.028) (Figure 1). In a multivariate model adjusted for age, sex and baseline adjustment. This prospective study showed a significant improvement in osteoporosis
CKD, the presence of a determination of eGFR lower than 60 ml/min/1.73m2 was an (at Dexa mean T-score  -1), but particular attention should be paid to ensuring that
independent predictor for the combined event (HR 3.9 [95% CI 1.4-11.3], p = 0.009). patients are calcium and Vitamin D replete.
In patients without chronic kidney disease at baseline, 13 (22%) combined events were
reported. The incidence of a determination of eGFR lower than 60 ml/min/1.73m2 was
associated with the combined event during follow-up (p = 0.012). In a multivariate

10.1093/ndt/gfab092 | i181
Abstracts Nephrology Dialysis Transplantation

MO200 COVID-19 PANDEMIC INCREASED ADVANCE CARE The documented reason for SZC use included hyperkalaemia secondary to dialysis
PLANNING DEMAND access failure, acute kidney injury, pharmacotherapy induced hyperkalaemia and pre-
emptive prescribing to allow time to create a new RRT access.
Alessandro Toccafondi1, Giuseppina Simone2, Marco Lombardi2, Pietro Thirty-three (56%) patients had their serum potassium level checked at start and 72hrs
Claudio Dattolo2 after treatment with SZC. The remaining patients had their biochemical profiles
1
Azienda USL Toscana Centro, Clinical Psychology, Firenze, Italy and 2Azienda USL checked more than 72 hours after starting SZC with inconsistent time frames and thus,
Toscana Centro, Division of Nephrology and Dialysis, Firenze 2, Bagno a Ripoli , Italy were excluded from the further analysis.
In haemodialysis patients, the median serum potassium level at start of treatment with
BACKGROUND AND AIMS: Advance care planning (ACP) enables competent SZC was 5.7mmol/L (range 4.6mmol/L – 6.3mmol/L) while in PD patients the median
patients to define goals and preferences for future treatments and care, to discuss these potassium level 6.4mmol/L (range 4.4mmol/L – 6.4mmol/L). The mean decrease in
goals and preferences with relatives, and if appropriate to record these preferences. serum potassium was 0.73mmol/L (range 0.1mmolo/L – 3mmol/L) and 1.7mmol/L
After many years of political and social debates, in December 2017 the first advance (range 0.1 -1.6mmol/L) in HD and PD patients respectively.
directive and care planning legislation was approved in Italy. Nevertheless, citizens’ For patients not on RRT prior to treatment with SZC, and median serum potassium
awareness of these issues is scarce as well as the integration of the advance care level at start of treatment was 6.0mmol/L (range 5.5mmol/L – 6.7mmol/L). In these
planning process into clinical routine. The latest data reported to the Italian Parliament patients, a mean decrease in serum potassium of 1.1mmol/L (range 0.2mmol/L –
by the Ministry of Health indicated that advance directives have been completed by 2.4mmol/L) was observed.
62030 people, approximately 1.1% of Italian adult population. Twenty-three patients (70%) received 10g and ten patients received the 5g dose of SZC.
However, during the last months, the COVID-19 pandemic solicited taking steps Patients who had the 10g doses had a mean reduction in serum potassium of 1.0mmol/
towards promoting an advance care planning culture. Indeed, the need of proposing L (range 0.1mmol/L - 3.0mmol/L) and patients who received 5g doses had a mean
ACP to patients have been recently stressed both by medical associations and national reduction of 0.97mmol/L (range 0.2mmol/L – 1.9mmol/L) over the 72-hour period.
and local institutional documents. There were no reported side effects.
METHOD: Since November 2020, our nephrology unit adopted a protocol approved It was found that SZC was initiated by a range of specialities (see Figure 1). The
by Ethical committee by Physician Order of Florence, aimed to conduct ACP nephrology team accounted for the majority (45%) of prescriptions.
interventions with dialysis patients.
Firstly, all patients were informed about the possibility to taking part in one or more
advance care planning conversations with their nephrologist. Secondly, a semi-
structured guide to the conversation was created in order to support physicians in
conducting the ACP intervention. Finally, patients along with nephrologist and their
relatives, could documented their preferences for future treatments and care.
RESULTS: From November to March only one patient asked to receive an ACP
intervention. However, since COVID-19 spread in Italy last March, the number of
patients who demanded ACP raised up. In the period from April to July, 15 out of 110
hemodialysis patients treated in our center asked for an ACP intervention and filled-in
an advance directive. Specifically, no patients required an immediate discontinuation
of dialysis, nevertheless 80% of them stated that would not like to continue with
dialysis in case he/she was no longer able to self-determine (e.g. permanent loss of
capacity to communicate with others).
All patients except one have appointed a personal representative (usually their
partner). In the eventuality of cardiac arrest, 60% of patients asked for
cardiopulmonary resuscitation. Finally, all patients expressed the wish to spend the last
days of life at home.
CONCLUSION: The COVID-19 pandemic raised up the number of dialysis patients
who required to taking part in a advance care planning intervention. In this sense, the
pandemic can be an opportunity for consolidate advance care planning in Italy as well
as in other countries, where these interventions are not well known by people and not
yet regularly offered in the clinical routine.
Using a semi-structured interview for the ACP interview can help the nephrologist to Notably, the cardiology team initiated only one prescription.
discuss future care and end-of-life topics with their patients. CONCLUSION: Our data from clinical practice indicates that SZC is effective and
well-tolerated treatment in the management of hyperkalaemia. Our results also suggest
that the reduction in potassium level was not vastly different for patients started on the
MO201 ANALYSIS OF USAGE OF SODIUM ZIRCONIUM 5g dose vs the 10g dose but this requires further research with larger study sample
CYCLOSILICATE (SZC) AT HULL UNIVERSITY TEACHING sizes.
HOSPITALS Limitations of the study included small sample size and retrospective nature of the
study.
Aaron Acquaye1, Tobi Babatunde-Ige1, Kristina Medlinskiene1, Stephanie Choo2,
Sunil Bhandari2
1
Hull Royal Infirmary, Pharmacy, Kingston upon Hull, United Kingdom and 2Hull Royal MO202 RITUXIMAB TREATMENT IN NEPHROLOGY
Infirmary, Renal Medicine, Kingston upon Hull, United Kingdom

BACKGROUND AND AIMS: Renin Angiotensin Aldosterone System (RASS) Mouna Malki abidi1,2, Samia Barbouch1,2, Hajji Mariem1, Tasnim Mesbahi2,
inhibitor therapy is key to the management of several chronic long term conditions; Amel Harzallah1, Imen Gorsane1, Hedri Hafedh1, Hayet Kaaroud1, Rym Goucha3,
however, RAAS inhibitors can cause hyperkalaemia and thus limiting its use. Sodium Fethi Ben hmida1,2
1
zirconium cyclosilicate, was approved in the UK as part of the management of charles nicolle hospital, nephrology, dialysis and renal transplantation, tunis, Tunisia, 2
hyperkalaemia in adults. Although the efficacy and safety of SZC has been research Laboratory LR00SP01, nephrology, dialysis and renal transplantation, tunis,
demonstrated in clinical trials, there isn’t an abundance of data of its use in clinical Tunisia and 3mongi slim hospital, nephrology, dialysis and renal transplantation, tunis,
practice. This study investigated the efficacy and safety of SCZ in the short-term Tunisia
management of hyperkalaemia in patients admitted acutely to hospital.
METHOD: This retrospective study analysed prescriptions and medical notes of BACKGROUND AND AIMS: The B cells have a central role in the pathogenesis of
patients who received SCZ treatment between June and December 2020 at Hull several renal pathologies. Rituximab, a monoclonal antibody directed against the CD20
University Teaching Hospitals. Eligible patients (>16years and received SCZ) were receptor expressed on the surface of B cells is an interesting alternative to conventional
identified from pharmacy dispensing data. Data collected included patient treatments of kidney pathologies.
demographics, prescribed medication that could affect serum potassium levels prior to METHOD: We conducted a descriptive retrospective study of the use of rituximab in
starting SZC, indication, dose of SCZ, potassium level at start and 72hrs after treatment nephrology patients.
and if the patient was on renal replacement therapy (RRT). In addition, speciality of RESULTS: We collected 25 patients including 12 women and 13 men. The mean age
the prescriber and reported adverse effects were noted. Data analysis was descriptive. was 33,5 [16-55] years. The rituximab was indicated for an extramembranous
RESULTS: During the study period, SZC was prescribed to 59 patients on 73 different glomerulopathy in 6 patients, a focal segmental glomerulosclerosis in 4 patients, a
occasions. Fifty-two (71%) were male, mean age was 58 years (range 17 – 88 years). minimal change disease in 4 patients, a lupus nephritis in 5 patients, and a
Twenty-two patients (37%) were on RASS inhibitors, six patients on a potassium granulomatosis with polyangiitis in 2 patients. Four kidney transplant patient received
sparing diuretic, and 21 on a beta-blocker before treatment with SZC. rituximab for the treatment of antibody mediated rejection in 3 cases and large cell
Thirteen patients (22%) were on a combination of at least two of these medicines. lymphoma in 1 case.
Nineteen patients (32%) were on haemodialysis and four patients (7%) were on The average time between the diagnosis of the renal disease and starting treatment with
peritoneal dialysis (PD) prior to treatment with SZC. rituximab was of 76 þ/- 46,5 months. And it was of 16 [ 0,7 ; 59,8] months after
transplantation in kidney transplant recipients.

i182 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Side effects have been observed in 11 cases (44%). A favorable response has been patients maintaining the dominant arm extended using the smartphone App Phyphox.
obtained in 10 cases (40 %), within an average of 2,27 months, with at least one relapse The tremor frequency spectrum was extracted by Fourier analysis.
in 4 cases. The follow-up time was 36,33 þ/- 31,67 months. RESULTS: The sleepiness score (ESS) was significantly increased in HD (ESS = 560.4)
CONCLUSION: Rituximab has been shown to be helpful in several cases of kidney compared to the healthy controls (ESS= 460.41) whereas was not significantly
disease. It may reduce the need for maintenance immunosuppression and help in some modified in CKD patients (3.246 0.32). The chronotype was also not significantly
cases that are refractory to other therapies. different among the various groups.
The mean score of the MoCA test was significantly lower in CKD, Tx, and HD groups
(CKD MoCA =24.560.3; Tx MoCA =25.460.6; HD MoCA =24.660.7) than controls
(MoCA score=2860.1). A different pattern of impairment in the cognitive domains of
MO203 ALTERATIONS IN T REGULATORY CELLS IN CHRONIC
MoCA was evidenced in the various groups using the CerebroViz projection and
KIDNEY DISEASE PATIENTS UNDERGOING HEMODIALYSIS
UMAP tools.
MoCA score was inversely correlated with proteinuria (Pearson coefficient=-0.47;
Erasmia Sampani1, Asimina Fylaktou2, Maria Stangou2, Xaralampos Vagiotas3,
p<0.05).
Efstratios Kasimatis2, Vasiliki Nikolaidou4, Dimitra Vasileia Daikidou2,
The higher frequencies of the physiological tremor (11-13 Hz) were significantly more
Nikolaos Antoniadis3, Aikaterini Papagianni2
1
represented in Tx patients compared to controls (p<0.05). Conversely, the lower
Ippokrateio - General Hospital of Thessaloniki, Nephrology, Greece, 2Ippokrateio - frequencies (1-4 Hz) were significantly less represented in the HD group compared to
General Hospital of Thessaloniki, Nephrology, Thessaloniki, Greece, 3Ippokrateio - controls (p<0.05). The peak frequency was inversely correlated with age in all patients
General Hospital of Thessaloniki, Division of Organ Transplantation, Department of (Pearson coefficient= -0.45; p<0.05) and inversely associated with azotemia levels,
Surgery, Thessaloniki, Greece and 4Ippokrateio - General Hospital of Thessaloniki, immu- particularly in HD patients (Pearson coefficient=0.43; p<0.05).
nology department, Thessaloniki, Greece CONCLUSION: Our results suggest that CKD patients present altered cognitive and
motor control patterns, linked in part to the proteinuria level, suggesting a
BACKGROUND AND AIMS: Disturbances in T cell immunity are frequently seen in pathogenetic role of endothelial dysfunction.
patients with end stage renal disease (ESRD), and the effect of long term hemodialysis The characteristic motor, sleepiness and cognitive patterns of HD patients might be
(HD) is still obscure, though extremely important, especially regarding T regulatory due to the arteriovenous fistula or the other peculiarities of these patients.
cells (Tregs, CD4þCD25þFoxP3þ) which seem to have a central role in immune These results might help identify new early markers of brain dysfunction in these
response and tolerance after renal transplantation. In the present study, we assessed the patients, with the possibility of delaying or reversing cognitive decay.
possible effect of HD vintage on Treg population.
METHOD: Cytometric analysis was performed in 66 patients with ESRD on HD, in
order to estimate CD4þ and CD4þCD25þFoxP3þ subtypes. According to HD
MO205 IMPACT OF THE COVID-19 PANDEMIC ON KIDNEY
vintage, patients were classified into two groups, group A: recently commenced on HD,
DISEASES REQUIRING RENAL BIOPSY: A SINGLE-CENTER
and group B: on long term HD (12months and >12months, respectively).
OBSERVATIONAL STUDY
RESULTS: In all 66 patients there was a negative correlation between time on HD and
lymphocyte count, both percentage (r=-0.34 p=0.005) and absolute lymphocyte
Björn Tampe1, Samy Hakroush2
number (r=-0.42 p<0.001) as well as CD4þ cells frequencies (r=-0.25 p=0.042) and 1
total numbers (r=-0.41 p=0.001). University Medical Center Göttingen, Department of Nephrology and Rheumatology,
Twenty eight patients (42%) were included in group A (HD vintage 963 months) and Göttingen, Germany and 2University Medical Center Göttingen, Institute of Pathology,
38 (58%) in group B, (HD vintage 99641 months). Compared to group A, patients in Göttingen, Germany
group B, showed a significant reduction in percentage of Tregs on total lymphocytes
(2.661.3% vs 1.960.9%, respectively, p<0.019) as well as absolute number of Tregs BACKGROUND AND AIMS: The coronavirus disease-2019 (COVID-19) pandemic
(34614 l/L vs. 21611 l/L, respectively, p<0.001). impacted healthcare services for kidney disease patients. Lockdown and social
CONCLUSION: Long term HD may act as an additional factor reducing lymphocyte distancing were mandated worldwide, resulting in closure of medical services. The
count, especially Tregs in ESRD patients. This result, apart from direct affecting diagnosis of various kidney diseases may have been delayed during the COVID-19
immunity of patients, is mostly important for those preparing for renal pandemic because non-urgent tests and visits were postponed due to closure of medical
transplantation, or being on the waiting list. services during the lockdown. Based on previous reports, this afftects especially kidney
diseases requiring renal biopsy and histological analysis for diagnosis. We have
previously reported that during the lockdown period in March and April 2020, an
incidence-shift with a COVID-19 gap of no diagnosed antineutrophil cytoplasm
MO204 CHRONIC KIDNEY DISEASE, SLEEPINESS, MILD COGNITIVE
antibodies (ANCA)-associated vasculitis (AAV) and ANCA glomerulonephritis (GN)
IMPAIRMENT AND FINE MOTOR CONTROL
based on renal biopsy was followed by a postlockdown phase in subsequent months
with a compensatory increased incidence rate. This has been attributed to a decreased
Davide Viggiano1,2, Francesco Lorusso1, Ilenia Gravina1, Maria Serena Russo3,
number of renal biopsies during the lockdown period and a compensatory increased
Maurizio Brigante 4 , Veronica Buonincontri1, Giovambattista Capasso1,2
1
number in the postlockdown phase. We here expanded our analysis to evaluate the
University of Campania “L. Vanvitelli”, Dept. Of Translational Medicine, Naples, Italy, effect of the COVID-19 pandemic on kidney diseases requiring renal biopsy.
2
BIOGEM, Ariano Irpino, Italy and 3Cardarelli Hospital, UOC Nephrology and Dialysis, Furthermore, we aimed to identify effects of the COVID-19 pandemic on clinical
Campobasso, Italy outcomes in patients with kidney diseases, including ANCA GN. With multiple
vaccines currently undergoing human trials to combat this pandemic, there is an
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a systemic condition urgent need for a clear sense for patient populations most susceptible to shutdown of
because it modifies all organs’ function due to an imbalance in plasma volume, medical services. We here report the impact of the COVID-19 pandemic on native
electrolytes, hormones, and proteins. kidney diseases requiring renal biopsy for diagnosis in a retrospective observational
Indeed, at the nervous system level, mild cognitive impairment (MCI), sleep disorders study from a tertiary hospital in Germany.
and depression often accompany CKD. MCI partially explains the low quality of life of METHOD: A total number of 209 renal biopsies performed on native kidneys of
CKD patients, comparable to that of metastatic cancer patients. patients hospitalized at the University Medical Center Göttingen in 2019 and 2020
Mild Cognitive Impairment (MCI) has a high prevalence in this cohort (27-62%). were included. Variables were tested for normal distribution using Shapiro-Wilk test.
Nevertheless, scattered literature data suggest that CKD patients can also have poor Non-normally distributed continuous variables are expressed as median and
motor control, evidenced by a higher risk of falls, postural instability, reduced gait interquartile range (IQR), categorical variables are presented as frequencies and
speed. In this cohort, few data are available regarding the motor circuits called central percentages. Statistical comparisons were not formally powered or prespecified. For
pattern generators, which control physiological tremor. Specifically, uraemic group comparisons, the Mann-Whitney U-test was used to determine differences in
encephalopathy accentuates physiological tremor, which is regulated by central and medians. Non-parametric between-group-comparisons were performed with Pearson’s
peripheral oscillators. Overall, subtle changes in motor control often accompany other Chi-square test. Data analyses were performed with GraphPad Prism (version 8.4.0 for
forms of MCI. MacOS, GraphPad Software, San Diego, California, USA).
Therefore, this study aimed at evaluating the effects of chronic kidney disease on RESULTS: The lockdown period in March and April 2020 primarily affected patients
cognitive and motor functions using up-to-date technologies to record physiological admitted to the normal medical ward with a compensatory increased rate of renal
tremor and innovative data analysis. biopsies in the postlockdown phase. In addition, there was a shift towards more
METHOD: This retrospective case-control study enrolled 313 patients (139 controls, patients admitted with hemoglobinuria during the COVID-19 pandemic. This
79 CKD patients stage III-IV, 35 kidney transplant (Tx), 60 dialysis (HD) patients). phenomenon of an increased number of patients with hemoglobinuria during the
These groups were comparable for age and weight. Creatininemia, azotemia, LDL, COVID-19 pandemic was specifically observed in a subgroup with ANCA GN and
HDL, hemoglobin, and proteinuria were used for correlative analyses. We evaluated hypertensive nephropathy requiring renal biopsy.
the chronotype using the Morningness-Eveningness Questionnaire (MEQ) and the CONCLUSION: To our knowledge, this is the first report of identifying a
degree of sleepiness using the Epworth Sleepiness Scale (ESS). Cognitive impairment subpopulation susceptible to closure of medical services during the COVID-19
was assessed by the Montreal Cognitive Assessment test (MoCA). Cognitive domains pandemic and diagnostic delay of specific kidney diseases. Therefore, the COVID-19
of the MoCA score were projected onto brain regions using CerebroViz library in R pandemic should be regarded as a risk factor especially in patients with diseases other
and a new transformation matrix derived from fMRI literature data. UMAP algorithm than COVID-19 primarily admitted to the normal medical ward.
was used to identify patients’ subgroups. The physiological tremor was recorded on

10.1093/ndt/gfab092 | i183
Abstracts Nephrology Dialysis Transplantation

MO206 MALE SEX IS ASSOCIATED WITH IN-HOSPITAL DEATH IN MO207 END-OF-LIFE CARE IN NEPHROLOGY INPATIENTS - ARE WE
NON-DIALYSIS CKD PATIENTS WITH COVID-19 GETTING IT RIGHT?

Armando Coca1, Carla Burballa2, Francisco Javier Centellas Pérez3, Catarina Mateus1, Ana Rita Martins1, Eunice Cacheira1, Maria Augusta Gaspar1
Isabel Acosta-Ochoa1, Marıa Dolores Arenas2, Juan Pérez Martınez3, 1
Hospital de Santa Cruz / Centro Hospitalar Lisboa Ocidental, Nephrology, Lisbon,
Veronica Fidalgo1, Julio Pascual2, Agustin Ortega Cerrato3 Portugal
1
Hospital Clinico Universitario de Valladolid, Nephrology, Valladolid, Spain, 2Hospital
del Mar, Nephrology, Barcelona, Spain and 3Complejo Hospitalario Universitario de BACKGROUND AND AIMS: Average life expectancy have been continuously
Albacete, Nephrology, Albacete, Spain increasing within the general population and, equally so, within Nephrology patients.
End-of-life (EOL) care is part of non-oncologic palliative care provided by Nephrology.
BACKGROUND AND AIMS: Coronavirus disease (COVID-19), caused by Severe The aim of our study is to evaluate the quality of EOL care provided in Nephrology,
Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) can lead to significant and to determine potential areas of improvement.
organ injury. CKD has been associated with increased mortality in previous epidemics, METHOD: Retrospective single-centre analysis of all nephrology and kidney
and male sex has been correlated with worse outcomes during COVID-19 in the transplant inpatients dying between January 2019 and June 2020. Clinical records were
general population. Our aim was to describe the differential effect of sex as a risk factor reviewed for evidence of recognition of end of life, resuscitation plans, acute
for in-hospital mortality among non-dialysis CKD subjects. interventions in the 48 hours previous to death, comfort care plans and symptoms
METHOD: Multicenter, observational cohort study including 136 adult patients with evaluation.
CKD and 136 age- and sex-matched controls who required admission for COVID-19 RESULTS: A total of 83 patients were included. 19.6% of patients had chronic kidney
in three academic hospitals in Spain. Viral infection was confirmed by real-time RT- disease, 60.2% were in haemodialysis, 14.5% were kidney transplanted patients and
qPCR and/or serologic testing in all cases. Disease severity on admission was classified 3.6% had acute kidney injury. 89.2% of the admissions were for acute events, 5% for
according to the WHO—China Joint Mission Report on COVID-19. The presence of symptom control and 4.8% for diagnosis.
CKD was defined as sustained eGFR <60 and >15 ml/min/1.73m2 within the 6 In 72.3% of admissions, EOL was recognised. Most patients were unable to discuss
months prior to COVID-19 hospitalization. Demographic and clinical data were EOL plans (67.5%), and the family was informed of the prognosis in only 61.4% of the
gathered from medical records. Outcomes were recorded during the following 28 days cases.
after admission. We applied Cox proportional hazards models, adjusted for age, sex, At the time of dead: only 62.7% of patients had a clear resuscitation plan, 44.6% were
hypertension, diabetes and severe or critical disease at presentation. on antibiotics and 26.5% died with nasogastric tube. Within 48h of death: invasive
RESULTS: Due to the matched design, no differences were found regarding age and interventions were still being given in 42.2%, blood samples were taken in 69.9%;
sex between cohorts. CKD patients suffered more frequently from hypertension and imaging was performed in 36.1% and 48.2% had a haemodialysis session. Comfort
diabetes and presented higher 28-day mortality after hospital admission due to measure were provided to 53% and only 60.2% had evidence of symptom evaluation.
COVID-19 compared with age- and sex-matched controls (40.4 vs. 24.3%; P=0.004). In 44.6% stopped invasive measures in the last 48h.
adjusted Cox regression analysis among CKD patients, only age (HR: 1.087, 95% CI: Recognition of EOL was associated with having a clear resuscitation plan (p<0.001),
1.047-1.128) and male sex (HR: 1.883, 95% CI: 1.045-3.391) were independent comfort measures (p<0.001), evidence of symptom evaluation (p=0.004), stopping
predictors of 28-day mortality. Comparatively, among patients without CKD, only age invasive measures (p<0.001), having less imaging (p=0.270) and discussing prognosis
acted as an independent predictor for 28-day mortality (HR: 1.082, 95% CI: 1.033- with the family (p<0.001). Despite recognition of EOL, there was no difference in
1.133). None of the variables included in adjusted regression was able to predict ICU dying with nasogastric tube (p=0.404) or dying on antibiotics (p=0.134).
admission in any of the cohorts. In a multivariable analysis (binary logistic regression), EOL recognition was associated
CONCLUSION: Male sex is associated with increased mortality, but not with ICU with a clear resuscitation plan (Exp(B) 0.088, (CI 95%: 0.018-0.419) p=0.002), with
admission, after hospitalization due to COVID-19 among non-dialysis CKD patients. discussion of prognosis with family ( Exp(B) 0.061 (CI 95%: 0.011-0.337) p=0.001),
That effect was not observed among hospitalized controls without CKD. and with reduced body mass index (Exp(B) 0.870, (CI 95%: 0.763-0.991), p=0.037,); in
a model adjusted to the age.
CONCLUSION: In our cohort, patient for whom EOL was recognized had better EOL
care. In conclusion, there are still areas in which EOL care can be improved. Palliative
care should be an investment area for training within the Nephrology core curriculum
and awareness for EOL care is needed.

MO208 ASSOCIATION OF SERUM BETA-2 MICROGLOBULIN LEVEL


WITH DIFFERENT CARDIAC AND METABOLIC RISK
FACTORS IN CKD PATIENTS

Nazia Arfin Siddiqui1, M Sahadat Hossain1, Babrul Alam1, SR Chaudhury1,


Maa Chowdhury1, Md M Iqbal1,2
1
NIKDU and 2KDRG

BACKGROUND AND AIMS: Serum b M is a middle molecule uremic toxin that


accumulates in serum and deposits at various tissues in chronic kidney disease (CKD),
especially more in dialysis patients. The b^a M is generally considered as a predictor of
cardiovascular morbidity and mortality and this is more investigated in dialysis group.
However its relationship with several cardiac and metabolic risk factors in all stages of
CKD is still under evaluation.
This study was undertaken to evaluate the association of plasma b^a M level in different
stages of chronic kidney disease patients with different cardiac, renal and metabolic
risk factors that can predict future cardiovascular events
METHOD: This cross-sectional study was conducted by selecting consecutive 132
CKD subjects of stages 1-5D including both patients not requiring dialysis and those
on maintenance hemodialysis. Their demographic, clinical and laboratory data were
recorded in a data sheet. Fasting blood samples in dialysis non requiring subjects and
predialysis samples in hemodialysis group (G5D) were taken for testin in laboratory for
CBC, serum b^a M, hCRP, iPTH, lipid profile, creatinine, uric acid and serum albumin
as cardiac, renal and metabolic risk markers. Urine sample was taken from predialysis
patients for chemical test and ACR. The CKD staging were done by MDRD criteria.
Additional 25 no CKD subject was taken as healthy referents.
RESULTS: Primarily Beta-2 microglobulin was higher in CKD patients than in healthy
group (13.53 6 14.74 vs. 1.81 6 0.47, mg/l; p<.001). The levels were gradually rising
with the advancing stages of CKD (G1&2-3.46 6 2.39, G3-3.66 6 1.08, G4-6.51 6
2.20, G5-11.43 6 2.98 and G5D-41.79 6 8.58, mg/l). A Beta-2 microglobulin cut-off of
>7.7 vs. < 7.7 mg/l showed significantly increased Systolic BP (136 622 vs. 123 6 22,
mmHg), diastolic BP (80 6 12 vs. 75 6 8.96, mmHg),( p<0.01); CRP (6.83 6 6.03 vs.
4.39 6 5.35, mg/l)( p<0.007); serum phosphate (4.84 6 1.79 vs. 3.85 6.92,mg/dl)(
p<0.001); uric acid (5.89 6 1.41 vs. 5.01 6 1.57,mg/dl)( p<0.01); TG (1896 103 vs.
155 6 88, mg/dl),( p<0.04); and PTH (239.83 6 186.50 vs. 90.52 6 81.77, pg/ml), (
p<0.001) indicating higher cardio metabolic risks in higher group. Similarly renal
parameters were also more altered in high Beta-2 microalbumin group for serum

i184 | Abstracts
Nephrology Dialysis Transplantation Abstracts
creatinine (6.89 6 3.54 vs. 1.58 6 .81, mg/dl) (p<0.001) and ACR (824 6 917 vs. 320 baseline), one patient died for Sepsis, All patients with CRR or PRR showed a complete
6 753, mg/g),( p<0.001). B-2 microglobulin also positively correlated with systolic cardiological response (normal BNP and SIV). Adverse events during therapy: HZV
blood pressure (r=.295, p<.001), serum creatinine (r=.879, p<.001), serum phosphate nevralgy in 3. The 9 patients in PRR were treated with Lenalidomide. After median 6
(r=.175, p =.047), serum iPTH (r=.403, p<.001) , hCRP ( r=.193, p =.050) , treatment cycles 7/9 (77.7%) patients showed a CRR and CHR. Haemodialysis was
Triglycerides (r=.196, p =.023) and urine ACR in CKD patients. started in 2/9 (22.2%) patients. We decided to discontinue the therapy for adverse
CONCLUSION: Beta-2 microglobulin level was significantly higher in CKD with an events in 3 patients: breast cancer in one, transient troponin I increase and angina in an
increasing pattern towards advancing stages. The higher levels positively correlated other patient, pneumonia events in one. The pneumoniae infectious and anginal
with cardio renal and metabolic risk factors. Hence measuring Beta-2 microglobulin episodes regressed with drug discontinuation. Median follow-up time from diagnosis
regularly can help to take preventive measures early to manage patients at risk. of Renal Amyloidosis was 46 months. Median follow-up from the start of
Lenalidomide was 36 months. One patients died for breast cancer, but in CRR. All the
others patients with CRR (9/13, 69.2%), including the two who suspended
Lenalidomide for its toxic effects have been in remission for 30 months on average.
MO209 NUOVI PROTOCOLLI TERAPEUTICI NEI PAZIENTI NON
CONCLUSION: We conclude the following Lenalidomide therapy is very effective at
IDONEI AL TRAPIANTO CON AMILOIDOSI AL: FOLLOW UP A
increasing the number of CRR. In addition, the two treatment regimens (induction
LUNGO TERMINE
therapy with CyBorD and conditioning with Lenalidomide) kept patients in remission
for more than 30 months on average. Further studies on larger samples are needed to
Rosita Greco1, Cirino Botta2, Massimo Gentile2, Teresa Papalia3
1
validate the data.
AO Annunziata, Nephrology Dialysis And Transplantation Department, cosenza, Italy,
2
Annunziata Hospital, Hematology Department, Cosenza, Italy and 3Annunziata
Hospital, Nephrology Dialysis And Transplantation Department, Cosenza, Italy
MO210 SERUM LEVELS OF PLASMINOGEN ACTIVATOR UROKINASE
RECEPTOR AND CARDIOTROPHIN-LIKE CYTOKINE FACTOR
BACKGROUND AND AIMS: Immunoglobulin light-chain (AL)amyloidosis is a rare
1IN PATIENTS WITH NEPHROTIC SYNDROME
life-threatening disease caused by light chains that are toxic to vital organs such as the
kidneys. New therapeutic strategies with bortezomib and lenalidomide have improved
Natalia Chebotareva1, Anatoliy Vinogradov2, Wenjing Cao1, Alla Gindis3,
the prognosis. The aim of our study was to evaluate the long term efficacy of
Igor Alentov4, Natalia Sergeeva4
therapeutic protocol utilizing bortezomib in induction and in conditioning with 1
lenalidomide for PRR (partial renal response) AL renal Amyloidosis transplant- Sechenov First Moscow State Medical University, Nephrology, Moscow, Russia,
2
ineligible patients. Lomonosov Moscow State University, Therapy, Moscow, Russia, 3Sechenov First
METHOD: This is a prospective analysis of 16 transplant-ineligible patients with Moscow State Medical University, Labor, Moscow, Russia and 4Hertsen Moscow
histological diagnosis of renal amyloidosis admitted to our Nephrology Department Oncology Research Institute, Prediction of Conservative Treatment Efficiency, Moscow,
from 01/2010 to 01/10/2020. All patients have overt nephrotic syndrome at the Russia
diagnosis. Two/thirds of them have renal failure. The diagnosis of amyloid is based on
the kidney biopsy finding, by light microscopic examination, of amorphous BACKGROUND AND AIMS: The pathogenesis of primary focal segmental
extracellular Congo red positive deposits, which display characteristic dichroism and glomerulosclerosis (FSGS) and minimal change disease (MCD) remains unknown to
apple green birefringence under polarised light. Bortezomib-based (BD) regimen is date. Some circulating permeability factors are discussed. This work assessed molecule
used (Bortezomib 1.3mg/m2 subcutaneously; Cyclophosphamide 200mg/m2 and candidates for permeability in serum samples of patients with nephrotic syndrome
Dexamethasone 40mg) for 9 cycles. Hematological and organ response were evaluated (NS).
according to the novel criteria of the International Society of Amyloidosis. The patients METHOD: Forty-one patients with chronic glomerulonephritis (CGN) were included
with partial renal response (PRR: decreased of 24 hour urine protein and serum in our study. Seventeen patients had FSGS, 7 patients had MCD, 5 patients had
creatinine > 50% over baseline) were treated with cycles of Lenalidomide (dose membranoproliferative glomerulonephritis (MPGN), 6 patients had IgA nephropathy,
adjustments for renal function, orally on days 1 trough 21 of each 28-days cycle) in and 6 patients had membranous nephropathy (MN). The laboratory data were
combination with dexamethasone and prophylactic anti-thrombotic treatment. compared with the clinical and histological features of nephritis. Serum levels of uPAR
RESULTS: The mean age was 6367 years and 7/16 (43.7%) were males. By and CLCF-1 were measured by ELISA.
immunohistochemistry the protein composition of the amyloid deposits was FLC k in RESULTS: The serum levels of plasminogen activator urokinase receptor (uPAR) were
6/16 and FLC lambda in 10/16. Periombelical fat aspirate was positive in 5 patients higher in FSGS patients before treatment than in patients with other morphological forms
(31.2%). At onset the mean proteinuria was 13.1 6 3.6 gr/24h with average MDRD of (MCD, IgA nephropathy, MN and MPGN). The levels of uPAR in serum did not correlate
37.2 ml/min (III stage CKD), average pro-BNP 420.1 and SIV 12.5 mm. At onset three with daily proteinuria, serum creatinine/eGFR, arterial hypertension, the number of
patients (18.7%) had confirmed multiple myeloma (Clone of plasma cells proliferation sclerosed glomeruli or tubulointerstitial fibrosis. No correlations were found between the
> 30% in the bone marrow). 3/16 patients died for cardiac arrhythmia at 3 and 4 levels of cardiotrophin-like cytokine factor 1 (CLCF-1) in serum and creatinine levels/
months after CyBorD cycles initiation. Therefore CyBorD regimen was completed in glomerular filtration rate, the percentage of sclerosed glomeruli or the severity of
13/16 patients. After 9 CyBorD cycles: 3/13 patients showed a complete renal response tubulointerstitial fibrosis. There were no significant differences between the histological
(CRR: MDRD > 90 ml/min, proteinuria/24h< 300 mg) and CHR (normal serum FLC variants of nephritis. However, we found correlations between CLCF-1 levels and
ratio); 10/13(76.9%) showed a PRR and PHR (dFLC decrease >50% compared to proteinuria (Rs = 0. 397, p = 0.015) and triglycerides levels (Rs = 0. 475, p = 0.003).

MO210 Figure 1: suPAR and CLCF-1 serum levels in patients with nephrotic syndrome
suPAR -soluble Plasminogen Activator Urokinase Receptor ; CLCF-1 • Cardiotrophin Like Cytokiue Factor I; MCD -minimal change disease; FSGS -focal segmental glomeni
losclerosis; MPGN -membranoproliferative glomenilouephritis; MN - membranous nephropathy.

10.1093/ndt/gfab092 | i185
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: The data indicate an increase in the serum uPAR levels of FSGS
before treatment. CLCF-1 levels in serum do not depend on histological forms of CGN,
kidney function or immunosuppressive treatment, but they correlate with proteinuria
and serum lipids in patients with NS.

MO210 Figure 2: suPAR and CLCF-1 serum levels in patients with nephrotic MO212 LATE EVIDENCE OF SARS-COV-2 INFECTION IN A PATIENT
syndrome depending on therapy WITH ACUTE KIDNEY INJURY (AKI) AND MASSIVE DEEP
suPAR -soluble Plasminogen Activator Urokinase Receptor: CLCF-1 • Cardiotrophin VEIN THROMBOSIS (DVT) STARTING FROM A
Like Cytokine Factor I: MCD -minimal change disease:FSGS - focal segmental HEMODIALYSIS CENTRAL VENOUS CATHETER (CVC)
glomenilosderosis:MPGN -membranopro liferative glomenilonephritis:MN-
membranous nephropathy: I -blood samples were taken before treatment: II -blood Deborah Di Vico1, Katia Cersosimo1, Claudia Fofi1, Alessandra Moioli1, Marcello
samples were taken during the treatment. Andrea Tipaldi2, Stefano Grossi1, Paolo Mene’1
1
Sant’Andrea Hospital, Sapienza University of Rome, Nephrology and Dialysis Unit,
Dept. of Clinical and Molecular Medicine, Roma, Italy and 2Sant’Andrea Hospital,
Sapienza University of Rome, Interventional Radiology Unit, Dept. of Radiology, Roma,
Italy
MO211 FORMALIZATION AND DEVELOPMENT OF A NEPHROLOGY
ELECTRONIC CONSULTATION (ECONSULT) IN COVID-19 BACKGROUND AND AIMS: COVID-19 has heterogeneous clinical manifestations.
PANDEMIC SARS-CoV-2 related AKI and hypercoagulability are negative prognostic factors. The
incidence of thromboembolic events is about 30%, of AKI up to 20%. We report a
Juan Carlos Herrero Berron1, Carolina Lentisco1, Aniana Oliet1, Andrea Suso1, patient with severe AKI who required hemodialysis (HD) and developed a massive
Irene Onate Alonso1, Maria Sanchez1, Rosa Camacho1, Carmen Mon1, DVT developing from the femoral CVC, and belatedly testing positive for SARS-CoV-
Milagros Ortiz1, Olimpia Ortega1 2 in the absence of typical pulmonary involvement.
1 METHOD: A 53-year-old male with a clinical history of hypertension, type II diabetes
SEVERO OCHOA UNIVERSITY HOSPITAL, NEPHROLOGY, LEGANES, Spain
mellitus, in therapy with metformin and ace-inhibitor, was admitted to our E.R. with
BACKGROUND AND AIMS: Due to COVID-19 pandemic we must continue diarrhea, nausea and vomiting for about 2 days. Main signs: ideomotor slowdown, mild
attending in our hospital consultations and, at the same time, avoid transfers and visit hypohydration and reduced urine output (unrelevant sediment). Initial blood tests
that involve risks to our patients. For this reason, we implemented new forms of care. showed severe AKI with hyperkalemic metabolic acidosis and hyponatremia
Mainly electronic consultation (eConsult) using institutional email as way of contact (sCreatinine 18.76 mg/dl, BUN 161 mg/dl, Kþ 7.8 mmol/l, Naþ 128 mmol/L, HCO3-
between Primary Care Providers (PCPs) and nephrologist, trying to decrease in-person 9.8 mmol/l). Mild neutrophilic leukocytosis with lymphopenia was detected, with
visit. slightly increased inflammation indices (CRP 1.05 mg / dl, D-dimer 720 ng / ml). CT
OBJECTIVE: To analyze the results of the creation in June 2020 of a Nephrology scan: absence of typical SARS-CoV-2 signs, normal kidneys, no dilation of urinary
electronic consultation in our hospital. tract. SARS-CoV-2 rapid antigen test and the first molecular swab test were negative.
METHOD: Retrospective observational study of eConsults made to our department, After femoral CVC insertion, HD was needed for a few sessions. Broad range antibiotic
which serves a population of 200.000 people, with total of 9 primary care centers. The therapy was also set.
study period was June 10, 2020 to December 31, 2020. We have studied the number of On Day 3: a second SARS-CoV-2 PCR swab test resulted negative. He never
eConsults, response time, type of consult made, problem resolution and subsequent manifested fever or dyspnea.
follow up. On Day 6, despite an improvement of renal function (sCr 2.7 mg/dl), the patient,
RESULTS: Of 141 workdays, in 61 days (43%) there was eConsult, total 80 eConsults, although he walked, presented right leg pain with signs of DVT. Ultrasound and angio-
mean 1.3 and median 1 daily (range 1 to 3). All primary care centers used this CT scan documented peri-catheter DVT extended to the common femoral and
communication way, as well as 50 PCPs. Median response time for eConsult was 1 day external iliac vein and superficial femoral vein involvement, without pulmonary
(range 1-4). 55% patient was male, mean age 70.8 years (SD 13.9) (range 16-95 years). embolism. I.v. therapy with sodium heparin was therefore started with quite a difficulty
64% it was his first assessment for Nephrology. The most frequent causes of eConsult: in reaching the expected range.
increase of creatinine (41.3%), uncontrolled blood pressure (12.5%), sodium and On day 8, massive flittene appeared, the CVC was removed and a caval filter was
potassium disturbances (11.3%), treatment adjustment (11.3%) and changes in placed; marked neutrophilic leucocytosis and increased inflammatory indices (CRP
previous appointment (8.8%). After assessment eConsult, to 55% of patients was 11.50 mg/dl) was documented. Nevertheless, thrombosis has progressed to the entire
treatment adjustment, 22.5% were converted to an in-person visit, 11% they didnt need venous axis and the inferior cava. Through a tibial vein introducer local i.v. alteplase
any action but only 1 patient was referred to the emergency room. 44% patient is was also started. Just after, copious bleeding from the site of the removed CVC
subsequent follow up by PCPs, 39% by nephrologist, 15% joint assessment PCP and followed by haemorrhagic shock occurred and the patient was transferred to the ICU
nephrologist and 2% by other specialists. Only 2 patients (2.5%) made second (D-dimer 219800 ng/ml). The same day a third swab for SARS-CoV-2 resulted positive
eConsult. while a further CT-scan did not show signs of virus-like interstitial pneumonia. On the
CONCLUSION: The eConsult is an important help to PCPs to solve doubts quickly, following day (day 9) the patient underwent thrombus aspiration (AspirexV R S device)

avoid unnecessary the travels to hospital the patients, treatment adjustment above all in and fasciotomy of the right leg for a compartment syndrome.
control of hypertension an ionic disturbance, and guide in handling of chronic kidney RESULTS: Despite the continuation of heparin, PTT ratio was never >1.5, with an
disease. The diffusion and empowerment of this type of consultation in a next future extension of DVT and also involvement of the contralateral iliac vein, as well as a
may decrease, partly, the usual saturation of face-to-face visit and optimize the patient worsening of the clinical-laboratory picture and patient’s death on day 14. Serum
population being seen by nephrologist. complement, autoantibodies (ANA, ANCA, ENA, ANTI-dsDNA, anti-cardiolipin,
AMA, anti-B-glycoprotein) and factor V Leiden test were normal. All blood cultures
were found to be sterile.

i186 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Our case confirms the heterogenicity of COVID-19 manifestations, MO214 EVALUATION OF THE EFFECT OF A POTASSIUM BINDER ON
often without pulmonary involvement. According to our experience from the onset of ARRHYTHMIA-RELATED CARDIOVASCULAR OUTCOMES IN
the pandemic, SARS-CoV-2 can also be found later in patients with already advanced PATIENTS ON CHRONIC HAEMODIALYSIS WITH
organ damage. In this case, in the absence of other possible factors, AKI and intestinal RECURRENT HYPERKALAEMIA: DESIGN AND RATIONALE
involvement may have been early signs of COVID-19, with a virus initially not FOR THE SODIUM ZIRCONIUM CYCLOSILICATE DIALIZE-
detectable in the nasopharyngeal mucosa. Furthermore, the increased thromboembolic OUTCOMES STUDY
risk of COVID-19 should not be underestimated in the presence of risk factors as
external devices, also given the difficult management of anticoagulation target. Steven Fishbane1, Michel Jadoul2, Laura M. Dember3, Csaba Kovesdy4,
Anticoagulant prophylaxis in cases with doubtful symptomatology and CVC must be Ian Sabir5, Ayman Al-Shurbaji6, Fredrik Thoren6, Brian G. Katona7,
considered even in non-bedridden patients, due to the current risk of SARS-CoV-2 Nicolas Guzman7, John Xu7, Charles A. Herzog8
1
infection. Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York, United States
of America, 2Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels,
Belgium, 3Perelman School of Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania, United States of America, 4University of Tennessee Health Science Center,
Memphis, Tennessee, United States of America, 5AstraZeneca, Cambridge, United
Kingdom, 6AstraZeneca, Gothenburg, Sweden, 7AstraZeneca, Gaithersburg, Maryland,
United States of America and 8Hennepin Healthcare/University of Minnesota,
Minneapolis, Minnesota, United States of America

BACKGROUND AND AIMS: Patients with end-stage renal disease (ESRD) on


chronic haemodialysis are at an elevated risk of arrhythmias that can increase the risk
of sudden cardiac death (SCD) and stroke, along with the need for hospitalisation and
interventions. These arrhythmias may be exacerbated by pre-dialysis hyperkalaemia
and rapid serum potassium (sKþ) shifts that occur during and after haemodialysis
sessions. The DIALIZE study (NCT03303521) demonstrated that sodium zirconium
cyclosilicate (SZC) was an effective and well-tolerated treatment for pre-dialysis
hyperkalaemia, when administered once-daily on non-dialysis days for 8 weeks in
patients with ESRD undergoing chronic haemodialysis. The DIALIZE-Outcomes study
(EudraCT 2020-005561-14) will evaluate the effect of SZC treatment on arrhythmia-
related cardiovascular (CV) outcomes in patients with ESRD on chronic haemodialysis
with recurrent hyperkalaemia.
METHOD: The DIALIZE-Outcomes study is an international, multicentre,
randomised, double-blind, parallel-group, placebo-controlled study, to be conducted at
300 study sites across 20 countries. Adults (18 years of age) with ESRD on
haemodialysis three times weekly and with recurrent pre-dialysis sKþ 5.5 mmol/L
after the long interdialytic interval (LIDI) will be eligible for enrolment. Approximately
MO213 GOOD PRACTICES FOR DIALYSIS EDUCATION, TREATMENT 2300 patients will be randomised 1:1 to SZC or placebo (Figure), starting at 5 g orally
AND EHEALTH: A SCOPING REVIEW once daily on non-dialysis days (4 days/week) and uptitrated weekly in 5 g increments
(maximum 15 g) to achieve pre-dialysis sKþ 4.0–5.0 mmol/L after the LIDI. Dose
Anita Van Eck van der Sluijs1, Sanne Vonk1, Anna Bonenkamp2, Brigit Van adjustments after the uptitration phase will be guided by sKþ monitoring, as per
Jaarsveld2, Alferso C. Abrahams1 clinical practice. The primary objective is to evaluate the efficacy of SZC versus placebo
1 in reducing the incidence of the primary composite endpoint of time to first occurrence
UMC Utrecht, Utrecht, The Netherlands and 2Amsterdam UMC, locatie AMC,
of SCD, stroke or hospitalisation/intervention/emergency department visit due to
Amsterdam, The Netherlands
arrhythmias (atrial fibrillation, bradycardia, asystole, ventricular tachyarrhythmia).
Secondary endpoints include the efficacy of SZC versus placebo in maintaining
BACKGROUND AND AIMS: Recommendations regarding dialysis education and normokalaemia (sKþ 4.0–5.5 mmol/L after the LIDI) and preventing severe
treatment are provided in various (inter)national guidelines, which should ensure that hyperkalaemia (sKþ 6.5 mmol/L after the LIDI) at 1 year (assessed through
these are applied uniformly in nephrology and dialysis centers. However, there is much measurement of sKþ at the 12-month study visit), and time to occurrence of CV
practice variation which could be explained by good practices: practices developed by outcomes. Safety and tolerability of SZC versus placebo will also be evaluated. The
local health care professionals, which are not evidence-based. Because an overview of study is event-driven, with patients remaining on study treatment until a pre-specified
good practices is lacking, we performed a scoping review to identify and summarize the number of primary endpoint events (770) has occurred. The anticipated average
available good practices for dialysis education, treatment and eHealth. treatment period is 25 months.
METHOD: Embase, Pubmed, and the Cochrane Library databases were searched for
relevant articles using all synonyms for the words ‘kidney failure’, ‘dialysis’ and ‘good
practice’. Relevant articles were structured according to the categories dialysis
education, dialysis treatment or eHealth, and assessed for content and results.
RESULTS: Nineteen articles (12 for dialysis education, 3 for dialysis treatment, 4 for
eHealth) are identified. The good practices for education endorse the importance of
providing complete and unbiased predialysis education, assisting PD patients in
adequately performing PD, educating HD patients on self-management, and talking
with dialysis patients about their prognosis. The good practices for dialysis treatment
focus mainly on dialysis access devices and general quality improvement of dialysis
care. Finally, eHealth is useful for HD and PD and affects both quality of care and
health-related quality of life.
CONCLUSION: The results of our scoping review can inspire nephrological health
care professionals to change their practices and these good practices could be used in
addition to guidelines. It is important to increase the attention for local good practices,
because they can truly support health care professionals and can improve outcomes
and quality of life for patients, even if they are not evidence-based. CONCLUSION: The DIALIZE-Outcomes study is the first evaluation of a Kþ binder
in improving CV outcomes in patients with ESRD on chronic haemodialysis and with
recurrent hyperkalaemia. The study findings will provide valuable information that
may help to further our understanding of the relationship between hyperkalaemia and
CV morbidity and mortality in patients on chronic haemodialysis, and to optimise
treatment regimens in this high CV and SCD risk population.

10.1093/ndt/gfab092 | i187
Abstracts Nephrology Dialysis Transplantation

MO215 DEPRESSIVE DISORDER IN LUPIC PATIENTS WITH LUPUS ALPS values compared to non-CKD patients. At variance, in patients with MCI, CKD
NEPHRITIS: DATA FROM A POPULATION OF 67 PATIENTS resulted in a significant increase of water diffusion in the glymphatic system compared
WITH BIOPSY PROVEN LUPUS NEPHRITIS to the controls.
CONCLUSION: In this preliminary study, MCI and CKD exerted opposite effects on
Anna Mirela Stroie1, Balanescu Paul2, Mircea Penescu1, the diffusion of water within the glymphatic system: MCI was accompanied by a
Beldea Geanina Eugenia3 reduction of water diffusion whereas CKD by an increased diffusion in the glymphatic
1
Nephrology Hospital Dr. Carol Davila, Nefrologie II, Bucures, ti, Romania, 2Carol Davila spaces.
University of Medicine and Pharmacy, Statistica medicala, Bucures, ti, Romania and It is possible that small modification of water balance in CKD may be responsible for
3
Nephrology Hospital Dr. Carol Davila, Bucures, ti, Romania the increased diffusion of water in glymphatics in CKD. Further studies are needed to
verify whether this unexpected phenomenon may modify cognitive function with a
BACKGROUND AND AIMS: Systemic lupus erythematosus is a multi-organ, multi- mechanism rather different from Alzheimer’s disease.
systemic autoimmune disease with significant burden on generally young patients.
Renal involvement is relatively frequent, recent studies cite a prevalence of 15-60% of
patients, and 25% develop end-stage renal disease after 10 years of disease onset. We MO217 ASSOCIATION BETWEEN SERUM VITAMIN-D LEVEL WITH
studied the incidence of depressive disorders in a population of 67 patients with biopsy LUNG INVOLVEMENT AND OUTCOME IN COVID-19
proven lupus nephritis. Data about depression in patients with renal involvement of PNEUMONIA
lupus is still scarce. We identified variables associated with the development of
depressive disorders in lupus patients. Alireza Abrishami1, Nooshin Dalili2
METHOD: We concluded a single center transversal study to assess the incidence of 1
depressive disorder in patients with biopsy proven lupus nephritis. We used the self- Shahid Beheshti University of Medical Sciences, Department of Radiology, Shahid
report Beck Depression/ Anxiety Inventory (BDI/ BAI), 1961/ 1990, translated in Labbafinejad Hospital, Tehran, Iran and 2Shahid Beheshti University of Medical
Romanian and validated in the Romanian population to diagnose depression. We also Sciences, Chronic Kidney Disease Research Center, Shahid Labbafinejad Medical Center,
wanted to identify risk factors associated with depression in such patients. We used Tehran, Iran
EpiInfo for the statistical analysis and data was extracted from medical records.
RESULTS: We included in the study patients diagnosed with systemic lupus BACKGROUND AND AIMS: Vitamin D deficiency has been reported as a key factor
erythematosus, and had renal biopsy between January 2008 – December 2018. Patients in the development of infectious diseases such as respiratory tract infections and
were followe-up until May 2020. Beck Depression/Anxiety Inventory was administered inflammatory processes like acute respiratory distress syndrome. However, the impact
a single time during the follow-up visit between (March 2019 – May 2020). In our of vitamin D on the severity and outcome of COVID-19 is still not fully known.
study group, 58 patients were female (86.5%). Median age at diagnosis of lupus disease Herein, we aimed to evaluate the prognostic role of serum vitamin D concentration on
was 29 years (min 10 years, max 62 years). Median duration of the disease until the the extent of lung involvement and final outcome in patients with COVID-19.
self-assessment inventory was 10 years (min 1.5 years, max 30 years). Median duration METHOD: Seventy-three subjects with confirmed diagnosis of COVID-19 were
of corticosteroid treatment was 10.1 years (min 1.58 years, max 29). 1 patient had class investigated in this study. The patients had been admitted to our academic hospital
I, 2 had class II, 12 had class III, 32 had class IV, 12 had class V, 1 had class VI, 1 had from February 28, 2020 to April 19, 2020. Demographic and clinical data, serum
classes IIIþV, 1 had classes IVþV of lupus nephritis (ISN classification of lupus 25(OH)D levels, and findings of initial chest computed tomography were recorded.
nephritis). 13 patients had normal scores of the Beck Inventory (0-9 points), 7 had Linear and binary logistic regression, cox regression and ROC curve tests were used for
mild depression (10 - 15 points), 37 had moderate depression (16- 23 points), 10 had statistical analysis.
severe depression (24-63 points). We identified female gender (p=0.009), duration of RESULTS: The mean age of patients was 55.18 Å} 14.98 years old; 46.4% were male.
corticosteroid therapy (p=0.036), duration of the lupic disease (p=0.036) to be Mean serum 25(OH)D concentration was significantly lower in the deceased (13.83 Å}
independently associated with depression development. Other variables, such as 12.53 ng/ mL compared with discharged patients (38.41 Å} 18.51 ng/mL) (P < 0.001).
creatinine levels at the moment of the assessment, duration of maintenance therapy Higher levels of 25(OH)D were associated with significantly less extent of total lung
with mycofenolate mofetil or azathioprine, proteinuria, inflammatory markers were involvement (b =  0.10, P = 0.004). In addition, vitamin D deficiency [25(OH) D <
not associated significantly with depression. 25 ng/mL] was associated with a significant increase in the risk of mortality (hazard
CONCLUSION: We identified clinical variables associated with depression ratio = 4.15, P = 0.04).
development in patients with lupus nephritis. The study brings data useful for the CONCLUSION: This study suggests that serum vitamin D status might provide useful
clinician, helping doctors focus on the variables that predict depression in lupus information regarding the clinical course, extent of lung involvement and outcome of
patients and making screening for depressive disorders more focused on the patients patients with COVID-19. However, further studies with larger sample size are needed
with risk factors. to confirm these findings.

MO216 PRELIMINARY STUDY OF THE GLYMPHATIC SYSTEM IN


CKD

Veronica Buonincontri1, Davide Viggiano1, Giovambattista Capasso2


1
Universita della Campania “Luigi Vanvitelli” and 2Universit
a della Campania “Luigi
Vanvitelli” and BIOGEM

BACKGROUND AND AIMS: The glymphatic system is a network of extracellular


spaces between neurons, glial cells, and capillaries that promotes the elimination of
soluble molecules from the brain. Its dysfunction is probably relevant for
neurodegenerative diseases such as Alzheimer’s disease (AD). It is widely accepted that
cognitive impairment accompanies chronic kidney disease (CKD). CKD is also a risk
factor for dementia. However, the role of the glymphatic system in this process is
unknown. A recent method to study the glymphatic system in human subjects has been
proposed based on Diffusion Tensor Imaging (DTI) data and water diffusion
calculation along with perivascular spaces. This approach is based on calculating a
diffusion index named ALPS and showed that the glymphatic flow is reduced in MCI.
METHOD: To analyze the role of glymphatic system in CKD patients, we took
advantage of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). ADNI is a
longitudinal multicenter study helping researchers to monitor Alzheimer’s disease and
Mild Cognitive Impairment (MCI) progression. This database has a cohort of control
patients and MCI patients, among which several patients with CKD stage II-III were
identifiable from the creatinine values. Patients with Alzheimer’s disease were excluded
for this study. Among the control and MCI patients, we identified 12 CKD patients and
pair-matched 12 non-CKD patients comparable for age, gender, and MoCA score. MO217 Figure 1: Log minus log of hazard function. The evaluation of the
Magnetic resonance data with DTI sequences were retrieved for all patients, and the assumption of proportionality of hazards in cox survival models. The parallel log
glymphatic system was characterized by the ALPS index. Tensor values were calculated minus log functions in 25(OH)D deficiency groups and Schoenfeld residues analysis
using the FSL software; the diffusion values were calculated on tensor images using the (chi-square = 8.02, DF = 4, P = 0.10) indicates that comparing hazard of death in two
ImageJ software. Differences in ALPS between CKD and non-CKD patients with and groups does not depend on time and the proportionality assumption is hold in cox
without MCI were tested. regression
RESULTS: Analysis of DTI data confirmed that control patients without CKD had
lower ALPS values when MCI was present compared to the non-MCI patients,
suggesting a reduction of water diffusion in the glymphatic system. However, the
presence of CKD had a different effect: in the absence of MCI, CKD did not modify

i188 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO218 ALTERNATING EPISODES OF TRUE HYPERKALEMIA AND
PSEUDOHYPERKALEMIA IN ADULT SICKLE CELL DISEASE -
A NEPHROLOGIST’S DILEMA

Macaulay Onuigbo1, Sarah Sherman1, Heng Tan1


1
The Robert Larner, M.D. College of Medicine at The University of Vermont, MEDICINE,
Burlington, United States of America
MO217 Figure 2: a–c A 55-year-old man presented with 5-day history of fever and
dry cough without any comorbidity [25(OH)D level was 40 ng/mL] with initial lung BACKGROUND AND AIMS: To illustrate the phenomenon of alternating true
computed tomography (CT) involvement score of eight/24. On admission, CT images hyperkalemia and pseudohyperkalemia in adult sickle cell disease.
showed subtle patchy groundglass opacities (GGO) (long arrows) predominantly in METHOD: Case Report
upper zones and reticular pattern (wide arrows) in lower zones. The patient discharged RESULTS: Sickle cell disease (SCD) predisposes the patient to recurrent episodes of
after 6 days. d–f A 54-year-old man presented with 4-day history of fever, dry cough acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult
and dyspnea and no other comorbidity [25(OH)D level was 7 ng/mL]. Lung CT score patients. The presence of sickled erythrocytes in the renal medullary vessels is the
involvement score of ninety/24. On admission, CT images showed diffuse GGO (long hallmark of the disease and renal manifestations include renal ischemia, microinfarcts,
arrows) with slight consolidation change (thick head arrow) in right mid zone. The renal papillary necrosis and renal tubular abnormalities with variable clinical
patient died after 19 days. presentations. Furthermore, acute hemolytic crisis can be complicated by sepsis.
Hemolysis, specifically, intravascular hemolysis, can produce hyperkalemia.
Additionally, reduced glomerular filtration rate from SCN predisposes to
hyperkalemia. Pseudo-hyperkalemia was first reported by Hartmann and Mellinkoff in
1955 as a marked elevation of serum potassium levels in the absence of clinical
evidence of electrolyte imbalance. In pseudohyperkalmia, simultaneously estimated
serum potassium exceeds plasma potassium by >0.4 mmol/L. This is often associated
with moderate to severe thrombocytosis or leukocytosis. Clearly, hyperkalemia is a
potentially lethal condition. At the same time, the institution of inappropriate
treatment of pseudo-hyperkalemia leading to hypokalemia is also equally potentially
lethal. We describe a 40-yo African American male patient with sickle cell anemia who
exhibited alternating episodes of hyperkalemia and pseudo-hyperkalemia, during
consecutive hospital admissions. Pseudohyperkalemia was associated with severe
thrombocytosis complicating sepsis. EKG was normal despite measured serum
potassium of 6.7 mmol/L (Figure).

MO217 Figure 3: ROC curve analysis results to achieve predictive values of


25(OH)D in classifying patients into dead or discharge
CONCLUSION: We believe that this is the first report of adult SCD demonstrating
alternating cycles of true hyperkalemia and pseudo-hyperkalemia at different times.
We must draw attention to the new availability of the new potassium binders,
Patiromer and sodium zirconium cyclosilicate. We would advocate for caution in the
use of these potent potassium binders and to always give consideration to the presence
of pseudo-hyperkalemia under appropriate clinical scenarios. We posit that providers
managing adult patients with sickle cell disease must be aware of such a phenomenon
to avoid the dangers of overtreatment of episodes of pseudo-hyperkalemia in such
patients.

MO219 EMPHYSEMATOUS PYELONEPHRITIS IN BANGLADESH

Muhammad Abdur Rahim1, Tabassum Samad1


1
BIRDEM General Hospital, Nephrology, Dhaka, Bangladesh

BACKGROUND AND AIMS: Emphysematous pyelonephritis (EPN) is an


uncommon, acute and severe form of necrotizing infection of the renal parenchyma,
collecting system and/or perinephric tissues and is characterized by accumulation of
gas within these structures. Patients may present with fever, loin pain, vomiting and
shock. Risk factors for EPN include diabetes mellitus (DM), renal stone, obstructive
uropathy and immunosuppression. In this report, we describe the clinical, laboratory
and imaging characteristics of patients with EPN in Bangladesh.
METHOD: This systematic review included all previously published English literature
containing information regarding EPN in/or from Bangladesh. Literature search was
conducted via “PubMed” using the key words “Bangladesh” and “emphysematous
pyelonephritis”. We also searched through Bangladesh Journals Online (BanglaJOL)
MO217 Figure 4: Cumulative hazard function of death in patients with and without
for articles published in local journals. The search engine “Google” was also used to
25(OH)D deficiency. The “death” status considered as the event and hospitalization
identify articles. All literature searches were conducted up to 10th January 2021.
days considered as the event time in cox regression
Unpublished but well-documented EPN cases (28 cases) were added. Cases mentioned

10.1093/ndt/gfab092 | i189
Abstracts Nephrology Dialysis Transplantation

elsewhere with inadequate information and possible repetition were excluded. MO221 ONLY A SIMPLE CASE OF AKI IN AN ONCOLOGIC PATIENT?
RESULTS: Seventeen papers were identified from published literature including 10
case reports, two original research articles, one image and four conference abstracts Sofia Giuliana1, Roberta Ranieri1, Carolina Ruosi1, Angela Cervesato1, Luigi
and one research paper was identified from other source. From them, two case reports Pio Guerrera2, Teresa Troiani2, Alessandra Perna1, Giovambattista Capasso1,
were excluded because EPN occurred in non-Bangladeshi nationals; one image and Mariadelina Simeoni1
four conference abstracts were also excluded because of inadequate information for 1
University of Campania “L. Vanvitelli”, Department of Translational Medical Sciences,
cases. Finally, a total of 10 papers (total 92 cases) were eligible for analysis, to which 28 Division of Nephrology, Naples, Italy and 2University of Campania “L. Vanvitelli”,
unpublished but well documented cases were added. Among the total 120 cases, Department of Precision Medicine, Medical Oncology Unit, Naples, Italy
females were 92 (76.7%). Age of the patients ranged between 20 and 77 years. DM was
the commonest risk factor (118, 98.3%); 16 (13.3%) patients had chronic kidney disease
BACKGROUND: Nivolumab is a drug belonging to the class of Immune Checkpoint
and nine (7.5%) had renal stones. Patients presented with fever (112, 93.3%), loin pain/
Inhibitors (ICPI), the use of which has improved the prognosis for patients with
renal angle tenderness (96, 80%), dysuria (76, 63.3%), altered sensorium (21, 17.5%),
various advanced malignancies. These agents are associated with several "immune-
anorexia (93, 77.5%), vomiting (101, 84.2%), dehydration (77, 64.2%) and shock (18,
mediated" adverse effects, although the literature on Nivolumab renal toxicity is poor
15%). Patients had neutrophil leukocytosis (total white cell counts 11,700–54,200/cmm
and anecdotal. A rare immune-mediated renal adverse event is acute interstitial
of blood) and 22 (18.3%) patients had thrombocytopaenia. All patients had high
nephritis (AIN) that often imposes Nivolumab suspension.
erythrocyte sedimentation rate (36–117 mm/1st h) and C-reactive protein (24–199 mg/
CASE REPORT: We present the case of a 75-year-old woman with stage IV melanoma
L). Overall glycaemic status was poor [random blood glucose during admission was
(inguinal and external iliac lymph node metastases without localization of the primitive
6.8–35.5 mmol/L and glycated haemoglobin (HbA1c) was 6.2–16.1%]. Fifty six (46.7%)
lesion). At diagnosis, renal function was normal by age (Creatinine 0.89 mg/dl; CKD
patients were complicated by acute kidney injury (AKI) and 32 (26.7%) patients had
EPI eGFR 71 ml/min/1.73 m2). After lymphadenectomy, an adjuvant treatment with
hyponatraemia. Diagnosis of EPN was confirmed by computed tomography scan. One
Nivolumab was initiated.
patient had EPN in ectopic right kidney, two patients had EPN along with
At 4-month follow-up, the patient was hospitalized for AKI (creatinine 2.6 mg/dl;
emphysematous cystitis and two patients were complicated with psoas abscess.
eGFR 17,3 ml/min/1.73 m2). Although, renal function decline was not accompanied by
According to Huang and Tseng classification, five (4.2%) patients had class 4 EPN, 35
signs of systemic immunoactivation, Nivolumab was suspended. In the following
(29.2%) patients had class 3, 66 (55%) patients had class 2 and 14 (11.7%) patients had
weeks, only a partial renal function recovery was observed, still limiting
class 1 EPN. Escherichia coli was the most common (67, 55.8%) organism identified on
immunotherapy reintroduction. Thus, the patient was referred to our Onconephrology
urine culture and 17 (14.2%) patients were complicated by bacteraemia. All patients
Outpatient Unit for a multidisciplinary approach. We performed a urinalysis with
were treated with resuscitative measures, intravenous antibiotics and other supportive
microscopy study of the sediment and observed rare dysmorphic red blood cells and
measures. Forty one (34.2%) patients required surgery/interventions [nephrectomy in
leukocytes. To exclude a glomerulopathy, a comprehensive screening for autoimmune
19 (15.8%), percutaneous drainage in two (1.7%), open drainage in 20 (16.7%)].
diseases and 24 hours proteinuria were also measured and found not significant (Table
Duration of hospital stay was 6–37 days. Nine (7.5%) patients died in hospital.
1). Renal ultrasound did not show any relevant alteration.
CONCLUSION: EPN occurred predominantly among female diabetic patients.
Clinical presentation included fever, loin pain, dysuria, vomiting, altered sensorium
and shock. Class 2 EPN was common. Almost half of all EPN cases developed AKI.
One-third EPN cases required surgical interventions including nephrectomy. In-
hospital mortality was 7.5%.

MO220 MID TERM E GFR AND ITS IMPACT ON ADVERSE


PREGNANCY OUTCOMES- IMPORTANCE OF GESTATIONAL
HYPERFILTERATION

Anupma Kaul1, Amita Pandey2


1
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Nephrology, Lucknow, India
and 2King George’s Medical University, Obstretrics and Gynecology, Lucknow, India

BACKGROUND AND AIMS: The hemodynamic adaptation plays a crucial role in


maintaining gestation, the clinical significance of midterm renal hyperfiltration on
pregnancy outcomes is unknown. The present study was retrospective study among all
pregnant ladies whose midterm eGFR wascompared with their baseline and its change
from baseline was considered as a surrogatemarker for Mid term hyperfilteration
among women without underlying evidence of CKD tofurther evaluate its value as a
prognostic factor of the eGFR during gestation
METHOD: All pregnant females aged 18-50 years whose pre gestational baseline
serum creatinine was available and had a singleton pregnancy were included in the
study .The study was conducted from January 2015 till December 2018 in a tertiary
care Institute in Northern India . MRH was represented by the highest eGFR, which
was calculated using the Chronic Kidney Disease Epidemiology Collaboration method.
An adverse pregnancy event was defined by the composition of preterm birth
(gestational age <37 weeks), low birth weight (<2.5 kg), and preeclampsia.
RESULTS: Total of 1045 pregnancies were evaluated to study. Among them, 15 , 305,
680, and 45 mothers had midterm eGFR levels of 60–90, 90–120, 120–150, and 150
ml/min per 1.73 m2, respectively. The adjusted odds ratio and associated 95%
confidence interval (95% CI) of an adverse pregnancy outcome for eGFR levels below
and above the reference level of 120–150 ml/min per 1.73 m2 were 1.97 (95% CI, 1.34
to 2.89; P<0.001) for 150 ml/min per 1.73 m2; 1.57 (95% CI, 1.23 to 2.00; P<0.001)
for 90–120 ml/min per 1.73 m2; and 4.93 (95% CI, 1.97 to 12.31; P<0.001) for 60–90
ml/min per 1.73 m2. Moreover, among mothers without baseline CKD, women with
adverse pregnancy outcomes had less prominent MRH than those without (P<0.001)
CONCLUSION: There was an unique relationship between the midterm eGFR and MO221 Table 1 Baseline Laboratory tests at first nephrologist referral
adverse pregnancy outcomes, and the optimal range of midterm eGFR levels was 120–
150 ml/min per 1.73 m2. In those females without evident functional renal impairment, Based on our original suspicion of AIN, although in absence of an history of fever, rush
the absence of prominent MRH could be a significant risk factor for poor pregnancy or eosinophilia, we introduced Prednisone 25 mg/day. In the following weeks, blood
outcomes and urine tests showed a significant improvement in renal function (serum creatinine
1.06 mg/dL, eGFR CKD-EPI 51 mL/min/1.73m2) and the absence of red blood cells,
leukocytes and proteinuria in the urinalysis.
Based on nephrologist advice, the patient was then able to resume the cancer treatment
with a maintenance dose of prednisone equal to 5 mg/day.
CONCLUSION: AIN is a rare adverse effect of ICPIs that mandates the close
monitoring of renal function in patients under immunotherapy with these agents.
AKI occurrence in patients treated with ICPIs should always lead to investigate a
possible AIN, even in the absence of the classic symptom set of fever, rush and
eosinophilia and with minimal changes in urinalysis. Based on our single observation,
and after an accurate literature review, we suggest the initiation of a corticosteroid

i190 | Abstracts
Nephrology Dialysis Transplantation Abstracts
treatment in oncologic patients on an ICPI complicated with AKI and with suspicion AS was diagnosed in 2014 by the presence of positive HLA-B27, and clinical and
of AIN at urinalysis. radiological manifestations of bilateral sacroiliitis without extra renal manifestations
Moreover, this case report thickens the importance of a multidisciplinary approach to treated by indometacin during periods of pain . A pure nephrotic syndrome was
oncologic patients not only when a conventional nephrotoxic chemotherapy has to be revealed with a 24h proteinuria of 12g / 24h.The patient’s Albumin levels were at 16g/l,
started, but also in case of ICIPs use. The nephrologist advice, in fact, could be useful in without HTA or hematuria, and with a correct renal function (Creatinine at 60mmol/
both preventing and treating severe renal complications such as AIN, also allowing the l). A renal biopsy showed a MN with type I polytypical. Light microscopy showed a
oncologic therapy maintenance. thickening of capillary loops, while IF staining revealed granular deposits of IgG along
the capillary wall. Investigations of further secondary MNs were negative, and the
patient was aPLA2R-negative.
RESULTS: A treatment by corticosteroids was initiated prior biopsy to her referral ,
MO222 DO WE OFTEN THINK OF MULTIPLE MYELOMA AS THE
which resulted in pain relief and urinary protein reduction (prot 24h 1.5g/24h). Given
CAUSE OF KIDNEY DISEASE?
her good response to this initial treatment, corticotherapy was maintained. As the
1, Nevena Grujic1, Bojan Stopic 1, Aleksandar Jankovi levels of inflammation and discomfort were low, the patient did not wish to be treated
Snezana Pesic c1,
by biotherapy.
Katarina Markovic2, Tatjana Damjanovic1, Radomir Naumovic3
1
CONCLUSION: This case suggests a secondary MN in association with AS.The
Zvezdara University Clinical Center, Clinical Department for Nephrology, Belgrade, discovery of new autoantibodies associated with AS opens up promising perspectives,
Serbia, 2Zvezdara University Medical Center, Clinical Department for Hematology, and could potentially lead to the characterization of biomarkers for screening and
Belgrade, Serbia and 3Medical Faculty, University Belgrade, Clinical Department for monitoring this disease. However, more studies are needed in order to improve our
Nephrology, Belgrade, Serbia understanding of the role played by possible immune complex diseases, (in particular
MN), in relation to this Ankylosing spondilitis.
BACKGROUND AND AIMS: Kidney disease is a common complication in patients
with multiple myeloma and other plasma cell dyscrasias. This disease can be
manifested by various kidney disorders, which can evolve as either an acute or chronic
MO224 VCAM-1 LEVELS ASSOCIATED WITH ALBUMINURIA IN
disorder. Cast nephropathy is the most common cause of severe acute kidney injury
MULTIBACILLARY LEPROSY
(AKI) in patients with multiple myeloma. Among newly diagnosed patients, 20 to 50 %
have AKI or cronic kidney disease (CKD) at the time of diagnosis. Treatment of acute
Louise Donadello Tessarolo1, Gdayllon Cavalcante Meneses2, Gabriela Freire
renal failure consists of good supportive care and anti-myeloma therapy. Introduction
Bezerra3, Geraldo Bezerra da Silva Junior4, Elizabeth De Francesco Daher2, Alice
of novel agents has considerably improved outcome in patients with multiple myeloma
Maria Costa Martins3
and renal failure. The aim of this study was to identify the most common risk factors 1
(RF) for mortality in patients with MM and renal failure. Federal University of Ceara, Postgraduate Program in Pharmaceutical Sciences,
METHOD: The study included 22 patients ( mean years 67 6 12 years, 12 men). Who Fortaleza, Brazil, 2Federal University of Cear
a, Medical Sciences Post-Graduate Program,
followed two years. We analyzed routine laboratory tests, Bence Jones protein, urinary Fortaleza, Brazil, 3Federal University of Cear
a, Pharmacology Post-Graduate Program,
protein excretion, and creatinine clearance. Plain radiography for the evaluation of Fortaleza, Brazil and 4University of Fortaleza, School of Medicine, Post-Graduation
skeleton lesions were performed for all patients. Programs in Public Health and Medical Sciences, Fortaleza, Brazil
RESULTS: Overall two years mortality of patients with MM was 38.1% with no
significant difference regard to patients’ age and gender. About 33% of patients BACKGROUND AND AIMS: Leprosy may present important renal and endothelial
required renal replacement therapy and 19% remained on a chronic dialysis treatment abnormalities, and this can worse patients’ prognosis. However, renal and vascular
program. Renal biopsy was performed in 9.1% of patients (1 - FSGS, 1 - LCCD, light involvement in these patients has been poor investigated. The aim of this study was to
chain deposition disease). Bone marrow transplant (stem cell transplant) was investigate if higher systemic endothelial biomarkers levels are associated with renal
performed in 9.1% of patients. Of the associated comorbidities, 19% had DM, 81% had abnormalities and clinical aspects of leprosy.
hypertension, CVD 52.4%. Osteolytic changes at the time of diagnosis were present in METHOD: This is a cross-sectional study with leprosy patients before initiation of
52.4%. In older patients, kappa chains have been identified to a much more extent. multidrug therapy enrolled in January 2017 to December 2018 in Fortaleza, northeast
Survival is significantly lower in dialysis dependent patients with a two-year survival of Brazil. Leprosy-associated clinical and epidemiological data were collected. Two groups
30%. Binary logistic regression revealed that platelet decrease (OR = 0.982< CI 0.961– were constructed: Paucibacillary (PB) and Multibacillary (MB) for comparisons. Serum
1.003< p = 0.09) and increase of IgA significantly influenced mortality (OR = and urine samples were obtained for laboratory analysis. In urine the following
103,867< CI 0.459–23567.201< p = 0.09) can be considered as potential predictors of parameters were evaluated: creatinine, proteinuria and albuminuria. In serum the
mortality. Comorbidity DM, HTA, CVD were not the predictors for mortality in endothelial biomarkers were evaluated: VCAM-1 and ICAM-1, using ELISA assay.
patients with MM RESULTS: A total of 101 leprosy patients were included, with mean age of 48615
CONCLUSION: Multiple myeloma associated with high mortality rate and kidney years, and 71 (70%) were male. The multibacillary form occurred in 81 cases (80%),
disease. High percentage of patients required renal replacement therapy (33%) and where 22 had a Virchowian form. VCAM-1 was elevated in MB group and was
19% remained on a chronic dialysis treatment program. Among the estimated correlated with the bacteriological index (skin smear) (r = 0.372, p <0.01), duration of
parameters, the risk factors for mortality were significant decrease of platelet (p = 0.09) disease symptoms (r = 0.234, p = 0.04), and number of skin lesions ( r = 0.331, p
and increase IgA (p = 0.09). Survival is significantly lower in in dialysis dependent <0.001). Moreover, in MB patients who presented albuminuria >15 mg/g of
patients with a two-year survival of 30%. creatinine, VCAM-1 showed a significant correlation (r = 0.341, p <0.05) with
increased albuminuria and improve the correlation with number of skin lesions (r =
0.653, p=0.003).
CONCLUSION: Multibacillary leprosy patients present high systemic levels of
MO223 MEMBRANOUS NEPHROPATHY ASSOCIATED TO
VCAM-1, associated with leprosy clinical features and increased albuminuria, an
ANKYLOSING SPONDYLITIS: CASE REPORT
important marker of kidney disease progression. Further prospective studies are
necessary to establish a cause-effect relation and evaluate the preventive role of these
Aldjia LAMRI1
1
biomarkers, aiming to improve clinical care.
University hospital of Beni Messous Algeria, Nephrology, Algiers, Algeria

BACKGROUND AND AIMS: Ankylosing Spondylitis (AS) is a chronic inflammatory


MO225 CMV ENCEPHALITIS IN A SLE FLARE
rheumatic disease diagnosed by the presence of the HLA-B27 antigen with joint and
extra-articular manifestations.
Its pathogenesis was initially based on auto-inflammatory phenomena, mainly Catarina Marouço1, Dulce Carvalho1, Francisco Ribeiro1, Rita Magriço1,
involving innate immunity. However, many studies carried out in the recent years Fernando Nolasco1
1
focus on its adaptive immunity aspect, especially autoimmune. These mechanisms Hospital Curry Cabral, Centro Hospitalar Lisboa Central, Nephrology, Lisboa, Portugal
seem to interact with each other, resulting in a complex pathophysiology.
The general autoimmune characteristics of AS were investigated by Yuan and al, who BACKGROUND AND AIMS: Cytomegalovirus (CMV) infection is an opportunistic
reviewed recent reports of autoantibodies levels in AS patients. Their analysis shows pathogen in immunocompromised patients and its management is well described after
that none of the autoantibodies considered in the study meet the criteria to be solid organ/bone marrow transplant or in HIV patients. Although less common, since
considered as a biomarker for the disease (including antibodies Anti- :CD74; beta2- Systemic Lupus Erythemathous (SLE) is a chronic auto immune disease often requiring
Microglobulin; mutated Citrullinated Vimentin (MCV); Heat Shock Protein 65 intense immunosuppression to induce remission of disease exacerbation, SLE patients
(HSP65); 14-3-3 eta autoantibodies (14-3-3g); 1A-dependent autoantibody magnesium are also prone to it. Besides complicating the course of the disease, it may be a life-
anti-protein phosphatase (PPM1A); sclerostin (SOST); and Anti-microbial antibodies). threatening infection. Due to the heterogeneity of SLE manifestations, usually is
Renal involvement in AS is dominated by amyloidosis and IgA nephropathy. In rare
cases, this disease has been associated with Membranous Nephropathy (MN). The
pathogenetic link between the two disorders remains obscure. However, the recent
connection of AS to autoantibodies potentially indicates the involvement of immune
complexes formed from these autoantibodies in the development of MN.
METHOD: We report the case of a 36-years-old woman with a 7 years history of
sacroiliitis, who also developed a pedal edema in May 2020.

10.1093/ndt/gfab092 | i191
Abstracts Nephrology Dialysis Transplantation

difficult to distinguish between a SLE flare and CMV active infection, making the
diagnose challenging. It has also been described in the literature as an exacerbating SLE
factor.
We report the case of an Asian, 27-year-old woman, with a recent SLE diagnosis that
was admitted with a SLE flare while developing a CMV encephalitis. She was
previously admitted due to a nephrotic syndrome. Immunological studies revealed an
ANA title of 1:640 and a positive anti dsDNA Ab with diminished C3 and C4 levels,
nephrotic range proteinuria and a diagnose of SLE was made. Renal biopsy revealed
class IV lupus nephritis. She started high dose intravenous methylprednisolone (3
pulses of 500mg) and mycophenolate mofetil (MMF) at a dose of 2g per day. She was
discharged taking 60 mg of oral prednisolone and the same dose of MMF. Two weeks
after being discharged, she was readmitted due to worsening anaemia (Hb 6.8 g/dL),
thrombocytopenia (Pl 27 000/mL) and deteriorating renal function with a sCr of 5.5
mg/dL with de novo haematuria. It was admitted a severe SLE flare and she was given
another 3 pulses of 500mg I.V methylprednisolone and cyclophosphamide (CYC) was
started (1 pulse of 500mg I.V). At the same time, she started to complain of myalgias
and malaise, generalized hypotonia, developed fever, leukopenia with neutropenia and
seizures. Serum CMV viremia was 71 000 copies and CMV polymerase chain reaction
was positive in cerebrospinal fluid. She was started on I.V Ganciclovir, CYC was
suspended and clinical improvement was observed.
CONCLUSION: Studies about the risk of different treatment drugs and other risk
factors on the development of CMV disease in SLE are lacking. These studies will be MO226 Figure: No enhancement in a suspected gallbladder tumor in a dialyzed
useful for establishing guidelines on the institution of prophylaxis or pre-emptive patient: surgery was avoided
treatment of CMV infection in SLE patients. Protocols for screening and prevention in
this population should be implemented to account for this emerging problem. Given
the rising prevalence of CMV infection in the past few years, the authors recommend
that patients recently diagnosed with SLE while taking high doses of corticosteroids,
which appears to be a risk factor for CMV reactivation, should be routinely tested for MO227 RELATIONSHIP BETWEEN KIDNEY DAMAGE AND
CMV viremia. COGNITIVE FUNCTIONS IN PATIENTS WITH
There should be a low threshold for suspicion, hence treatment should be started as GLOMERULOPATHIES
soon as possible given the high morbidity and mortality in severe cases.
Gianmarco Borriello1, Davide Viggiano2, Giovambattista Capasso3
1
university of Campania ‘Luigi Vanvitelli’, department of translational medicine, naples,
MO226 A NEW DIAGNOSTIC TOOL FOR CKD PATIENTS: CONTRAST- , 2university of Campania ‘Luigi Vanvitelli’ - Biogem, Ariano Irpino, department of trans-
ENHANCED ULTRASONOGRAPHY. A SINGLE CENTER lational medicine, naples, and 3university of Campania ‘Luigi Vanvitelli’ - Biogem,
EXPERIENCE Ariano Irpino, department of translational medicine, naples, Italy

Mirela Liana Gliga1,2, Cristian Chirila3, Paula Chirila4, Adriana Gomotarceanu5, BACKGROUND AND AIMS: Mild Cognitive Impairment (MCI) has been found to
Imola Torok6, Mihail Gheorghe Gliga7 be highly prevalent amongst patients with Chronic Kidney Disease (CKD). In this
1
University of Medicine, Pharmacy, Science and Technology “George Emil Palade”, cohort, the prevalence of MCI was estimated to be between 30% and 63%. Mild
Internal Medicine, T^argu Mures, , Romania, 2Diaverum Dialysis Center Tirgu Mures, cognitive impairment is an intermediate state between normal aging and dementia. An
3
University of Medicine and Pharmacy Science and Technology “George Emil Palade” individual suffering from MCI has difficulty in remembering, sustaining attention, or
of T^argu Mureş, Nephrology, 4Mures University County Hospital, 5TOPMED Medical decision making which can negatively affect their daily lives.
Center, Tg Mures, Romania, 6University of Medicine, Pharmacy, Science and Technology The aim of this study was to verify the role of different glomerular diseases diagnosed
“George Emil Palade” Tg Mures, Romania, Republic Of North Macedonia and by kidney biopsy on the MCI through a retrospective study.
7
University of Medicine, Pharmacy, Science and Technology “George Emil Palade” Tg METHOD: We recruited 45 patients with bioptic diagnosis of the following
Mures, Romania glomerular diseases: Focal Segmental Glomerulo Sclerosis (FSGS), minimal change
disease (MCD), membranous glomerular disease (MG), IgA nephropathy. The renal
BACKGROUND AND AIMS: Contrast-enhanced ultrasonography (CEUS) is a function was analyzed using clinical variables, while Cognitive functions using the
minimally invasive diagnostic tool available for diagnosing microvascular disturbances MoCA test. Patients were divided into two groups based on 24h proteinuria.
in tumors and many vascular pathologies. Unlike other radiological contrast agents, it RESULTS: The MoCA score was directly correlated to the uric acid levels (R=0.13;
is completely harmless for CKD patients and therefore it is used for the safe diagnosis p=0.03). The MoCa score in the group with higher proteinuria levels was significantly
of many diffuse or focal pathologies. lower than those of the group with lower proteinuria levels (p = 0.03). Finally, the
METHOD: We used CEUS examination in 50 CKD patients for the following MoCA score in subjects with FSGS or MCD is significantly higher compared the other
pathologies: 10 atypical cysts, 15 liver focal lesions, 2 splenic focal lesions, 3 renal groups (p<0.05).
infarcts, 12 kidney focal lesions and 8 other organ involvements. CONCLUSION: Our data suggest that serum uric acid and proteinuria in glomerular
Examination was made using a VOLUSON E8 machine (GE Medical System diseases influence cognitive functions. Interestingly, uric acid plays a neuroprotective
Kreztechnik GmbH Tiefenbach 15, Austria) with a 3.5 MHz convex array abdominal role, as low levels of uric acid reduce the MoCA score. This result agrees with previous
transducer. 2.4 ml of microbubble contrast-agent was administered intravenously and observations of a protective role of uric acid on dopamine neurons. Conversely, the
recording of the results were made for 3-5 minutes after injection. extent proteinuria seems to negatively affect cognitive functions, suggesting a role of
RESULTS: Depending on the organ vascular characteristics, contrast enhancement the endothelial dysfunction. Finally, glomerulopathies with a lower degree of
and/or wash-out were suggestive for the final diagnosis. In liver lesions there are three inflammation (FSGS, MCD) have minor impact on cognitive functions.
phases and in kidneys, spleen, gallbladder, adenopathies there are two vascular phases.
We obtained a very good positive predictive value and sensitivity in detecting
malignant lesions. MO228 NATIVE KIDNEY BIOPSIES: DIAGNOCTIC VALUE AND
CONCLUSION: According to The EFSUMB Guidelines and Recommendations for COMPLICATIONS
the Clinical Practice of Contrast-Enhanced Ultrasound they are used both for hepatic
and Non-Hepatic Applications. Being non-invasive and non-irradiating it could be the Vadim Stepanov1, Elena Prokopenko1,2, Aleksei Zulkarnaev1,
main diagnostic examination in CKD population in the future. Olga Vetchinnikova1, Andrey Yankovoy1
1
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Kidney Transplantaion
Department, Moscow, Russia and 2Moscow Regional Research Institute of Obstetrics
and Gynecology, Outpatient Department, Moscow, Russia

BACKGROUND AND AIMS: Percutaneous renal biopsy is essential tool in


nephrology but it is invasive procedure that can lead to complications, including gross
hematuria, clinical significant haematoma and infection. The aim of the study was to
determine the nature and incidence of PRB complications and the impact of biopsy
results on treatment strategy.
METHOD: 82 patients (male – 42, female – 40) with a median age of 43.5 (Q1; Q3 –
34;71) years, BMI 26.4 (22.9; 30.6) were included in retrospective study of all native
kidney biopsies performed at our institute from January 1, 2016 to December 31, 2019.
An informed consent was mandatory in all patients. The indications for biopsies were

i192 | Abstracts
Nephrology Dialysis Transplantation Abstracts
nephrotic syndrome, 24-hour proteinuria  1g, nephritic syndrome, renal failure of METHOD: Retrospective case record based study of consecutive TB patients visiting a
unknown origin. The median duration of kidney disease was 9.5 (3.0; 26.6) months, Tertiary care hospital attached to a Medical College diagnosed by standard methods to
serum creatinine level - 135 (87; 197) lmol/l, eGFR (CKD-EPI formula) – 52.9 (26.6; demonstrate TB bacilli in sputum or affected tissue. CKD was diagnosed based on
83.7) ml/min/1.73 m2, 24-hour proteinuria – 2.8 (1.2; 5.4) g. All biopsies were estimated Glomerular filtration rate less than 60 ml/min/m2 for at least three months.
percutaneous, ultrasound-guided and were performed under local anesthesia in prone Pattern of TB and adverse drug effects were studied. Statistical analysis was done on
position with a 16G needle. Medications that may increase bleeding risk SPSS version 20
(anticoagulants, antiplatelet agents, and nonsteroidal anti–inflammatory drugs) was RESULTS: Over ten months, of 746 TB patients seen, 41(5.4%) had CKD, Stage 3b,4
stopped before PRB. Immediately after the biopsy, bed rest and vital signs monitoring and 5 in 7/41(17.1%), 11(26.8%), 23(56.1%) respectively. Among CKD 24(58.5%) had
was prescribed for 12 hours. In the absence of complications, a control kidneys Diabetes Mellitus, 1(2.4%) HIV and 37(90.2%) hypertension. Pattern of TB is shown in
ultrasound was performed 24 hours after biopsy; if complications were suspected, table 1. Adverse drug reactions were significantly higher in CKD 24/41(54.5% vs 17%
regarding to the local protocol. We prescribed prophylactic antibiotics to the patients in non CKD, P < 0.05). Mortality in CKD was 3/41(7.3%) and not significantly higher
with a hematoma volume > 100 ml. All biopsy specimens were sent to tertiary on multivariable analysis than in those without CKD.
laboratory of renal pathology and evaluated by light and immunofluorescence (IF) CONCLUSION: In this retrospective survey of TB patients CKD constituted 5.4%, was
microscopy; electron microscopy was not used in our study. Biopsy samples were associated with more adverse drug reactions but did not impact on mortality.
considered satisfactory for diagnosis if they contained five or more glomeruli. Pulmonary TB was the common pattern in CKD.
RESULTS: Post-biopsy complications included gross hematuria – 19 of 82 (23.5%)
patients, haematomas  100 ml – 17 (20.7%), haematomas > 100 ml – 8 (20.7%), pain
in the puncture site requiring the administration of analgesics – 2 (2.4%). No death,
infections, bladder obstruction or nephrectomy due to biopsy complications was
registered. One (1.2%) patient required blood transfusion. We identified renal
arteriovenous fistula which did not require special treatment in one (1.2%) patient 2
months after PRB.
We found no differences in the incidence of post-biopsy haematomas by gender, age,
or BMI. Haematomas were significantly more common in patients with higher mean
blood pressure and serum creatinine levels (Fig.1, A, B).

MO228 Figure 1: A - mean arterial blood pressure in patients with and without
haematomas after kidney biopsy; B -serum creatinine level inpatients with and without
haematomas after kidney biopsy.

In one case (1.2%) the biopsy was inadequate. The results of PRB were varied,
including unexpected findings. IgA nephropathy was found in 23 of 81 (28.4%)
patients, focal segmental glomerulosclerosis – in 21 (25.9%), membranous
nephropathy – in 9 (11.1%), pauci-immune crescentic glomerulonephritis – in 6 Type of TB Site of TB (no.)
(7,4%), lupus nephritis – in 2 (2.4%), membranoproliferative glomerulonephritis – in 2
(2.4%) - one with polyclonal Igþ/C3þ on IF and one - with monoclonal IgG kappaþ, (%)
C3 nephropathy – in 1 (1.2%), AL-amyloidosis – in 2 (2.4%), light chain deposit Pulmonary 28 (68.3 %)
disease – in 1 (1.2%), hypertensive nephropathy – in 1 (1.2%), diabetic nephropathy –
Extra Pulmonary 13(31.7 %) Milliary 3 (7.3 %)
in 3 (3.7%), tubulointerstitial nephritis – 5 (6.2%), thrombotic microangiopathy – in 2
(2.4%), diffuse nephrosclerosis – in 2 (2.4%), renal tuberculosis – in 1 (1.2%). Pleural & Prostate 1 (2.4 %)
According to the results of the biopsy, pathogenetic treatment was first prescribed to 43 Lymph node 3 (7.3 %)
of 81 (53.1%) patients, changed – in 17 (21%), treatment remained unchanged – in 8
(9.9%) cases. Thirteen (16%) patients were referred for additional examination by a Meningitis 2 (4.87%)
hematologist and rheumatologist. Genito urinary 1 (2.4%)
CONCLUSION: Biopsy of native kidney is a high diagnostic value and safe procedure Abdominal 3 (7.3%)
with a low risk of major complications. Treatment was changed significantly after
biopsy in 74% of patients in our study.

MO229 PROFILE OF TUBERCULOSIS AND ITS MANAGEMENT IN


CHRONIC KIDNEY DISEASE

Divya Datta1, Ravindra Attur Prabhu1, Indu Ramachandra Rao1, Srinivas


Vinayak Shenoy1, Shankar Prasad Nagaraju1, Mohan V Bhojaraja1, Nisha
Abdul Khader1
1
Kasturba Medical College, Manipal, Manipal Academy of Higher Education,
Nephrology, MANIPAL, India

BACKGROUND AND AIMS: Estimates of Tuberculosis(TB) burden indicate an


estimated incidence and mortality of 199 and 32 respectively per 100000 in our
country. Risk factors for acquiring TB disease include HIV infection, Diabetes Mellitus,
Tobacco consumption and undernutrition. We retrospectively studied profile of TB in
Chronic Kidney disease(CKD) in our population.

10.1093/ndt/gfab092 | i193
Abstracts Nephrology Dialysis Transplantation

MO230 A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO MO232 BORTEZOMIB INDUCED PERIPHERAL AND CENTRAL
CONTROLLED STUDY OF ATRASENTAN IN PATIENTS WITH NEUROPATHY : ABOUT 3 CASE REPORTS
IGA NEPHROPATHY (THE ALIGN STUDY)
Rawnak Houli1, Samia Barbouche1, Hajji Mariem1, Amira Sakay1,
Hiddo Lambers Heerspink1, Donald Kohan2, Richard Lafayette3, Adeera Levin4, Samarra Badrouchi1, Cherni Nadia1, Fethi Ben Hmida1
Hong Zhang5, Aland Glicklich6, Marianne Camargo6, Andrew King6, 1
charles nicolle teaching hospital, nephrology, tunis, Tunisia
Jonathan Barratt7
1
University Medical Center Groningen, Groningen, The Netherlands, 2The University of BACKGROUND AND AIMS: Bortezomib is a proteasome inhibitor, whose efficacy in
Utah, Salt Lake City, United States of America, 3Stanford Health Care, Palo Alto, United the treatment of multiple myeloma has been proven over the last years. However, its
States of America, 4The University of British Columbia, Vancouver, Canada, 5Peking side effects may cause concern for patients as well as physicians. We focused in this
University First Hospital, Beijing, P.R. China, 6Chinook Therapeutics, Seattle, United study on Bortezomib-induced neuropathy, one of the most frequent complications. We
States of America and 7University of Leicester, Leicester, United Kingdom present 2 cases of peripheral sensory neuropathy and one intriguing case of central
neurological manifestation, all caused by Bortezomib administration.
BACKGROUND AND AIMS: IgA nephropathy (IgAN) is the most common primary CASE 1: A 62-year-old man, with a history of diabetes and hypertension, was
glomerulonephritis globally and an important cause of chronic kidney disease (CKD). diagnosed with multiple myeloma in 2019. He received 2 cycles of Bortezamib (2,5
Up to 40% of IgAN patients are at risk of progressing to end-stage kidney disease mg), Dexamethasone , and Cyclophosphamide. Each cycle included 4 doses of
(ESKD) and proteinuria is the strongest predictor of progression. There are no Bortezomib, and the cycles were 21 days apart. At the end of the second cycle the
approved therapies for IgAN, leaving an important need for new strategies to lower patient developed posterior cord syndrome with balance disorder and lower
proteinuria and preserve kidney function in high-risk patients. extremities paresthesia. Axonal sensitivo-motor polyneuropathy was confirmed by
Endothelin A (ETA) receptor activation drives proteinuria, along with kidney electromyography. A pharmacology investigation was conducted, and the symptoms
inflammation and fibrosis. Atrasentan, a potent and selective ETA antagonist, has been were attributed to Bortezomib toxicity. Evolution was favourable after change in
studied extensively in >5,000 patients with type 2 diabetes and kidney disease (DKD), protocol to Revlimide. No recurrence was noted.
demonstrating clinically significant and sustained reductions in proteinuria when CASE 2: A 64-year-old man with no prior history was diagnosed with multiple
administered on top of a maximum tolerated dose of RAS inhibitor (RASi). In a global myeloma in 2020. She received a protocol of 4 cycles, 21 days apart, of Bortezomib (2.1
Phase 3 outcome study in DKD (SONAR), atrasentan demonstrated a 35% reduced mg) ,Dexamethasone and Thalidomide . Three weeks after the first cycle, the patient
risk of the primary composite outcome of doubling of serum creatinine or end stage presented with confusion, gait disturbance and four-limb pyramidal deficiency
kidney disease (95% CI: 0.49, 0.88; P = 0.005). The most common adverse event was syndrome. Electromyography showed axonal sensitivo-motor polyneuropathy .In the
fluid retention. absence of other causes, Bortezomib toxicity was suspected and the patient underwent
Selective ETA blockade represents a promising approach to reduce proteinuria and an emergency epurative hemodialysis session, after which symptoms completely
preserve kidney function in high risk IgAN patients. disappeared. Bortezomib doses were then reduced. The evolution was favourable.
This is a presentation of a global, phase 3, double-blind, placebo-controlled trial to CASE 3: A 50-year-old woman was diagnosed with multiple myeloma in 2018 with
determine the effect of atrasentan in IgAN patients at high risk of kidney function loss. Randall’s disease and quadri-pyramidal syndrome. She was put on 4 courses of
METHOD: Approximately 320 patients across North America, South America, Bortezomib 2.4mg Cyclophosphamide and Dexamethasone, 21 days apart. After 2
Europe, and Asia-Pacific with biopsy-proven IgAN will be randomized to receive 0.75 coursess, she presented a generalized tonic-clonic seizure preceded by headache,
mg atrasentan or placebo daily for 132 weeks. Patients will continue receiving a dizziness and followed by speech disturbances. Biological screening for metabolic
maximally tolerated and stable dose of a RAS inhibitor as standard of care. The study disorders and toxins was unremarkable. Cerebral MRI showed no abnormalities. Doses
will also include patients that are unable to tolerate RAS inhibitor therapy. Additional of Bortezomib were reduced during the following course. We then witnessed an
eligibility criteria include urine protein creatinine ratio (UPCR) 1 g/g and eGFR 30 improvement in speech and no recurrence of seizures.
mL/min/1.73 m2. Participants will have study assessments over two and a half years CONCLUSION: Bortezomib induced neuropathy is a serious and debilitating
with options for remote study visits using telemedicine and home health visits. The complication to which physicians must pay special attention. This side effect can be
primary objective is to evaluate the effect of atrasentan versus placebo on proteinuria at managed by dose reduction or change of molecules. Outcomes are often favourable.
Week 24. Secondary objectives include evaluating the change from baseline in eGFR,
safety, and tolerability, and quality of life.
RESULTS: N/A
MO233 RENAL ARTERY STENOSIS: DO NOT FORGET INHERITED
CONCLUSION: N/A
THROMBOPHILIA

Marwa Omrane1, Yosra Ben Ariba1, Imen Ouertani1, Jannet Labidi1


1
MO231 INFECTIVE ENDOCARDITIS IN CHRONIC KIDNEY DISEASE: Military Hospital of Instruction of Tunis, Nephrology, Tunis, Tunisia
CLINICAL AND OUTCOME’S FEATURES
BACKGROUND AND AIMS: Inherited thrombophilia can be defined as a genetically
Amel Harzallah1, Soumaya Chargui1, Mariem Hajji1, Samia Barbouch1, determined predisposition to develop thromboembolic complications. Inherited
Mondher Ounissi1, Imen Gorsane1, Fethi Ben Hamida2 prothrombotic risk factors include antithrombin deficiency, protein C and protein S
1
Charles Nicolle Hospital, Department of Medicine A, Tunis, Tunisia and 2Charles Nicolle deficiencies, activated protein C resistance due to Leiden factor V mutation, inherited
Hospital, Laboratory of Renal pathology LR00SP01, Tunis, Tunisia hyperhomocysteinemia, prothrombin G20210A variant, dysfibrinogenemia and
elevated factor VIII levels.
BACKGROUND AND AIMS: Infective endocarditis complicating chronic kidney METHOD: We report the case of a patient with history of bilateral renal artery stenosis
disease is associated with high morbidity and mortality among this population who presented with renal artery bypass thrombosis related to an inherited
particularly exposed to bacteremia.The aim of our study was to study the clinical and thrombophilia.
evolutionary features of infective endocarditis among patients with chronic renal RESULTS: We report a case of 40-year-old male patient who presented with extremely
failure. high blood pressure and hypokalemia without other biological abnormalities. The
METHOD: It is a retrospective and descriptive study including patients with chronic duplex ultrasound showed bilateral renal stenosis with chronic occlusion of the right
kidney disease hospitalized in our department, whom presented an infective renal artery and a tight stenosis of the left renal artery estimated at 50%. Renal
endocarditis confirmed by modified DUKE criteria angiography confirmed the bilateral stenosis, associated to a small right kidney. Renal
RESULTS: 13 patients were included aged meanly of 42.69 years [27-63 years] with a scintigraphy with DMSA showed normal left renal function and right renal function
sex-ratio of 0.85. Twelve were in end stage renal disease with an average duration of estimated at 2%. The therapeutic decision was to perform an aorto-renal bypass
dialysis of 52 months [1-180 months] and in stage 5 in one case. At the time of surgery by the saphenous vein.After renal artery bypass the blood pressure improved
diagnosis, vascular access was fistula in one case and a central venous catheter in 11 markedly, maintaining this result at 12 months follow-up at clinical examination and
cases. The catheter was simple in 3 cases and tunnelled in eight cases. The duplex ultrasound. One year later, the patient presented with high blood pressure. The
circumstances of discovery were fever in 12 cases associated with an alteration of the duplex ultrasound showed a stenosis of the bypass with a double stenosis of the left
general state with asthenia in 10 cases. Low blood pressure was present in seven cases. aorto renal bypass on renal angioscanner. The patient underwent angioplasty of the
At biology, the mean hemoglobin level was 8.28 g/dl [6.1-10.8 g/dl]. Leukocytosis was venous bridge with implantation of 2 stents with improvement of blood pressure after
noted in 8 cases. Mean albuminemia was 30.61g/l [24-41g/l]. Albuminemia below 35 g/ angioplasty. Six months later, the patient presented an unbalanced blood pressure, the
l was objectified in 6 cases. Major causative organisms were Staphylococcus species in ultrasound control with a vascular Doppler showed a stenosis at the stent. The
10 cases. Trans-thoracic echography shows vegetation in 11 cases with an average size antihypertensive treatment was increased, a thrombophilia balance was requested
of 17.4 mm [6-37 mm] and aortic annular abscess in 2 cases. Antibiotherapy was concluding a combined protein C and protein S deficiency.
conducted in all cases. Complications were frequent, including congestive heart failure CONCLUSION: An etiological assessment should be carried out systematically in the
in 2 cases, secondary septic localisations in 3 cases, hemoptysis in one case and valve event of thrombosis occurring before the age of 40 or in the case of iterative venous or
perforation in 2 cases. Five patients underwent surgery after a mean delay of 32.75 days arterial thrombosis. A genetic study where appropriate and a family screening are then
[6-47 days]. Death occurred in 8 cases. recommended.
CONCLUSION: Infective endocarditis is severe during chronic kidney failure and
more frequent among patients on dialysis by catheter. It is associated with high
morbidity and mortality. Management of central venous catheter must be enhanced.
Treatment must be early to improve the prognosis of this complication.

i194 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO234 LIFE THREATENING MALIGNANT HYPERCALCEMIA IN RESULTS: After three months of supplementation, the changes in serum creatinine,
BREAST CANCER: CAN THE NEPHROLOGIST CHANGE THE uric acid, eGFR and urinary albumin excretion levels did not reach statistical
PATIENT DESTINY? significance. There was no difference between serum glucose, HbA1C and lipid profile
values before and after the n-3 PUFA supplementation in patients. Only serum
Matilde Pensabene1, Claudia Von Arx1, Sofia Giuliana2, Filomena Calabrese1, albumin significantly increased from 4.1060.26 to 4.2860.31 g/dL (p=0.016), and
Paola Capodanno3, Anna Maria Piscopo4, Ernesta Cavalcanti4, Arturo Cuomo3, systolic blood pressure decreased from 121.4614.5 to 116.6614.9 mmHg (p=0.001).
Giovambattista Capasso5, Michelino De Laurentiis1, Mariadelina Simeoni2 CONCLUSION: Short-term n-3 PUFA supplementation did not affect renal function
1
INT IRCCS Foundation “G.Pascale”, Experimental Clinical Oncology of Breast Cancer, and glycemic control in patients with type 2 diabetes with chronic kidney disease.
Naples, Italy, 2University of Campania “L. Vanvitelli”, Department of Translational
Medical Sciences, Division of Nephrology, Naples, Italy, 3INT IRCCS Foundation
“G.Pascale”, Intensive Care Unit, Naples, Italy, 4INT IRCCS Foundation “G.Pascale”, Dept
of Biochemistry Unit, Naples, Italy and 5Biogem Research Institute s.c.a.r.l, Molecular MO236 IGA NEPHROPATHY IN SOUTHERN MOROCCO
Biology and Genetics, Ariano Irpino, Italy
Sara Allibou1, Ramia BENHAMOU1, Wadi Ouhamou1, Meriem Chettati1,
BACKGROUND: Malignant hypercalcemia is a common complication in cancer Wafaa Fadili1, Inass Laouad1
1
patients and can be predictive of poor prognosis and advanced malignancy. Cancer- Mohammed VI University Hospital Center of Marrakesh, Cadi Ayyad University,
related mechanisms of hypercalcemia depends either on ectopic hypersecretion of Nephrology, marrakech, Morocco
humoral factors (PTH, PTH-like molecules, Vit D) by the tumoral mass, or on
osteolysis due to bone invasion. In consideration of the high renal and cardiac impact BACKGROUND AND AIMS: Originally described in 1968 by Jean Berger and Nicole
of severe hypercalcemia, its prompt recognition and treatment can be lifesaving. AKI is Hinglais, IgA nephropathy is the most common primary glomerulonephritis in
frequently associated with malignant hypercalcemia and recognizes a multifactorial developed countries. This immune complex nephropathy is associated with various
pathogenesis (direct renal vasoconstriction, volume depletion, tubule-interstitial glomerular histological lesions making classification difficult. Its prognosis was long
damage, etc.). Substitutive renal treatment can be necessary, but not always viable in considered favorable, although it remains the leading cause of end-stage renal disease
patients with poor physical performance and is a difficult choice in cancer patients with from chronic glomerulonephritis.
advanced malignancies. METHOD: It’s a retrospective descriptive study over 5 years from January 2015 to
CASE REPORT: We present the case of a 46 years old woman with an infiltrating non December 2019 of the data of 45 patients hospitalized in nephrology with IgA
special type (NST) carcinoma of the right breast (luminal B, ER 70%, PgR 60%, Ki67 nephropathy proven by anatomopathological study. Kidney biopsies were reread for
35%, HER2 1þ). Unfortunately, she quickly progressed after a neoadjuvant treatment the Oxford classification.
with Epirubicin/Cyclophosfamide (4 cycles) followed by Paclitaxel (10 cycles). A first RESULTS: Forty five patients had IgA nephropathy, predominantly male (SR = 1.2).
line hormonal treatment (Palbociclib, Letrozole and LHRH analogous) was then The mean age of our patients at diagnosis was 35.09 years 6 15.7 (6-66 years). Non-
started, but a further rapid disease progression was observed. A new biopsy showed a nephrotic proteinuria and microscopic hematuria, the main reasons for hospitalization,
muted and more aggressive cancer phenotype (high grade triple negative carcinoma were found in 73.1% and 78.1% of patients. Macroscopic hematuria has not been
with no PDL1 expression). Due to a rapid worsening of general conditions with described. Arterial hypertension was present during hospitalization in 15.6% of
cognitive impairment, the patient was admitted to the Oncology department. Blood patients, nephrotic syndrome was found in 14.6% of cases. Our study found that severe
test showed severe hypercalcemia (corrected calcium: 23.26 mg/dl) and severe acute renal failure was present in 21.9% of patients. Three patients were started on
hypokalemic metabolic alkalosis (blood pH 7.57; HCO-3 32 mmol/l; Kþ 2.6 mmol/l) hemodialysis.
associated to AKI (creatinine doubled to 1.42 mg/dl; eGFR 45 ml/min/1,73 mq). Lesions observed by light microscopy were classified according to the Oxford
Alkaline phosphatase and Vitamin D were normal and iPTH was < 2 pg/ml. ECG classification: M1 (46.9%), E1 (53.1%), S1 (59.4%), T1; T2 (21.9%; 6.3%).
showed a significant QTc prolongation to 550 msec. Imaging exams revealed lung Immunofluorescence performed in 96.7% of patients found deposits of IgA in all
metastasis, lung carcinomatous lymphangitis and bilateral pleural effusion, while Bone patients, IgM (19.4%), C3 (48.4%), IgG (12.9%) and C1q (6,5%). The aetiological
Scan showed a low caption limited to right ribs. Oncologists and Intensive Care assessment had demonstrated rheumatoid purpura in 14 patients (31.1%), b-
Physicians referred to our Nephrology and Dialysis Unit proposing Hemodialysis thalassemia in one patient and Berger’s disease in 66.6% of cases.
support. In consideration of the preserved diuresis, the advanced disease stage and the From a therapeutic standpoint, 78.1% of patients were placed on nephroprotective
unstable hemodynamics, our advice was instead for a conservative medical approach. ACE inhibitors or ARBs2, including 31.3% associated with corticosteroid therapy and /
An i.v. infusion of 4000 ml NaCl 0.9% þ KCl 60 mEq/24h; a continuous i.v. infusion of or immunosuppressants. Among patients treated with corticosteroid therapy, GFR
Furosemide 5mg/h were started and maintained for several days, leading to a significantly increased (65.5 [2-176] vs. 63.5 [6-138] mL / min / 1.73m2, p <0.001)
progressive and full renal function recovery (creatinine decreased to 0.7 mg/dl) and Progression to end-stage renal disease was noted in 6 patients (18.5%). Complete
metabolic alkalosis correction. However, corrected calcium remained largely over remission of proteinuria is noted in 62.2% of patients and GFR significantly increased
target, being 16.3 mg/dl. Sodium bicarbonate 80 mEq, Zoledronic acid 4 mg and (67.53 [2-270] vs 63.90 [6-169] MmL / min / 1.73m2, p <0.001) between M0 and the
Desametasone 4mg/day were administered and at day 16 even calcium was in normal last follow-up.
range. We realized that this was a favourable window for acting on the underlaying CONCLUSION: The evolving profile of IgA nephropathy, which has become
cause of malignant hypercalcemia, that likely was the aberrant secretion of non-dosable increasingly common in Morocco especially in children, remains extremely variable
PTH-like molecule(s). Thus, we suggested the Oncologist to start chemotherapy, and with progression to end-stage renal disease estimated in less than a third of cases.
they were allowed to treat the patient with Carboplatin/Gemcitabine. The patient was Corticosteroid therapy alone appears to be effective with a significant improvement in
successfully treated with stabilization of normocalcemia and is still alive. renal survival.
CONCLUSION: Malignant hypercalcemia is a life-threatening complication in
advanced malignancies. Our case report highlights the key role of the nephrologist in
treating a complex and fragile oncologic patient, achieving the full correction of several
severe renal disorders, hemodialysis avoidance and survival improvement. MO237 A SERUM COMPLEMENT ABNORMALITY REVEALED BY
THROMBOTIC MICROANGIOPATHY DURING INTERFERON
TREATMENT OF MULTIPLE SCLEROSIS

MO235 EFFECT OF OMEGA-3 POLYUNSATURATED FATTY ACID Dahmane Rihem1, Mrabet Sanda1, Boukadida Raja1, Guedri Yosra1,
SUPPLEMENTATION ON GLYSEMIC CONTROL AND RENAL Fradu Asma1, Sahtout Wissal1, Azzabi Awatef1, Ben aicha Narjess1,
FUNCTION IN TYPE 2 DIABETIC PATIENTS WITH CHRONIC Zellama Dorsaf1, Achour Abdellatif1
KIDNEY DISEASE 1
sahloul hospital, nephrology, Sousse, Tunisia
Mehmet Usta1, Alpaslan Ersoy2, Canan Ersoy3, Yavuz Ayar1, Gultekin Goksel4,
_Isminur Saka Karagoz5 BACKGROUND AND AIMS: Multiple sclerosis (MS) is a chronic and potentially
1 disabling disease of the central nervous system and is the leading cause of non-
University of Health Scienses, Faculty of Medicine, Bursa City Hospital, Nephrology, traumatic neurological disability in young adults. Beta interferons (IFN-b) are the
Bursa, Turkey, 2Uludag University, Faculty of Medicine, Nephrology, Bursa, Turkey, most-widely prescribed medications for this disease. Despite good overall long-term
3
Uludag University, Faculty of Medicine, Endocrinology and Metabolic Diseases, Bursa, safety data with prolonged use of this group of drugs, they can rarely cause serious and
Turkey, 4University of Health Scienses, Faculty of Medicine, Bursa City Hospital, sometimes life threatening adverse effects. We report a case of thrombotic
Hemodialysis, Bursa, Turkey and 5University of Health Scienses, Faculty of Medicine, microangiopathy (TMA) in a patient treated with IFN-b-1a for 03 years. The serum
Bursa City Hospital, Biochemistry, Bursa, Turkey complement study revealed a decrease in Factor I.
METHOD: Case report
BACKGROUND AND AIMS: The aim of this study was to evaluate the short-term RESULTS: A 28-year-old man was diagnosed with relapsing remitting multiple
effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on sclerosis in 2007. Subcutaneous IFNb-1a 44 lg was commenced three times a week in
glycemic control and renal function in type 2 diabetic patients with chronic kidney 2017. He had not had a relapse since 2012. In July 2020, he was admitted to intensive
disease. care unit for a status epilepticus associated with severe arterial hypertension and then
METHOD: Twenty-five diabetic patients received medication containing 2 g/day n-3 transferred to our department for management of malignant arterial hypertension with
PUFA orally in addition to standard treatments. Their estimated glomerular filtration acute renal failure.On examination, he did not present any neurological disorder but
rates (eGFR) were <80 mL/min/1.73 m2. Biochemical values were evaluated before had very unbalanced blood pressure under triple therapy. Biology had shown an
and 3 months after treatment. hemoglobin at 9, 7 g / dl; no thrombocytopenia with a collapsed haptoglobin, very high

10.1093/ndt/gfab092 | i195
Abstracts Nephrology Dialysis Transplantation

LDH with absence of schizocytes, positive non-specific ANCA and proteinuria at 7g/ complications. Hence a study was done to assess the oral health condition, cytological
24hour. changes, and presence or absence of candida in patients with chronic renal disease
The renal puncture biopsy showed chronic vascular and glomerular TMA with IgG undergoing dialysis aged between 30 to 65 years and controls in South India.
and fibrinogen deposits. The course was marked by the rapid deterioration of renal METHOD: A cross sectional study was conducted among 80 adults with CKD and
function. The patient received flash corticosteroid therapy 10 mg / kg IV for 3 controls, attending KMC and MCODS, Mangalore. Oral manifestations and oral
consecutive days switched to oral corticosteroid therapy 0.5 mg / kg / day and received hygiene were assessed; Cytological smears were taken for morphometric analysis of
supportive treatment including plasma exchange and hemodialysis. He was discharged buccal mucosal cells from the subjects. Oral smears were cultured to check for the
after a prolonged admission. growth of fungal species in subjects and controls. Statistical analysis was done using
At follow-up 6 months later, he had not regained kidney function and remained on SPSS Version 13. Chi square test was used to compare categorical variables between the
hemodialysis and was still taking 3 antihypertensive treatments. A follow-up groups.
immunological workup showed a decrease in Factor I: 26,83 mg/l (32,3-87,5). RESULTS: There was a significant difference in oral hygiene status and cytological
The patient was diagnosed with drug-induced TMA favored by complement changes in patients with CKD. Oral Fungal Infection was found in 32% of our patients
abnormality. Treatment with Eculizimab is under discussion. on dialysis and oral lesions, defined as clinical signs associated with OFI such as
CONCLUSION: IFN-b are main therapies for relapsing remitting multiple sclerosis. erythematous oral stomatitis, membranous candidiasis, or angular cheilitis, were found
Serious complications are relatively rare and IFN-bs are generally considered to be safe. in 37% of the patients with OFI, while 5% of the patients without findings of fungal
Nevertheless, rare serious and/or life-threatening side effects have been reported such infection presented oral lesions associated with OFI (p=0.0002). Furthermore, patients
as TMA. This can, as in our patient, be favored by an abnormality of the serum with self-reported mouth dryness were three times more likely (p=0.02) to be
complement. Thus, a study on serum complement would be recommended before diagnosed with OFI.
IFN-b prescription. CONCLUSION: Hemodialysis patients are found to have significantly more OFI than
controls. Oral dryness and dental plaque formation also seem to be at risk of
developing OFI. Detection of oral lesions associated with OFI should be combined with
a histopathological diagnosis before antifungal treatment. The prevalence of oral
MO238 CHALLENGING BEVACIZUMAB RELATED KIDNEY DAMAGE:
candida in these cases is alarming and can be a predictor of a poor prognostic index.
A SUCCESSFUL STRATEGY BY THE NEPHROLOGIST
As medicine advances, oral health care professionals should have a holistic approach to
the management of patients with complex medical problems especially to diseases of
Roberta Ranieri1, Angela Cervesato1, Sofia Giuliana1, Carolina Ruosi1,
the renal system as it is pivotal in maintaining a stable internal environment and
Giovambattista Capasso1,2, Mariadelina Simeoni1
1
homeostasis.
University of Campania “L.Vanvitelli”, Department of Translational Medical Sciences,
Division of Nephrology, Naples, Italy and 2Biogem Research Institute “Gaetano
Salvatore”, Ariano irpino, Italy
MO240 A FATAL CASE OF VASCULITIS AFTER SARS-COV-2
NEGATIVIZATION
BACKGROUND : Renal complications in cancer patients are frequently associated
with chemotherapy, immunotherapy and targeted drugs.
Maria Elena Bracaccia1, Nicolo De Cicco1, Alessandra Moioli1, Simona Barberi1,
Inhibitors of vascular endothelial growth factor(anti-VEGF) advent has permitted a
Claudia Fofi1, Paolo Mene’1
significant survival improvement in metastatic patients, promising less renal 1
complications than conventional chemotherapy .Indeed, direct nephrotoxicity is not Rome, Azienda Ospedaliera Sant’Andrea, Rome, Italy
typical, but immune-mediated glomerular damage is increasingly reported as a
common complication of anti-VEGFs.The blockade of VEGF in podocytes BACKGROUND AND AIMS: Spectrum of acute severe respiratory syndrome
mightimpair the filtration barrierintegrity leading to proteinuria appearance.In Coronavirus 2 (SARS-CoV-2) ranges from mild to critical and probably mortality rate
addition, anti-VEGFs activate NFkb triggering pro-inflammatory cytokines. The lack is largely underestimated.
of integrity of the filtration membrane and the inflammatory milieu could probably Complications may represent different manifestation of a profound endothelial
lead to the exposure of normally unexposed antigens and consequently predispose, by a dysfunction and injury.
mimicry mechanism, to autoantibodies and immunocomplex formation/deposition Biopsies reveal macro and microvascular thrombosis involving larger and smaller
and renal damage occurrence. vessels. Different Authors described accumulation of inflammatory cells across
CASE REPORT: We report the case of a 59-year-old male with a history of vascular bed, viral inclusions and apoptotic bodies across vascular bed. Endotheliitis
adenocarcinoma of sigma-rectumand peritoneal carcinosis, who underwent several leads to loss of vessel integrity with bleedings and lumen restriction with tissue
cycles of chemotherapy. ischemia and necrosis. SARS-CoV-2 also can cause vasculitis and a systemic
In 2015, the patient presented with gastro-intestinal obstruction. A laparoscopic rectal inflammatory vascular disease with COVID-19-associated coagulopathy.
resection was first performed, followed by colostomy and two cycles of the FOL-FOX Several cases of vasculitis have been described during COVID-19 pandemy but in
protocol. Between 2016 and 2019, due to disease progression, the patient received literature, to our knowledge, there are few cases of patients developing vasculitis after
FOLFIRI protocol and, subsequently, the anti-VEGF Bevacizumab. During the SARS-CoV-2 infection.
treatment course, laboratory tests documented moderate proteinuria (1 g/day METHOD: A 59-year-old male patient in chronic haemodialysis with hypertension,
approximately) and normal kidney function. End of 2019,due to a creatinine rise to 1.6 chronic thrombocytopenia, uncertain history of type 2 diabetes mellitus and recent
mg/dl, Bevacizumab was suspended. COVID-19 pneumonia (1 month before) was admitted to our E.R. with psycho-motor
However, in the next three months the kidney function continued to worsen and slowdown, dyspnoea, profound hypotension, diffuse and extensive purpura especially
reached a level of 3.2 mg/dl. The patient was referred to our Nephrology Unit and on extremities and nose with petechiae and ecchymoses, thrombocytopenia,
admitted to the ward showing an increase of 24 h proteinuria to 2 g/day with stable widespread arthritis and myalgia and atrial fibrillation with high ventricular response.
high creatinine and normal renal ultrasound parameters. In the suspect of a Laboratory tests revealed leucocytosis with elevation of inflammatory markers (GB
dehydration, patient was infused with saline solution without any significant GFR 15.6 x 103/mL CRP 6.61 mg/dl, procalcitonin 2.64 ng/ml), thrombocytopenia (PLTs 55
improvement. Suspecting an anti-VEGF mediated glomerulopathy, we checked the x 103/mL), Hb 11.2 g/dl, increased amylase (444 UI/L) and lipase (608 UI/L),
patient for an autoimmunity panel and found a positivity for ANA anti- Ro, anti Mi-2 hyperkaliaemic metabolic acidosis, mild impaired blood clotting with normal
and ASMA. A renal biopsy was not performed because the patient did not release the fibrinogen and severe D-Dimer elevation (3453 mcg/ml), normal haptoglobin and
consent and a 2-month course of prednisone 25 mg/day was introduced and bilirubin.
successively tapered to a maintenance dose of 5 mg/day. A prompt improvement of the SARS-CoV-2 rapid antigen test and three molecular swab tests (at admission and
kidney function (creatinine decreased to 1.5 mg/dl) and proteinuria (240 mg/24h)was during recovery) were negative.
observed and allowed a new oncological evaluation in order to start a new cycle of Contrast-enhanced chest-abdomen CT did not demonstrate relevant findings.
targeted-therapy. RESULTS: We suspected thrombotic thrombocytopenic purpura, COVID-19 related
CONCLUSION: Our case report suggests the need for an accurate investigation of the vasculitis or an autoimmune disease reactivation after SARS-CoV-2 or other
pathophysiological mechanisms of kidney damage linked to anti-VEGF agents. concurrent viral infections.
Moreover, based on our clinical experience, it appears that the multidisciplinary A peripheral blood smear excluded presence of schistocytes, HBV, HCV, HIV, c-
approach, with a key role of the nephrologist, to oncologic patients on anti-VEGF ANCA, p-ANCA, LAC anti-mitochondrial and ENA antibodies were negative, such as
agents complicated with renal damage, is fundamental for achieving a double goal: complement factor C4 (C3 at low limits). IgA immunoglobulins resulted increased
oncologic therapy maintenance and renal function preservation. (952 mg/dl).
We administered intravenous (IV) hydration, analgesic therapy, broad spectrum
antibiotics and Methylprednisolone 40 mg IV without benefit.
Three days after clinical conditions were critical with further neurological deterioration
MO239 ORAL FUNGAL INFECTION IN ESRD PATIENTS
and haemodynamic instability, consequently we started methylprednisolone 1 g/day IV
for three days, followed by oral prednisone 25 mg/die with rapid improvement of
MohanKumar Nedunchezhiyan1, Afza Anjum1, Nandita Shenoy1, Rohith Nayak1 clinical conditions and laboratory findings.
1
Manipal University, Nephrology, Mangalore, India A skin biopsy revealed a variable and discontinuous presence of C4d and IgM along
capillary walls and traces of IgG, supporting the hypothesis of an immune-mediated
BACKGROUND AND AIMS: Chronic Kidney Disease is an increasing health alarm vasculitic process.
worldwide with systemic signs like hematologic changes, bone metabolic error, and Patient was discharged in stable condition with Prednisone 25 mg/die per os.
compromised immune status presenting to a dental practitioner with oral

i196 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Later we learned that patient had been hospitalized again for severe anaemia, intercommunication system between Primary Care Physicians and external
thrombocytopenia and septic shock with fatal outcome. nephrology consultations, to FILTER consultations that did not require unnecessary
CONCLUSION: SARS-CoV-2 clinical spectrum appears to be extremely varied; the exposures and reducing the cost of healthcare and the waiting time among others.
direct cytolysis and the immune-mediated damage are among the most accredited Between June 2020 and December 2021, we received 372 cases referred from Primary
hypotheses on disease physiopathology, but molecular mimicry mechanisms may also Care for a first virtual assessment in the high-resolution nephrology clinic, clinical
be involved. Vascular endothelium can be considered among the first targets. Vasculitis recommendations were effectively issued regarding complementary tests, treatment . . .
are frequently described in literature during COVID, this case, instead, is an anecdotal and the need to refer to our Nephrology outpatient clinic for study and follow-up or
report of severe angiitis arising after swab negativization, underlying the possibility that not.
hyperinflammation can either cause an autoimmune syndrome de novo or trigger a RESULTS: Of the 372 patients evaluated VIRTUALLY, 38 were referred by Acute
flare-up of a pre-existing condition. Kidney Injury (AKI) of which 35 were discharged with follow-up by their Primary
Care Physician, 37 patients were referred by eGFR <30 ml / min / 1.73m2 being
discharged 29, 66 patients were referred by eGFR between 30-60 ml / min / 1.73m2,
being discharged 51 , 15 had Albumin / creatinine ratio (ACR ) between 30-300 mg /
gr discharging 100%, 22 cases were consulted for ultrasound renal abnormalities and
18 of them were discharged, 5 were referred for apparently non-urological hematuria,
not requiring nephrological follow-up in any case, the reason for referral "other causes"
had n = 102 of which the main reason was "loss of an appointment in consultation
during the pandemic", nephrectomy, kidney transplants with decompensation, family
history of hereditary kidney disease (PKD, Alport . . .) without follow up need in n=95
of cases
In Spain the activity of presential care in outpatient Nephrology consultations was
suspended in 47% of the services, carrying out activity through telephone calls in
98.9%, that is, in the majority of Spanish hospitals. In 16.5% of the centers,
telemedicine was the only form of external clinical visits. In 57% of the centers,
outpatient follow-up tests were stopped during the pandemic.
CONCLUSION: The actual COVID-19 pandemic has demonstrated that a
transformation and adaptation plan based on the optimization of resources, the
implementation of telemedicine and the reorganization of our healthcare activity is
necessary. The activity of presential care in outpatient Nephrology consultations was
suspended in 47% of the Spanish Nephrology services(1).
Humanity has demonstrated once again that it is capable of overcoming adversity,
readjusting to change. In our virtual consultation, we attended 372 cases of which 288
(66.6%) were discharged with recommendations to their Primary Care Physician.
Avoiding costs, unnecessary exposure of patients, relatives and healthcare personnel,
giving an almost "real time” response to the patient and avoiding unnecessary travels.
A model of care in external consultations that has come to stay in the future.

MO242 RECTAL ADENOCARCINOMA IN TUBEROUS SCLEROSIS: A


CASE REPORT

Marwa Omrane1, Amel Babchia1, Raja Jaballah1, Afef Mahersia1, Olfa Saidane1
1
Reginal hospital of Ben Arous, Hemodialysis, Ben Arous, Tunisia

BACKGROUND AND AIMS: Tuberous sclerosis (TS) is an autosomal dominant


genetic disorder that is characterized by a neurocutaneous syndrome. Usually, the
disease is diagnosed in childhood but there are frustrates form of tuberous sclerosis
with or without genetic mutation.
METHOD: This clinical case is about a women with tuberous sclerosis on
hemodialysis who is diagnosed a colonic polyposis and a rectal adenocarcinoma.
RESULTS: We report the case of a 64-year-old patient with no particular family
MO241 TELEMEDICINE : COVID -19 PANDEMIC AND THE RISE OF history, followed for renal failure discovered at the end stage with TS. She was treated
THE VIRTUAL CARE IN NEPHROLOGY IN SPAIN with intermittent hemodialysis. During his follow-up, she presented melena stools and
she reported lightheadedness when standing. Physical examination revealed
Javier De Teresa Alguacil1, Elisa Pereira Pérez1, José Manuel Osorio Moratalla1, conjunctival pallor. The patient’s heart rate was normal; her blood pressure was 120/80
Antonio Osuna Ortega1 mmHg supine and 120/70 mmHg standing. There was no distention or peritoneal
1
Virgen de las Nieves University Hospital, Nephrology, Granada, Spain irritation. The hemoglobin level was 78 g/L; three weeks previously, it had been stable
at 106 g/L. The platelet count, prothrombin time and partial thromboplastin time were
all normal. The patient was admitted to hospital. Two units of packed red blood cells
BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic,
were transfused. Gastroscopy was performed and it was normal. Colonoscopy revealed
has required a rapid and drastic transformation of health systems worldwide, and
a fixed, circumferential rectal tumor at 6 cm and multiple colorectal polypes. Rectal
consequently also of Spanish Nephrology Units, to respond to the critical situation.
biopsy confirmed a moderate to poorly differentiated adenocarcinoma of large bowel
The adaptation and transformation of nephrology services during the COVID-19
type. Computed tomography scan showed no metastases. She was operated and
pandemic in Spain was a urgent need. During this period is worth noting that
actually she is receiving chemotherapy cures.
outpatient nephrology consultations were carried out largely virtually. In conclusion,
CONCLUSION: In the literature, there is a case of invasive rectal adenocarcinoma in a
the pandemic has clearly impacted clinical activity in Spanish Nephrology departments
17-year-old girl with TS. We do not yet have enough data on the other types of polyps
including ours at Virgen de las Nieves University hospital (Granada), reducing elective
encountered. In the two small series described, the prevalence of colonic polyps is high
activity.
unlike cancer which could be an isolated event. In view of all these data, it seems
METHOD: At the beginning of the pandemic, we quickly adapted by designing an
judicious to us to carry out a national register of patients with TS and to specify the
outpatient healthcare model adapted to the situation. With a virtual model we
prevalence of digestive disorders in order to organize a systematic screening if it is high,
established direct communication via online almost in "real time" between primary
in the same way as the familial polyposis as well as to confirm or refute the hypothesis
care and our Nephrology Service consultation, avoiding unnecessary travel of patients
of the link between polyposis of TS and colorectal cancer.
and relatives, risk exposures to interpersonal and reducing the cost and the public
crowds in the hospital. Based on inter-consultation criteria adapted to the guidelines
and consensus documents of different societies, we established a new

10.1093/ndt/gfab092 | i197
Nephrology Dialysis Transplantation 36 (Supplement 1): i198–i235, 2021
10.1093/ndt/gfab104

GLOMERULONEPHRITIS CONCLUSION: CD4þCD126lowFoxp3þ Treg may inhibit the Akt-mTOR signaling


pathway by expressing PD-1, and maintain stable immunomodulatory function in the
inflammatory state, thus producing immunotherapeutic effect on lupus nephritis mice.

MO243 STUDY ON THE EFFECT AND MECHANISM OF NOVEL


REGULATORY T CELL (CD4+CD126LOWFOXP3+ TREG)
IMMUNOTHERAPY IN LUPUS NEPHRITIS*

Zhenjian Xu1, Junzhe Chen1, Anping Xu1


1 MO244 CD47 BLOCKADE AMELIORATES AUTOIMMUNE
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Department of Nephrology,
VASCULITIS VIA THE EFFEROCYTOSIS OF NEUTROPHIL
Guangzhou, P.R. China
EXTRACELLULAR TRAPS*

BACKGROUND AND AIMS: Our previous study found a new regulatory T cell Satoka Shiratori-Aso1, Daigo Nakazawa1, Yusho Ueda1, Takashi Kudo1,
subpopulation, CD4þCD126lowFoxp3þ regulatory T cells (CD4þCD126lowFoxp3þ Nishio Saori1, Utano Tomaru2, Akihiro Ishizu3, Tatsuya Atsumi1
Treg). This cell can maintain a stable immune regulatory function in the inflammatory 1
Hokkaido University, Department of Rheumatology, Endocrinology and Nephrology,
state. Through in vivo and in vitro experiments, we have confirmed that
Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan, 2Hokkaido
CD4þCD126lowFoxp3þ Treg has an immunotherapeutic effect on T cell-mediated
University, Department of Pathology, Faculty of Medicine and Graduate School of
mouse models of autoimmune diseases such as colitis and collagen-induced arthritis
Medicine, Sapporo, Japan and 3Hokkaido University, Department of Medical
(CIA). Further experimental studies showed that CD4þCD126lowFoxp3þ Treg could
Laboratory Science Faculty of Health Sciences, Sapporo, Japan
reduce the kidney injury caused by autoantibodies and prolong the survival time of
lupus mice. However, the mechanism of CD4þCD126lowFoxp3þ Treg
immunotherapy in lupus nephritis is not clear. The purpose of this study was to BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibody (ANCA)-
explore the mechanism of CD4þCD126lowFoxp3þ Treg immunotherapy in mice with associated vasculitis (AAV) is characterized by systemic necrotizing vasculitis in small
lupus nephritis. vessels. The necrotic lesions consist of ANCA-mediated neutrophil extracellular traps
METHOD: (NETs) which represent a form of lytic cell death. The persistent NETs serve as
IN VITRO EXPERIMENTS: CD4þCD126lowFoxp3þ Treg or autoantigens against ANCAs and cause organ damage in a vicious cycle. Considering
CD4þCD126lowFoxp3þ Treg pretreated with PD-1 inhibitor were co-cultured with T dead cells are essentially cleared by phagocytic cells as a process of efferocytosis, why
or B lymphocytes of lupus mice under different in vitro culture condition. The the NETs persist in tissue remains unclear. During efferocytosis, macrophages engulf
expression levels of Akt and mTOR of Treg in each group were measured under apoptotic cells to prevent the leakage of intracellular components including toxic
immunoinflammatory conditions. To observe the effects and differences of Treg enzyme into the surrounding cells and these processes are regulated by the expression
groups on the activation, proliferation and differentiation of T or B cells and other of CD47 as a “don’t eat me” signal. In this study, we hypothesized that ANCA-
immunomodulatory effects. mediated NETs in AAV escape from efferocytosis via the up-regulation of CD47 and
IN VIVO EXPERIMENTS: CD4þCD126lowFoxp3þ Treg (2  106/mouse) and the persistent NETs amplify the disease.
CD4þCD126lowFoxp3þ Treg (2  106/mouse) pretreated with PD-1 inhibitor and PBS METHOD: Human data: Human kidney biopsy specimens from patients with AAV
were injected into NZM2328 lupus mice, respectively. After cell injection, urine protein was and minor glomerular abnormality (MGA, as a case control) were subjected to
measured weekly. Autoantibody expression in lupus mice was measured every two weeks. immunohistochemistry (IHC) staining for CD47. In vitro: The expression of CD47 on
The effects of Treg on the proliferation and differentiation of T/B cells in lupus mice were neutrophils was evaluated by flow cytometry (FCM). Human neutrophils from healthy
observed. The therapeutic effects of Treg on lupus mice were observed. donor were treated with ANCA-IgGs from MPO-AAV patients or control IgGs. For
RESULTS: Compared with CD4þCD126lowFoxp3þ Treg, the expression of Akt and the efferocytosis assay, macrophages were co-incubated with unstimulated, apoptotic,
mTOR increases in PD-1 inhibitors pretreatment cells. The activation, proliferation and ANCA-IgGs treated neutrophils in the presence of anti-CD47 monoclonal
and differentiation functions of T or B lymphocytes of lupus mice were significantly antibody (mAb) or a control antibody. The neutrophils were labeled with CFMDA cell
weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vitro, tracker (fluorescent probe) and the efferocytosis was evaluated as neutrophil engulfed
indicating that CD4þCD126lowFoxp3þ Treg may inhibit Akt-mTOR signaling (CFMDA positive) macrophages using fluorescent microscopy. In vivo: Spontaneous
pathway through PD-1 in in vitro. crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mice (8-week-old age) were
Compared with CD4þCD126lowFoxp3þ Treg, the activation, proliferation and treated with intraperitoneal injection of anti-CD47 mAb or a control antibody every 5
differentiation functions of T or B lymphocytes of lupus mice were significantly weakened days for two weeks. The severity of glomerulonephritis was assessed by the levels of
by immunosuppression of PD-1 inhibitors pretreated Treg in vivo. And its therapeutic effect serum creatinine, haematuria, mRNA expression of pro-inflammatory genes, and
on lupus mice was ineffective, indicating that CD4þCD126lowFoxp3þ Treg may inhibit histopathological findings. To address the immune response against the CD47
Akt-MTOR signaling pathway through PD-1 in vivo. blockade, the titre of MPO-ANCA and the number of splenic cell subset was assessed
by ELISA and FCM analysis, respectively.
RESULTS: Human data: The IHC analysis of human renal specimens revealed that the
positive area of CD47 of AAV was greater than that of MGA. In particular, the CD47-
overexpressed cells were seen in glomeruli with necrotic crescent formation. In vitro:
Mean fluorescence intensity (MFI) of CD47 in ANCA-IgGs treated neutrophils (NETs)
was significantly higher than that in control IgGs treated neutrophils (ANCA-IgG;
442621.4 a.u. vs control IgG; 402610 a.u., p<0.05). In efferocytosis assay, apoptotic
neutrophils were engulfed by macrophages (efferocytosis rate/ apoptotic neutrophil;
20.563.8%, live neutrophils; 0.960.5%). The efferocytosis rate of ANCA-induced
NETs significantly decreased compared to apoptotic neutrophil, but anti-CD47 mAb
improved the efferocytosis of ANCA-NETs (efferocytosis rate/ anti-CD47 mAb;
19.164.2%, control antibody; 7.762.2%, p<0.05). In vivo: the renal histopathological
severity score, serum creatinine level of AAV mice treated with anti-CD47 mAb
decreased compared to that of AAV mice treated with a control antibody (anti-CD47
mAb; 0.9660.30 vs control antibody; 0.6160.32 mg/dL). Although there was no
significant difference in the number of splenic cells between anti-CD47 and control
antibody treated mice, CD47 blockade therapy significantly reduced serum MPO-
ANCA titre (28.5610.4 vs 45.2614.5 lg/mL) and renal mRNA expression (IFNa,
IFNc, MCP-1 and perforin) of AAV mice.
CONCLUSION: ANCA-mediated NETs might escape from efferocytosis through up-
regulation of CD47 and provoke necrotizing vasculitis. CD47 blockade could be a
potential novel therapeutic strategy for AAV.

MO243 Figure: Blocking PD-1 reverses CD4þCD126lowFoxp3þ Treg stability.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
MO245 OUTCOME OF DIFFERENT INDUCTION REGIMENS IN ANCA-
ASSOCIATED GLOMERULONEPHRITIS ACCORDING TO THE
HISTOPATHOLOGICAL CHARACTERISTICS: THE REASSESS
STUDY*

Martina Uzzo1, Jennifer Scott2, Alice Guerini3, Jennifer O’brien4, Anna Ricchiuto5,
Kresimir Galesic6, Stefania Affatato3, Vladimir Stoyanov2, Rosanna Lacetera1,
Anna Juto7, Andreas Kronbichler8, Giorgio Trivioli9, Iva Gunnarsson7,
Marco Allinovi10, Gaetano La Manna11, Mario Gennaro Cozzolino5,
Annette Bruchfeld12, Federica Mescia13, Federico Pieruzzi1, Stephen Mcadoo4,
Renato A. Sinico1, Matija Crnogorac14, Francesco Scolari3, Mark Little2,
David Jayne13, Federico Alberici3
1
University of Milano-Bicocca and ASST Monza, Department of Medicine and Surgery,
Monza, Italy, 2Trinity College Dublin, Trinity Health Kidney Centre, Dublin, Ireland,
3
University of Brescia, Department of Medicine and Surgery, Brescia, Italy,
4
Hammersmith Hospital, Imperial College Healthcare NHS Trust, Department of Renal
Medicine, London, United Kingdom, 5ASST Santi Paolo e Carlo, University of Milano,
Department of Health Sciences, Renal division, Milano, Italy, 6Dubrava University
Hospital, Department of Nephrology and Dialysis, Zagreb, Croatia, 7Karolinska
University Hospital, Department of Medicine Solna, Division of Rheumatology,
Stockholm, Sweden, 8Medical University Innsbruck, Department of Internal Medicine IV
(Nephrology and Hypertension), Innsbruck, Austria, 9University of Firenze, Department
of Experimental and Clinical Medicine, Firenze, Italy, 10Careggi University Hospital,
Nephrology, Dialysis and Transplantation Unit, Firenze, Italy, 11University of Bologna,
Dialysis and Renal Transplant Unit, Department of Experimental, Diagnostic and
Specialty Medicine, Bologna, Italy, 12Linköping University Hospital, Department of
Health, Medicine and Caring Sciences, Linköping, Sweden, 13University of Cambridge,
Department of Medicine, Cambridge, United Kingdom and 14Agram Special Hospital,
Department of Nephrology and Dialysis, Zagreb, Croatia

BACKGROUND AND AIMS: Renal involvement in ANCA-associated vasculitis


(AAV) impacts significantly on patients’ prognosis. The role of different induction
regimens on remission rates and long-term renal outcomes according to renal
histological characteristics has not been explored yet. This was confirmed also with a Cox regression analysis adjusted for sex, age, ANCA
METHOD: AAV patients with biopsy-proven renal involvement were collected type, AAV diagnosis, creatinine and proteinuria when comparing the RTX group with
retrospectively from eleven centers and stratified according to the induction regimen the CYC one (HR 8.30 [95% CI 1.64 to 42.01], p=0.011); figure 2:
employed: Rituximab (RTX), Cyclophosphamide (CYC) or both (RTX-CYC). Kidney
biopsies were classified according to the Berden and Brix classifications.
Renal remission rate was assessed 6 months after the induction regimen and defined as
a renal Birmingham Vasculitis Activity Score (BVAS) of 0.
Among patients who achieved remission at 6 months, renal relapse was defined as a
renal-BVAS>0 associated with an increase in immunosuppressive treatment.
ESRD was defined as an eGFR<15 ml/min/1,73m2, need for dialysis or renal
transplant.
RESULTS: 323 patients were identified and followed-up for a median time of 36
months (IQR 18-72). The cohort included 38% patients with GPA and 62% with MPA,
53% patients were MPO-ANCA and 41% PR3-ANCA positive. The median baseline
eGFR in the overall cohort was 19 ml/min/1,73m2 (IQR 12- 34). 58% of patients were
treated with CYC, 24% with RTX-CYC and 18% with RTX.
According to the Berden classification, 24% biopsies were classified as Focal, 31% as
Crescentic, 33% as Mixed and 12% as Sclerotic. The Brix score was assessable in 270/
323 (84%) patients: 17%, 52% and 31% were respectively in the Low, Medium and
High-risk class.
The overall renal remission at 6 months was 90%; according to the Berden
classification, 94% patients achieved remission in the Focal, 88% in the Crescentic, 91%
in the Mixed and 86% in the Sclerotic class. According to the Brix risk score, 88%
patients achieved remission in the High risk, 91% in the Medium and 96% in the Low-
risk class. According to induction regimen employed, 91%, 90% and 90% patients
achieved remission in the RTX, CYC and RTX plus CYC group respectively.
In a logistic regression model adjusted for sex, age, ANCA type, AAV diagnosis,
creatinine and proteinuria at onset, the induction regimen employed was not predictive
of renal remission at 6 months, neither in Berden Focal plus Crescentic and Mixed plus
Sclerotic classes, nor in Brix High and Low plus Medium risk classes.
Of the 185 patients with at least 6 months of follow-up available after remission, 25%
experienced a renal relapse. In a Cox regression model adjusted for sex, age, ANCA
type, AAV diagnosis, creatinine and proteinuria at onset, the induction regimen or
histological score were not predictive of renal relapse. In the unadjusted survival
analysis with the Kaplan-Maier curve, patients in the Crescentic group treated with
RTX had a shorter ESRD-free survival compared to the CYC group (p=0.033) and the
RTX-CYC group (p=0.044); figure 1:
While the eGFR changes over time in the Focal plus Crescentic and Mixed plus
Sclerotic classes showed a similar trend between treatment groups, in the Crescentic
class the median eGFR values in the RTX group tended to be lower compared to the
CYC and the RTX-CYC ones; figure 3:

10.1093/ndt/gfab104 | i199
Abstracts Nephrology Dialysis Transplantation

MO247 NOVEL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES


REVEAL CHANGED METABOLOMIC PROFILE IN
RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS*

Janina Müller-Deile1, George Sarau2, Ahmed Kotb1, Christoph Daniel3,


Stefan Kalkhof4, Silke Christiansen2, Mario Schiffer1
1
University of Erlangen, Nephrology, Erlangen, Germany, 2Institute for Nanotechnology
and Correlative Microscopy, Forchheim, Germany, 3University of Erlangen,
Nephropathology, Erlangen, Germany and 4Helmholtz-Centre for Environmental
Research, Department of Molecular Systems Biology, Leipzig,

BACKGROUND AND AIMS: Idiopathic forms of Focal Segmental


Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can
lead early recurrence of FSGS and kidney failure after kidney transplantation. In the
past three decades, many research endeavors were undertaken to identify these
unknown factors. Even though some potential candidates have been recently discussed
in the literature, “the” actual factor remains elusive. Therefore, there is an increased
demand in FSGS research for the use of novel technologies that can allow us to study
FSGS from a yet unexplored angle.
METHOD: We used novel treatment options, a personalized in vitro and in vivo assay
as well as Raman spectroscopy and mass spectrometry for recurrent FSGS.
RESULTS: Here, we report the successful treatment of recurrent FSGS in a patient
The rate of severe infections in the RTX, CYC and RTX-CYC group was respectively after living related kidney transplantation by removal of circulating factors with
6.3, 8.5 and 8.8 per 100 patient-years during the first 12 months. CytoSorb apheresis (Fig. 1). Interestingly, the classical published circulating factors
CONCLUSION: in a retrospective multicenter survey, response rates and relapse risk were all in normal range in this patient but early disease recurrence in the transplant
after different induction regimens in AAV patients with renal involvement were kidney and immediate response to CytoSorb apheresis were still suggestive for
comparable in the overall cohort and in the different histopathological subgroups. pathogenic circulating factors. To proof the functional effects of the patient’s serum on
Although in a small subset of patients, the ESRD-free survival in the Crescentic class podocytes and the glomerular filtration barrier we used a podocyte cell culture model
was shorter in the RTX group compared to the CYC one. and a proteinuria model in zebrafish to detect pathogenic effects on the podocyte’s
actin cytoskeleton inducing a functional phenotype (Fig. 2, Fig. 3). We then performed
Raman spectroscopy in the <50 kD serum fraction (Fig. 4), on cultured podocytes
treated with the FSGS serum (Fig. 5), and in kidney biopsies of the same patient at the
MO246 ESTIMATING DELAY IN TIME TO ESKD FOR TREATMENT time of transplantation and at the time of disease recurrence (Fig. 6). The analysis
EFFECTS ON PROTEINURIA IN IGA NEPHROPATHY AND revealed metabolomic changes in podocytes induced by the FSGS serum as well as in
FSGS* focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several
disturbed Raman spectra were identified in the fractionated serum and metabolome
Kevin Carroll1, Leah Conley2, Alex Mercer3, Moin A. Saleem4, Jonathan Barratt5 analysis by mass spectrometry detected lipid profiles in the FSGS serum, which
1
KJC Statistics Ltd., Cheshire, United Kingdom, 2Travere Therapeutics, Inc., San Diego, corresponded to disturbances in the Raman spectra.
United States of America, 3JAMCO Pharma Consulting AB, Stockholm, Sweden, 4Bristol
Royal Hospital for Children, Bristol, United Kingdom and 5University of Leicester,
Leicester, United Kingdom

BACKGROUND AND AIMS: Reduction in proteinuria is associated with lower risk


of end-stage kidney disease (ESKD) in IgA nephropathy (Thompson et al, 2019) and
focal segmental glomerulosclerosis (FSGS) (Troost et al, 2017). Sparsentan, a dual
endothelin receptor and angiotensin II receptor antagonist, is in phase 3 clinical trials
in IgA nephropathy (PROTECT) and FSGS (DUPLEX), that are powered to detect a
treatment benefit on proteinuria-based endpoints versus standard of care angiotensin
receptor blockade (irbesartan). In this study, we aim to estimate the delay in time to
ESKD conferred by the hypothesized treatment effect of sparsentan on proteinuria in
these phase 3 trials; for PROTECT, a 30% reduction in urine protein to creatine ratio
(UP/C) vs irbesartan in IgA nephropathy patients, and for DUPLEX, 30% more
patients achieving the new FSGS Partial Remission Endpoint (UP/C <1.5 g/g
associated with a 40% reduction in UP/C) versus irbesartan.
METHODS: We analysed individual patient level data from two UK registries: the first
is provided by Leicester General Hospital, UK and consists of IgAN patients, and the
second is the UK National Registry of Rare Kidney Disease (RaDaR) Nephrotic
Syndrome cohort, with access provided by the University of Bristol, UK, including
FSGS patients. IgAN patients with urine total protein value 1.0 g/day or UP/C 1.0
g/g and eGFR >30 mL/min at the initiation of renin-angiotensin system blockade
(RASB) were identified, as were patients with primary or genetic FSGS with UP/C 1.5
g/g and eGFR 30 mL/min. The time to ESKD (eGFR <15 mL/min, initiation of
dialysis, transplantation) or death from any cause over the patient follow-up period
was analysed using accelerated failure time modelling; Weibull, Log Logistic and Log
Normal distributions were applied with the fitted survivor function reported from the
CONCLUSION: Our novel innovative analysis reveals changed lipid metabolome
model with the lowest AIC. The time gained for a given reduction in risk in ESKD/
profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.
death and 5-year survival was estimated under proportional hazards.
RESULTS: A 30% reduction in proteinuria in IgAN patients confers a 50% lower risk
of ESKD, extending the median time to ESKD by 10.7 years, from 12.4 to 23.1 years; 5-
year ESKD free survival rate is also increased, from 77.7% to 88.1%. Similarly, ongoing MO248 P-GLYCOPROTEIN EXPRESSING IL-17A+IFN-GAMA+ TH17/1
analysis in FSGS patients indicates 30% more patients achieving the FSGS Partial CELLS ARE REFRACTORY TO GLUCOCORTICOID IN
Remission Endpoint confers lower risk for ESKD and increase in 5-year ESKD free NEPHROTIC SYNDROME*
survival.
CONCLUSION: The data from the Leicester General Hospital, UK and RaDaR Akhilesh Kumar Jaiswal1, Narayan Prasad1, Vikas Agarwal2
provide invaluable insight into the longer-term natural history of IgAN and FSGS 1
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of
patients and time to ESKD. Therapeutic interventions that reduce proteinuria and the Nephrology, Lucknow, India and 2Sanjay Gandhi Post Graduate Institute of Medical
risk of ESKD can confer important and clinically meaningful extensions in the time Sciences, Clinical Immunology, Lucknow, India
patients are alive and free from ESKD.
BACKGROUND AND AIMS: Th17 cells are critical effectors mediating the
autoimmunity in nephrotic syndrome (NS). Elevated IFN-c has also been involved in
NS; however, it remains unclear to what extent Th1 cells contribute to glucocorticoids
resistance in NS. P-glycoprotein (P-gp) effluxes glucocorticoids outside the cells and
selectively expressed differentially on T cell subtypes. In this study, we investigated the

i200 | Abstracts
Nephrology Dialysis Transplantation Abstracts
role of P-gp and cellular source of IFN-c and assessed its contribution to towards CD8 lymphocytes and NK(T) cells (Figure 2). NK cells were solely present in
glucocorticoids resistance in NS. IgA nephropathy compared to healthy kidney (1.5% versus 0% in all healthy kidneys).
METHOD: We analyzed the frequency of pathogenic IL-17AþIFN-cþ Th17/1
lymphocytes and P-gp expression on their surface by flow cytometry in SSNS (n = 32;
mean age: 9.06 6 5.84) and SRNS (n = 28; mean age: 11.29 6 3.73) patients. We also
included 15 age- and sex-matched healthy controls. All patients were of biopsy proven
minimal change disease and all patients were treated with steroids. All patients were
recruited as per the criteria of ISKDC.
RESULTS: We found a significant IL-17AþIFN-cþ Th17/1 population (P < 0.001) in
steroid resistant NS (SRNS) as compared to steroid sensitive NS (SSNS) patients. IL-12
and IL-23 are significantly higher in SRNS as compared to SSNS patients which are
require for transition of pathogenic Th17 cells to IFN-c producers. Of the IL-
17AþIFN-cþ Th17/1 population 95.8% cells were expressed P-gp on their surface in
SRNS; however only 30.1% cells expressed P-gp in SSNS group (Figure 1). We also
observed that P-gp expression correlate positively with IL-17AþIFN-cþ Th17/1
population (r= 0.739, p< 0.001) significantly.
CONCLUSION: The above findings clearly show that higher expression of P-gp on IL-
17AþIFN-cþ Th17/1 cells associated with steroid resistance in nephrotic syndrome
through both IL-17A and IFN-c.

MO249 SINGLE-CELL TRANSCRIPTOME OF COVID19 ASSOCIATED


IGA NEPHROPATHY* Several genes involved in immune activation, oxidative stress and injury were
upregulated in podocytes and mesangial cells. For example, one of the genes
1 2 3 4
Line Heylen , Bram Boeckx , Tim Jacobs , Francesca Maria Bosisio , upregulated in podocytes was macrophage migration inhibitory factor (MIF) which is
Birgit Weynand4, Lukas Marcelis4, Amélie Dendooven5, Liesbet Hendrickx1, known to be involved in podocyte injury and mesangial sclerosis. In endothelial cells
Sabine Fransis6, Deborah Steensels7, Sam Van Boxstael3, Pieter Jan Van pathways involved in NK cell immunity, antigen presentation, interferon gamma
Asbroeck3, Kristof Thevissen8, Peter Van Eyken6, Diether Lambrechts2 signaling, and viral entry were upregulated. In T lymphocytes pathways of antigen
1
ZOL Genk, Nephrology, Genk, Belgium, 2VIB - Center for Cancer Biology, Leuven, presentation and T cell cytotoxicity were enriched.
Belgium, 3ZOL Genk, Emergency Medicine, Genk, Belgium, 4UZ Leuven, Pathology, In the skin biopsy, immunohistochemistry was positive for SARS-CoV-2 spike protein
Leuven, Belgium, 5Ghent University Hospital, Pathology, Gent, Belgium, 6ZOL Genk, inside inflammatory cells, while the ACE2 receptor was positive in the same
Pathology, Genk, Belgium, 7ZOL Genk, Microbiology, Genk, Belgium and 8ZOL Genk, inflammatory cells, as well as inside endothelial cells.
Rheumatology, Genk, Belgium CONCLUSION: Although both innate and adaptive immunity are considered to be
involved in IgA nephropathy, our single cell sequencing data demonstrates that mainly
T-lymphocytes, especially CD8 cells and NK cells, are enriched in COVID19 associated
BACKGROUND AND AIMS: Acute kidney injury is common in patients infected IgA nephropathy. Further elucidation of the involved pathways and the T cell receptor
with the novel coronavirus SARS-CoV-2. Predominant findings in case series of kidney is planned. Interestingly, the SARS-CoV-2 virus could be identified inside the
biopsies include acute tubular injury and collapsing podocytopathy. We performed inflammatory cells in the skin in the context of cutaneous vasculitis, suggesting a direct
single-cell RNA sequencing on kidney biopsy of a patient with COVID19-associated pathologic effect.
Henoch-Schönlein vasculitis, to investigate the underlying molecular changes.
METHOD: A 46-year-old woman presented with cutaneous vasculitis, arthritis, fever
and microscopic hematuria. SARS-CoV-2 PCR on nasopharyngeal swab turned
positive. Despite quick spontaneous resolution of symptoms, hematuria persisted and
proteinuria increased in the next weeks. Subsequent kidney biopsy showed IgA
nephropathy. Kidney biopsy was dissociated into a single-cell suspension and RNA was
sequenced. 6126 kidney cells passed quality filters. Publicly available single cell
sequencing data of 3 healthy kidney samples were integrated to allow comparison. The
skin biopsy, performed at the initial presentation, was stained for the SARS-CoV-2
spike protein and the ACE2 protein using immunohistochemistry.
RESULTS: Unsupervised clustering analysis of kidney identified 12 distinct cell types
(Figure 1). T-lymphocytes were significantly enriched in COVID19 associated IgA
nephropathy (16.7% versus 0.5%, 1.2% and 4.1% in healthy kidney, IgA nephropathy/
healthy kidney ratio of relative % of T-/NK-cell clusters of 8.5), with a deviation

10.1093/ndt/gfab104 | i201
Abstracts Nephrology Dialysis Transplantation

MO250 URINARY DICKKOPF-3 (UDKK3): A NEW BIOMARKER FOR RESULTS: Progreser cohort and Pronedi cohort did not differ in their clinical baseline
LONG-TERM CKD PROGRESSION AND MORTALITY?* characteristics except in proteinuria. At baseline, uDKK3 levels were not different
between different etiologies or both cohorts, median uDKK3 was 2199 (IQR: 658-7618)
Beatriz Sanchez Alamo1, Francisco Jose Garcia In ~igo2, Amir Shabaka1, Juan
pg/mg in the Progreser cohort and 3041 (IQR: 653-9777) pg/mg in the Pronedi cohort
Manuel Acedo2, Clara Maria Cases Corona1, Patricia Dominguez Torres1, (p:0.56). Median time of follow-up was 36 months. Forty-nine patients (19 %) in
Alberto Martinez-Castelao3, Juan F. Navarro-Gonz alez4, Jose Luis Gorriz Teruel5, Progreser cohort and 31 patients (31%) in Pronedi cohort reached the primary
Gema Maria Fernandez Juarez1 composite outcome. Baseline uDKK3 was significantly higher in patients who reached
1
Hospital Universitario Fundaci on Alcorc on, Nephrology, Alcorcon, Spain, 2Hospital primary outcome. In Cox multivariate model, after adjustment for potential
Universitario Fundaci on Alcorcon, Department of Clinical Biochemistry, Alcorc on, confounders, the highest levels of uDKK3 were found to be an independent factor for
Spain, 3Bellvitges University Hospital, Nephrology, L’Hospitalet de Llobregat, Spain, renal progression in Progreser cohort (HR 1.83, CI95% 1.11-3.31) and in Pronedi
4
Hospital Universitario Nuestra Se~ nora de Candelaria, Research Department, Santa cohort (HR 2.74, CI95% 1.09-6.98). Both in the Progreser and the Pronedi cohorts,
Cruz de Tenerife, Spain and 5Hospital Universitario Valencia, Nefrologıa, València, Spain uDKK3 levels above 5050 pg/mg, were associated with a lower eGFR, higher
proteinuria and were independently associated with a worse renal survival. uDKK3
BACKGROUND AND AIMS: Kidney fibrosis has been reported to be a key gradually increased in the following months, especially in patients with higher
progression hallmark of chronic kidney disease (CKD). It seems likely that a precise proteinuria. Treatment with RAAS-blockers did not modify uDKK3 after 4 or 12
biomarker of renal fibrosis extension would contribute to predict accurately the risk of months of treatment.
a decline in glomerular filtration rate (eGFR). Previous studies have shown that the CONCLUSION: In this study, uDKK3 ratio identified patients at high risk for long-
assessment of urinary Dickkopf-3 (uDKK3), a stress induced tubular epithelial-derived term kidney disease progression regardless of the etiology of CKD. The hypothesis was
profibrotic glycoprotein, might be a potential tubulointerstitial fibrosis biomarker and generated in a cohort of patients with CKD of heterogeneous etiologies and was further
might identify patients at short-term risk of eGFR loss. We aim to evaluate uDKK3 as a confirmed in a cohort with overt diabetic nephropathy. The predictive role of uDKK3
potential biomarker for long-term CKD progression in a cohort with various etiologies persisted after adjusting by eGFR and proteinuria. uDKK3 is the first non-invasive
of CKD, and subsequently in an overt diabetic nephropathy cohort. We also tested the biomarker of renal fibrosis and might serve as a useful biomarker for kidney disease
role of treatment with RAAS blockers on the uDKK3 levels and if the treatment could progression. Therefore uDKK3 could be used by clinicians to optimize staging for renal
modify them. progression and monitor therapeutic efficacy of different measures to halt CKD
METHOD: We prospectively studied two independent cohorts consisted of 356 progression.
patients with stage 2-3 CKD. Progreser cohort comprised 255 patients with
heterogeneous etiologies of CKD and Pronedi cohort 101 patients with overt diabetic
nephropathy. The primary outcome was the time to the first event of the composite MO251 HIGHLY SENSITIVE FLOW CYTOMETRIC DETECTION OF
endpoint (>50% increase in serum creatinine concentration, end-stage kidney disease RESIDUAL B-CELLS AFTER RITUXIMAB IN ANTI-
[ESKD], or death). We divided patients into tertiles according to their baseline uDKK3 NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED
levels: less than 1092 pg/mg (Tertile 1, T1), between 1092-5050 pg/mg (Tertile 2, T2) VASCULITIS PATIENTS*
and higher than 5050 pg/mg (Tertile 3, T3). We used the cut point of T3 as an
exploratory cut-off. Cox regression models were used to adjust for potential effects of Y.K.O. Teng1, L. Van Dam1, Jelle Oskam1, S.W.A. Kamerling1, E.J. Arends1,
confounders or modifiers: age, gender, mean arterial pressure, body mass index (BMI), Edwin Bredewold1, M.A. Berkowska@lumc.nl2, J.J.M. Van Dongen2,
urine albumin/creatinine ratio, urine protein/creatinine ratio and serum creatinine. T.J. Rabelink1, Cees Van Kooten1
Mixed-effects models were adjusted to study longitudinal data. 1
Leiden University Medical Center (LUMC), Internal Medicine - Section Nephrology,
Leiden, The Netherlands and 2Leiden University Medical Center (LUMC), Immunology,
Leiden, The Netherlands

BACKGROUND AND AIMS: B-cell depletion with rituximab (RTX) is an effective


treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis
(AAV) patients. Nevertheless, relapses are frequent after RTX, often preceded by B-cell
repopulation suggesting that residual autoreactive B-cells persist despite therapy.
Therefore, this study aimed to identify minimal residual autoimmunity (MRA) in the
B-cell compartment of AAV patients treated with RTX.
METHOD: EuroFlow-based highly-sensitive flow cytometry (HSFC) was employed to
study B-cell and plasma cell (PC) subsets in-depth in AAV patients before and after
RTX treatment. Additionally, peripheral blood mononuclear cells (PBMCs) of these
RTX-treated AAV patients were cultured and in vitro stimulated with CpG, IL-2, and
IL-21 to induce antibody-secreting cells (ASC). (ANCA)-IgG was measured in these
supernatants by ELISA.
RESULTS: By employing EuroFlow-based HSFC, we detected circulating CD19þ B-
cells at all timepoints after RTX treatment, in contrast to conventional low-sensitive
flow cytometry. Pre-germinal center (Pre-GC) B-cells, memory B-cells and
CD20þCD138 plasmablasts (PBs) were rapidly and strongly reduced, while
CD20CD138 PrePC and CD20-CD138þ mature (m)PCs were reduced slower and
remained detectable. Both memory B-cells and CD20 PCs remained detectable after
RTX. Serum ANCA-IgG decreased significantly upon RTX. Changes in ANCA levels
strongly correlated with changes in naive, switched CD27þ and CD27 (double-
negative) memory B-cells, but not with plasma cells. Lastly, we demonstrated in
vitro ANCA production by AAV PBMCs, 24 and 48 weeks after RTX treatment
reflecting MRA in the memory compartment of AAV patients.
CONCLUSION: We demonstrated that RTX induced strong reductions in circulating
B-cells, but never resulted in complete B-cell depletion. Despite strongly reduced B-cell
numbers after RTX, ANCA-specific memory B-cells were still detectable in AAV
patients. Thus, MRA is identifiable in AAV and can provide a potential novel approach
in personalizing RTX treatment in AAV patients.

MO250 Figure 1: Kaplan Meier Curves for combined primary outcome according to
baseline uDKK3 tertiles for PRONEDI (A) and PROGRESER (B) cohorts.

i202 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO252 PLA2R -VE MEMBRANOUS GLOMERULONEPHRITIS METHOD: Forty-six adult patients with primary or genetic FSGS were randomized
PATIENTS SHOWS MORE EFFECTIVE RESPONSE THAN into a double-blind, placebo-controlled Phase 2 dose-ranging study designed to
PLA2R +VE ON TACROLIMUS PLUS LOW DOSE evaluate the safety and efficacy of CCX140. Changes of urinary protein excretion
PREDNISOLONE THERAPY* estimation (UPCR) from baseline to Week 12 were measured in four blinded treatment
groups (three active CCX140 doses of 5 mg once daily, 10 mg and 15 mg twice-daily
Akhilesh Kumar Jaiswal1, Narayan Prasad1, Vikas Agarwal2, Manas (BID) vs placebo). Starting at Week 12, all subjects including those in the placebo
Ranjan Behera1 group received the CCX140, 15 mg BID for an additional 12 weeks, and UPCR changes
1
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Nephrology, Lucknow, from Week 12 to Week 24 were assessed. There was a 4-week follow-up period from
India and 2Sanjay Gandhi Post Graduate Institute of Medical Sciences, Clinical Week 24 to Week 28 where no CCX140 was administered.
Immunology, Lucknow, India RESULTS: In the intent to treat (ITT) analysis of UPCR changes at Week 12 relative to
baseline, the 15 mg BID CCX140 group exhibited the greatest reduction of UPCR
BACKGROUND AND AIMS: PLA2R is an autoantigen present in glomerular (median reduction from baseline 0.9 g/g or approximately 30%, and approximately
podocytes of Membranous Nephropathy (MN) patients. Several drugs have been tried 25% reduction from baseline for the geometric mean), but that did not differ
which included nonspecific anti-proteinuric agents; corticosteroids, alone or with significantly from the placebo group (median reduction from baseline 0.45 g/g; or
alkylating agents; cyclosporine; intravenous Ig; mycophenolate mofetil; and rituximab. approximately 22%, and approximately 23% reduction from baseline for the geometric
There is no standard therapy for patients with frequent relapsing or steroid-dependent mean). Also, after crossover of the blinded portion of the trial to 15 mg BID active
MN. We propose the efficacy of low dose Tacrolimus (TAC) plus prednisolone and dosing, the previous placebo group did not appear to exhibit an additional reduction of
associated changes in anti-PLA2R in adult IMN. UPCR. CCX140 at all doses was well-tolerated, with no serious adverse events (SAEs)
METHOD: Total 101 membranous nephropathy patients were treated with during the blinded trial and a numerically lower rate of treatment-emergent adverse
combination of prednisolone 1mg/kg alt-day) and Tac 0.1mg/kg/day (trough 6-10 ng/ events in the CCX140 treatment groups.
ml first 6M and 4-6 ng/ml for next 3M) then both taper by 1/3 every month up to 12M. CONCLUSION: In the study, CCX140 did not demonstrate a therapeutically
Out of 101 patients; 15 diabetic; 7 lupus; 1HBV and 1 ankylosing spondylitis patients meaningful reduction in proteinuria relative to the control group after 12 weeks of
were excluded. Finally; 77 Patients were followed and evaluated for the anti-PLA2R blinded treatment. The study provides insights into the natural disease progression of
level at baseline; 3M; 6M; 12M and end of follow-up (17-61 ; median 38 months). CR; patients with primary or genetic FSGS as part of a clinical trial setting.
PR; relapse; and side-effects were recorded.Of the 77 patients; at 3M 60(77.92%; CR-37;
PR-23); at 6M 61(79.22%; CR-53; PR-8); at 12M 53(68.86%; CR-47; PR-6) achieved
remission. Eight (10.38%) relapsed and 16(20.77%) showed no response at 12M. At MO254 PREGNANCY OUTCOMES AND COMPLICATIONS IN
end of follow-up; out of 54 responsive patients 37(68.51%; CR-36; PR-1) remained in PATIENTS WITH CHRONIC GLOMERULONEPHRITIS*
remission and 17(31.48%) patients relapsed.
RESULTS: Out of 77 patients; 51 (66.3%) were anti-PLA2R positive. Remission rate Elena Prokopenko1,2, Aleksei Zulkarnaev1, Irina Nikolskaya2, Andrey Vatazin1,
was significantly low in PLA2Rþve than PLA2R-ve (36/51 vs 24/26; p=0.03) at 3M; Daria Penzeva1
(36/51 vs 25/26; p=0.009) at 6M and (31/51 vs 22/26; p=0.03) at 12M. PLA2R level was 1
decreased by 60.38% and 77.56% at 3M and 6M respectively (1A & 1B). There were M.F. Vladimirsky Moscow Regional Research Clinical Institute, Kidney Transplantaion
significant correlations between PLA2R level and 24h proteinuria at baseline; 3M and Department, Moscow, Russia and 2Moscow Regional Research Institute of Obstetrics
at 6M (1C). During therapy 4 patients develop cutaneous tenia; 1 osteonecrosis of the and Gynecology, Outpatient Department, Moscow, Russia
femur head; 1 corpus tunnel syndrome; 4 onset diabetes; 3 tremor; and 14 patients
experienced GI symptoms. The eGFR was decreased significantly (p=0.003) by 26.5% BACKGROUND AND AIMS: Pregnancy in patients with chronic glomerulonephritis
at the end of therapy and was normalized after stopping Tac; and 5 non-responsive (CGN) is associated with higher risk of complications and unfavorable outcomes
patients had doubling of serum creatinine and progressively deteriorated eGFR. To compared to the general population. The aim of the study was to determine the
note; 4 females had pregnancy and successful delivery in our cohort of patients. incidence of pregnancy complications and outcomes in patients with preexisting CGN.
CONCLUSION: PLA2Rþve patients showed poor response compare to PLA2R-ve METHOD: 126 pregnancies in 119 women with CGN and CKD 1-4 stages: 1 st. – 86
patients. Remission with Tacrolimus and prednisolone therapy is comparable to patients, 2 st. – 17, 3 st. – 20, 4 st. – 3 and 20 pregnancies in 20 age-matching healthy
historical Ponticelli (Pred plus CYP) regimen. Successful pregnency was ovserved on women were included. Patients with secondary CGN, multiple pregnancy, pregnancy
Tac based regimen. after IVF were excluded. A kidney biopsy was performed in 18 of 119 (15.1%) women:
15 – before conception and 3 – after delivery. IgA-nephropathy was detected in 11 of
18 (61.1%) patients, MCD/FSGS – in 4 (22.2%), MPGN – in 3 (16.7%). The incidence
of unfavorable pregnancy outcome, preeclampsia (PE), preterm delivery, cesarean
section (CS), low birth weight (LBW < 2500 g), small for gestational age (SGA)
newborn (birth weight < 10th percentile), mean term of delivery, mean birth weight,
frequency of treatment in neonatal intensive care unit (NICU) and achieving of end-
stage kidney disease in mothers after delivery were evaluated.
RESULTS: CKD was first diagnosed during pregnancy in 34.1% women with CGN.
The incidence of adverse pregnancy outcomes, preterm delivery, LBW, SGA, and
treatment in the NICU did not differ between groups, while the frequency of PE and
CS were higher, and mean gestational age at delivery, birth weight were lower in the
CGN group compared to the healthy control (Table).
Severe PE was observed in 6 of 32 (18.7%) patients with PE and CGN. The incidence of
PE increased in advanced stages of CKD, but the differences were not significant: 19.8%
- in CKD1, 35.3% - CKD2, 35% - CKD3, 66.7% - CKD4, p=0.112. The frequency of PE
depended on the presence of baseline nephrotic-range proteinuria (NPU) and chronic
MO253 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED arterial hypertension (AH): PE was observed in women w/o NPU and w/o AH in 8.3%
DOSE-RANGING STUDY (LUMINA-1 STUDY) TO EVALUATE cases, w/o NPU and with AH – in 39%, with NPU and w/o AH – in 44,4%, with NPU
THE SAFETY AND EFFICACY OF CCX140 IN SUBJECTS and with AH – in 43.8%, p=0.00048.
WITH FOCAL SEGMENTAL GLOMERULOSCLEROISS (FSGS)* Preterm delivery, CS and LBW were more common in women with chronic renal
failure, and their frequency increased with increasing severity of CKD: CKD1 – 3.5%,
Frank Cortazar1,2, John L. Niles3, Thomas J. Schall4, Peter Staehr5 21.2%, 3.5% resp.; CKD2 – 6.7%, 53.3%, 20%; CKD3 – 40%, 70%, 40%; CKD4 – 100%,
1
Massachusetts General Hospital, Division of Nephrology, Boston, United States of 100%, 100% (p<0.0001, for all characteristics). We found differences in gestational age
America, 2New York Nephrology Vasculitis and Glomerular Center, Albany, United at delivery depending on the stages of CKD: in CKD1 it was 38.9 6 1.3 wks, CKD2 –
States of America, 3Massachusetts General Hospital, Vasculitis & Glomerulonephritis 38.2 6 2.1 wks, CKD3 – 36.3 6 3.5 wks, CKD4 – 32.4 wks (one child), p=0.00013. The
Center, Boston, United States of America, 4ChemoCentryx, Inc., Mountain View, United proportion of newborns requiring intensive care was higher in mothers with CKD3
States of America and 5ChemoCentryx, Inc., Translational Medical and Clinical (30%) and CKD4 (100%) compared with CKD1 (0%) and CKD2 (13.3%), p<0.0001.
Development, Mountain View, United States of America Five of 126 (4%) patients in CGN group achieved stage 5 CKD with average
postpartum follow-up period of 92.6 6 20.5 months; 4 women had CKD3 during
BACKGROUND AND AIMS: Primary Focal Segmental Glomerulosclerosis (FSGS) is pregnancy, one – CKD1. Now 2 patients are treated with regular hemodialysis, 3 - live
the most common primary glomerular disease in patients with end stage renal disease with kidney transplant.
in the United States. Current treatment regimens target reduction in proteinuria, but CONCLUSION: Chronic glomerulonephritis has a negative effect on pregnancy
may have limited response or exhibit disease recurrence. CCX140 is an orally- course, increasing the incidence of PE and CS and contributing to reduce gestational
administered selective small molecule inhibitor of the C-C chemokine receptor 2 age and birth weight. Incidence of preterm delivery, CS, LBW and proportion of
(CCR2) under investigation for the treatment reduction of proteinuria in patients with newborns treated in NICU were highest in patients with CKD 3-4.
FSGS.
The primary objectives of this study were to evaluate the safety and efficacy of CCX140
in patients with FSGS and a urine protein to creatinine ratio (UPCR) of 1 g/g.
Efficacy was assessed by the change in UPCR.

10.1093/ndt/gfab104 | i203
Abstracts Nephrology Dialysis Transplantation

event (defined as 50% decline in eGFR, CKD Stage 5, dialysis or transplantation) was
required for the renal event analysis and similarly, at least 12 months follow-up was
required for the decline in eGFR analysis. For the relationship between proteinuria and
risk of renal events, 4 studies including 5 comparisons were identified, while 9 studies
including 10 comparisons were identified for the analysis of proteinuria vs eGFR
decline. Proteinuria change from baseline was calculated from the value closest to 6
months. If annualized change in eGFR was reported, these data were used, otherwise
annualized change in eGFR was calculated per year of follow-up. Methods as described
by Burzykoski & Buyse (2006) and Joffe & Greene (2008) were used for TL meta-
regression analyses; the resulting meta-regression line was displayed with an 80%
credible interval band (CB). Given the assumptions made in this analysis, a SWR
analysis was also performed; to compensate for potential underestimation of error
associated with the regression line, a 99.9% CB was applied in the SWR analysis.
RESULTS: For RASB treatment effects on renal events, a statistical association was
found with treatment effects on proteinuria with a TL slope estimate = 15.30 95% CI
(0.57, 38.79), R2 = 0.88 95% CI (0.22, 1.00); using the lower CI of 0.75 for the estimated
slope, a 30% treatment effect on proteinuria would be expected to result in at least a
25% reduction in the risk of renal events. As individual subject level data were not
available, the correlation between errors on treatment effects for proteinuria and
treatment effects for renal events were unknown, resulting in a wide CB on the meta-
regression line and a wide CI for the slope estimate. The SWR approach is not
hampered by lack of subject level data and gave a slope estimate of 3.5 95% CI (2.1, 5.0)
MO255 LONG-TERM MAINTENANCE TREATMENT WITH RITUXIMAB with R2 = 0.97, such that a 30% treatment effect on proteinuria would be expected to
IN ANCA-ASSOCIATED VASCULITIS: A RETROSPECTIVE result in at least a 64% reduction in the risk of renal events. For treatment effects on
COHORT STUDY annualized eGFR versus effects on proteinuria, the TL slope estimate was -5.1 95% CI
(-30.2, 35.0), R2 = 0.89 95% CI (0.15, 1.00); the corresponding SWR slope estimate was
Aglaia Chalkia1, Konstantinos Thomas2, Dimitrios Kourniotis1, -7.6, 95% CI (-12.3, -2.8) with R2 = 0.71. A 30% treatment effect on proteinuria would
Alexandros Panagiotopoulos2, Zoe Alexakou1, Margarita Mpora1, be expected to result in a 2.6 mL/min (TL analysis) to 3.9 mL/min slower decline (SWR
George Aggelis1, Dimitrios Vasilopoulos2, Dimitrios Petras1 analysis) in annualized eGFR.
1
Hippokration General Hospital, Athens, Greece, Nephrology Department, ATHENS,
Greece and 2National and Kapodistrian University of Athens, School of Medicine -
Clinical Immunology - Rheumatology Unit, 2nd Department of Medicine, Athens,
Greece, Joint Rheumatology Program, ATHENS, Greece

BACKGROUND AND AIMS: There is limited guidance and evidence for the ideal
duration of maintenance treatment in ANCA-associated vasculitis (AAV) with
rituximab (RTX). This study aimed to describe the efficacy and safety of long-term
maintenance treatment with RTX, in a cohort of patients with AAV.
METHOD: Retrospective, descriptive study of 62 patients with AAV. We included 42
patients, who received RTX maintenance treatment in a newly diagnosed or a relapsed
disease. We recorded the duration, dosage, and adverse events (infections, infusion-related
events, relapses, late onset leukopenia, malignancy and hypogammaglobulinemia).
RESULTS: 43 patients (average age 60.33 years, 49% women) received fixed interval dosing
with RTX maintenance 1000 mg every 6 months. The most frequent organ involvement
(74%) was lung and/or kidney. 33% (14/43) of the patients received RTX maintenance in a
relapsed disease. The RTX regimen was followed after induction treatment with rituximab
(47%), cyclophosphamide (33%), combination cyclophosphamide and rituximab (14%) or
methotrexate/MMF (6%). Median total duration of maintenance treatment was 24 months
(range 6-72 months). The most frequent adverse event was serious infections in 23% of the
patients, including SARS-CoV-2 in two patients, while four of these patients died. We also
recorded: hypogammaglobulinemia in 14%, malignancy in 5% and infusion-related events
in 2%. The rate of the major relapses in our cohort during RTX maintenance was quite low MO256 Figure 1: Trial Level (A, C) and Simple Weighted Linear Regression (B, D)
at 7% (3/43), the time between 24-60 months, and the rate of the major relapses dependent analyses of the relationship between treatment effects of RASB on proteinuria and (i)
on the induction treatment was quite the same: cyclophosphamide group vs rituximab renal events (A, B) and (ii) annualized change in eGFR (C, D)
group (7 vs 10%, p=0.786).
CONCLUSION: In our cohort long-term maintenance treatment in AAV with
rituximab maintains remission for longer time, with a quiet safety profile. This could
suggest that in selected patients, extended periods of rituximab treatment might be safe.

MO256 THE TREATMENT EFFECT OF RAS BLOCKADE ON


PROTEINURIA IN IGA NEPHROPATHY PATIENTS AS A
SURROGATE FOR RENAL EVENTS AND DECLINE IN EGFR:
AN ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Alex Mercer1, Kevin Carroll2, Leah Conley3, Jonathan Barratt4


1
JAMCO Pharma Consulting AB, Enskede, Sweden, 2KJC Statistics Ltd., Cheshire, United
Kingdom, 3Travere Therapeutics, Inc., San Diego, United States of America and
4
University of Leicester, Leicester, United Kingdom

BACKGROUND AND AIMS: Renin-Angiotensin System Blockade (RASB) is the


cornerstone of standard-of-care in IgA nephropathy. Randomized controlled trials
(RCTs) have shown the treatment benefit of RASB therapy on proteinuria and risk of
renal failure. The objective of this study was to describe the relationships between the
treatment effect of RASB on proteinuria and (i) risk of renal events, and (ii) decline in
eGFR, as an endpoint proximal to renal failure. To this aim, trial level (TL) and simple
weighted linear regression (SWR) analyses were conducted on RCTs identified through
a systematic literature review, with RASB as the active intervention.
METHODS: A systematic literature review of available peer-reviewed literature from
1990 to 2020 was performed applying the following inclusion criteria: RCT in patients
with biopsy-proven IgAN, investigating the effects of RASB as an intervention, sample
size >25, measurement of proteinuria at baseline and at >3 months. At least 1 renal

i204 | Abstracts
Nephrology Dialysis Transplantation Abstracts
or without the addition of BLM.

CONCLUSION: In patients with IgAN, associations were seen between treatment


CONCLUSION: The addition of BLM compared to standard of care in SLE patients
effects of RASB on proteinuria and on the clinically relevant endpoints of renal events
leads to an increase of memory B cells in the circulation which appeared independent
and annualized change in eGFR. Consistent with TL analyses of RCTs across a variety
of proliferation. The process was accompanied with a strong modulation of gene-
of mechanisms of actions, these data, specific to RASB, contribute to the growing
expression levels including a reduced expression of migration markers pointing
evidence base supporting the use of proteinuria as a valid surrogate endpoint in IgAN.
towards disrupted lymphocyte trafficking. Altogether, these data could have important
implications to further improve treatment strategies in severe SLE or lupus nephritis
patients, for instance by establishing a deeper depletion of (autoreactive) memory B
MO257 BELIMUMAB ADD-ON THERAPY MOBILIZES MEMORY B cells by the addition of rituximab after the initiation of belimumab.
CELLS INTO CIRCULATION OF SLE PATIENTS

E.J. Arends1, Mihaela Zlei2, Christopher M. Tipton3, Zgjim Osmani1,


MO258 SAFETY, TOLERABILITY, PHARMACOKINETICS AND
S.W.A. Kamerling1, Ton Rabelink1, Ignacio Sanz3, J.J.M. Van Dongen2, Cees Van
PHARMACODYNAMICS OF VIS649, AN APRIL-
Kooten1, Y.K.O. Teng1
1
NEUTRALIZING IGG2 MONOCLONAL ANTIBODY, IN
Leiden University Medical Center (LUMC), Nephrology, Leiden, The Netherlands, HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-
2
Leiden University Medical Center (LUMC), Immunology, Leiden, The Netherlands and BLIND, PLACEBO-CONTROLLED, SINGLE ASCENDING DOSE
3
Emory University School of Medicine, Lowance Center for Human Immunology, STUDY
Division of Rheumatology, Department of Medicine, Atlanta, United States of America
Yusuke Suzuki1, Mohit Mathur2, Jonathan Barratt3, Frank Engler4, Jill Yarbrough2,
BACKGROUND AND AIMS: Belimumab (BLM), a recombinant human IgG-1k Susan Sloan2, David Oldach2
monoclonal antibody directed against B-cell activating factor (BAFF), is the first 1
Juntendo University Faculty of Medicine, Department of Nephrology, Tokyo, Japan,
approved biological agent for patients with active severe systemic lupus erythematosus 2
Visterra Inc., Waltham, United States of America, 3Leicester General Hospital, John
(SLE) and lupus nephritis (LN). There is clinical evidence that combining belimumab Walls Renal Unit, Leicester, United Kingdom and 4Certara USA Inc., Princeton, United
with B cell depleting therapy can ameliorate disease activity in severe, refractory SLE States of America
patients. Although BLM is a B cell directed therapy and has been shown to significantly
decrease total B cells, flow cytometry observations suggest a rapid increase of
BACKGROUND AND AIMS: Immunoglobulin A (IgA) nephropathy (IgAN) is a
circulating memory B cells. The present study investigated the dynamics of B cell
glomerulonephritis characterized by the presence of circulating and glomerular
subsets in patients treated with or without BLM, with a special focus on the memory
immune complexes containing galactose-deficient (Gd) IgA1. A proliferation-inducing
compartment in order to assess the characteristics of these memory B cells.
ligand (APRIL), a member of the tumor necrosis factor superfamily of ligands, is
METHOD: We first performed extensive B cell subset phenotyping by high sensitivity
thought to play a key role in the pathogenesis of IgAN by virtue of its role in class-
flowcytometry according to the Euroflow protocol on whole blood from active lupus
switching to IgA production. VIS649, a humanized immunoglobulin G (IgG2)
nephritis or SLE patients with other major organ involvement treated with standard of
monoclonal antibody that binds to and blocks the biological actions of APRIL, is in
care (SOC) consisting of high dose steroids and mycophenolate mofetil combined with
clinical development as a potential treatment for IgAN. The primary objective of this
or without the addition of BLM. Next we characterized memory B cell gene expression
first-in-human study was to evaluate the safety and tolerability of VIS649 in healthy
profiles with single-cell RNA and V(D)J sequencing (ScRNA-SEQ).
volunteers. Secondary objectives included characterization of the pharmacokinetics
RESULTS: By employing high sensitivity flowcytometry, we established that the absolute
(PK) and pharmacodynamics (PD) of VIS649.
increase in circulating memory B cells in SLE and LN patients was significant for patients
METHOD: This was a Phase 1, randomized, double-blind, placebo-controlled, single
who initiated BLM but not for patients treated with standard of care (Figure 1). The increase
ascending dose study of VIS649 in healthy adult male and female volunteers
was observed in a broad range of memory B cell subsets (Unswitched, IgG1þ, IgG2þ,
(ClinicalTrials.gov identifier: NCT03719443). The study was conducted in sequential dosing
IgA1þ, IgA2þ) at 2 and 4 weeks following initiation of BLM treatment. This rise in
cohorts. The first four cohorts (0.5, 2.0, 6.0, and 12.0 mg/kg, respectively) each enrolled 9
memory B cells could hypothetically be attributed to either proliferation or homeostatic
participants (4 of Japanese descent and 5 of non-Japanese descent) who were randomized to
modulation of tissue-resident memory B cells causing a release into the circulation. ScRNA-
VIS649 or placebo in a ratio of 7:2. In addition, a fifth cohort enrolled 15 adults randomized
SEQ cell cycle gene-expression was performed and established in both groups a non-
to receive VIS649 6.0 mg/kg or placebo (10:5), followed by tetanus/diphtheria vaccine
proliferating phenotype [in approximately 94%] of memory B cells post-treatment, RV
challenge after 28 days (TENIVAC , Sanofi Pasteur Limited; the effect of APRIL inhibition
including absence of MKI67 as active proliferation marker. Additionally, BLM treatment did
on vaccine response is described in a companion abstract). Participants received intravenous
not result in an increased, and even in a severe reduction of the largest memory B cells
administration of study drug on Day 1, were discharged from the institution on Day 2, and
clones after two weeks. In contrast, no change in clonality was seen after treatment with
were followed for 16–24 weeks on an outpatient basis. Standard safety assessments and
SOC. Together these data indicate that proliferation is not likely to be responsible for the
blood sampling for PK and PD were performed at regular intervals.
observed increase in memory B cells by BLM. Furthermore, a clear difference was found in
RESULTS: 51 participants were randomized and dosed with study drug, of whom 47
gene-expression levels between both treatment groups: BLM was responsible for the
(92.2%) completed the study. VIS649 was well tolerated, with no serious adverse events
upregulation of 72 vs 10 genes in SOC, likewise 162 vs 32 genes were downregulated. Most
(AEs) or AEs that led to study discontinuation. Most treatment-emergent AEs
importantly, a significant downregulation of the migration genes SELL (CD62L), CCR7,
(TEAEs) were mild; the incidence and severity of TEAEs were not dose dependent.
ITGB1, RAC2 and ICAM2, were specifically seen in BLM treated patients, possibly
One participant in the 2.0 mg/kg group experienced a severe TEAE of syncope
reflecting disrupted lymphocyte trafficking preventing memory B cells to either transmigrate
following phlebotomy that the investigator considered unlikely to be related to study
into tissue or be retained at the tissue level.
drug. There was no clinically relevant effect of treatment on laboratory tests, vital signs,
electrocardiogram parameters, or physical examinations. VIS649 had non-linear PK:
half-life (t1=2) increased with dose, while drug exposure (AUC) increased in a greater
than dose proportional manner. Serum IgA, Gd-IgA1, IgG, and IgM were reversibly
suppressed in a dose-dependent manner following VIS649 administration. The
maximum mean percentage reductions from baseline occurred at Week 12 for the 12.0
mg/kg dose: IgA, -57.2% (Figure); Gd-IgA1, -71.6% (Figure); IgG, -33.6%; and IgM, -
67.2%. These reductions were reversible and showed a dose-response effect with
respect to time-to-recovery. Mean free (non-VIS649 bound) serum APRIL levels
decreased to the lower limit of quantification (50 pg/mL) for all VIS649 doses at Week
1, and also showed a dose-response effect with respect to time-to-recovery. No
depletions in circulating lymphocyte populations were observed. There were no
significant PK or PD differences between Japanese and non-Japanese participants.

MO257 Figure: Depicted are the absolute pre-germinal center and memory B cell
counts at week 0 compared to week 4 of 19 SLE or LN patients treated with SOC with

10.1093/ndt/gfab104 | i205
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: A single dose of VIS649, up to 12.0 mg/kg, was safe and well tolerated
in healthy adults and was able to suppress free serum APRIL to the lower level of
quantification. Serum Gd-IgA1 decreased in parallel with total serum IgA and MO260 PERFORMANCE ANALYSIS OF AN ARTIFICIAL NEURAL
recovered in a dose-dependent manner following reappearance of free APRIL in NETWORK TOOL TO PREDICT ESKD IN PATIENTS WITH
serum. These data support the further clinical development of VIS649 as a potential IMMUNOGLOBULIN A NEPHROPATHY (IGAN)
treatment for IgAN.
Francesco Paolo Schena1, Carlo Manno1, Vto Walter Anelli2, Tommaso Di Noia2,
Giovanni Luigi Tripepi3, Daniela Isabel Abbrescia4, MARIA STANGOU5,
Aikaterini Papagianni5, Maria Luisa Russo6, Rosanna Coppo6
MO259 LYMPHOPENIA AT ANCA-GLOMERULONEPHRITIS 1
university of bari, Emergency and Organ Transplantation, Bari, Italy, 2Polytechnic of
DIAGNOSIS IS CORRELATED WITH SEVERITY AND RENAL Bari, Electrical Information Engineering, Bari, Italy, 3CNR-IFC, Clinical Epidemiology and
PROGNOSIS Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy, 4Schena
Foundation, Bari, Italy, 5Hippokration General Hospital, Aristotle University of
Samuel Wacrenier1,2, Jeremie Riou3,4, Pierre Jourdain2, Fanny Guibert2,5, Thessaloniki, Dept of Nephrology, Thessaloniki, Greece and 6Fondazione Ricerca
NICOLAS HENRY2,6, DJEMA Assia5, Jean Philippe Coindre1, Romain Crochette1, Molinette, Torino, Italy
Maud Cousin2, Anne Croue7, SUBRA Jean François2, Giorgina Piccoli1,
AUGUSTO Jean François2, Benoit Brilland2
1 BACKGROUND: During the last twenty years many tools, based on mathematical
Centre hospitalier du Mans, Service de Néphrologie, Le Mans, France, 2Centre hospital- models, have been developed to predict ESKD at the time of kidney biopsy in patients
ier universitaire d’Angers, Service de Néphrologie, Angers, France, 3Université d’Angers, with IgAN. The main limitation of these tools is the time frame to reach the ESKD.
Micro et Nanomédecines Translationnelles, MINT, UMR INSERM 6021, UMR CNRS 6021, Recently, we have developed a Clinical Decision Support System (CDSS) (KI 2020)
Angers, France., Angers, France, 4Université d’Angers, Methodology and Biostatistics which includes 6 variables at the time of kidney biopsy: age, sex, hypertension, serum
Department, Delegation to Clinical Research and Innovation, Angers, France, 5Centre creatinine, daily proteinuria and score of the renal lesions according to the MEST-C
hospitalier de Cholet, Service de Néphrologie, Cholet, France, 6Centre hospitalier de classification. The tool (www.igan.poliba.it) is based on two different artificial neural
Laval, Service de Néphrologie, Laval, France and 7Centre hospitalier universitaire networks of which the first predicts ESKD and the second one predicts the time to
d’Angers, Département de pathologie cellulaire et tissulaire, Angers, France reach this outcome.
AIM: of our study has been to analyze the causes of discordance to predict or not
BACKGROUND AND AIMS: Lymphopenia is commonly observed in various ESKD in a cohort of 1116 IgAN patients (VALIGA cohort and external cohort) with a
autoimmune diseases, such as systemic lupus erythematosus, where it has been median follow-up of 88 months (49-135). To our knowledge this is the first report
associated with disease activity or prognosis. However, in ANCA-associated vasculitis which analyzes the discrepant results of a toll to predict ESKD in IgAN patients.
(AAV) only few, small-scale studies have been targeted to this issue. Research has not METHOD: Demographic and laboratory data have been analyzed using means and
yet focused on ANCA-glomerulonephritis (ANCA-GN) patients. Thus, the aim of this standard deviations (SD) for continuous variables normally distributed, median in
study was to analyze the association between lymphocyte counts and outcomes in a presence of non-normally distribution. Categorical variables are expressed as
large cohort of ANCA-GN patients. percentages. The means have been compared by the Student’s test and the medians
METHOD: We used the Maine-Anjou AAV registry that retrospectively gathers data using the Mann-Whitney U test. All the data were collected and stored in a standard
on consecutive patients affected by AAV in four French Nephrology Centers, recorded Excel database. The statistical significance value p< 0.05 has been adopted.
since January 2000. We analyzed clinical, biological, and histological data at diagnosis RESULTS: Discordance to reach or not ESKD was found in 216 patients (19.4%). In 77
of ANCA-GN. Biological data, including lymphocyte counts, were collected before the patients with no prediction of ESKD, 25 patients with proteinuria > 0.5 g/day did not
administration of any immunosuppressive treatment. Risk factors for end-stage kidney receive therapy after kidney biopsy or were cared very late. Failure of therapy (RASBs
disease (ESKD) were analyzed. Event-free survival was also assessed. alone in 44 subjects and corticosteroids in 8 individuals) was observed in 52 patients.
RESULTS: Among the 145 patients included in the study, 53 (37%) patients presented In 139 patients who did not reach ESKD but our tool predicted this outcome,
with lymphopenia at ANCA-GN diagnosis. Lymphopenic patients were older (72 [63– interestingly, we found that 106 proteinuric patients (22 with GFR >50 ml/min/1.73
79] vs 66 [56–73] years old, p = 0.010), had a lower renal function at baseline (eGFR 13 m2 and 84 with GFR < 50 ml/min/1.73 m2) had an improvement of the clinical course
mL/min vs 26 mL/min, p = 0.002), and a higher proteinuria (1.86 [1.21–3.52] g/g vs (reduction of proteinuria and stabilization of GFR value) after corticosteroid therapy.
1.30 [0.75–2.65] g/g, p = 0.042). There was a trend for a higher BVAS (18 [14–22] vs 15 The remaining 33 patients benefited of RASB therapy. Among 84 patients with GFR<
[12–20], p = 0.076) in lymphopenic patients. Therapeutic management between the 50 ml/min/1.73 m2 36 had nephrotic proteinuria and were responsive to
two groups was similar. There was no difference in relapse rate between the two groups corticosteroids. These results suggest that we cannot rule out corticosteroid therapy in
but lymphopenic patients were more likely to require kidney replacement therapy patients with reduced GFR and proteinuria > 3 g/day. Furthermore, our tool predicts
(51% vs 25%, p = 0.003) and were more likely to die (34% vs 17%, p = 0.039). the time frame to reach ESKD and indicates the potential effect of some drugs (RASBs,
Lymphopenia was correlated with histological lesions and especially with the corticosteroids or their combination) to delay the outcome. We observed that
percentage of sclerotic glomeruli (p = 0.0027). ESKD-free survival and overall survival corticosteroids combined with RASBs delayed more than 10 years the time to reach
were lower in lymphopenic patients (p < 0.0001 and 0.0051 respectively). In ESKD.
multivariate Cox analysis, lymphopenia, but not death, was an independent risk factor CONCLUSIONS: Our tool predicted ESKD in a percentage higher than that observed
for ESKD (HR 4.47 (95% confidence interval: [2.06–9.72], p < 0.001). but, interestingly, it was found that a high number of patients benefited of
CONCLUSION: Lymphopenia correlates with severity of ANCA-GN at diagnosis and corticosteroids in combination with RASBs. Furthermore, our tool predicted time to
predicts poor renal outcome. In this view, lymphopenia could be used as a simple and reach ESKD and indicated the potential benefit of therapy to delay the crude outcome.
cost-effective biomarker to assess renal prognosis at ANCA-GN diagnosis. In fact, therapy delayed the outcome of more than 10 years when combination of
corticosteroids and RASBs was administered. Therefore, our tool shows to physicians
that their patients may delay the ESKD receiving corticosteroids alone or in
combination with RASBs. This approach is important because in many cases it is a
strengthen point to convince patients to accept the prescribed therapy. Moreover, this
report shows for the first time that predicted ESKD may be delayed administering
personalized therapy suggested by our tool. Essentially, in a high percentage of patients
the failure of our tool is not an error but the positive effect of therapy or misconduct of
patients management.

MO261 LUPUS NEPHRITIS AND COVID-19 INFECTION

Daniela Valentinova Monova1, Simeon Monov2


1
Medical Institute, Medical University - Sofia, Department of Internal Mediicine
Nephrology and Rheumatology, Sofia, Bulgaria and 2Medical University - Sofia,
Department of Rheumatology, Sofia, Bulgaria

BACKGROUND AND AIMS: Covid-19 infection poses a serious challenge for


immune-compromised patients with autoimmune systemic diseases. This is likely due
to a combination of immune dysfunction, immunosuppressive therapy and excess co-
morbidities.
The aim of this study is to describe clinical characteristics of patients with lupus
nephritis (LN) and Coronavirus disease 2019 (COVID-19), and to identify baseline
variables associated with a severe infection requiring hospitalization.

i206 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: A telephone survey investigating the impact of COVID-19 on patients with (A) Fourteen distinct cell clusters identified by UMAP plotting, and clusters were
biopsy - proven LN was administered. Data extraction included diagnosis, disease colored and labeled distinctively. The color of cells represented the group origin. (B)
activity status, demographics, occupational exposure, adherence to social distancing UMAP plot of cell clusters from different subjects of IgAN patients (n=4) and control
advise, therapy, comorbidities, and laboratory tests. Covid-19 was classified as definite (n=1). The color of cells reflected the individual origin. (C) Bar plots represented
diagnosis of Covid-19 disease (presence of symptomatic Covid-19 infection, confirmed frequency of cell clusters in kidneys from different subjects. Blocks represented
by a nasopharyngeal SARS-CoV-2 polymerase chain reaction test). Comparisons different subjects, and block height was in proportion to the number of cells. (D)
between patients with or without hospitalization were performed. Heatmap of top 20 specific marker genes for each cluster from kidney. Each column
RESULTS: 114 patients (median age 34,9 6 12,4 years) with LN were included in the represented a kind of cell cluster, and each row corresponded to marker gene for
study. All were on different doses glucocorticoids, 82 were taking hydroxychloroquine individual cluster. (E) Violin plot of selected marker genes that identified the clusters
and 30 took immunosuppressants. 31 patients (26 women, 5 men) developed generated by UMAP plotting. It was colored by different cell subtypes. Abbreviations
symptomatic COVID-19 infection - they have at least one symptom (chest pain, fever, were as follows: PTC, proximal tubule cells; LOH, loop of henle cells; PC, principal
asthenia, chills, cough, sore throat, dyspnea, headache, arthralgia, myalgia, cells; IC, intercalated cells; DTC, distal tubule cells; EC, endothelial cells; POD,
odynophagia, diarrhea, conjunctivitis, hypo-, ageusia, hypo-, anosmia) of COVID-19 podocytes; MES, mesangial cell; SMC, smooth muscle cells; DC, dendritic cells; MC,
and were PCR test positive. These 31 patients prior to their COVID-19 illness were macrophages; MON, monocytes; CC, cycling cells; FIB, fibroblasts.
treated with methylprednisolone, 16 - with cyclophosphamide, 8 - with azathioprine, 3
– with hydroxychloroquine. Six patients (4 men, 2 women) required hospitalization -
these were more frequently older and with comorbidities (cardio-respiratory illness,
hypertension and other) and active LN (3 –class IV LN, 2-class V LN, 1 class III LN
and 1 Class II LN, according the 2003 ISN/RPS classification). Adherence to therapy
MO263 KLOTHO IS PROTECTIVE IN THE CONTEXT OF ACUTE
and to social distancing advise was high. The median time from onset of symptoms to
GLOMERULAR INJURY BUT IS NOT EXPRESSED IN
hospital admission was 6 (3-11) days. The median length of stay was 12 days (8-20)
PODOCYTES
days. No deaths occurred.
CONCLUSION: Covid-19 is more frequent in the subgroup of LN patients without
Emmanuelle Charrin1, Dina Dabaghie1, Rik Mencke2, Ilke Sen3, Katja Möller-
therapy with hydroxychloroquine, which might play some protective role against the
Hackbarth1, Sonia Zambrano1, Hannes Olauson4, Jaakko Patrakka1
most harmful manifestations of Covid-19. Male sex, previous lung disease, serum 1
creatinine level, proteinuria, glucocorticoids use > 5 mg/day, were associated to Karolinska Institutet Campus Huddinge, Laboratory Medicine, Huddinge, Sweden,
2
hospitalization of patients with LN. University of Groningen, Pathology and Medical Biology, Groningen, The Netherlands,
3
Karolinska Institutet Campus Solna, Physiology and Pharmacology, Stockholm,
Sweden and 4Karolinska Institutet Campus Solna, Clinical Science, Intervention and
Technology, Stockholm, Sweden
MO262 THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA
NEPHROPATHY
BACKGROUND AND AIMS: Podocyte integrity is crucial for the maintenance of
glomerular function in health and disease. Numerous studies have reported that Klotho
Yong Zhong1, Xiangcheng Xiao1
1
overexpression, or treatment with recombinant Klotho, reduces glomerular and
Xiangya hospital,central south university, Nephrology, changsha, P.R. China tubular damage in mouse models of renal disease. However, the mechanism(s) of
action are not fully understood. Several recent studies have also reported that Klotho is
BACKGROUND AND AIMS: The exact molecular mechanisms underlying IgA expressed in podocytes, where it protects against various types of injury. These findings
nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further conflict with previous studies, which have shown that renal Klotho expression is
elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. exclusively confined to proximal and distal tubular cells.
METHOD: Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies METHOD: To address this discrepancy and enhance our understanding of the
from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the putative glomeruloprotective effects mediated by Klotho, we examined the expression
single-cell resolution. Unsupervised clustering analysis of kidney specimens was used pattern of Klotho in human and mouse kidney by several different methods, and
to identify distinct cell clusters. Differentially expressed genes and potential signaling explored its protective effects by overexpressing full-length human Klotho directly in
pathways involved in IgAN were also identified. podocytes or in a distant organ (i.e. liver).
RESULTS: Our analysis identified 14 cell subsets in kidney biopsies from IgAN RESULTS: Data at the mRNA and protein levels all converged towards an absence or
patients, and analyzed changing gene expression in distinct renal cell types. We found very low expression of Klotho in podocytes. The generation of a podocyte-specific
increased mesangial expression of several novel genes including MALAT1, GADD45B, Klotho knockout mouse further demonstrated that its deletion did not affect
SOX4 and EDIL3, which were related to proliferation and matrix accumulation and glomerular structure or function. Moreover, Klotho deficiency did not worsen
have not been reported in IgAN previously. The overexpressed genes in tubule cells of glomerular injury in an experimental model of glomerulonephritis (anti-GBM).
IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 However, when Klotho was overexpressed in hepatocytes (Alb-cre;hKlothofl/þ - Alb-
signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk hKL), serum Klotho increased drastically with no changes in Fgf23 or phosphate
analysis revealed potential interactions between mesangial cells and other cells in metabolism. In mice challenged with anti-GBM, renal histology and ultrastructure of
IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating the filtration barrier was less severely affected in Alb-hKL compared to WT mice.
in several signaling pathways which may be involved in pathogenesis of progression of There were also significantly less albuminuria, podocyte loss and interstitial fibrosis in
IgAN. Alb-hKL mice compared to their WT littermates. In contrast, mice which
CONCLUSION: The comprehensive analysis of kidney biopsy specimen demonstrated overexpressed Klotho in podocytes (Pod-hKL) were not protected from renal injury.
different gene expression profile, potential pathologic ligand-receptor crosstalk, CONCLUSION: Taken together, these results strongly suggest that Klotho is not
signaling pathways in human IgAN. These results offer new insight into pathogenesis expressed in any substantial amounts in human or mouse podocytes, and that
and identify new therapeutic targets for patients with IgA nephropathy. membrane-bound Klotho does not play a role in podocyte biology. Importantly, our
results confirm a beneficial role for soluble Klotho in protecting podocytes against
injury, and in maintaining glomerular integrity and function.

MO264 COMPLEMENT PATHWAY MIGHT HAVE A ROLE IN FOCAL


SEGMENTAL GLOMERULOSCLEROSIS: A RETROSPECTIVE
SINGLE CENTER STUDY OF 15 YEARS

Rezzan Eren Sadiog lu1, Saba Kiremitçi2, Merve Aktar1, S¸ule S¸engül1,
Derya Gokmen3, Serkan Akturk1, Kenan Keven1, Gökhan Nergizoglu1,
S¸ehsuvar Ertürk1, Kenan Ateş1, Arzu Ensari2, Sim Kutlay1
1
Ankara University School of Medicine, Department of Nephrology, Ankara, Turkey,
2
Ankara University School of Medicine, Department of Pathology, Ankara, Turkey and
3
Ankara University School of Medicine, Department of Biostatistics, Ankara, Turkey

BACKGROUND AND AIMS: The role of complement in focal segmental


glomerulosclerosis (FSGS) is an area of interest and C4d staining could indicate
complement related renal damage. We investigated detailed C4d staining properties in
native kidney biopsies and possible relation to clinical features.
METHOD: We retrospectively evaluated the renal biopsies of 114 patients diagnosed
with FSGS within last 15 years. C4d expressions examined in glomeruli (mesangial
MO262 Figure 1: Cell lineage analysis by comprehensive single-cell RNA-sequencing and/or capillary wall, vascular pole, sclerotic areas), tubular region (basement
in IgAN and control subjects membrane, adsorbtion droplet) and vascular areas (arteriols and arteries) via
immunohistochemistry. A novel glomerular C4d score (G-C4d-S) was achieved on the

10.1093/ndt/gfab104 | i207
Abstracts Nephrology Dialysis Transplantation

basis of the localization, pattern, extent and intensity of the C4d expression (min-max, BACKGROUND AND AIMS: IgA nephropathy (IgAN) is the most common form of
0-13). primary glomerulonephritis worldwide and is a frequent cause of end-stage renal
RESULTS: Of the patients (56 females, mean age 43614 years) with a median follow- disease. The best predictors of progression are histologic parameters. Nevertheless,
up time of 3563 months, mean proteinuria, eGFR, and albumin level were 4984 mg/ there is a pressing need to identify suitable noninvasive biomarkers in IgAN, to aid
day, 72.2 ml/min/1.73m2, 3.56 g/dL, respectively. Median G-C4d-S was 6 (IQR, 4-7) with diagnosis, treatment decisions, and prediction of the disease progression.
and it was negatively correlated with serum creatinine at diagnosis (r=-0.21, p=0.02). Our aim was to assess diagnostic value of urinary excretions of transferrin and IgG in
Glomerular staining (both focal and diffuse, higher than moderate in intensity) was prediction of morphological lesions in patients with IgAN.
positive in 78 (68.4%) of the patients. C4d on glomerular sclerotic area was positive in METHOD: 37 patients [19 female, age Me 33 (25; 48) years] with biopsy proven IgAN
43 (37%) patients and it was associated with lower eGFR at diagnosis. and without acute kidney injury, infectious diseases, severe heart failure, respiratory
Forty five patients achieved remission during the follow-up. Among the pathological insufficiency, cancer were included in the study. 24-hour urinary excretions of
features only glomerular C4d staining was associated to remission (p=0.02). There transferrin (uTr), IgG (uIgG) were measured by immunoturbidimetric method
were 20 (18.7%) patients who need renal replacement theraphy (RRT) and 7 deaths (Furuno CA-90, Furuno Electric Co., Ltd., Japan). Tubulointerstitial fibrosis (TIF) and
(6.1%) at the end of the cohort. Lower rate of C4d staining on tubular adsorption tubular atrophy (TA) were assessed semi-quantitatively (0-lesions absent; 1-mild focal
droplets and arteriols/arteries were found to be associated need for RRT (p=0.013, tubular and interstitial lesions; 2-moderate tubular and interstitial lesions; 3-diffuse
p=0.012, respectively). There were no significant relationship between mortality and tubular and interstitial lesions). All patients consistently were separated into two
C4d staining features. groups according to the degree of each morphological lesion (TIF or TA): “mild” (TIF
CONCLUSION: In conclusion, we noted that significant number of patients had or TA grade 0 or 1) and “severe” (TIF/TA grade 2-3).
positivie C4d on glomeruli, arteiroles and tubular area. We indicated that C4d staining RESULTS: uTr, uIgG positively correlated (p<0,05) with TIF (r=0,38, r=0,43) and TA
at diagnosis could help to distinguish active glomerulonephritis. Additionally, it seems (r=0,38, r=0,45), respectively. We did not find correlations between uTr, uIgG and
to be essential to examine non-glomerular area of native kidney biopsies, as well. glomerulosclerosis.
Using ROC-analysis all patients were separated in two groups using uTr or uIgG
according to the degree of morphological lesions (“mild” or “severe) (Table 1,2;
Figure 1).

MO266 Figure: ROC curves of urinary transferrin and IgG excretions in prediction: A
MO265 LONGITUDINAL CHANGE IN PROTEINURIA AND KIDNEY – TIF; B –TA.
OUTCOMES IN C3 GLOMERULOPATHY

Fernando Caravaca-Font an1, Elena Goicoechea de Jorge2, Manuel Praga1,3


1
University Hospital 12 de Octubre, Madrid, Spain, 2Complutense University of Madrid, MO266 Table 1. Diagnostic value of urinary Transferrin excretion in prediction of
Immunology, Madrid, Spain and 3on behalf of the Spanish Group for the Study of tubulointerstitial lesions
Glomerular Diseases (GLOSEN)
Urinary transferrin excretion, mg/24hour
BACKGROUND AND AIMS: The association between a change in proteinuria over Sn,% Sp% ACC,% AUC Cut-off value, p
time and its impact in kidney prognosis has not been analyzed in C3 glomerulopathy.
This study aims to investigate the association between the longitudinal change in mg/24hour
proteinuria and the risk of kidney failure. TIF 0-1 grade 81,3 69,2 75,9 0,726 31,92 0,031
METHOD: Retrospective, multicenter observational cohort study in 35 nephrology
departments belonging to the GLOSEN group. Patients diagnosed with C3
TA 0-1 grade 88,9 100,0 89,7 0,994 5,10 <0,001
glomerulopathy between 1995 and 2020 were enrolled. A joint modeling of linear
mixed-effects models was applied to assess the underlying trajectory of a repeatedly
measured proteinuria, and a Cox model to evaluate the association of this trajectory
MO266 Table 2. Diagnostic value of urinary IgG excretion in in prediction of
with the risk of kidney failure.
tubulointerstitial lesions
RESULTS: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15
dense deposit disease, with a median age of 26 years (range 13–41). During a median
follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in Urinary IgG excretion, mg/24hour
proteinuria showed a strong association with the risk of this outcome, with a doubling Sn,% Sp% ACC,% AUC Cut-off value, p
of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed
that a 50% proteinuria reduction over time was significantly associated with a lower mg/24hour
risk of kidney failure (HR: 0.79; 95%CI:0.56–0.97; p<0.001). This association was also TIF 0-1 grade 81,3 69,2 75,9 0,726 22,59 0,023
found when the 50% proteinuria reduction was observed within the first 6 and 12 TA 0-1 grade 85,2 100,0 86,2 0,926 10,67 <0,001
months of follow-up.
CONCLUSION: The longitudinal change in proteinuria is strongly associated with the
risk of kidney failure. The change in proteinuria over time can provide clinicians a According to the results of ROC-analysis we also found that all cut-off values of uTr,
dynamic prediction of kidney outcomes. uIgG corresponded to the level of urinary protein excretion not more than 1,25 g/
24hour.
CONCLUSION: Our results show that uTr and uIgG can be used as markers of early
tubulointerstitial lesions in patients with IgA nephropathy with mild protein excretion.
MO266 URINARY TRANSFERRIN AND IGG EXCRETIONS PREDICT
TUBULOINTERSTITIAL LESIONS IN PATIENTS WITH IGA
NEPHROPATHY

Saganova Elena1, Olga Galkina1, Vasiliy Sipovskii1, Alexei Smirnov1


1
Pavlov First Saint Petersburg State Medical University, Research institute of
Nephrology, Saint Petersburg, Russia

i208 | Abstracts
Nephrology Dialysis Transplantation Abstracts
the importance of the C3 positive staining in glomeruli and that there could be
differences between clinical, serological and histological phenotypes in AAV
patients.
MO267 HIGHER FRACTIONAL EXCRETION OF TOTAL PROTEIN IS A METHOD: This study included 106 consecutive AAV patients with renal involvement
PREDICTOR OF PROGRESSION IN IDIOPATHIC in the period from 2007-2017. We performed renal biopsy on patients using automatic
MEMBRANOUS NEPHROPATHY 16 Gauge needle. Light, immunofluorescent and electronic microscopy were
performed. Category variables were analysed with Fisher Exact testom and continuous
Hideaki Kuno1, Go Kanzaki1, Rina Oba1, Saeko Hatanaka1, Takaya Sasaki1, with Kruskal-Wallis testom. Statistical difference was then analysed posthoc with Chi-
Yusuke Okabayashi1, Kotaro Haruhara1, Kentaro Koike1, Nobuo Tsuboi1, square test. Primary outcomes were combined outcome progression to end-stage renal
Takashi Yokoo1 disease, defined as persistent (more than three months) need for renal replacement
1
The Jikei University School of Medicine, Division of Nephrology and Hypertension, therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI
Department of Internal Medicine, Tokyo, Japan formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse.
Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression
BACKGROUND AND AIMS: Lower estimated glomerular filtration rate (eGFR) and analysis were used to explore difference between phenotypes and finding significant
higher proteinuria are the most sensitive predictor of the development of progressive predictors regarding outcomes.
renal insufficiency in various glomerular diseases. On the other hand, the onset of RESULTS: The study included 106 AAV patients with renal involvement: 66 (61,1%)
idiopathic membranous nephropathy (iMN) shows insidious progression, and the MPA, 20 (18,5%) GPA, 20 (18,5%) RLV. There were 14 (13%) PR3-ANCA positive
prognosis varies significantly. Therefore, it is difficult to predict the renal outcome in patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCAþMPO-ANCA and 32
MN, using only the severity of proteinuria. Fractional excretion of total protein (29,6%) ANCA negative patients. Average SCr was 316,5 lmol/l (IQR 207,0-548,5), 24-
(FETP), which was protein clearance divided by creatinine clearance (Ccr), may be a hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). Histologicaly (Berden
better indicator of protein leak per functioning nephron. A recent study has also classification) 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed
reported that FETP accurately predicted transplant failure and was more sensitive and and 12 (11,1%) sclerotic class. Out of all, 48,5% MPA patients had C3 deposits in
specific than protein creatine ratio (PCR). Few studies, however, have analyzed the glomeruli compared to 25% GPA and 35% RLV though statistical significance was not
FETP to evaluate their relationship with renal function and histologic lesions in reached (p=0,1). Same applied for serological phenotypes: MPO-ANCA and ANCA
glomerular diseases. Thus, this study aims to assess the relationship between FETP and negatives had more C3 deposits but statistical significance was not reached (p=0,6).
the clinicopathological findings and whether FETP predicts outcome in iMN. When comparing histopathological classes there was strong tendency of crescentic
METHOD: This study included patients with iMN that underwent kidney biopsies class having more C3 deposits (p=0,076) compared to focal and mixed. In sclerotic
during the period from 2002 to 2020. We analyzed 24-h urinary protein excretion, class 50% had C3 deposits but C3 deposits can be ordinary found in sclerotic lesions so
FETP, and other clinicopathological findings at the kidney biopsy. The FETP was the interpretation is more challenging. Interestingly patients requiring haemodialysis
determined by the standard clearance technique based on 24-h urine collection: FETP had strong tendency of having more C3 deposits compared to those not needing
= (urinary total protein / serum total protein) / (urinary creatinine / serum creatinine) haemodialysis treatment (p=0,09).
 100. A 30% decrease in eGFR or the occurrence of ESRD were the endpoints. The CONCLUSION: Glomerular C3 deposits in kidney tissue samples could prove to be a
multivariate factors affecting the prognosis were analyzed with the Cox proportional- useful tool for perhaps predicting the severity and the course of the disease. Though
hazards model, and the cumulative risk of risk factors was analyzed by Kaplan-Meier differences between various groups in our cohort didn’t have statistical significance,
curve. there was a tendency for MPA patients, those with MPO-ANCA and those with
RESULTS: A total of 153 subjects with MN were identified and were followed up for a crescentic class of having higher proportion of C3 deposits in glomeruli compared to
median of 5.4 years. (age 64.9613.6 [mean 6 SD] years, male 73.2 %, hypertension other groups. This could suggest more aCP activation in MPO positive AAV. Also
42.5 %, diabetes 10.5 %, nephrotic Syndrome 67.3 %, chronic kidney disease [CKD: there was strong tendency of patients requiring dialysis having higher proportion of C3
eGFR<60ml/min/1.73m2] 51.9 %, eGFR 61.6622.6 mL/min/1.73m2, urinary protein deposits compared to non-dialysis patients which could signify C3 deposition of being
excretion [u-TP] 4.363.6 g/day, PCR 5.464.5 g/gCr, FETP 0.1260.18 %, Selectivity the hallmark of more severe renal involvement in AAV patients. This data needs
Index [S.I] 0.2360.39, fractional excretion of IgG [FEIgG] 0.06560.170 %, further confirmation from future studies.
glomerulosclerosis [GS] 13.9613.7 %, interstitial fibrosis and tubular atrophy [IFTA]
12.2610.0 %). FETP was more significantly associated with clinical parameters than
PCR and FEIgG (Table.1). The high FETP group had a significantly worse renal MO269 INCREASED RISK OF DEATH IN PATIENTS WITH DOUBLE
prognosis during the follow-up periods than the low FETP group (Figure.1). Using Cox POSITIVE SEROLOGY OF ANTI-GLOMERULAR BASE
proportional hazards models, with FETP entered, and age, sex, eGFR,u-TP as MEMBRANE (ANTI-GBM) ANTIBODIES AND ANTI-
covariates, FETP predict the primary endpoint with a hazards ratio of 0.343 (P<0.05). NEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)
CONCLUSION: These results suggest that FETP would be superior to PCR, the
standard measure of proteinuria, in predicting outcome in patients with iMN. FETP Karl Emil Nelveg-Kristensen1, Nicholas Carlson1, Christian Torp-Pedersen2,3,
could indicate the increased glomerular protein permeability and decreased glomerular Jon Waarst Gregersen4, Elizabeth Krarup5, Per Ivarsen6, Martin Egfjord1,
filtration function in iMN. Wladimir Szpirt1
1
Rigshospitalet, Nephrology, København, Denmark, 2North Zealand Hospital - Hillerød,
Cardiology, Hillerød, Denmark, 3Aalborg University Hospital South, Aalborg, Denmark,
4
Aalborg University Hospital South, nephrology, SLE and Vasculitis linic, 5Herlev
Hospital, Nephrology, Herlev, Denmark and 6Skejby Sygehus, Nephrology, Aarhus,
Denmark

BACKGROUND AND AIMS: Double positivity of anti-GBM and ANCA


serology is uncommon but may represent a distinct disease entity of small vessel
vasculitis. Previous research has been challenged by low disease incidence, and
conflicting results pertaining to risk of death and ESRD. Accordingly, we examined
incidence and outcomes based on data from multiple Danish nationwide healthcare
registries.
METHOD: All patients with incident positive anti-GBM serology between 2013 and
MO267 Table 1: Transplant Kidney Biopsy Findings from Positive COVID-19 Cases 2018 were identified from 3 of 4 administrative regions in Denmark. Serological
positivity was defined as serum concentrations exceeding the upper reference level.
Double positivity was defined by either presence of PR3-ANCA or MPO-ANCA within
a margin of 30 days from inclusion. Baseline information and clinical diagnoses
defined by administrative diagnoses were subsequently ascertained by cross-
MO268 GLOMERULAR C3 DEPOSITS IN ANCA ASSOCIATED referencing of data from the Danish nationwide administrative registries. Risks of
PATIENTS – IS IT AN IMPORTANT FINDING? death or ESRD were compared based on adjusted absolute risk ratios (ARR) and
cumulative incidences assessed based on the Aalen-Johansen estimator.
Matija Crnogorac1, Ivica Horvatic 2, Patricia Kacinari2, Miroslav Tisljar2, RESULTS: A total of 118 patients with positive anti-GBM serology (4.4 cases/million/
Ana Brechelmacher2, Petar Senjug3, Danica Galesic 3,
 Ljubanovic year) were identified. Concomitant ANCA serology was tested in 104 (88.1%), with 39
Kresimir Galesic2 patients (37.5%) demonstrating double positivity (20 and 13 patients positive for PR3-
1 ANCA (51.3%) and MPO-ANCA (33.3%), respectively, and 6 patients positive for all
Agram Special Hospital, Nephrology, Zagreb, Croatia, 2Dubrava University hospital,
autoantibodies (5.8%)). Mean follow-up for the total study population was 1.9 (SD
DEpartment of Nephrology and dialysis, Zagreb, Croatia and 3Dubrava University hos-
61.6) years. Compared with patients positive for anti-GBM alone, double positivity
pital, Department of clinical pathology, Zagreb, Croatia
was associated with female gender (61.5%, P=0.02), and more frequent employment of
plasma exchange (53.8%, P=0.04). No difference was observed with regard to age (63.2
BACKGROUND AND AIMS: In recent years there were many studies explaining the years [SD 18.5], P=0.60), and mean anti-GBM concentration (125.5 [SD 182.4] IU/L
role of alternative complement pathway (aCP) in etiopathogenesis of the ANCA vs. 108.9 [SD 212.7] IU/L, P=0.30). One-year mortality was 17.7% (n=14) in patients
associated vasculitis (AAV) and weather it affects patient outcomes. We hypothesized positive for anti-GBM alone, and 28.2% (n=11) in patients positive for both anti-GBM

10.1093/ndt/gfab104 | i209
Abstracts Nephrology Dialysis Transplantation

and ANCA. Double positive serology was associated with increased risk of death (ARR
2.10 [CI 1.20-3.65], P=0.009) (figure); however, there was no difference in risk of ESRD
(ARR 1.28 [0.66-2.50], P=0.46). MO270 Table 1. Univariable and multivariable Cox regression analysis for risk factors
Of all identified patients, only 32 (27%) were diagnosed with anti-GBM disease for not reaching remission
according to ICD10 code (1.2 cases/million/year). In patients with confirmatory
serology and ICD-10 code, 13 (40%) had double positive serology (46.2% PR3-ANCA Variable HR (95% CI) p
and 53.8% MPO-ANCA). In the subset of patients with confirmatory ICD-10 code, Univariable
double positivity was associated with male gender (63.2%, P=0.07), numerical lower
mean age (56.1 [SD 25.2], P=0.50), and increased mean anti-GBM concentration Age (older) 0.99 (0.96, 1.01) 0.5
(333.3 [SD 278.7] vs 150.7 [SD 146.5] P= 0.026). There was no difference in risk of Higher PLA2R Ab titer 1.00 (0.99, 1.00) 0.3
death or ESRD between the two groups.
CONCLUSION: Double positivity of anti-GBM and ANCA serology plausibly defines
Anti-PLA2R Ab negativization (vs absent) 0.44 (0.19, 1.00) 0.05
a distinct group of patients and is associated with a higher risk of death. While the Higher serum creatinine 0.64 (0.29, 1.42) 0.2
association between an ICD10-confirmed diagnosis of anti-GBM disease and anti- Lower serum albumin 2.44 (1.39, 4.30) 0.002
GBM serology is well established, the significance of serology alone remains uncertain.
Higher proteinuria 0.97 (0.91, 1.03) 0.3
Multivariable
Age (older) 0.97 (0.94, 1.00) 0.09
Higher serum creatinine 0.83 (0.44, 1.54) 0.5
Anti-PLA2R Ab negativization (vs absent) 0.40 (0.17, 0.97) 0.04
Higher proteinuria 1.04 (0.99, 1.10) 0.07
Lower serum albumin 3.02 (1.59, 5.74) 0.001

HR, hazard ratio; PLA2R, phospholipase A2 receptor

During the follow up period 6 (10%) patients died. Cardiovascular disease and
infections were the main causes of death. A total of 5 (9%) patients started RRT during
the study period. The mean renal survival time was 50.3 (95%CI 46.5, 54.0) months.
We found no difference in renal survival regarding anti-PLA2R Ab titer or
negativization.
CONCLUSION: Negativization of anti-PLA2R antibodies in the first three months
MO270 PROGNOSTIC ROLE OF ANTI-PHOSPHOLIPASE A2 from diagnosis was a predictor for remission in patients with membranous
RECEPTOR ANTIBODY NEGATIVIZATION AT THREE nephropathy.
MONTHS IN MEMBRANOUS NEPHROPATHY

Gabriel Stefan1,2, Simona Stancu1,2, Otilia Popa1,2, Adrian Dorin Zugravu1,2, MO271 PROGNOSIS OF NON-PR3 ANCA-ASSOCIATED
Nicoleta Petre3,4, Gabriel Mircescu1,2 VASCULITIDES WITH RENAL INVOLVEMENT
1
University of Medicine and Pharmacy Carol Davila, Nephrology, 2Dr Carol Davila
Teaching Hospital of Nephrology, Nephrology, 3University of Medicine and Pharmacy Aurélien Chepy1, Hélène Behal2, KARRAS Alexandre3, Xavier Puéchal4,
Carol Davila, Pathology and 4Dr Carol Davila Teaching Hospital of Nephrology, Benjamin Terrier4, David Jayne5, Thomas Quéméneur6, Mary-Jane Guerry6
Pathology 1
Centre hospitalier universitaire de Lille, Département de Médecine Interne et
Immunologie Clinique, Lille, France, 2Centre hospitalier universitaire de Lille,
BACKGROUND AND AIMS: The predictive value of anti-phospholipase A2 receptor Epidémiologie et Qualité des Soins, Department of Biostatistics, Lille, France, 3Hôpital
antibody (anti-PLA2R ab) levels at three-months from diagnosis in patients with Européen Georges Pompidou, Département de Néphrologie, Paris, 4Cochin Hospital,
membranous nephropathy (MN) is not proven. National Referral Center for Rare Systemic Autoimmune Diseases, Paris University,
METHOD: We retrospectively examined the renal outcome on 1 August 2020 of 59 Department of Internal Medicine, Paris , France, 5Cambridge University Hospitals,
adult patients (age 54 (44, 68) years, 69% male, serum creatinine 1.0 (0.9, 1.3) mg/dL) Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, United Kingdom and
who were diagnosed with MN by kidney biopsy and had positive serum anti-PLA2R ab 6
CH Valenciennes, Internal Medicine, valenciennes, France
during 2016-2019.
The outcomes were: kidney survival defined as renal replacement therapy (RRT) BACKGROUND AND AIMS: Immunosuppressive treatments have improved the
initiation; partial (proteinuria 0.5 to 3.5g/24h) or complete remission (proteinuria prognosis of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides
<0.5g/24h and serum albumin 3.5g/dL) - whichever came first. (AAV), transforming these formerly fatal diseases into chronic conditions, with
Variables related to renal outcome were further evaluated in univariate and periods of remission and relapse.
multivariate Cox proportional hazard (CPH) models. Relapse prevention is based on remission-maintenance immunosuppressive treatment
RESULTS: Forty (69%) patients had negative anti-PLA2R ab at 3 months; there were with a usual duration of 18 to 24 months. Recent studies demonstrated that a
no differences regarding age, serum creatinine, serum albumin, proteinuria and prolonged - 48 to 54 months - maintenance treatment reduced the risk of relapse and
treatment when compared to the group with positive ab at 3 months. could reduce end-stage renal disease (Karras A 2017, Charles P 2020). However,
Fifty-seven (97%) patients received immunosuppressive treatment, cyclophosphamide- prolonged maintenance treatment may not be necessary for all patients. On the one
based regimens were the most frequent (87%), followed by cyclosporine (10%). hand, MPO-ANCA (vs PR3-ANCA) and decreased estimated glomerular filtration rate
Overall, 64% of the patients reached a form of remission. Cumulative remission rates (eGFR) have been associated with a low risk of relapse (Walsh 2012). On the other
were 34% after 6 months, 54% after 12 months, 68% after 18 months and 73% after 24 hand, treatment of AAV is not devoid of risk. Flossman et al showed that mortality
months. Only five patients (9%) relapsed during the study period. Median time to after the first year of treatment was mainly related to cardiovascular, infectious and
cumulative remission was 12.0 (95%CI 8.2, 15.7) months. neoplastic complications (Flossman 2011). Thus, it has been well demonstrated that
In the CPH models, negativization of the anti-PLA2R antibodies at three months was patients with renal AAV without PR3 ANCA have the lowest risk of relapse and the
an independent predictor for remission, however lower serum albumin was also highest mortality rate (Mahr A 2013).
retained as a risk factor for absence of remission (Table 1). This study aimed to determine: first, the risk of late relapse in AAV patients with renal
involvement and without PR3-ANCA after end of remission-maintenance treatment,
and second, risk factors for relapse in this population.
METHOD: Patients with renal involvement without PR3-ANCA recruited to
prospective, randomized trials of the European Vasculitis Study group (EUVAS):
CYCAZAREM, CYCLOPS, MEPEX, IMPROVE and the French Vasculitis Study
Group (FVSG): WEGENT were included in the analysis if their disease was in
remission at the end of relapse-prevention therapy. This consisted in azathioprine,
methotrexate or mycophenolate mofetil and was stopped after 18-24 months (around
24-27 months after diagnosis). Cumulative incidence of relapse was estimated using
the Kalbfleich and Prentice method, considering death as a competing event. Risk
factors for relapse were assessed using the Fine and Gray competing risk regression
model.
RESULTS: 108 patients were included, 64 of whom (59.3%) were male, 79 were MPO-

i210 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO271 Figure 3: Cumulative incidence of relapse by eGFR level (1:<15 / 2 :15-30 / 3
:30-45 / 4:>=45 ml/min/1.73m2)
ANCA positive (73.1%) and 29 ANCA negative (26.9%). Average age at diagnosis was
59.6 þ/- 12.4 years. Relapse rate was 25.5% 60 months after cessation of maintenance
treatment (figure 1) of which 46.2% were renal relapses (figure 2). Lower GFR at
CONCLUSION: Even in this population of renal AAV without PR3-ANCA, there
diagnosis was correlated with a lower risk of relapse. For every 15-point decrease in
remains a risk of late relapse, after the end of a two-year conventional maintenance
GFR at diagnosis, the risk of relapse decreased by a factor of 0.72 (HR 95% CI: 0.59 to
regimen. Using additional criteria (such as eGFR at diagnosis < or > 45 ml/min/
0.88). Figure 3 represents the cumulative incidence of relapse by eGFR level. Relapse
1.73m2) could help select a group of patients who are at lower risk of relapse. Factors
risk did not appear to be impacted by the presence at diagnosis of systemic/
that potentially increase (ENT or eye disease) risk of relapse need to be explored
constitutional (HR: 0.70; CI 95%: 0.30-1.65; p: 0.47), lung (HR: 0.87; CI 95%: 0.40-1.86;
further. If these data are confirmed, sub-groups could be identified who could receive
p: 0.71), skin involvement (HR: 0.84; CI 95%: 0.29-2.39; p: 0.74), ear, nose and throat
only a short maintenance treatment, or perhaps none. These findings also need to be to
(HR: 1.53; CI 95%: 0.74-3.27; p: 0.28) or eye disease (HR: 1.58; CI 95%: 0.62-4.10; p:
be analysed following rituximab maintenance.
0.34). Presence of MPO-ANCA at diagnosis did not influence relapse-risk.

MO272 CLINICOPATHOLOGICAL CORRELATION OF APRIL AND


BAFF IN IG A NEPHROPATHY- A SINGLE CENTER
LONGITUDINAL OBSERVATIONAL STUDY

Anjana Gopal1, Noble Gracious1


1
Trivandrum medical college, nephrology , Trivandrum, India

BACKGROUND AND AIMS: Aberrantly glycosylated IgA1 molecules are important


in the pathogenesis of IgA nephropathy. A proliferation-inducing ligand (APRIL) and
B-cell activating factor (BAFF) are cytokines involved in immunoglobulin class
switching and production of galactose deficient IgA1(Gd IgA1). We aimed to study the
association of serum levels of APRIL and BAFF with the clinical severity and
pathological grading of IgA nephropathy (IgAN) and to assess the strength of the
association by studying the clinicopathological correlation.
METHOD: The research study was conducted as a single-center longitudinal
observational study. The study subjects were recruited based on the pathological
diagnosis of primary IgA nephropathy. The plasma levels of APRIL, BAFF and Gd
IgA1 were estimated using enzyme-linked immunosorbent assay (ELISA). All the study
subjects were followed up for one year to study the renal outcome.

MO271 Figure 1: Cumulative incidence of relapse over time

MO271 Figure 2: Cumulative incidence of renal relapse over time

10.1093/ndt/gfab104 | i211
Abstracts Nephrology Dialysis Transplantation

patients in the US identified via physician notes.


RESULTS: In our study group of thirty-eight patients, the median estimated METHOD: This is a descriptive, retrospective study of adult ( 18 years) IgAN
glomerular filtration rate(eGFR) was 33.9(15.9,79.4) ml/minute/1.73m2. The median patients in OptumV R Electronic Health Records (EHRs), between January 2007 and
levels of the cytokines APRIL and BAFF were 170.81(82.45, 550.61) ng/L and December 2019. OptumV R EHRs contain de-identified clinical and medical
6.66(3.39,16.33) ng/ml respectively. The baseline characteristics of the study group is administrative data from 96 million people in 50 states that come from more than
given in table 1. APRIL levels had significant positive correlation with Gd IgA1 levels 140,000 providers at 740 hospitals and over 7,000 clinics. Identification of IgAN
(correlation coefficient 0.556, p=0.003) in patients with IgAN. We also observed that patients is challenging because there are no specific ICD codes for this disease so we
patients with elevated APRIL levels had elevated BAFF levels also (correlation used natural language processing of physician notes and chose patients with at least
coefficient 0.657, p <0.001). Patients who had crescents, mesangial hypercellularity two IgAN records with the first one considered to be the index date, and no negative
and endocapillary proliferation in biopsy had elevated APRIL and BAFF levels whereas mention, as well as a biopsy procedure. Here, we present the baseline demographic and
patients with segmental sclerosis and tubular atrophy had low levels of APRIL(Table clinical characteristics of the identified patients up to 12 months before and at the
2). However, the levels of APRIL and BAFF did not show any significant correlation index date.
with eGFR and proteinuria at time of presentation. At the end of one year, 12(31.5%) RESULTS: A total of 1803 patients with a biopsy record (22% of all patients with at
patients reached end stage renal disease (ESRD) and these patients had lower levels of least two IgAN records in their EHRs in our study) were included in this analysis;
APRIL, BAFF, and Gd IgA1. It was also seen that eighty-three percent of those who results are presented in Table 1. The mean age was 48 years, and the majority of
reached ESRD had chronic changes in biopsy like tubular atrophy and interstitial patients were male (60.9%) and white (75.7%). Proteinuria levels of 1 g/day were
fibrosis(p=0.05). Hence the severity of tubulointerstitial fibrosis in histology correlated found in 34% of patients. The mean eGFR was 45 ml/min/1.73m2 and 21.6% of
well with progression to end stage renal disease as seen in most glomerular diseases. patients had severe deterioration of kidney function (eGFR <15). The mean creatinine
But we did not find any association between APRIL, BAFF, and Gd IgA1 levels and the level was 3 mg/dL. Pain, edema and fatigue/tiredness were reported in 39.6%, 18.1%
decline in eGFR over one year. and 13.4% of patients, respectively. Hypertension was reported in 73% of patients.
CONCLUSION: We conclude that levels of APRIL and BAFF are associated with Based on the ICD 9 (585.6) and ICD-10 (N18.6) codes for diagnosis, 17.5% of patients
elevated levels of Gd IgA1 in patients with IgAN and had a significant association with had ESKD in our study.
proliferative lesions in renal biopsy. But these cytokines levels did not have any CONCLUSION: In our cohort, a significant proportion of patients were found to have
association with the eGFR at time of presentation nor decline in eGFR over one year. high proteinuria levels and severe deterioration of kidney function or ESKD. Moreover,
edema and fatigue were recorded for a noticeable proportion of patients. In addition to
the commonly reported symptoms, our study also found that pain was reported in a
MO273 A NOVEL APPROACH TO ASSESS THE DEMOGRAPHIC AND high proportion of patients. These findings highlight the clinical and symptom burden
CLINICAL CHARACTERISTICS OF IMMUNOGLOBULIN A to patients with IgAN, suggesting that future targeted interventions are needed to
NEPHROPATHY (IGAN) PATIENTS IN A US REAL-WORLD reduce the burden and delay the progression of this disease.
SETTING

Raymond Przybysz1, Rina Mehta1, Gisela Rovira Tomas2, Carolina Aldworth2,


Jim Doherty2, Rachel Studer2
1
Novartis Pharmaceuticals Corporation, East Hanover, United States of America and
2
Novartis Pharma AG, Basel, Switzerland

BACKGROUND AND AIMS: Immunoglobulin A nephropathy (IgAN) is a chronic


glomerular disease that affects approximately 100,000-200,000 people in the US.
Approximately 15-40% of IgAN patients will eventually progress to end stage kidney
disease (ESKD) within 10-20 years of diagnosis, and there is currently no targeted
therapy for this disease. Decreased kidney function, persistent proteinuria and
hypertension are some of the clinical manifestations of IgAN, and with demographic
aspects (e.g. ethnicity) are considered as predictors of disease progression. The aim of
this study is to better understand the demographic and clinical characteristics of IgAN

i212 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Low serum C3 levels at diagnosis may be an independent prognostic
factor for ESRD progression in patients with AAV. This should be taken into account
in therapeutic and monitoring strategies.

MO275 RARE VARIANTS OF COMPLEMENT FACTOR H AND


THROMBOMODULIN ARE OVER-REPRESENTED IN A
COHORT OF SEVERE IGA NEPHROPATHY PATIENTS

Nicolas Maillard1, Veronique Fremeaux Bacchi2, Paula Vieira-Martins2,


Perrine Jullien1, Eric Alamartine1, Christophe Mariat1
1
CHU Saint Etienne, Nephrologie, Dialyse, Transplantation and 2Assistance Publique
Hôpitaux de Paris, Service d’Immunologie Biologique Hôpital Européen Georges
Pompidou

BACKGROUND AND AIMS: IgA nephropathy is the most frequent primary


glomerulonephritis leading to end stage renal disease (ESRD) in about 30% of cases
within 20 years after diagnosis. Complement activation through alternative and lectin
pathways has been described to impact the pathogeny of the disease. We hypothesized
in this study that rare variants of alternative pathways regulatory genes could be
overrepresented and could play a role at initiating the disease and could harm the
prognosis of IgA Nephropathy.
METHOD: Patients with biopsy proven IgA nephropathy with markers of severity
comprising an evolution through ESRD and/or a proteinuria >0.5g/day with available
DNA sample were included. All coding sequences of CFH, CFI, MCP, C3, Factor B
THBD and CFHR5 genes were analyzed by next generation sequencing. We defined a
variant as rare when its minor allele frequency was below 0.1% in the general
population. Frequencies were compared to a French volonteers cohort (n=80) and a
European large cohort (n=503)
RESULTS: We screened 128 patients with IgA N, with following characteristics at
diagnosis: median age 42.4 yo, proteinuria (median) 1.4g/day, hypertension 66%,
median eGFR 48.7 mL/min/1.73m2. The median follow-up was 99 months and 58% of
patients progressed to ESRD.
We identified rare variants with MAF<0.1% in 10.2 % (n=13) including 1 patient with
two rare variants. The functional consequences of the 12 out the 14 variants are
unknown. Two variants in CFH are located in function domains and are pathogenic.
Patients with IgA N have high rates of rare variants in CFH (n=9/128 ; 7 %) versus
normal controls (n=9/503 ; 1.8%) (p=0.004); Pathogenic Variants with minor allele
frequency <0.1% in CFH were found in 2 IgA N (2 out of 128, 1.5%) versus 1
European controls (1 out of 503)
In total, 11 % (14/128), 3.8 % (5/128) and 0.8 % (1/128) of the 128 patients were
homozygous for the at-risk haplotype MCP ggaac, CFH tgtgt or both, respectively
MO274 EVALUATION OF SERUM C3 LEVELS AND C3 (versus 6.2 % (5/80), 3.8 % (3/80) and 0% in the controls)
IMMUNOFLUORESCENCE IN PATIENTS WITH ANCA- 6 patients carried the pathogenic variant in THDM gene p.Ala43Thr (6/128) versus 5
ASSOCIATED VASCULITIS: A RETROSPECTIVE COHORT in 508 controls population (p=0.01).
STUDY No difference in term of hypertension, proteinuria, eGFR, Oxford classification,
vascular score at diagnosis was noticed between patients without any rare variant
Aglaia Chalkia1, Konstantinos Thomas2, Panagiota Giannou1, compared to patients with at least one rare variant. The progression through ESRD was
Alexandros Panagiotopoulos2, Emilia Hadziyannis2, Athanasia Kapota1, not different between groups.
Harikleia Gakiopoulou3, Dimitrios Vasilopoulos2, Dimitrios Petras1 CONCLUSION: In this cohort of Caucasian IgA nephropathy patients, rare variants of
1
Hippokration General Hospital, Athens, Greece, Nephrology Department, ATHENS, CFH and THBD were found significantly overrepresented compared to a French and
Greece, 2National and Kapodistrian University of Athens, School of Medicine - Clinical European control cohort. Rare variants of alternative pathway regulatory genes were
Immunology - Rheumatology Unit, 2nd Department of Medicine, Athens, Greece, Joint not associated with particular severity or prognosis.
Rheumatology Program, ATHENS, Greece and 3National and Kapodistrian University of
Athens, School of Medicine, Athens, Greece, 1st Department of Pathology
MO276 TOTAL AND SPECIFIC IGE IN PATIENTS WITH IGA
BACKGROUND AND AIMS: The role of complement activation, mainly alternative NEPHROPATHY
system, has been recently proposed to play an important role in the pathogenesis of
ANCA associated vasculitis (AAV). Real life data assessing its predictive role in renal Darya Nizheharodava1,2, Kirill Komissarov3,4, Victoria Shadrina1,
outcomes are limited. In this study, we evaluated the value of serum and kidney Alena Minchenko5, V. Pilotovich6, Maryna Zafranskaya1,2
deposited C3 in predicting renal outcomes in patients with AAV. 1
Belarusian Medical Academy of Postgraduate Education, Immunology and Biomedical
METHOD: In this retrospective study, patients with AAV were categorized according Technology Department of Scientific and Research Labour, Minsk, Belarus,
to their baseline serum C3 levels as hypo- or normo-complementemic and to those 2
International Sakharov Environmental Institute of Belarusian State University,
with positive or negative kidney biopsy immunofluorescence (IF) for C3. Clinical, Immunology Department, Minsk, Belarus, 3Minsk Scientific and Practical Center of
serologic, treatment and histopathologic characteristics, as well as prognosis between Surgery, Transplantology and Hematology, Nephrology, Dialysis and Kidney
the 2 groups were compared. Transplantation Department, Minsk, Belarus, 4Belarusian Medical Academy of Post-
RESULTS: : Forty-seven patients (51% men) were enrolled with a mean age at Grtaduate Education, Transplantology Department, Minsk, Belarus, 51st City Clinical
diagnosis of 65 years and were followed up for a median period of 56 months. At Hospital, Nephrology Department, Minsk, Belarus and 6Belarusian Medical Academy of
baseline, 23% (11/47) of the patients were hypocomplementemic (C3 <75 mg/dL). Postgraduate Education, Urology and Nephrology Department, Minsk, Belarus
These patients were older (74 vs. 65 years,p=0.013), had higher creatinine levels (4.9 vs.
2.2 mg/dL, p=0.006), were more often hemodialysis dependent (64% vs. 19%, p=0.009)
BACKGROUND AND AIMS: IgA nephropathy (IgAN) is the most common form of
and progressed more often to ESRD (55% vs .11%,p=0.01) compared to normo-
primary glomerulonephritis characterized by impaired immunological tolerance. One
complementemic patients (n=36). On multivariate analysis, serum Cr at diagnosis
of possible trigger factors for IgAN initiation and development are allergens which
(HR=16.8, 95%CI: 1.354-208.62,p=0.028) and low serum C3 (HR=2.492; 95% CI:
have been described to form IgA complexes deposited in the mesangium. Previous
1.537-11.567,p=0.044) were independent predictors for ESRD. Among 25 patients with
studies reported that serum immunoglobulin class E (IgE) levels are elevated and
kidney biopsy data, those with positive IF staining for C3 (56%, n=14) had more often
suggested as a prognostic indicator in glomerular diseases. However, mechanisms of
a mixed histological pattern (72% vs. 27%,p=0.033), low serum C3 levels (42% vs.
IgE/IgG4-mediated allergic reactions involvement in IgAN as well as specific allergens
18%,p<0.001) and serious infections during follow-up (57% vs. 18%,p=0.047)
and their clinical significance have poorly been investigated. The aim of the study was
compared to those with negative (n=11) IF staining.
to assess the total serum IgE and IgG4 level and to determine the allergoprofile in IgAN
patients.

10.1093/ndt/gfab104 | i213
Abstracts Nephrology Dialysis Transplantation

METHOD: The peripheral blood was obtained from 21 IgAN patients (aged of 32.0
(27.0 36.0) y.o., male/female ratio as 14/7) and 18 donors (aged of 38.0 (30.0 46.0)
y.o., male/female ratio as 10/8). IgAN diagnosis was confirmed in patients’ biopsy
materials according to the Oxford classification (MEST-C score). The concentrations
of total IgE and IgG4 were determined using «IgE total-ELISA-BEST» kit («Vector-
Best», RF) and «Human IgG4 Platinum ELISA» kit («eBioscience», Austria)». Allergen-
specific IgE to 55 inhalation (domestic, epidermal, fungal, plant) or food allergens were
measured using «EUROLINE Atopy Screen IgE» immunoblot kit («Euroimmun»,
Germany). Statistical analysis was done in Statistica 8.0.
RESULTS: The increased level of total IgE (in 47,4% of cases) but not IgG4 was
established in sera of IgAN patients as compared to donors (p=0.004). Moreover,
proteinuria was lower in IgAN patients with a high IgE level as compared to normal
one (610 (220 910) mg/day vs 1545 (600 2200) mg/day, p=0.01) as well as there
were no any crescent formation. The investigation of allergen-specific IgE in IgAN
patients revealed a strong positive reaction to dust mite allergens of Dermatophagoides
pter. (22,75 (16,72 35,69) IU/ml – in 29% of cases) and Dermatophagoides farinae
(38,24 (12,19 65,88) IU/ml – in 43% of cases) correlated with the total IgE (R=0,57,
p=0,03) and IgM (R=0,54, p=0,04). The more concentration of specific IgE to dust mite
allergens was the lower the severity of segmental glomerulosclerosis (R= -0.55, p=0.04),
crescent formation (R= -0.56, p=0.03), proteinuria (R= -0.65, p=0.01) and haematuria
(R = -0.55, p = 0.04) were reported. A weak positive reaction was established to other
domestic (house dust, honey bee venom, common wasp venom, cockroach), epidermal
(cat), plant (sweet vernal grass, orchard grass, timothy grass, cultivated rye, alder, birch,
hazel, oak, common ragweed, mugwort, plantain) and food (carrot, sesame, hazelnut,
apple) allergens in 9–18% of IgAN patients.
CONCLUSION: The prevailing of specific IgE to dust mite allergens of
Dermatophagoides pter. and Dermatophagoides farinae but not to food or plant
allergens was determined in IgAN patients. The obtained data demonstrated that IgAN
pathogenesis in patients with latent sensibilization to dust mite allergens is
characterized by a milder disease course what allows to identify this cohort as possible
secondary form of IgAN.
MO277 Figure 1: Comparison of NLR between SLE group and control groups, LN
group and non-LN group, severely active group and mildly active group. *P< 0.05,
***P< 0.001
MO277 THE RATIO OF NEUTROPHIL TO LYMPHOCYTE AS A
POTENTIAL MARKER OF CLINICOPATHOLOGICAL ACTIVITY
FOR SYSTEMIC LUPUS ERYTHEMATOSUS

Qianqian Han1, Peifen Liang1, Jiajia Li1, Bo Liu1, Rong Hu‘an’g1,


Qiongqiong Yang1
1
Sun Yat-sen Memorial Hospital, Nephrology, Guangzhou, P.R. China

BACKGROUND AND AIMS: The ratio of neutrophils to lymphocytes (NLR) is a


novel inflammatory factor that is elevated in systemic lupus erythematosus (SLE) and
related to disease activity. However, the relationship between NLR and renal
pathological manifestations in patients with lupus nephritis (LN) has not been studied.
METHOD: In this retrospective study, 240 SLE patients were recruited. 186 patients
with renal involvement and 124 LN patients underwent renal biopsy. In the
meanwhile, control groups included 125 chronic kidney disease (CKD) patients and MO277 Figure 2: Correlations between NLR between NLR and Log2(24h urine
125 healthy volunteers. Patients with SLE disease activity 2000 (SLEDAI-2K) >9 and  protein) (A), albumin (B).
9 were defined as severely active and mildly active, respectively. Clinical parameters
and pathological data were collected. The correlations between NLR and
clinicopathological features were analyzed.
RESULTS: The NLR of SLE group was significantly higher than that of the sex-age
matched control groups. Patients with nephritis had higher NLR levels than those
without nephritis [2.88(1.81,4.32) vs. 2.43(1.55,3.90), P=0.044; Figure 1]. Increased
NLR was observed in severely active group compared to mildly active group
[3.00(1.84,4.28) vs.2.36(1.61,3.51), P=0.020; Figure 1]. NLR was significantly positively
related with SLEDAI score (r=0.131, P=0.043), Renal SLEDAI score (r=0.173,
P=0.023), C-reactive protein (CRP; r=0.213, P=0.002), 24-hour urine protein (r=0.274,
P<0.001; Figure 2A), renal activity index (AI; r=0.192, P=0.033), cellular crescents
(r=0.274, P=0.006) and tubular atrophy (r=0.226, P=0.011), and negatively correlated
with serum albumin (r=-0.187, P=0.004; Figure 2A). Based on the receiver operating
characteristic (ROC) curve, the best NLR cut-off value to predict severe activity and
cellular crescents was 2.19 and 3.16, respectively. The ability of NLR to differentiate MO277 Figure 3: ROC curves of the NLR for differentiating severe disease activity (A)
severely active from mildly active SLE was stronger than CRP and weaker than C3 and cellular crescents (B).
(Figure 3A). The ability of NLR to predict cellular crescents was better than C3, but not
superior to SLEDAI and RSLEDAI. Interestingly, the ROC fitted by NLR and
RSLEDAI had a higher AUC and sensitivity [AUC=0.75(0.66,0.84), sensitivity=82.6%, CONCLUSION: NLR was a non-invasive and potential inflammatory factor to
specificity=63.6%; Figure 3B]. evaluate clinical and renal pathological activity in patients with SLE.

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Nephrology Dialysis Transplantation Abstracts
MO278 IMMUNOSUPPRESSIVE THERAPY VERSUS SUPPORTIVE been questioned. Because therapeutic decision making is crucial in these critically ill
CARE IN IGA NEPHROPATHY PATIENTS WITH STAGE 3 AND patients, we here aimed to identify determinants for PEX consideration in a
4 CHRONIC KIDNEY DISEASE retrospective study from a single center tertiary hospital in a real-world population of
46 patients with severe AAV requiring intensive care treatment.
Gabriel Stefan1,2, Simona Stancu1,2, Adrian Dorin Zugravu1,2, Nicoleta Petre3,4, METHOD: A total number of 46 patients with biopsy-proven AAV at the University
Gabriel Mircescu1,2 Medical Center Göttingen were retrospectively included between 2015 till 2020. While
1
University of Medicine and Pharmacy Carol Davila, Nephrology, 2Dr Carol Davila no formal approval was required for the use of routine clinical data, a favorable ethical
Teaching Hospital of Nephrology, Nephrology, 3University of Medicine and Pharmacy opinion was granted by the local Ethics committee. Medical records were used to
Carol Davila, Pathology and 4Dr Carol Davila Teaching Hospital of Nephrology, obtain data on age, sex, diagnosis (MPO or PR3) and laboratory results (serum
Pathology creatinine, C-reactive protein/CRP, urinary albumin/creatinine ration). The estimated
glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease
BACKGROUND AND AIMS: The use of immunosuppressive therapy for IgA Epidemiology Collaboration (CKD-EPI) equation. A renal pathologist (SH) evaluated
nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is all biopsies. Within a renal biopsy specimen, each glomerulus was scored separately for
controversial. the presence of necrosis, crescents and global sclerosis. Consequently, the percentage of
METHOD: We performed a monocentric retrospective study on 83 consecutive IgAN glomeruli with any of these features was calculated as a fraction of the total number of
patients (age 41 [33-56] years, 72% male, eGFR 36.1 [25.4-47.5] mL/min) with stage 3 glomeruli in each renal biopsy. Apart from these categories, the degree of interstitial
or 4 CKD and proteinuria  0.75g/day who received uncontrolled supportive care fibrosis/tubular atrophy (IF/TA) was quantified. Based on these scorings,
(Supp) (n=36), corticosteroids (CS) (n=14) or CS combined with monthly pulses of histopathological subgrouping according to Berden et al (focal, crescentic, mixed or
cyclophosphamide (CSþCFM) (n=33) between 2010-2017. Patients were followed sclerotic class) and ARRS according to Brix et al (low, medium or high risk) were
until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal performed.
transplant) or death, whichever came first) or end of study (May 2018). RESULTS: The decision to consider PEX was more likely in patients with need for
RESULTS: Patients were followed for a median of 29 (95%CI 25.2, 32.7) months, and intensive care treatment and severe renal dysfunction. In contrast, short-term
12 (15%) patients experienced the composite endpoint. outcomes did not depend on clinical or laboratory characteristics assessed at
There were no differences between the three studied groups regarding age (Supp 46 admission. Histopathological analysis confirmed active disease reflected by increased
[33.5-61.0] vs CS 40 [33-47] vs CSþCFM 41 [34-48] years), eGFR (Supp 37.7 [27.5- glomerular necrosis and crescents, but these histopathological findings did not
49.2] vs CS 40.3 [32.5-54.6] vs CSþCFM 31.5 [22.7-44.3] mL/min), proteinuria (Supp associate with short-term outcome either. Interestingly, only increased global
1.9 [1.4-3.5] vs CS 1.3 [1.0-1.7] vs CSþCFM 1.7 [1.1-2.9] g/g creatinine), MESTC score glomerular sclerosis in renal biopsies associated with a detrimental short-term
(Supp 2.5 [1.5-4.0] vs CS 2 [0-2] vs CSþCFM 3 [2-3]), hypertension (Supp 94% vs CS outcome.
86% vs CSþCFM 94%) and therapy with renal angiotensin system inhibitors (Supp CONCLUSION: In conclusion, our study investigated determinants for the
83% vs CS 64% vs CSþCFM 67%). consideration of therapeutic PEX in patients with severe AAV requiring intensive care
Mean renal survival time for the entire cohort was 81.0 (95%CI 73.1, 89.0) months; we treatment. This aspect underscores the need for renal biopsy and requires further
found similar renal survival time between the three groups (Supp 79.0 (95%CI 66.5, investigation in a prospective controlled setting for therapeutic decision making
91.6) vs CS 69.3 (95%CI 47.7, 91.0) vs CSþCFM 73.7 (95%CI 66.0, 81.4) months, especially in patients with severe AAV requiring intensive care treatment, especially
p=0.4). important for treating intensivists.
In univariate and multivariate Cox regression analysis adjusted for IgAN progression
factors, immunosuppressive therapy was not associated with better renal survival when
compared to supportive therapy (Table 1). MO280 VALIDATION OF AN ANCA ASSOCIATED VASCULITIS RENAL
CONCLUSION: Within the limitation of a retrospective study, we found no benefit RISK SCORE IN THE SOUTH WEST OF ENGLAND
from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as
compared to supportive care. Ailish Nimmo1, Arvind Singh2, Jena Hopkins2, Anna Rixon2, Spoorthy Sreerama2,
Christina Tran2, Saira Risdale1
1
Southmead Hospital, United Kingdom and 2Derriford Hospital, United Kingdom
MO279 DETERMINANTS TO CONSIDER THERAPEUTIC PLASMA
EXCHANGE FOR TREATMENT OF SEVERE ANCA- BACKGROUND AND AIMS: Determining the renal prognosis for patients with
ASSOCIATED VASCULITIS: A RETROSPECTIVE STUDY ANCA associated vasculitis (AAV) is important in guiding treatment decisions,
FROM A SINGLE CENTER including balancing the risks and benefits of aggressive immunosuppression, and
informing patients of their likely trajectory. We examined the performance of the
Björn Tampe1, Samy Hakroush2 clinicopathologic risk stratification tool developed by Brix et al. 1 in determining renal
1
University Medical Center Göttingen, Department of Nephrology and Rheumatology, outcomes in a cohort of AAV patients in the South West of England.
Göttingen, Germany and 2University Medical Center Göttingen, Institute of Pathology, METHOD: A retrospective review of case notes of patients diagnosed with AAV between
Göttingen, Germany 2010 and 2020 from two renal units (Bristol and Plymouth) was performed. Patients were
followed up until 1st August 2020. Demographic details, kidney function at presentation
BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibody (ANCA)- and initial treatment regime were collected alongside kidney biopsy data.
associated vasculitis (AAV) is a systemic vasculitis, most frequently presenting as The renal risk score divides patients into three groups determined as being at low,
microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). medium and high risk of adverse renal outcomes based on (1) the percentage of normal
Pathogenic ANCAs trigger a deleterious immune response resulting in pauci-immune glomeruli on kidney biopsy, (2) the percentage of tubular atrophy and interstitial
necrotizing and crescentic glomerulonephritis (GN). Standard therapeutical regimens fibrosis on kidney biopsy and (3) eGFR at diagnosis.
include aggressive immunosuppressive therapy. Since some patients require RRT The outcome of interest was the development of end stage kidney disease (ESKD),
despite intensive immunosuppressive therapy, additional therapeutic plasma exchange defined as a dialysis requirement >3months or kidney transplantation. Patients were
(PEX) to deplete pathogenic ANCAs has been recommended but its value has recently censored for death.

MO278 Table 1. Effects of immunosuppressive therapy on renal survival (composite endpoint) in IgAN patients - Cox regression analysis

Immunosuppressive therapy Supportive care CSþCFM CS only


HR (95% CI) p HR (95% CI) p HR (95% CI) p
Univariate 1.34 (0.43, 4.19) 0.6 Ref. 0.51 (0.12, 2.05) 0.3 1.34 (0.33, 5.40) 0.6
Multivariate model 1a 1.45 (0.44, 4.71) 0.5 Ref. 0.25 (0.05, 1.22) 0.08 1.01 (0.24, 4.26) 0.9
Multivariate model 2b 2.10 (0.56, 7.81) 0.2 Ref. 0.16 (0.03, 1.32) 0.09 0.78 (0.16, 3.64) 0.7
Multivariate model 3c 2.17 (0.54, 8.64) 0.2 Ref. 0.18 (0.02, 1.20) 0.07 0.85 (0.17, 4.19) 0.8
a
Model 1 was adjusted for age, sex, hypertension, proteinuria, eGFR
b
Model 2 was adjusted for age, sex, hypertension, proteinuria, eGFR, RASI
c
Model 3 was adjusted for age, sex, hypertension, proteinuria, eGFR, RASI, MESTC score
CI, confidence interval; CS, corticosteroids; CFM, cyclophosphamide; eGFR, estimated glomerular filtration rate; HR, hazard ratio; MESTC, Oxford classifica-
tion; RASI, renin angiotensin system inhibitor; ref., reference

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RESULTS: In total 93 individuals were diagnosed with AAV over the study period; CONCLUSION: Healthy population showed low titer PLA2RsAb positive according
51% were female and the median age at diagnosis was 69 years [IQR 60-78]. ANCA to a lower cut-off. The validation showed relative high coefficient of variation on intra
subclass was MPO positive in 73% of cases, PR3 positive in 19% and ANCA negative in and inter-batch precision of low titer PLA2RsAb.
8%. At presentation, 42% had an eGFR below 15ml/min/1.73m2. With respect to risk
scores, 17% of individuals were low risk (n=16), 52% were medium risk (n=48) and
31% were high risk (n=29).
MO282 EARLY RENAL RECOVERY AFTER A FIRST FLARE OF PAUCI
Median follow up was 3.2 years [IQR 1.3-5.9], over which time 18% of patients
IMMUNE GLOMERULONEPHRITIS
developed ESKD (1 in the low risk group, 7 in the medium risk group and 9 in
the high risk group). A further 20% of patients died. A Kaplan-Meier survival curve
Jeremy Zaworski1, Cyrille Vandenbussche1, Pierre Bataille2, Eric Hachulla3,
(Figure 1) demonstrated worsening renal survival with rising risk group (Log-rank test,
Francois Glowacki4, Jean baptiste Gibier5, Maı̈té Daroux2,
p=0.05). At 1 year, 74 patients (80%) were alive and in these individuals renal survival
Anderson Rastimbazafy6, Laura Bitton5, Sarah Humez5, Thomas Guincestre7,
was 100% in the low risk group, 91% in medium risk group and 75% in the high risk
Raymond Azar8, Maxime Hoffmann9, Franck Bourdon10, Corinne Lemoine11,
group.
Gerard Cardon12, Helene Behal13, Viviane Gnemmi5, Thomas Quemeneur1
1
centre hospitalier de valenciennes, nephrology, Valenciennes, France, 2Boulogne-sur-
Mer, nephrology, Boulogne-sur-Mer, France, 3Lille, médecine interne, Lille, France, 4Lille,
Nephrology, Lille, France, 5Institut de pathologie, Lille, France, 6Béthune, nephrology,
Béthune, France, 7Roubaix, nephrology, Roubaix, France, 8Nephrology, Dunkirk, France,
9
Hôpital privé la louver, Lille, France, 10Lille, Hôpital privé le bois, Lille, France, 11Bois-
Bernard, Nephrology, Bois-Bernard, France, 12Douai, Nephrology, Douai, France and
13
Biostatistique, Lille, France

BACKGROUND AND AIMS: Renal involvement is a severe manifestation of ANCA-


associated vasculitis. Patients often progress to end-stage renal disease. The potential
for renal recovery after a first flare has seldom been studied. Our objectives were to
describe the evolution of the estimated glomerular filtration rate (eGFR) and identify
factors associated with the change in eGFR between diagnosis and follow-up at 3
months (DeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune
glomerulonephritis.
METHODS: This was a retrospective study over the period 2003–2018 of incident
patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first
histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of
follow up. Kidney function was estimated with MDRD-equation and analysed at
diagnosis, 3rd, 6th and 12th months. The primary outcome was DeGFRM0–M3. Factors
evaluated were histological (Berden classification, interstitial fibrosis, percentage of
crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute
MO280 Figure 1: Kaplan-Meier curve demonstrating renal survival by risk score. kidney injury, dialysis, ANCA subtype).
RESULTS: One hundred and seventy-seven patients were included. The eGFR at 3
months was significantly higher than at diagnosis (mean 6 standard deviation, 40 6
CONCLUSION: Overall, 18% of patients developed ESKD over a median follow up of 24 vs 28 6 26 ml/min/1.73 m2, p < 0.001), with a DeGFRM0–M3 of 12 6 19 ml/min/
3.2 years. The renal risk score developed by Brix et al. helps prognosticate renal survival 1.73 m2. The eGFR at 12 months was higher than at 3 months (44 6 13 vs 40 6 24 ml/
and may assist in shared decision making with patients regarding treatment options. min/1.73m2, p = 0.003). The factors significantly associated with DeGFRM0–M3 in
The score demonstrates the importance of the degree of chronicity in determining univariate analysis were: sclerotic class according to Berden classification, percentage of
renal survival. Further work in larger cohorts to compare the performance of the risk interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological
score in different subgroups of patients with AAV would be informative. involvement. The factors associated with DeGFRM0–M3 in multivariate analysis were
the percentage of cellular crescents and neurological involvement. The mean increase
in eGFR was 2.90 6 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of
References cellular crescents. DeGFRM0–M3 was not associated with the risks of end-stage renal
1. Brix SR, Noriega M, Tennstedt P et al. Development and validation of a renal risk disease or death in long-term follow-up.
score in ANCA-associated glomerulonephritis Kidney International. 2018;94(6): CONCLUSIONS: Early renal recovery after a first flare of pauci-immune
1177–1188. doi:10.1016/j.kint.2018.07.020 glomerulonephritis occurred mainly in the first three months of treatment. The
percentage of cellular crescents was the main independent predictor of early renal
recovery.

MO281 THE EVALUATION OF TEST EFFICIENCY ON LOW TITER MO283 IMPACT OF VIS649, AN APRIL-NEUTRALIZING IGG2
SERUM PHOSPHOLIPASE A2 RECEPTOR ANTIBODY MONOCLONAL ANTIBODY, ON TETANUS- AND DIPHTHERIA-
TOXOID VACCINATION-ELICITED IMMUNE RESPONSES IN
Haoyuan Cui1, Chao Li1, Hang Li1, Lin Duan1, Yan Li1, Limeng Chen1, Xuemei Li1 HEALTHY VOLUNTEERS: PHASE 1, RANDOMIZED, DOUBLE-
1
Peking Union Medical College Hospital, Nephrology Division, Beijing, P.R. China BLIND, PLACEBO-CONTROLLED STUDY

Jonathan Barratt1, Mohit Mathur2, Yusuke Suzuki3, Frank Engler4, Jill Yarbrough2,
BACKGROUND AND AIMS: Antibody to phospholipase A2 receptor (PLA2R) was Susan Sloan2, David Oldach2
widely detected for a decade as a diagnostic marker of idiopathic membranous 1
nephropathy. Recently, several studies reported that a lower cut-off of serum PLA2R Leicester General Hospital, John Walls Renal Unit, Leicester, United Kingdom, 2Visterra
antibody (PLA2RsAb) could improve diagnostic efficacy. The recommend cut-off Inc., Waltham, United States of America, 3Juntendo University Faculty of Medicine,
ranged from 2.0 to 2.7 RU/ml which was considered largely improving the sensitivity of Department of Nephrology, Tokyo, Japan and 4Certara USA Inc., Princeton, United
the assay. Other reported that although sensitivity of the measurement might loss to States of America
some extent cut-off at 14 RU/ml might of the best clinical performance. However, the
lower cut-off was slightly higher than the minimum detection limit, that was 2.0 RU/ BACKGROUND AND AIMS: VIS649, a humanized immunoglobulin G (IgG2)
ml. There was no study evaluated the test efficiency of low titer antibody of the monoclonal antibody that binds to and blocks the biological actions of a proliferation-
measurement. inducing ligand (APRIL), is in clinical development as a potential treatment for
METHOD: The reference range of PLA2RsAb was validated by testing 40 serum from immunoglobulin A (IgA) nephropathy (IgAN). In a Phase 1 study, VIS649 was
health volunteer, male/female ratio was 20/20. The samples for intra and inter-batch associated with dose-dependent reductions in serum IgA, IgG and IgM, which were
precision test were prepared by mixing low titer PLA2RsAb serum. The intra-batch reversible and showed a dose-response effect with respect to time-to-recovery. The aim
precision was performed by repeating six times of the validation sample in one plate. of the present analysis was to determine if VIS649 suppression of APRIL influences
The inter-batch precision was performed by repeating four times of validation samples antibody responses to tetanus and diphtheria toxoid vaccination.
in one plate on five days. METHOD: This was a Phase 1, randomized, double-blind, placebo-controlled, single
RESULTS: The medium age of male was 34 (31, 53) and 46 (31, 54) for female, ascending dose study of VIS649 in healthy adult male and female volunteers
respectively. PLA2RsAb was ranged from 2.0 to 4.3 RU/ml for male and 2.0 to 4.0 RU/ (ClinicalTrials.gov identifier: NCT03719443). In one cohort within the study,
ml for female. The average of intra-batch validation sample was 8.1 6 1.2 RU/ml. The participants were randomized in a 2:1 ratio to receive intravenous administration of
intra-batch precision was presented by coefficient of variation, that was 15%. The VIS649 6.0 mg/kg or placebo, followed by a vaccine composed of tetanus and
V R
average of inter-batch validation samples were 4.0 6 0.4 RU/ml and 5.2 6 0.5 RU/ml, diphtheria toxoids (TENIVAC , Sanofi Pasteur Limited), in order to evaluate the effect
respectively. The inter-batch precision was 10% for both validation serum. of VIS649 on recipients’ ability to generate a vaccine booster response (exploratory

i216 | Abstracts
Nephrology Dialysis Transplantation Abstracts
endpoint). Participants received intravenous administration of study drug on Day 1,
were discharged from the institution on Day 2, received a single intramuscular dose of
vaccine at the Week 4 visit, and were followed for 16 weeks in total on an outpatient
basis. Blood samples were taken at regular intervals, and anti-tetanus toxoid and anti-
diphtheria toxoid IgG, IgM and IgA quantitative ELISA assays were performed.
Tetanus and diphtheria anti-toxoid IgG titers 0.1 IU/mL are generally considered to
be protective.
RESULTS: In the vaccination cohort, 15 participants were randomized and dosed with
study drug or placebo, of whom 14 completed the study, and one participant who
received VIS649 was lost to follow-up prior to receiving the vaccine. Both groups
(placebo and VIS649) demonstrated increased tetanus anti-toxoid IgG titers following
immunization, with a mean 7.9-fold increase in IU/mL at Week 6 for placebo
recipients and a mean 6.4-fold increase in IU/mL for VIS649 recipients (Figure). At
visits after Week 6, tetanus anti-toxoid IgG titers declined faster in the VIS649 group
than in the placebo group (consistent with the reduction in total IgG associated with
VIS649 administration) but remained above the protective threshold of 0.1 IU/mL for
all participants throughout the study. Similar trends were observed for diphtheria anti-
toxoid IgG titers, with a mean 5.5-fold increase in IU/mL at the Week 6 visit for
placebo recipients and a mean 5.1-fold increase for VIS649 recipients (Figure). There
was no evidence of tetanus- or diphtheria-toxoid elicited IgM responses in either the
placebo or VIS649 groups, consistent with the recall nature of the vaccination. In a post
hoc analysis, pre-existing serum tetanus/diphtheria anti-toxoid IgA titers fell between
Day 1 and Week 4 in the VIS649 group, consistent with the overall suppression of total
serum IgA, were boosted after vaccination in both groups, and declined faster in the
VIS649 recipients thereafter.
MO284 Figure 2: Correlation between IgA/C3 ratio and decline in EGFR at five years
follow-up

CONCLUSION: Patients with higher IgA/C3 ratio had a higher drop in estimated
glomerular filtration rate at five years of follow-up. Validation in a larger sample is
warranted before this can be used clinically.

MO284 Table 1: Decline in eGFR at two and five years of follow- up between the
groups

IgA/C3 </=3 IgA/C3> 3 p-Value


Group A Group B Mann-
Whitney
U
CONCLUSION: VIS649 treatment did not interfere with participants’ ability to mount
an antigen-specific serum IgG or IgA boost response to tetanus and diphtheria toxoid 2 years
vaccination. There was no evidence of tetanus- or diphtheria-specific IgM responses in Number of patients 26 20
either the placebo or VIS649 groups, consistent with recall vaccination exposure. These
Decline in eGFR 2.63 (-4.4 to 9.2) 2 (-1.7 to 10) 0.557
data indicate that qualitative antibody responses are preserved during APRIL
suppression. 5 years
Number of patients 13 15
Decline in eGFR 4.6 (-3.5 to 11) 9.3 (-.02 to 19.4) 0.475
MO284 UTILITY OF SERUM IGA/C3 RATIO IN PREDICTING RENAL
DISEASE PROGRESSION IN IGA NEPHROPATHY 2
eGFR- ml/min/1.73m calculated by CKD-EPI formula
1 2 2
Sophia Mohammed , Rajkumar Chinnadurai , Arvind Ponnusamy
1
The University of Manchester, United Kingdom and 2Royal Preston Hospital,
Department of Renal Medicine, Fulwood, United Kingdom
MO285 CLINICAL PRESENTATION OF IGA NEPHROPATHY AND
BACKGROUND AND AIMS: : IgA nephropathy is the most prevalent and LONG-TERM RENAL OUTCOME
predominantly slow progressing glomerular disease. Risk prediction tools like the
international IgAN help to guide the prognosis in this group of patients. The IgA/C3 Gabriel Stefan1,2, Simona Stancu1,2, Adrian Dorin Zugravu1,2, Nicoleta Petre3,4,
ratio has been shown to be a useful predictor of poor outcomes in Chinese cohort but Gabriel Mircescu1,2
such a study is lacking in the Caucasians. The study aims to investigate the utility of 1
University of Medicine and Pharmacy Carol Davila, Nephrology, 2Dr Carol Davila
IgA/C3 score in predicting renal outcome in 5 years (50% decline in five years or
Teaching Hospital of Nephrology, Nephrology, 3University of Medicine and Pharmacy
reaching ESRD) in a Caucasian cohort.
Carol Davila, Pathology and 4Dr Carol Davila Teaching Hospital of Nephrology,
METHOD: All available patients with biopsy-proven IgA nephropathy in our centre
Pathology
between January 2001 and December 2013 were included in this observational study
(115 patients). Baseline (biopsy date) data relevant to the scores including
demographics, laboratory and the histopathological features were collated at the time BACKGROUND AND AIMS: There is a wide range of clinical presentation of IgA
of biopsy. Follow up data on renal functions and renal outcome (50% decline in eGFR nephropathy (IgAN), from asymptomatic microscopic hematuria to rapidly
at 5 years) were collected until an arbitrary end date 31/12/2018. IgA/C3 ratio was progressive glomerulonephritis. However, there is little epidemiologic data on the
available in 46 (40%) of the patients and this cohort wase split into two groups based relationship between the clinical pattern at diagnosis and long-term renal outcome.
on IgA/C3 ratio (A- ratio </=3 and B- ratio >3) and analysed. METHOD: We performed a unicentric retrospective study on 299 consecutive IgAN
RESULTS: We had a total of 115 patients recorded over this 13-year period. The patients (age 43 [35-56] years, 71% male, eGFR 42.1 [25.2-62.8] mL/min, proteinuria
median age of our cohort at time of biopsy was 41 years with a predominance of male 1.3 [0.6-2.6] g/g creatinine) - kidney biopsy proven - between 2010-2017. Patients were
gender (71%). At baseline 84% were hypertensive and 11% diabetic. 77% were on a followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or
renin-angiotensin blocker, with 53% being on a statin. renal transplant) or death, whichever came first) or end of study (May 2018).
At 2 years follow-up the median decline in estimated glomerular filtration (eGFR) RESULTS: Patients were followed for a mean of 41 (95%CI 38, 44) months, and 80
between the groups was similar (Group- A 2.65 ml/min vs Group- B 2 ml/min, (27%) patients experienced the composite endpoint.
p=0.557). At 5 years, the median decline in eGFR was higher in Group B though not The most frequent clinical presentation at diagnosis regardless of age was nephritic
statistically significant (9.3ml/min vs 4.6ml/min, p=0.475) (Table-1). At 5 years a syndrome (68%), followed by asymptomatic urinary abnormalities (AUA) (19%),
higher IGA/C3 ratio was showing appositive corelation to the decline in eGFR (Figure– macroscopic hematuria (15%), acute kidney injury (AKI) (14%) and nephrotic
2). syndrome (10%).
The clinical pattern varied in frequency with age: macroscopic hematuria had a
bimodal distribution in the 20- and 60-years groups, AKI was more frequent in the 50

10.1093/ndt/gfab104 | i217
Abstracts Nephrology Dialysis Transplantation

to70 years groups, AUA was more often present in the 30 to 50 years groups (Figure MO286 DESIGN OF A PH1, MULTICENTER TRIAL TO INVESTIGATE
1). THE SAFETY, TOLERABILITY, PK/PD OF BION-1301 IN
HEALTHY VOLUNTEERS AND ADULTS WITH IGAN AND A
MULTICENTER, OPEN-LABEL EXTENSION STUDY FOR IGAN
PATIENTS WHO PARTICIPATED IN A PRIOR TRIAL OF BION-
1301

Jonathan Barratt1, Angelique Mittan2, Suzanne Roy2, Cailin Sibley2,


Colleen Stromatt2, Aaron Endsley3, Jeannette Lo2, Alan Glicklich2
1
University of Leicester, 2Chinook Therapeutics, Inc. and 3Certara, Inc

BACKGROUND AND AIMS: IgA nephropathy (IgAN), the leading cause of primary
glomerulonephritis, is an autoimmune disease with no approved treatments.1
Progression to end-stage-renal disease occurs in up to 45% of IgAN patients, requiring
dialysis or kidney transplant to manage.2-4 A critical step in IgAN pathogenesis is the
production of galactose-deficient IgA1 (Gd-IgA1) leading to the generation of anti-Gd-
IgA autoantibodies and the formation of immune complexes that result in kidney
inflammation and damage.5 A Proliferation-Inducing Ligand (APRIL), a soluble factor
that regulates B cell differentiation, proliferation and survival of plasma cells, and IgA
class-switching is elevated in patients with IgAN6, 7. IgAN patients with high plasma
APRIL levels are reported as having higher levels of Gd-IgA1 and proteinuria and
lower estimated glomerular filtration rates compared to those with lower plasma
APRIL levels.7 BION-1301 is a novel humanized blocking antibody targeting APRIL.
MO285 Figure 1: Clinical presentation of IgA nephropathy (IgAN) in relation to age; The primary objective of Study ADU-CL-19 is to assess the short-term safety and
AKI, acute kidney injury; AUA, asymptomatic urinary abnormalities tolerability of BION-1301 in Healthy Volunteers (HV) and IgAN patients and to
secondarily assess the short-term pharmacokinetics (PK), pharmacodynamics (PD),
Mean renal survival time for the entire cohort was 70 (95%CI 65, 75) months; patients immunogenicity, and preliminary clinical activity of BION-1301. The primary
with AKI (40 (95%CI 27, 54) vs 75 (95%CI 69, 80) months, p<0.001), nephrotic objective of Study ADU-CL-24 is to characterize the long-term safety of BION-1301 in
syndrome (42 (95%CI 26, 57) vs 73 (95%CI 67,78 months, p<0.001)) at diagnosis had IgAN patients who completed treatment in ADU-CL-19 while secondarily assessing
significantly shorter renal survival time. the long-term PK, PD, immunogenicity, and preliminary clinical activity of BION-
In multivariate Cox regression analysis adjusted for IgAN progression factors, presence 1301.
of nephritic syndrome at diagnosis was associated with good renal outcome, while METHOD: The Phase 1 study (ADU-CL-19; NCT03945318) comprises 3 parts. Parts
clinical presentation as AKI or nephrotic syndrome were associated with poor renal 1 and 2 are double-blind, randomized, placebo-controlled single and multiple
survival (Table 1). ascending dose designs in HV; both parts have been completed.
Part 3 is an ongoing multicenter (US and UK), multiple-dose, two cohort design in
approximately 20 patients with IgAN (10/cohort). Key eligibility criteria for Part 3
MO285 Table 1. Effect of clinical presentation at diagnosis on renal outcome - Cox includes: (1) urine protein 0.5 g/24h or baseline UPCR 0.5 g/g, (2) stable/optimized
regression analysis dose of ACE-I/ARB or intolerant to ACE-I/ARB, and (3) biopsy-verified diagnosis of
IgAN within the past 10 years. In Part 3, patients in Cohort 1 are receiving BION-1301
Univariate Multivariate at 450mg every 2 weeks for 3 months. The dose and schedule for Cohort 2 will be
determined by the Safety Review Team (SRT) based on data from the first 5 patients.
95%CI p 95%CI p
After 3 months of treatment, patients continue safety follow-up for approximately 6
Nephritic 1.24 (0.99, 1.55) 0.05 1.36 (1.08, 1.71) <0.01 months unless deciding to enroll in the open-label extension (OLE) study, withdraw
syndrome from the study, or are lost to follow up.
Study ADU-CL-24 (NCT04684745) is a Phase 2 Open-Label Extension (OLE) of Study
vs absent1 ADU-CL-19. Eligibility for the OLE study is restricted to those patients who completed
Nephrotic 0.56 (0.42, 0.74) <0.001 0.53 (0.39, 0.72) <0.001 at least 75% of their intended doses as well as the End of Treatment (EOT) visit in
syndrome Study ADU-CL-19. Patients who enroll directly from the ADU-CL-19 EOT visit are
not required to attend an additional screening visit. This is encouraged to maintain un-
vs absent2 interrupted dosing. Once enrolled in the OLE, patients receive BION-1301 at the same
Acute kidney 0.51 (0.40, 0.65) <0.001 0.66 (0.49, 0.88) <0.01 dose and regimen as assigned in the parent study for up to 2 years. The dose, route, and
regimen of BION-1301 may change after review of emergent safety, PK, PD and
injury
efficacy data by the SRT.
vs absent3 RESULTS: Parts 1 and 2 of the Phase 1 study in HV are complete and the data were
Macroscopic 0.82 (0.62, 1.09) 0.1 0.95 (0.70, 1.28) 0.7 presented at ASN in 20208 Part 3 of the Phase 1 and the Phase 2 OLE study are
ongoing, and interim results from the first dose cohort in IgAN patients are being
hematuria presented in a separate poster at this meeting.
vs absent4 CONCLUSION: The design of the Phase 1 and Phase 2 OLE studies described in HVs
AUA vs absent5 1.15 (0.85, 1.55) 0.3 0.92 (0.67, 1.26) 0.6 and IgAN patients have enabled the generation of short- and long-term safety, PK, PD,
immunogenicity and preliminary efficacy data for BION-1301. The Phase 1 short-term
data will guide the design of future later-stage trials of BION-1301, while the long-term
1
Adjusted for age, sex, hypertension, eGFR, MESTC score, RASI therapy, data from OLE will enable a greater understanding of the potential long-term risk/
immunosuppression therapy benefit profile of BION-1301 in IgAN patients.
2
Adjusted for age, sex, hypertension, eGFR, MESTC score, RASI therapy,
immunosuppression therapy MO287 REAL WORLD COMPARISON OF THE PREDICTIVE UTILITY
3
Adjusted for age, sex, hypertension, eGFR, proteinuria, MESTC score, OF INTERNATIONAL IGA RISK PREDICTION SCORE AND
RASI therapy, immunosuppression therapy KIDNEY FAILURE RISK EQUATION IN IGA NEPHROPATHY
4 PATIENTS
Adjusted for age, sex, hypertension, eGFR, proteinuria, MESTC score,
RASI therapy, immunosuppression therapy Sophia Mohammed1, Rajkumar Chinnadurai2, Arvind Ponnusamy2
1
5
Adjusted for age, sex, hypertension, eGFR, proteinuria, MESTC score, University of Manchester, Manchester, United Kingdom and 2Royal Preston Hospital,
Department of Renal Medicine, Fulwood, United Kingdom
RASI therapy, immunosuppression therapy
AUA, asymptomatic urinary abnormalities; CI, confidence interval; eGFR, BACKGROUND AND AIMS: IgA nephropathy is the most prevalent cause of
estimated glomerular filtration rate; MESTC, Oxford classification score glomerular disease worldwide. The international IgA risk prediction (IgAN) score is a
well validated tool to predict the risk of 50% decline in eGFR or end stage renal disease
(ESRD) at five years after biopsy in patients with IgA nephropathy. Also, the four
CONCLUSION: Although AKI and nephrotic syndrome are uncommon in IgAN at variable kidney failure risk equation (KFRE) is another validated tool used to predict
diagnosis, their presence seems to be associated with poor renal survival. the two- and five-year risk of progression to ESRD of all cause chronic kidney disease
(CKD 3-5).
Our aim is to compare the predictive utility of IgAN score and the KFRE in a real-
world cohort of Caucasian patients with long-term follow-up data.

i218 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: All available patients with biopsy-proven IgA nephropathy in our centre METHOD: All patients with NS at our center between January 2013 and December
between January 2001 and December 2013 were included in this observational study. 2019 were included. Demographical and clinical data, and laboratory results were
Baseline (biopsy date) data relevant to the scores including demographics, laboratory collected, as well as all tests performed for cancer screening. Patients who presented
and the histopathological features were collated at the time of biopsy. Follow up data cancer the year before or 24 months after the diagnosis of NS were identified. We
on renal functions and renal outcome (50% decline in eGFR or reaching ESRD) were performed a logistic regression model to identify independent risk factors for cancer in
collected until an arbitrary end date 31/12/2018. this population.
RESULTS: We had a total of 115 patients recorded over this 13-year period. The RESULTS: During the study period, 47 patients presented with NS at our center. 38.3%
median age of our cohort at time of biopsy was 41 years. Men represented 71% of the were women and mean age was 57.28617.3 years. 46.8% patients presented high blood
cohort. At baseline 84% were hypertensive and 11% diabetic. 77% were on a renin- pressure and 23.4% type 2 DM. 5 patients presented HIV infection, and 4 hepatitis C.
angiotensin blocker, with 53% being on a statin. Out of the 115 patients, 74 were 51% reported smoking, and 19% of alcohol consumption. Mean creatinine at NS
eligible to undergo analysis. The percentage risk of reaching the endpoint (50% decline diagnosis was 2.4862.30 mg/dL, and proteinuria 10.966.7 g per day. Histologic
in eGFR or reaching ESRD) was calculated at 2 years and 5 years for all patients. These diagnosis were: MN (n=7), membranoproliferative glomerulonephritis (n=5), diabetic
results can be seen in table 1 and 2. At 2 years, 7 patients had reached the endpoint: 2 nephropathy (n=5), and focal and segmental glomerulosclerosis (n=4). 9 out 47
patients had a >50% decline in eGFR, 3 patients received RRT and 2 patients patients presented cancer: 6 patients had a malignancy diagnosed the year before the
underwent transplantation. At 5 years, 14 patients had reached the endpoint: 3 patients NS onset (prostate carcinoma n=2, gastrointestinal carcinoma n=2, lung carcinoma
had a >50% decline in eGFR, 6 patients received RRT and 5 underwent n=1, and Hodgkin lymphoma n=1), and 3 patients one the year after the NS onset
transplantation. (thyroid carcinoma n=1, melanoma n=1, and multiple myeloma n=1). In the
CONCLUSION: Our data suggests that the KRFE tool underpredicts the risk of univariate analysis, patients with cancer were older (69.3612.1 vs 54.4617.2 years old,
reaching endpoint, compared to the IgAN. Our study has helped to compare the two p=0.018) and had more frequently alcohol consumption (33.3% vs 15.8%, p=0.0187).
tools, but further statistical validation is required using a larger cohort. There were no differences in terms of smoking, viral infections, renal function,
proteinuria or type of glomerulopathy. In multivariate analysis including these two
variables and gender, neither age nor alcohol intake were a risk factors for the presence
MO287 Table 1: Comparing KFRE and IgAN tool at 2 years after baseline. of cancer in patients with NS.
CONCLUSION: : 19.1% patients with NS presented also concomitant cancer in our
2 years Percentage Risk of cohort, without association to the type of glomerulopathy, age or known risk factors for
Reaching Endpoint (%) neoplasia such as alcohol, tobacco or viral infection. As our data showed, the presence
of cancer in patients with NS is considerable, so the development of screening
<1 1-5 5 - 20 > strategies to find occult malignancies in this group of patients is necessary since this
20 condition compromises renal outcome and life expectancy
No. of patients KFRE 48 18 6 2
at each %
MO289 IS THERE A ROLE OF INTERSTITIAL CHANGES ON THERAPY
IgAN 17 28 23 6 OUTCOME AMONG PATIENTS WITH FOCAL-SEGMENTAL
GLOMERULAR SCLEROSIS AND MINIMAL CHANGE
DISEASE?
No. of patients KRFE 0 4 3 0
reaching endpoint Aleksandar Jankovic1, Petar Djuric1, Ana Bulatovic1, Dragana Markovic1,
IgAN 0 0 3 4 Snezana Pesic 1, Nada Dimkovic2, Radomir Naumovic1,3
1
University Medical Center Zvezdara, Nephrology Department, Belgrade, Serbia,
2
Academy of Medical Sciences, Serbian Medical Society, Belgrade, Serbia and
3
University of Belgrade, Medical Faculty, Belgrade, Serbia

MO287 Table 2: Comparing KFRE and IgAN tool at 5 years after baseline. BACKGROUND AND AIMS: It is well-known that interstitial changes in patients
with focal-segmental glomerulosclerosis (FSGS) and minimal change disease (MCD)
5 years Percentage Risk of Reaching are linked with disease chronicity and progression. The aim of this study was to analyze
Endpoint (%) is there any connection between interstitial changes and outcome after “first line”
therapy in patients with FSGS/MCD.
<1 1-5 5 - 20 > 20 METHOD: From 2014 till 2019, biopsy proven diagnosis of FSGS/MCD was
No. of patients KFRE 37 15 15 7 established in 40 patients. Interstitial changes were classified in three groups as
following: 0-w/o changes; 1-mild changes; 2-severe changes. Patients with nephrotic
at each % syndrome (No=29) were treated with prednisolone (1mg/kg) and after six months we
IgAN 2 18 26 28 have registered therapy outcome as: CR-complete remission; PR-partial remission; EX-
death; NO-no effect.
RESULTS: Among treated patients (age 50.4615.3 years, 15 men), CR was achieved in
No. of patients KRFE 2 2 7 3 10 patients (34.5%) and 6 out of these 10 (60%) had no interstitial changes. Partial
reaching endpoint remission was observed in 11 patients (37.9%), in 4 patients (13.8%) therapy did not
IgAN 0 2 3 9 have any effect, and 4 patients (13.8%) deceased (table 1). All patients in EX and NO
group had interstitial changes. There were no significant difference in age, gender,
proteinuria, albuminaemia, creatinine and glycaemia levels between groups P except for
hemoglobin levels that were significantly lower in EX group than in others
P ( 15.144;
p=0.002) and urea levels that were significantly higher in EX group ( 138.057;
MO288 NEPHROTIC SYNDROME AS A PARANEOPLASTIC ENTITY: p=0.024).
ARE WE KEEPING IT IN MIND?

Arianne Aiffil Meneses1, Clara Garcıa Carro1, Nancy Daniela Valencia1, MO289 Table 1. Therapy effect according to presence of interstitial changes
Elena Valdés Franci1, Ma Dolores Sa nchez de la Nieta1, Mercedes Velo1,
Antolina Rodrıguez-Moreno1, Elena Ruiz1, Jesu s Domınguez Delgado-Palacios1,
Ana I. Sa nchez-Fructuoso1 Therapy effect
1
Clınico San Carlos Hospital, Nephrology, Madrid, Spain CR PR NO EX
Interstitial changes 0 6 (60%) 2 (18.2%) 0 0
BACKGROUND AND AIMS: Association between nephrotic syndrome (NS) and 1 3 (30%) 7 (63.6%) 3 (75%) 3 (75%)
cancer is well known. However, it has been barely studied and scarcely sustained.
Membranous nephropathy (MN) has been identified often as a glomerular 2 1 (10%) 2 (18.2%) 1 (25%) 1 (25%)
paraneoplastic disease. Reported incidence of cancer at the time of biopsy or one year
CONCLUSION: Patients with FSGS/MCD respond well on standard
follow-up of MN is 10-20%. Incidence rates in other glomerulopathies are limited.
immunosuppressive protocol, particularly in absence of interstitial changes what may
Concomitant malignancy is associated with poor renal outcome in NS. Therapy for
increase the chance for achieving complete remission.
cancer is priority and immunosuppressives therapies should be restricted.
Furthermore, there is no consensus for cancer screening in patients with NS with or
without known risk factors for cancer, as smoking or alcohol consumption.
The aim of our study is to stablish the incidence of neoplasia in a cohort of patients of a
tertiary hospital of Spain who develop NS. We analyze clinical characteristics,
glomerular disease, type of malignancies, screening procedures and risk factors for
cancer in this population.

10.1093/ndt/gfab104 | i219
Abstracts Nephrology Dialysis Transplantation

MO290 CLINICAL DIFFERENCES AND OUTCOMES IN ANCA 0.9960.01 respectively; the mean number of ISs was 2.3960.89 and the mean annual
ASSOCIATED VASCULITIS PATIENTS ACCORDING TO rate of relapses was 2.260.9.
SEROLOGICAL PHENOTYPE – EXPERIENCE FROM RESULTS: Patients were followed over a mean follow-up of 64 months (range: 12-
CROATIAN REFERRAL CENTER 144). After RTX (mean dose: 1202.16372.4 mg) the rate of relapses was virtually
nullified (p<0.001). eGFR remained roughly stable (62.1619.8 ml/min/1.73 m2,
Matija Crnogorac1, Ivica Horvatic 2, Patricia Kacinari2, Miroslav Tisljar3,
p=NS), while proteinuria, albumin, CD19/CD20 and BMI all significantly improved (p
Ana Brechelmacher3, Petar Senjug3, Danica Galesic 3,
 Ljubanovic
ranging from 0.01 to 0.001). The mean number of additional ISs was also reduced
Kresimir Galesic2 (0.4460.12; p<0.001) and RTX enabled discontinuation of steroids in 13/23 (56.5%)
1
Agram Special Hospital, Nephrology, Zagreb, Croatia, 2Dubrava University hospital, patients. No major adverse events related to therapy were recorded.
Department of Nephrology and dialysis, Zagreb, Croatia and 3Dubrava University hos- CONCLUSION: Findings from this large case-series with a remarkable very long
pital, Department of clinical pathology, Zagreb, Croatia follow-up reinforce the role of RTX as an efficient and safe weapon to improve
outcomes in adult patients suffering from SDNS.
BACKGROUND AND AIMS: ANCA associated vasculitis (AAV) are usually
classified according to clinical presentation (Chapel-Hill consensus conference). There
is however suggestion by some authors that AAVs could be classified according to MO292 MALIGNANT DISEASE IS MORE COMMON WITH
ANCA specificity. We aimed to compare AAV patients in our cohort according to DETERIORATING KIDNEY FUNCTION IN PATIENTS WITH
serological phenotype. MEMBRANOUS NEPHROPATHY
METHOD: This study included 106 consecutive AAV patients with renal involvement
in the period from 2007-2017. We performed renal biopsy on patients using automatic Ivana Vukovic Brinar1,2, Karlo Kurtov3, Mario Laganovic1,2, Zivka Dika1,2,
16 Gauge needle. Light, immunofluorescent and electronic microscopy were Marijana Ćoric2,4, Lana Gellineo1, Margareta Fistrek Prlic1, Bojan Jelakovic1,2
performed. Category variables were analysed with Fisher Exact testom and continuous 1
with Kruskal-Wallis testom. Statistical difference was then analysed posthoc with Chi- University Hospital Centre Zagreb, Department of Nephrology, Art.Hypertension,
square test. Primary outcomes were combined outcome progression to end-stage renal Dialysis and Transplantation, Zagreb, Croatia, 2University of Zagreb, School of
disease, defined as persistent (more than three months) need for renal replacement Medicine, Zagreb, Croatia, 3Croatian Institute of Emergency Centre, Department of
therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI Emergency Medicine Sisak Moslavina County, Sisak, Croatia and 4University Hospital
formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Centre Zagreb, Department of Pathology and Citology, Zagreb, Croatia
Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression
analysis were used to explore difference between phenotypes and finding significant BACKGROUND AND AIMS: Membranous nephropathy (MN) can be associated
predictors regarding outcomes. with tumor and present a paraneoplastic condition. Recently, development of tumors
RESULTS: The study included 106 AAV patients with renal involvement: 66 (61,1%) during the course of follow up is more in focus. It is especially interested whether
MPA, 20 (18,5%) GPA, 20 (18,5%) RLV. There were 14 (13%) PR3-ANCA positive patient with MN are prone to tumors, or tumors are condition indipendent of
patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCAþMPO-ANCA and 32 membranous nephropathy or consequence of imunosupressive therapy (IS).
(29,6%) ANCA negative patients. Average SCr was 316,5 lmol/l (IQR 207,0-548,5), 24- METHOD: Retrospective data of all adult patients diagnosed with MN from 1987 to
hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). Clinicaly PR3 positive AAVs had 2017 at the Department of Nephrology of University Hospital Centre Zagreb were
significantly more ENT (p<0,001) and skin (p=0,001) involvement, and ANCA analysed. Medical data regarding antropometric measeures and preexsisting comorbid
negatives had significantly less lung involvement (p<0,001), and less expressed disease at presentation and during follow up were derived from medical records and
constitutional symptom (p=0,031). Interestingly both MPO and PR3 positive AAV hospital informatic system. Furthermore, data regarding kidney function were used,
patients had approximately equal percentage of lung involvement. Both PR3 (p=0,021) namely serum creatinine (SCr), proteinuria. Renal function was assessed using CKD-
and MPO (p=0,009) positive AAVs had higher BVAS score compared to ANCA EPI equation. CKD stages, partial and complete remission were defined according to
negatives, while on average there was no significant difference between MPO, PR3 and KDIGO guidelines.
double positives. PR3 (p=0,007) and MPO (p=0,003) positive AAVs had higher CRP RESULTS: From 1987 till 2017 a total of 122 patients were diagnosed with MN. Eighty
levels than ANCA negatives, and PR3 AAVs had on average higher CRP than MPO nine (72.9%) were treated with imunosupressive therapy. Most commonly prescribed
AAVs though not statistically significant. There was strong tendency (p=0,087) to PR3 initial therapy was combination of corticosteroids and cyclophosphamide (N=66;
AAVs having more acute tubular damage than other groups and also strong tendency 74%). Three (0,02%) patients had history of tumor with median of 3y (min – max 1-4
(p=0,092) of having more crescentic formations than MPO AAVs and ANCA y) before glomerular disease presentation, two solid tumor, adenocarcinoma
negatives but similar to double positives. Though it was not statistically significant pulmonum and carcinoma prostatae, and one condition after allogenic haematopoetic
ANCA negatives had higher median of IFTA compared to other groups. PR3 AAVs transplantation due to acute myeloid leukemia. There was no difference in clinical
and double positives required significantly more often treatment with PLEX (p=0,042) presentation between those with positive history of malignant disease and others
and dialysis (p=0,04) compared to MPO positive AAVs and ANCA negatives. We then (proteinura 11.7 g/du (25-75C 3.4-15.7) vs. 5.8 g/dU (25-75C 3.4 – 8.5); p=0.232 and
grouped patients into ANCA positives and ANCA negatives. ANCA negative patients eGFR 57 ml/min/1,73m2 (25C-75C 14 – 59) vs. 81 ml/min/1.73m2 (25-75C 54 – 100);
were younger (p=0,02), expressed clinicaly more as RLV (p<0,001). BVAS score was p=0.066). During follow up 11 (9%) patients developed tumor, median age of pts 67 y
lower in ANCA negative group (p= 0,003). ANCA positive patients presented more (min – max 59 – 71); nine solid tumors most comonly of gastrointestinal origin
often with RPGN (p=0,027) and ANCA negatives with nephrotic syndrome. There was (pancreas, colon N=5 (45%)), then pulmonum (N=2(18%)) and urogenithal origin (ca
tendency of ANCA positives being treated with PLEX more often (p=0,074). In the renis and prostate N=2 18%). Also two hematological malignancies (B-ALL, B-NHL)
primary outcome analysis there were no statistically significant differences between occurred. Median time till confirmed malignant disease was 9 y (min – max 5 -24). At
serological phenotypes though for relapse rate (p=0,155) curve dynamics through the time of detecting the tumor six (54%) patients were in complete and partial
follow up time seems to show higher relapse rate for PR3 and double positive AAVs remission (4 and 2) and 2 (18%) patients had nephrotic syndrome. No difference was
after 2 years of follow up. observed in proteinuria between those with malignant condition and other MN
CONCLUSION: Serological classification of AAVs is an interesting way for patients (1,4 g/dU (25 – 75C 0.2 – 5.6) vs. 0,29 g/dU (25 – 75C 0.13 – 0.74); P=0.154).
overcoming the limitations of clinical classification. Apart from differences between MN patients with malignant disease during follow up had lower estimated glomerular
MPO, PR3 and double positive AAVs, it appears there are even more significant filtration rate (eGFR 45 ml/min/1,73m2 (25 – 75C 22 – 70) vs. 77 (25 – 75C 58 – 92);
differences between ANCA positive and negative ones. p=0.010). There was no difference in cummulative dose of cyclophosphamide between
those who developed tumor with others (24 g(25 – 75C13.5 – 30) vs. 27 g(25 – 75C 15
– 38)p=0.592).
CONCLUSION: Our data emphasize the need for long term follow up of patients with
MO291 RITUXIMAB IS EFFECTIVE AND SAFE IN ADULTS WITH membranous nephropathy despite accomplishing remission of MN and period
STEROID-DEPENDENT NEPHROTIC SYNDROME: A LONG- screening for malignant disease, especially in those with deteriorating kidney function.
TERM, SINGLE-CENTER EXPERIENCE

Gemma Patella1, Alessandro Comi1, Giuseppe Coppolino1, Nicolino Comi1,


Giorgio Fuiano1, Michele Andreucci1, Davide Bolignano1 MO293 NEUTROPHIL-TO-LYMPHOCYTE RATIO AND OUTCOME IN
1
Magna Graecia University, Nephrology and Dialysis Unit, Catanzaro, Italy CRESCENTIC GLOMERULONEPHRITIS

Otilia Popa1, Tudor Popa1, Nicoleta Petre2, Ana Stanciu3, Cristina-


BACKGROUND AND AIMS: Steroid-dependent nephrotic syndrome (SDNS) may Stela Capusa1,4, Gabriel Mircescu1,4
require a prolonged multi-drug therapy with risk of drug toxicity and renal failure. 1
Rituximab (RTX) treatment has been found to be helpful in reducing the steroid Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, 2“Dr. Carol
dosage and the need for immunosuppressants (ISs), but little data are currently Davila” Teaching Hospital of Nephrology, Nephropatology, Bucharest, Romania, 3“Dr.
available regarding very long-term outcomes in adults. We herein describe a long-term, Carol Davila” Teaching Hospital of Nephrology, Hematology Laboratory, Bucharest,
single-center experience of RTX use in a large series of adults with SDNS. Romania and 4“Dr. Carol Davila” Teaching Hospital of Nephrology, Nephrology and
METHOD: We studied 23 adult patients with SDNS (mean age 54.2617.1 y; 65% Internal Medicine, Bucharest, Romania
male; BMI 28.564.7), mostly consequent to membranous (47.8%) or focal
glomerulonephritis (30.2 %) who were eligible to start a RTX regimen. Before entering BACKGROUND AND AIMS: Crescent formation is a nonspecific response to severe
the RTX protocol, proteinuria and eGFR were 7.0663.87 g/24h and 65.9628.2 ml/ injury to the glomerular capillary wall, which may be seen with any form of
min/1.73 m2, respectively; albumin and CD19/CD20 ratio were 2.960.9 g/L and inflammatory glomerulopathy. Despite improved therapeutic interventions, patients

i220 | Abstracts
Nephrology Dialysis Transplantation Abstracts
with crescentic glomerulonephritis (CGN) still have a severe kidney prognosis and MO294 COMPARISON OF TIP AND CELLULAR VARIANT OF
high mortality. Since neutrophil-to-lymphocyte ratio (NLR) is an inflammatory PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS
marker linked to worse outcomes in patients with malignancies, chronic kidney
Nikola Zagorec1, Ivica Horvati c1,2, Dino Kasumovic 
1, Petar Senjug 3
,
disease, myocardial infarction, and other clinical settings, we aimed to assess if NLR
can predict kidney outcome and mortality in subjects with CGN. Matija Horac ek2, Marko Prazetina4, Marko Lucijani c5, Danica Galesic
METHOD: Eighty-four adults with biopsy-proven CGN between 1st Jan. 2008 and Ljubanovi c2,3, Kresimir Galesic1,2
1
31st Dec. 2017 [age 56 (95%CI 53 to 59) years, 50% males, eGFR 9.3 (95%CI 7.8-12.7) Dubrava University Hospital, Department of Nephrology and Dialysis, Zagreb, Croatia,
2
mL/min] were retrospectively enrolled in this single-centre study. Subjects were University of Zagreb, School of Medicine, Zagreb, Croatia, 3Dubrava University
followed for a median of 31 (95%CI 6 to 56) months, until 31st May 2018. Seven Hospital, Department of Pathology, Unit for Nephropathology and Electron Microscopy,
subjects with inadequate biopsy sample and insufficient data were excluded. Zagreb, Croatia, 4Dubrava University Hospital, Department of Anesthesiology, Zagreb,
Demographic (age, gender), clinical and laboratory data at the time of biopsy were Croatia and 5Dubrava University Hospital, Department of Hematology, Zagreb, Croatia
obtained from medical records. Kaplan-Meier method was used to evaluate kidney and
patient survival. Variables related to kidney outcome were evaluated in a multivariate BACKGROUND AND AIMS: After membranous nephropathy, focal segmental
Cox proportional hazard (CPH) model. glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in
According to median NLR value (4.3, 95%CI 3.5 to 5.2) subjects were clustered in low European population. According to Columbia classification, there are five histological
NLR group (4.3; n=38 pts.) and high NLR group (>4.3; n=38 pts.). The primary variants of FSGS defined on light microscopy (tip, cellular, perihilar, collapsing and not
endpoints were time to renal replacement therapy (RRT) initiation and all-cause otherwise specified - NOS) and this classification has a prognostic significance. The
mortality. aim is to compare features and outcomes of tip and cellular variant of primary FSGS.
RESULTS: The most common CGN subtype was pauci-immune GN (76.3%; i.e. METHOD: All patients with FSGS were identified by a retrospective review of the
myeloperoxidase-ANCA vasculitis - 48.7%, PR3-ANCA vasculitis - 15.8% and ANCA- Registry of kidney biopsies at the Department of Nephrology and Dialysis, Dubrava
negative vasculitis - 11.8%) followed by. anti-GBM antibody and immune complex University Hospital, Zagreb, from 2003 until 2020. Each kidney specimen was analyzed
related GN, with similar frequencies (11.8% each). According to kidney biopsy (KB) by light, immunofluorescent and electron microscopy and Columbia classification was
findings, half of the subjects had fibro-cellular crescents (55.3%), while cellular and applied by experienced nephropathologist. Patients with primary FSGS met following
fibrous crescents were found in 35.5% and 9.2%, respectively. Almost all subjects criteria: full nephrotic syndrome and diffuse podocyte foot process effacement in
received corticosteroids (97.4%) and 82.9% received cyclophosphamide. absence of secondary causes of FSGS. Laboratory findings were obtained for every
Baseline eGFR was lower in the high-NLR group (8.5 vs. 11.6 mL/min, p=0.04), but no patient at the time of biopsy and following outpatient visits. Complete remission was
other differences in laboratory findings at baseline between the two groups were found. defined as proteinuria < 0.3 g/day with normal kidney function and partial remission
In bivariate analysis, NLR was negatively associated with serum albumin (rs=-0.26, as proteinuria 0.3 - 3.5 g/day. Variables are expressed as median 6 IQR (interquartile
p=0.02). NLR was not associated with other inflammation markers, Charlson range) and frequencies. Statistical comparison between groups of patients with tip and
comorbidity score, nor with the type of crescents at KB. cellular variant of primary FSGS and disease outcome analysis were done.
During the follow-up period 53.9% started RRT and 19.7% died. There were no RESULTS: Out of 200 patients with FSGS, 59 (29.5 %) had primary form of disease.
differences regarding mortality between the two groups. Tip variant was the most common form of primary FSGS (22 patients, 37 %) followed
The mean kidney survival time was 47.6 (95%CI 33.5, 61.7) months. Kidney survival at by NOS (20, 34 %), cellular (13, 22 %), perihilar (2, 3.5 %) and collapsing (2, 3.5 %)
12, 24, 48 and 60 months were 44, 41, 38, and 33% respectively. In univariate time- variant. Demographic and clinical features with initial laboratory findings are shown in
dependent analysis (Figure) patients with low-NLR (68.95%CI 48 to 88 months) had Table 1. There were no significant differences between two groups in all analyzed
better kidney survival than those with high-NLR (25, 95%CI 13 to 38 months; log rank variables in Figure 1. All patients were treated by anti-RAAS agents and steroids.
p=0.004). Moreover, the kidney survival advantage remained (OR 1.06, 95%CI 1.002 to Median follow-up was 55 months (range 1 – 196 months), and followup data were
1.16) after adjusting for eGFR, proteinuria, C reactive protein, immunosuppressive unavailable for three patients. Figure 2 shows treatment regimens in both patient
treatment and CGN etiology. Lower eGFR-ul was also associated with poor kidney grouos with treatment outcomes. Remission rate was significantly higher in tip variant
survival (OR 0.96, 95%CI 0.88 to 0.97). (90 % vs. 41 %, p = 0.002). There was no difference in relapse rate between the two
CONCLUSION: In adults with biopsy-proven crescentic glomerulonephritis and groups (p = 0.717).
advanced kidney function decline, a higher neutrophil-to-lymphocyte ratio seems to CONCLUSION: There were no significant differences in clinical features and
predict worse kidney survival, but not the risk of mortality. laboratory findings at the time of clinical presentation between tip and cellular variant
of primary FSGS. Patients with tip variant had significantly higher remission rate than
patients with cellular variant.

FSGS variant Tip Cellular P


value
No. of patients 22 13 -
Male (%) 9 (41) 7 (54) 0.458
Age (years) 52 (20 - 74) 51 (20 - 77) 0.945
Arterial hypertension (%) 18 (82) 9 (69) 0.668
Diabetes mellitus (%) 1 (7.5) 2 (15) 0.541
Systolic BP (mmHg) 140 (130 - 153) 140 (120 - 150) 0.796
Diastolic BP (mmHg) 90 (80 - 94) 80 (80 - 90) 0.433
Serum creatinine (lmol/L) 91.5 (63 - 132) 93 (87 - 169) 0.412
24-hour proteinuria (g/day) 12.2 (7.9 - 17.8) 12.67 (9.5 - 23.28) 0.141
Massive proteinuria (%) 14 (64) 9 (69) 0.560
Serum albumin (g/L) 20 (19 - 26) 26 (20 - 29) 0.238
Total cholesterol (mmol/L) 9.63 (7.11 - 1.2) 10 (8.1 - 13) 0.550
Kaplan–Meier curve of kidney survival rate in patients with NLR4.3 compared with Triglycerides (mmol/L) 2.3 (1.8 - 3.62) 3.25 (2.8 - 4.1) 0.177
NLR>4.3 IgG (g/L) 4.75 (3.63 - 5.73) 5.1 (4.69 - 6.53) 0.869
Hemoglobin (g/L) 124 (118 - 141) 131 (120 - 142) 0.513
Hematuria (%) 15 (68) 7 (53) 0,480
C3 (g/L)* 1.23 (1.09 - 1.40) 1.37 (1.33 - 1.67) 0.060

10.1093/ndt/gfab104 | i221
Abstracts Nephrology Dialysis Transplantation

MO296 MEAN PLATELET VOLUME IN FAMILIAL MEDITERRANEAN


FEVER RELATED AMYLOIDOSIS AND COMPARISON WITH
COMMON PRIMARY GLOMERULAR DISEASES

Treatment regimen Tip (22) Cellular Tolga Yildirim1, Berranur Kutahya2, Fatma Is2, Mehmet Erdevir2, Muge Uzerk
(13) Kibar1, Neriman Sila Koc1, Arzu Saglam3, Seref Rahmi Yilmaz1, Yunus Erdem1
1
Steroids alone* 7 (32 %) 2 (15 %) Hacettepe University Faculty of Medicine, Nephrology, Ankara, Turkey, 2Hacettepe
University Faculty of Medicine, Internal Medicine, Ankara, Turkey and 3Hacettepe
Steroids þ cyclosporine* 11 (50 %) 10 (77 %) University Faculty of Medicine, Pathology, Ankara, Turkey
Steroids þ cyclophosphamide* 4 (18 %) 1 (8 %)
Mycophenolate (sec. line of therapy) 1 (4,5 %) 4 (31 %) BACKGROUND AND AIMS: Compared to healthy controls, mean platelet volume
(MPV) is frequently higher in patients with Familial Mediterranean fever (FMF) but
Cyclophosphamide (sec. line of therapy) 3 (14 %) 0 lower in amyloidosis patients. The cause of differing MPV levels in FMF patients with
Three or more lines of therapy 1 (4,5 %) 0 and without amyloidosis is not clear. We hypothesized that severe proteinuria and
Median follow-up in months (IQR) 57 (18 - 114) 42 (31 - 74) renal dysfunction in amyloidosis could be responsible from low MPV in contrast to
FMF patients without amyloidosis. We aimed to compare MPV levels of FMF patients
Remission on last follow-up** 18 (90 %) 4 (33 %) with amyloidosis and MPV values of patients with different glomerular diseases to
Complete/partial remission*** 9/9 4/1 understand if low MPV is unique to amyloidosis or MPV is similar in all glomerular
Relapsing disease 7 (37 %) 5 (42 %) diseases indicating that it is a consequence of proteinuria and/or renal dysfunction.
METHOD: We compared pre-biopsy MPV levels of patients with amyloidosis
secondary to FMF, to MPV levels of patients with membranous glomerulonephritis,
*first line of therapy; ** p = 0,002; ***p = 0,007 focal segmental glomerulosclerosis (FSGS) and IgA nephropathy that all present with
proteinuria and renal dysfunction. Factors affecting MPV were also determined.
RESULTS: 703 patients (411 male, 292 female) were included in the study. Mean age
was 42.6614.3 years. There were 124 patients with amyloidosis, 224 patients with IgA
nephropathy, 188 patients with membranous glomerulonephritis and 167 patients with
FSGS. Patients with amyloidosis had lower MPV compared to patients without
amyloidosis (7.961.2 fL vs. 8.260.9 fL respectively, p=0.008). Patients with
amyloidosis had also significantly lower MPV compared to patients with each of the
MO295 RESULTS OF 30 YEARS OF RENAL BIOPSIES IN THE other diagnoses. MPV was negatively correlated with platelet count (r = - 0.351, p
GENERAL HOSPITAL OF CIUDAD REAL. WHAT HAS <0.001). There was no significant correlation of MPV with serum creatinine and
CHANGED? proteinuria.
CONCLUSION: This study is the largest study of MPV in patients with biopsy proven
Esperanza Moral Berrio1, Carmen Vozmediano Poyatos1, Minerva Arambarri amyloidosis and confirms previous studies reporting low MPV in amyloidosis. This
Segura1, Lucıa Gonz alez Lo pez2, Agustın Carren~o Parrilla1, Paz Castro study indicates that low MPV in amyloidosis cannot be explained with severe
Fernandez1, Guillermo Ferrer Garcıa1, Gloria Garcıa Conejo1, Sara Anaya proteinuria and renal dysfunction.
Fernandez1, Eliana Olazo Gutierrez1, Luis Guillermo Piccone Saponara1
1
Hospital General Universitario de Ciudad Real, Nephrology, Ciudad Real, Spain and
2
Hospital General Universitario de Ciudad Real, Pathological Anatomy, Ciudad Real, MO297 MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A
Spain REPORT OF CASES FROM FOUR PORTUGUESE CENTERS

BACKGROUND AND AIMS: The renal biopsy (RB) has been performed in the Joana Tavares1, Marina Sofia Rodrigues Reis2, Filipa Silva1, Hugo Ferreira3,
General Hospital of Ciudad Real (HGUCR) since the year 1989. It allows kidney Teresa Chuva2, Ana Paiva3, Ana Marta Gomes2, Carla Moreira2, Maria
diseases to be diagnosed and treated and pronostics to be made. We will analyse the Teresa Santos4, Sandra Silva4, José Maximino Costa3
results of these 30 years as well as the evolution of the various parameters studied. 1
ario do Porto, Nephrology, 2Centro Hospitalar Vila Nova de
Centro Hospitalar Universit
METHOD: Descriptive study of the RB carried out in the HGUCR between 1989 and Gaia e Espinho, Nephrology, 3Instituto Portugu^es de Oncologia do Porto Francisco
2019. Age, sex, clinical syndrome (CS) at the time of the RB, number of glomeruli and Gentil, Nephrology and 4Hospital Pedro Hispano, Nephrology, Senhora da Hora,
histological diagnosis will be analysed. The patients are divided into 3 groups according Portugal
to age: children (<15), adults (15-65) and the elderly (>65). We will establish three
periods of 10 years: period A (1989-1998), period B (1999-2008) and period C (2009-
BACKGROUND AND AIMS: Monoclonal gammopathy of renal significance
2019). The categorical variables are expressed as percentages and the quantitative
(MGRS) refers to any plasma cell or B cell clonal lymphoproliferation that has at least
variables average 6 standard deviation. Statistical analysis with SPSS 25.0.
one kidney lesion related to the monoclonal immunoglobulin productions plus, the
RESULTS: 898 RB have been performed, average number of glomeruli 16, 70% of the
underlying clone is not responsible for tumour complications. Plus, does not meet any
RB with more than 10 glomeruli. The average age of the patients was 53619 years old,
haematological criteria for specific treatment.
58% male. The most frequent CS was acute kidney failure (AKF) (35%), followed by
Although considered a non-malignant or smouldering hematologic condition, its
nephrotic syndrome (NS) (30.5%), asymptomatic urinary disorders (19%), chronic
effects on the kidney are not benign since it frequently evolves to end-stage renal
kidney disease (11%), nephritic syndrome (3.6%), haematuria (0.7%) and arterial
disease. There has been some reluctance in treating these patients but increasing
hypertension (0.7%). The most common in children were asymptomatic urinary
evidence has shown that renal outcomes are closely associated with the haematological
disorders (50%), in adults NS (34%) and in the elderly AKF (55.5%). The predominant
response to chemotherapy.
primary glomerulonephritis (GN): IgA nephropathy (IgAN) (15%), followed by
We aimed to evaluate the incidence of MGRS in the North of Portugal and to assess
membranous nephropathy (MN) (12%) and focal segmental glomerulosclerosis (FSGS)
patients’ characteristics, treatment and follow-up.
(11%). The most frequent secondary GN: vasculitis (11%) and lupus nephropathy
METHOD: We have, retrospectively, collected information of all patients with a
(10%). 164 RB were performed in period A, 370 in period B and 346 in period C. In all
biopsy proven MGRS diagnosis, from four Portuguese centers.
three periods the predominant sex was male and the average age increased: 48 years old
Demographic, clinical, laboratorial data and treatment were analysed. Follow-up was
in A, 51 years old in B and 56 years old in C. Together with the increase in age, the
made until dialysis start, death of until December 2020. Survival curves were analysed
indication of RB changes: NS in the first two periods and AKF in period C. The most
according to the treatment performed, the histological diagnosis, the type of chains, the
frequent pathology in period A: FSGS (17%), IgAN (16%) in period B and IgAN (15%)
estimated glomerular filtration rate (eGFR) and proteinuria at the time of diagnosis.
followed by vasculitis (11%) in period C.
Baseline characteristics were reported as mean 6 standard deviation (SD) and median
CONCLUSION: In the HGUCR the most common biopsied kidney pathology is
(min-max) for continuous variables or as number (percentage) for categorical
IgAN, followed by MN. There has been an increase in the age of the patients as well as
variables. Survival curves were analysed using Kaplan–Meier method. Statistical
an increase in AKF and vasculitis. The KB constitutes a highly useful diagnostic test
calculations were performed using SPSS.
that allows us to establish prognostics and appropriate treatments.
RESULTS: Our study included 36 patients, with a mean age of 69 6 11 years old and
52,8% were males.
At baseline, the median value of serum creatinine (sCr) was 1,2 (0,4-6,3) mg/dL, which
represented a mean eGFR of 55,4 6 30,4 ml/min/1,73 m2 according to the CKD-EPI
formula. The nephrotic syndrome was the most common (72%) renal presentation.
The median proteinuria value was 8,0 (0,5-28) g per day and the mean albumin value
was 2,7 6 0,8 g/dL.
The mean value of monoclonal protein was 5,5 6 4,8 g/L with 62,5% of the patients
having an abnormal serum free light chain ratio. Table 1 describes the type of
gammopathy found, being the IgG/Kappa the most observed.
The immunoglobulin light chain amyloidosis (AL amyloidosis) and the monoclonal
immunoglobulin deposition disease (MIDD), mainly light chain deposition disease

i222 | Abstracts
Nephrology Dialysis Transplantation Abstracts
(LCDD) were the most frequent histological diagnosis (Table 2). Monoclonal
gammopathy of undetermined significance (MGUS) was the most frequent
haematological diagnosis (Table 3).
Treatment was done in 75% of the cases and bortemozib-based regimens were the most
used. Three patients (8,3%) received a bone marrow auto transplant. Approximately
40% of the patients had complete haematological and renal response. Treatment
regimens and haematological and renal responses are summarized in Table 4 and 5.
Survival curves (Figures 1–2) were significantly higher in younger patients (p=0,039)
and both renal and global survival were better (p=0,023) in MIDD compared to AL
amyloidosis. No statistically significant differences were detected when analysing
according to treatment, type of chain, eGFR, proteinuria and serum albumin at
admission.

CONCLUSION: The incidence of MGRS is probably underestimated and its treatment


is yet far to be universal. In our series, 25% of the patients weren’t proposed to any
treatment.
MGRS approach requires a multidisciplinary team composed by Nephrologists,
Pathologists, Onco-Haematologists and a Bone Marrow Transplantation department.
Since not all hospitals meet these conditions, referral centers of greater expertise are
required for a prompt diagnosis and to provide the most adequate treatment.
We hope that in a near future more centres join this project and that this represents the
first step towards the creation of a Portuguese group dedicated to the study and
treatment of MGRS.

10.1093/ndt/gfab104 | i223
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: The localization of ApoA-I at the brush border of the tubular cells is a
specific feature of primary FSGS in relapse. This suggests that ApoA-I staining in
kidney biopsies, coupled with ApoA-Ib measurement in urine, could be used as a
diagnostic tool of primary FSGS relapse after kidney transplantation due to its highly
specific tubular distribution.

MO299 RELATIONSHIP BETWEEN LOW-TITER PHOSPHOLIPASE A2


RECEPTOR ANTIBODY AND TREATMENT RESPONSE OF
IDIOPATHIC MEMBRANOUS NEPHROPATHY

Haoyuan Cui1, Chao Li1, Hang Li1, Yu-bing Wen1, Limeng Chen1, Xuemei Li1
1
Peking Union Medical College Hospital, Nephrology Division, Beijing, P.R. China

BACKGROUND AND AIMS: The circulating anti-Phospholipase A2 receptor


(PLA2R) antibody has been widely detected since its discovery in 2009. It was
suggested that the cut-off of serum PLA2R antibody (PLA2RsAb) should be reset at
below 20 RU/mL to prove diagnostic efficacy. The correlation between low titer
PLA2RsAb and treatment response has not been discussed. In this study, we focused
on the low titer PLA2RsAb during follow-up of PLA2R-related IMN.
METHOD: We retrospectively enrolled 43 Chinese patients with biopsy-proved
PLA2R-related IMN from March 2017 to October 2019. Baseline data were collected
including age, gender, serum creatinine (Scr), albumin (Alb), 24h urine protein
(24hUP), and PLA2RsAb at biopsy. PLA2RsAb was detected at one month, three
MO298 A SPECIFIC TUBULAR APOA-I DISTRIBUTION IS months, six months and one year. The patients were stratified into three groups by the
ASSOCIATED TO FSGS RECURRENCE AFTER KIDNEY lowest PLA2RsAb titer during follow up. Low titer group was defined as anti-PLA2R
TRANSPLANTATION antibody <2RU/mL (53.5%, n=23). Median titer group was defined as anti-PLA2R
antibody >2 but <20RU/mL (32.6%, n=14). High titer group was defined as anti-
Conxita Jacobs Cach a1, Nat
alia Puig Gay2, Ander Vergara1, Alejandra Gabaldon3, PLA2R antibody >20RU/mL (13.9%, n=6). Complete remission (CR) was defined as
Joana Sellares1, Yolanda Villena2, Irene Agraz1, Daniel Seron Micas1, 24hUP <0.3g/d. Partial remission (PR) was defined as 24hUP at the range of 0.3-3.5g/d
Francesc Moreso1, Marıa José Soler1, Joan Lo pez Hellın2 and a reduction >50% of the baseline proteinuria. No remission (NR) was defined as
1
Vall d’Hebron Barcelona Hospital Campus., Nephrology, Barcelona, Spain, 2Vall absence of CR or PR at one-year.
d’Hebron Barcelona Hospital Campus., Biochemistry, Barcelona, Spain and 3Vall RESULTS: In the entire cohort, patients were 49 6 16 years old with 28/15 male/
d’Hebron Barcelona Hospital Campus., Pathology, Barcelona, Spain female ratio. Baseline data of low, mid and high titer group were as follows: the median
PLA2RsAb were 34.3(22.1, 314), 103(55.8, 361), 73.6(53.0, 215)RU/mL, P = 0.305; the
BACKGROUND AND AIMS: A major complication primary focal segmental median 24hUP were 6.8(3.5, 12.4), 6.4(5.6, 8.9), 4.9(3.4, 7.2)g/d, P = 0.493; the average
glomerulosclerosis (FSGS) is its recurrence after kidney transplantation that happens Scr were 100.4 6 60.0, 92.3 6 29.2, 82.0 6 21.9 umol/L, P = 0.681; the median Alb
in 30 to 40% of the patients. The diagnosis of this relapses is not always easy as the were 27.0 6 5.7, 23.8 6 5.8, 30.2 6 3.3 g/L, P = 0.054. The rate of CR, PR, NR were
histological lesions are not highly specific and appear after the proteinuria increase. 34.8% (8/23), 34.8% (8/23), 30.4% (7/23) in low titer group, 7.1% (1/14), 71.4% (10/14),
Currently, there are no accurate biomarkers to detect FSGS recurrence. Our group 21.4% (3/14) in mid titer group, 0% (0/6), 66.7% (4/6), 33.3% (2/6) in high titer group,
identified a modified form of Apolipoprotein A-I (ApoA-I), named ApoA-Ib, P = 0.119
specifically present in urine of recurrent FSGS patients after kidney transplantation. CONCLUSION: The correlation between low titer PLA2RsAb and treatment response
Aberrant forms of ApoA-I have also been described in urine of native primary FSGS showed no statistical significance.
patients and have associated this feature to a prominent staining of ApoA-I at the
apical membrane of the tubular cells. In this study we aim to analyze the ApoA-I
distribution in kidney allograft biopsies of recurrent FSGS patients. MO300 PHOSPHOLIPASE A2 RECEPTOR ANTIBODY SCREENING IN
METHOD: We detected ApoA-I by immunohistochemistry in kidney allograft NEPHROTIC SYNDROME MAY IDENTIFY A DISTINCT
biopsies of patients with FSGS relapse after kidney transplantation (urinary ApoA-Ib SUBSET OF PATIENTS WITH PRIMARY MEMBRANOUS
positive) and in kidney allograft biopsies of patients with a disease different from FSGS NEPHROPATHY
in the native kidney (No-FSGS, urinary ApoA-Ib negative).
RESULTS: In ApoA-Ib positive recurrent FSGS patients, ApoA-I was prominently Roxana Jurubita1, Bogdan Obrisca1, Bogdan Marian Sorohan1, Maria Gaman1,
localized at the brush border of the tubular cells while in the No-FSGS patients ApoA-I Alexandra Vornicu1, Gabriel Mircescu2, Gener Ismail1
was found along the cytoplasm of the tubular cells (Figure 1). 1
Fundeni Clinical Institute, Nephrology, Bucharest, Romania and 2Carol Davila
Teaching Hospital of Nephrology, Nephrology, Bucharest, Romania

BACKGROUND AND AIMS: Primary membranous nephropathy (MN) is a


glomerulus-specific autoimmune disorder caused by anti-phospholipase A2 receptor

i224 | Abstracts
Nephrology Dialysis Transplantation Abstracts
(anti-PLA2R) antibodies in 70-80% of cases. We sought to investigate the utility of that have a preserved renal function and a negative work-up for secondary causes a
anti-PLA2R antibody as a non-invasive screening method for the diagnosis of primary positive anti-PLA2R antibody test highly predicts a diagnosis of primary MN.
MN in patients with nephrotic syndrome (NS).
METHOD: A total of 203 consecutive patients with NS admitted in the Nephrology
Department of Fundeni Clinical Institute, Bucharest, Romania, between January 2015 and
MO301 RITUXIMAB FOR RELAPSING MEMBRANOUS
December 2019 were screened for anti-PLA2R antibodies by an ELISA assay (Euroimmun,
NEPHROPATHY: A SPANISH HOSPITAL EXPERIENCE
Lubeck, DE). A positive anti-PLA2R serology was defined as an ELISA value over 2 RU/ml.
Subsequently, all patients underwent kidney biopsy to confirm the histological diagnosis.
Loreto Fernandez Lorente1, Joaquin Manrique1, Maria Teresa Visus1,
RESULTS: Of the 203 patients with NS, 113 (55.7%) patients tested negative for anti-
Diana Izquierdo1, Itziar Castan
~o1, Maria Fernanda Slon Roblero1, Nerea Gomez1,
PLA2R antibodies, while 23 (11.3%) and 67 (33%) patients had an anti-PLA2R antibody
Gregorio Romero1, Carolina Purroy Iruzun1
titer of 2-20 RU/ml and >20 RU/ml, respectively. Mean age and serum creatinine of the 1
entire cohort were 53 6 13 years and 1.84 6 1.63 mg/dl, respectively, while median 24-h Complejo Hospitalario Navarra, Nephrology, Pamplona, Spain
proteinuria was 6.8 g/day (IQR: 4.8 – 10.6). Thirty patients (14.7%) were identified to
have a potential secondary cause of NS. Ninety-five patients (46.8%) had a histological BACKGROUND AND AIMS: B cell targeting agent Rituximab has been proven to be
diagnosis of MN, while 108 patients were diagnosed with other glomerular disorders. In effective and safe for the treatment of idiopathic membranous nephropathy (iMN) in
patients with anti-PLA2R antibody titer > 20 RU/ml, the most frequent histological previous studies with nearly 75% achievement of partial or complete remission of
diagnosis was MN (n=61, 91%) with 6 patients having other glomerular patterns of injury nephrotic syndrome. The aim of this study was to evaluate this treatment in a cohort of
(two FSGS, one minimal-change disease, one membrano-proliferative patients at Complejo Hospitalario de Navarra with relapsing disease.
glomerulonephritis, one diabetic nephropathy and one postinfectious glomerulonephritis) METHOD: This is a retrospective, cross sectional study including 12 patients with
(Figure 1). Of patients with intermediate anti-PLA2R antibody titer (2-20 RU/ml), 39% membranous nephropathy diagnosed by means of a kidney biopsy. All of them were
had MN and 61% had other glomerular disorders (Figure 1). Eighteen patients with MN treated before with different immunosuppressive regimens and had a relapse at the
had a positive work-up for secondary causes, eight patients (44%) having an anti-PLA2R time of the inclusion. All of them were treated with two iv infusions of Rituximab. In
antibody titer > 20 RU/ml. Additionally, patients with anti-PLA2R antibody titer > 20 this study we report patient clinical and immunological baseline characteristics and
RU/ml had a lower serum creatinine (1.5 6 0.89 mg/dl) than patients with intermediate treatment response at 12 months of follow up.
titer (1.89 6 1.21 mg/dl) and those with negative titer (2.03 6 1.98 mg/dl) (Figure 2). RESULTS: Between 2015-20 a total of 12 patients (41,6% women and 58,3% men)
When analyzing the diagnostic performance of anti-PLA2R antibodies in the entire were treated with two iv infusions of Rituximab with a total mean dose of 2gr. All of
cohort we identified an AUC of 0.83 (95%CI, 0.78-0.89; p<0.001), the cut-off titer of 20 them diagnosed previously of iMN, and 10/12 were PLA2r positive. Baseline laboratory
RU/ml having a sensibility, specificity, positive predictive value (PPV) and negative data showed serum creatinine levels 1,360,9 mg/dl, serum albumin 2969 g/L, 24
predictive value of 65%, 94%, 91% and 75%, respectively. The accuracy of anti-PLA2R hour- urinary protein excretion of 6,863,2 and serum PLA2R levels of 50,54663,2
antibodies for non-invasive diagnosis of primary MN was improved in the subgroup of RU/ml. Either complete or partial response (CR and PR) were achieved in 83,3% of the
patients that were younger than 60 years (AUC=0.88; 95%CI, 0.82-0.95; p<0.001, with a cases, however only 3/12 (25%) patients had a complete response at 12 months follow
PPV and NPV of 91% and 80%), had an estimated glomerular filtration rate over 60 ml/ up. All patients who responded had also a significative decrease PLA2r antibodies.
min (AUC=0.85; 95%CI, 0.77-0.93; p<0.001, with a PPV and NPV of 95% and 69%) or Three of the patients who did a PR were treated with an incomplete dose of iv
had a negative work-up for secondary causes of NS (AUC=0.88; 95%CI, 0.82-0.93; Rituximab (two infusions of 500mg).
p<0.001, with a PPV and NPV of 93% and 80%).

CONCLUSION: Serum anti-PLA2R antibody screening in patients with NS is a useful


method for the diagnosis of primary MN. In younger patients (less than 60 years-old)

10.1093/ndt/gfab104 | i225
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: Rituximab was effective in our cohort of patients with iMN with CONCLUSION: Early identification of patients who mostly benefit from aggressive
achievement of 83,3% response at 12 months of follow up, however only 25% of immunosuppressive therapy is of clinical importance. Our observation that uACR
patients had complete response maybe due to incomplete dosing. Immunological levels at disease onset predict necrotizing and crescentic ANCA GN requires further
response was seen in all patients. Still, a longer follow up of these patients is needed in investigation for therapeutic decision especially in patients with severe deterioration of
order to evaluate Rituximab response. kidney function.

MO302 ACUTE POST-INFECTIOUS GLOMERULONEPHRITIS IN MO304 COMPLEMENT INHIBITION FOR REFRACTORY


ADULTS: A TUNISIAN SINGLE CENTER EXPERIENCE GLOMERULONEPHRITIS IN SYSTEMIC VASCULITIS

Imen El Meknassi1, Mrabet Sanda1, Guedri Yosra1, Zellema Dorsaf1, Miguel Uriol1, Aina Obrador Mulet1, Gemma Arrufat2, Ana Escriva2,
Azzabi Awatef1, Sahtout Wissal1, Toumi Salma1, Fradu Asma1, Ferdaous Sabri1, Mario Lado Fuentes1, José Luis Garcia1, Lucio Pallares3
Samira Ben Amor1, Achour Abdellatif1 1
Son Espases University Hospital, Nephrology, Palma, Spain, 2Son Espases University
1
Sahloul University Hospital, Department of nephrology, dialysis and renal transplanta- Hospital, Pharmacy, Palma, Spain and 3Son Espases University Hospital, Internal
tion, Sousse, Tunisia Medicine, Palma, Spain

BACKGROUND AND AIMS: Acute post-infectious glomerulonephritis (APIGN) is a BACKGROUND AND AIMS: Systemic vasculitis(SV) is a life-threatening disease
reactive immunological disease. Its prevalence in industrialized countries is declining and, in some cases, refractory to intensive multi-immunosuppressant drugs.
contrasting with developed ones. It is uncommon in adults but the prognosis may be Complement hyperactivation has gained interest in the pathogenesis of the SV. We
reserved. The aim of our study was to evaluate the epidemiological, clinical and report the efficacy of the short course of C5-inhibitor (eculizumab) in refractory cases
histological features of APIGN as well as its prognosis. of lupus nephritis (r-LN) and refractory ANCA-associated glomerulonephritis (r-
METHOD: A retrospective and descriptive study was conducted in our department. AGN).
Were included all cases of histologically proven APIGN between December 2006 and METHOD: In this retrospective study, eight consecutive patients were assessed (r-
December 2017. LN:n=3 and r-AGN:n=5). All patients were previously treated with three or more
RESULTS: We had collected 38 cases. The mean age was 37.7 6 17.8 years. The sex drugs included: corticosteroids (n=8), mycophenolate (n=8), rituximab (n=7),
ratio was 1.92. Twelve (31.6%) patients were diabetic and four of them had already a immunoglobulins (n=5), therapeutic plasma exchange (n=4), cyclophosphamide
chronic kidney disease (CKD). APIGN was preceded by an infection in 27 cases with (n=1), and belimumab (n=1). Eculizumab was considered for use in off-label
an average interval of 10 6 5 days. The most common site of infection was the indication in patients with progressive renal deterioration (worsening creatinine,
respiratory tract (15 cases). At presentation, 27 patients had nephritic syndrome and 13 protein-to-creatinine ratio) or developing a high-risk lethal complication after the
had nephrotic-range proteinuria. Hematuria was observed in 97.4%, peripheral edema induction immunosuppressive therapy. The histologic lesson observed were: a) r-LN:
in 84.2% and hypertension in 73.7% of cases. Most patients (78.9%) had acute kidney Type VI (n=1), Type V(n=1), and type IV(n=1), and b) r-AGN: sclerotic (n=3), and
injury and 10 (26.3%) patients required dialysis. Renal biopsy had shown benign acute malignant hypertensionþ/-thrombotic microangiopathy (n=1), in one patient who
glomerulonephritis in 31 cases and malignant form in 7 cases. An underlying developed pulmonary hemorrhage no renal biopsy was performed.
nephropathy was found in 12 cases with mostly a diabetic nephropathy. RESULTS: Mean age (SD): 51(17)years. Median (p25-p75) of follow-up: 19(12-28)
Corticosteroids were used in 3 cases of benign APIGN and 5 cases of malignant form. months. Overall, 2(25%) of the patients needed chronic renal replacement therapy (one
During the follow-up, CKD was noted in 14(36.8%) patients including 7(18.4%) r-AGN patient who required urgent haemodialysis at presentation and one r-LN
patients who progressed to end-stage renal disease. Poor prognostic factors were within 12 months after the onset eculizumab). During the follow-up the
diabetes, the presence of an underlying nephropathy in the biopsy, acute kidney injury eGFR(mean(95%CI) changed from 28(16-40) to 30(20-41)mil/min/1.73m2(P = 0.51)
and the need for dialysis. and the median(p25-p75) protein-to-creatinine ratio decreased from 2.3(1.5-6.4) to
CONCLUSION: The APIGN is uncommon in adults, yet its prognosis may be 0.6(0.3-1.7) mg/mg(P= 0.028). The mean eculizumab cycle dose number was
reserved with progression to CKD. 5(95%CI:3-6), four patients required two cycles. Overall, the mean eculizumab dosage
required was 7162 mg (95%CI: 2969-11355). No major side effects were recorded.
CONCLUSION: The coadyuvant complement inhibition with eculizumab stabilized
renal function and decreased proteinuria in six out of the eight previously refractory
MO303 URINARY ALBUMIN-TO-CREATININE RATIO INDICATES
patients and represents a promising tool in treating lupus and ANCA vasculitis
NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS
nephritis.
IN ANCA-ASSOCIATED VASCULITIS

Samy Hakroush1, Björn Tampe2


1
University Medical Center Göttingen, Institute of Pathology, Göttingen, Germany and MO305 NEPHROTIC SYNDROME AND NEPHROTIC-RANGE
2
University Medical Center Göttingen, Department of Nephrology and Rheumatology, PROTEINURIA - CLINICOPATHOLOGICAL DIAGNOSES AND
Göttingen, Germany PATIENT CHARACTERISTICS IN A MULTIETHNIC SINGLE
CENTRE POPULATION
BACKGROUND AND AIMS: Renal involvement is a common and severe
Selene TY Teoh1, Su Mein Goh2, Eileen LK Pang2, See Cheng Yeo2
complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis 1
(AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or Khoo Teck Puat Hospital, Department of General Medicine, Division of Nephrology,
death. We have previously reported that elevated urinary albumin-to-creatinine ratio Singapore and 2Tan Tock Seng Hospital, Department of Renal Medicine, Singapore
(uACR) correlates with rapid deterioration of kidney function in ANCA GN.
Therefore, we here aimed to describe the association between proteinuric findings and BACKGROUND AND AIMS: Nephrotic syndrome (NS) is a common indication for
histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary renal biopsy, and a frequent presenting clinical syndrome for certain
samples at admission and corresponding renal biopsies of patients with AAV. glomerulonephritis (GN), particularly minimal change disease (MCD), focal segmental
METHOD: A total number of 50 urinary samples at admission and corresponding glomerulosclerosis (FSGS) or membranous nephropathy (MN). However, less is
renal biopsies with confirmed renal involvement of AAV were retrospectively included known on the spectrum of clinicopathological diagnosis and characteristics in patients
between 2015 till 2020 in a single-center observational study. with nephrotic-range proteinuria without nephrotic syndrome (NRP). We aim to
RESULTS: Renal involvement of AAV revealed variable proteinuria ranging from low- evaluate the differences in clinicopathological diagnosis and characteristics of patients
range to nephrotic syndromes, however most patients presented with subnephrotic with NS versus NRP.
proteinuria predominated by albumin (uACR). Severely increased uACR levels >300 METHOD: All patients who underwent a renal biopsy from the 1st January 2014 to
mg/g correlated with reduction of normal glomeruli (P<0.001), attributed to increased 31st December 2016 were included in the study. Patients with no urine protein
glomerular crescents (P<0.001) and necrosis (P=0.008). By contrast, no such quantification, serum albumin or lipid panel done at the time of renal biopsy or no
association was observed for global sclerotic glomeruli (P=0.58), revealing that uACR glomeruli seen on renal histology were excluded. Data for renal histopathology, clinical
reflects necrotizing and crescentic ANCA GN rather than adaptive glomerular diagnosis and patient characteristics were obtained from review of medical records.
hyperfilitration in chronic sclerosing stage. These findings were additionnaly bolstered RESULTS: A total of 362 patients underwent a renal biopsy from the 1st January 2014
by histopathological subgrouping and ARRS: patients with uACR levels >300 mg/g to 31st December 2016. Of these, 76 patients had NS and 106 patients had NRP. Mean
were classified either into Berden’s crescentic class (P=0.002) or ANCA renal risk score age was 51.1617.0, 51.5% were male and 70.9% were Chinese. In the NS group, there
(ARRS) high/intermediate risk (P=0.003). No association between uACR levels and were 25 (32.9%) MCD, 10 (13.2%) FSGS of which 8 were primary, 14 (18.4%) lupus
extrarenal manifestation of AAV disease could be observered, suggesting that uACR nephritis (LN), 11 (14.5%) MN, 8 (10.5%) diabetic glomerulosclerosis, 2 (2.6%)
levels reflected specific renal involvement with ANCA GN and further confirmed by Immunoglobulin A nephropathy (IgAN), 2 (2.6%) amyloidosis and 4 (5.3%) with other
survival analysis for cumulative incidence of RRT during the short-term course of diagnoses (2 membranoproliferative GN, 1 acute interstitial nephritis, 1 chronic
disease. In summary, uACR measurements at admission were associated with renal glomerulosclerosis). In the NRP group, there were 26 (24.5%) diabetic nephropathy, 21
biopsy findings thereafter. Levels of uACR >300 mg/g were more frequently observed (19.8%) IgAN, 15 (14.2%) LN, 13 (12.3%) FSGS of which 12 were secondary FSGS, 12
in necrotizing and crescentic ANCA GN with classification either into Berden’s (11.3%) chronic glomerulosclerosis, 8 (7.5%) MN, 4 (3.8%) pauci-immune GN and 7
crescentic class or ARRS high/intermediate risk and specific for renal involvement in (6.6%) with other diagnosis (2 infection-related glomerulonephritis, 3 had mild
AAV. chronic changes with proteinuria attributable to overflow proteinuria from myeloma, 1

i226 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Alport syndrome, 1 thrombotic microangiopathy). There were significantly more cases MO307 POLYCLONAL FREE LIGHT CHAINS AS A PREDICTOR OF
of primary GN in the NS group (63.2% versus 28.3%, p<0.001), while the NRP group CKD PROGRESSION IN NONPROLIFERATIVE
had more secondary GN and non-GN cases. The most common cause of primary GN GLOMERULOPATHIES
is MCD in the NS group and IgAN in the NRP group. LN is the most common
secondary GN in both NS and NRP groups. There was no significant difference in age, Anna Churko1, Maria Khrabrova1, Alexei Smirnov1,2, Vassili Sipovski2,
gender and race between the NS and NRP group. The NS group had a significantly Iraida Panina1
1
higher proteinuria (10.865.5 versus 6.363.5, p<0.001) and lower serum albumin Pavlov First Saint Petersburg State Medical University, Department of propaedeutics of
(17.065.7 versus 28.067.6, p<0.001). The NRP group had significantly more patients internal diseases, Saint Petersburg, Russia and 2Pavlov First Saint Petersburg State
with abnormal renal function at the time of biopsy (83 (78.30%) versus 39 (51.32%) Medical University, Research Institute of Nephrology, Saint Petersburg, Russia
patients, p<0.001), a higher mean systolic BP (144.1626.3mmHg versus
134.2626.2mmHg, p=0.014) and a higher percentage of diabetes mellitus (38 (35.85%) BACKGROUND AND AIMS: The mechanism of the epithelial-mesenchymal
versus 15 (19.74%) patients, p=0.018) compared to the NS group. transition of kidney tubular cells leading to kidney fibrosis formation and CKD
CONCLUSION: The clinicopathological diagnosis between patients with NS and NRP progression is well described for monoclonal free light chains (FLC) in patients with
differ significantly. Patients with NRP are more likely to have secondary glomerular monoclonal gammopathies. As far as the interaction of FLC with megalin/cubulin
disease or non-glomerular disease, with abnormal renal function and higher prevalence receptors on proximal tubular epithelial cells is considered to be universal we
of hypertension and diabetes mellitus. hypothesize that polyclonal free light chains (pFLC) could have the same effect on
tubulointerstitial compartment in patients with primary glomerulopathies. This
retrospective study was performed to reveal the association of serum pFLC kappa
MO306 IGA NEPHROPATHY: A 20 YEAR RETROSPECTIVE SINGLE (pFLC-j) and lambda (pFLC-k) assessed by FreeliteV R with clinical and morphological

CENTRE EXPERIENCE parameters and CKD progression in patients with nonproliferative glomerulopathies.
METHOD: 36 patients with morphologically proven diagnosis of nonproliferative
Josh Storrar1, Fahmida Mannan1, Reuben Roy1, Rajkumar Chinnadurai1, glomerulopathies (minimal changed disease (n=11), membranous nephropathy (n=11) and
Smeeta Sinha1, Philip A. Kalra1 focal segmental glomerulosclerosis (n=14)) were included. Serum levels of pFLC-j and
pFLC-k were assessed by FreeliteV R (normal ranges: j=3.3-19.4 mg/l; k=5.7-26.3 mg/l; j/k
1
Salford Royal NHS Foundation Trust, Renal, Salford, United Kingdom ratio=0.26-1.65) at the time of kidney biopsy (KBx) in all cases. Patients with abnormal j/k-
ratio due to monoclonal gammapathies were excluded. Apart demographical parameters,
BACKGROUND AND AIMS: IgA nephropathy is the most common glomerulonephritis serum creatinine, estimated GFR (eGFR) by CKD-EPI, serum albumin and 24-hour
worldwide. The clinical course is heterogeneous and not always easy to predict. As such, proteinuria were measured. Morphological findings defined by light microscopy were
determining which patients to treat with immunosuppression has been the cause of much measured semiquantitatively according to currently accepted criteria (0 - <10%, 1 - 10-25%,
debate. Over recent years there has been a focus on risk prediction to help with treatment 2 – 26-50%, 3 - >50% of tissue involved). Data are presented as median and interquartile
decisions (such as the widely validated International IgA Risk Prediction Tool). Here, we range (M (25%; 75%)) and mean and the standard error of mean (m6SEM) for
present a 20 year retrospective study from a single centre with the following aims: to describe semiquantitative parameters or %. Correlation between parameters was assessed by
the epidemiology of our cohort, to assess outcomes (such as progression to ESKD requiring Spearman’s coefficient. Progression of CKD was determined as decline of eGFR >15% from
RRT, mortality), and to determine if treatment choices have changed over time. the initial level at the end of follow-up. Cox proportional hazards regression was used to
METHOD: We collected all cases of IgA nephropathy from our biopsy database estimate the association of pFLC and other parameters with CKD progression. Differences
between January 2020 and December 2019. This totalled 525 biopsies. Of these, a were considered statistically significant at p <0.05. Median follow-up was 11 (1; 53) months.
number were excluded from analysis, including transplant biopsies and repeat biopsies RESULTS: Demographic and clinical parameters at the time of KBx are shown in the
in the same patient. After exclusion, the original 525 biopsies were narrowed down to Figure 1.
452 patients for analysis. We collected demographic data for each patient, along with
creatinine and proteinuria values over time, MEST-C scores, progression to ESKD,
mortality, use of RAAS blockade and immunosuppressants. Initial analysis was
performed using Excel. We plan to perform further multivariate Cox regression
analysis to determine if there are associations with progression to ESKD such as degree
of proteinuria, MEST-C scores and immunosuppression treatment.
RESULTS: We identified 452 patients with biopsy confirmed IgA nephropathy at our
centre between January 2000 and December 2019. 138 (30.5%) were female and 314
(69.4%) were male. The average age at time of biopsy was 45.7 years. Mortality over
this period was 19.2% (87 patients). 126 (27.9%) progressed to ESKD requiring RRT, 6
(1.3%) required temporary dialysis whilst 313 (69.2%) did not require RRT. With
regards to treatment, 329 (72.8%) were treated with RAAS blockade in comparison to
85 (18.8%) who were not (in 38 patients this was unclear). No immunosuppression was
used in 349 (77.2%), whilst a combination of prednisolone; IV cyclophosphamide and
prednisolone; and MMF and prednisolone was used in 97 (21.5%).
CONCLUSION: We present here a large single centre dataset of IgA nephropathy
patients over a 20 year period. We show that there remains a significant risk of
progression to ESKD over time. It is important to identify those patients most at risk of
progression early on in their disease course so that optimal treatment can be initiated.
Further analysis of this dataset will allow us to assess whether treatment strategies in
recent years has had a beneficial effect on outcomes, and also to assess the correlation Clinical and morphological parameters as well as correlation analysis data are
between MEST-C scores and treatment decisions. presented in the Figure 2.

MO306 Figure: Different immunosuppression treatment options used in our cohort of


452 patient with biopsy-confirmed IgA nephropathy.

10.1093/ndt/gfab104 | i227
Abstracts Nephrology Dialysis Transplantation

Univariant Cox regression shows that pFLC-k >N (Exp(b)=5.120; 95% CI: 1.011- The aim of this work is to highlight the particularities of CV in this case
25.924, p<0.05), both pFLC-j and pFLC-k >N (Exp(b)=6.646; 95% CI: 1.327-33.287, CASE PRESENTATION: We report a case of a 62-year-old woman followed since
p=0.02), j/k ratio (Exp(b)=4.656; 95% CI: 1.411-15.362, p=0.01), as well as percent of 2014 for CV type 1 IgG Lambda revealed by vascular purpura and nasal septal
sclerotic glomeruli (Exp(b)=1.039; 95% CI: 1.006-1.073, p=0.01), glomerular basement perforation. the etiological assessment was negative. Hepatitis C virus serology was
membrane segmental thickening (Exp(b)=3.129; 95% CI: 1.213-8.071, p<0.01), negative. A corticosteroid therapy at a dose of 1 mg/kg/day was started with partial
mesangial proliferation (Exp(b)=5.177; 95% CI: 1.146- 23.396, p=0.03), interstitial cell improvement. Then the cyclophosphamide at a dose of 150 mg/d was added with a
infiltration (Exp(b)=3.777; 95% CI: 1.258-11.340, p=0.02) and peritubular capillaritis fairly good clinical result but stopped for hemorrhagic cystitis.
(Exp(b)=5.177; 95% CI: 1.146- 23.396, p=0.03) were associated with CKD progression. Chlorominophene was started at a dose of 6 mg/d and then reduced to 4 mg/d for
CONCLUSION: In nonproliferative glomerulopathies increased level of pFLC, either leuconeutropenia but the peripheral arterial manifestations (acrocyanosis of the limbs
kappa or lambda, is associated with glomerular lesion, interstitial inflammation, and ears) were not treated.
tubular atrophy and interstitial fibrosis. Moreover, elevated levels of pFLC could be The evolution was marked by the appearance of renal failure (creatinine 482.33 umol/l)
proposed as a predictor of CKD progression in studied patient cohort. The associated with proteinuria at 1.32 g/24h. An outbreak of cryoglobulinemia was
mechanisms of kidney injury by pFLC requires further investigation. suspected.
Plasma exchange was discussed as a therapeutic alternative and the patient was
scheduled for a renal biopsy.
However, the patient became febrile with the appearance of a dry cough and the
MO308 COULD THE PRESENCE OF ANCAS IN IGA NEPHROPATHY presence of a biological inflammatory syndrome (CRP at 72). A SARS-CoV-2 PCR was
WITH CRESCENTS HAVE A CLINICAL IMPLICATION? completed which was positive. Therefore, she was put on antibiotic therapy
(Azythromycin and Cefotaxime) associated with vitamin therapy and anticoagulant
Zaira Castan ~eda Amado1, Alejandra Gabaldon2, Marıa Teresa Sanz3, treatment.
Roxana Bury1, Cinthia Baldallo1, Jose Zun ~iga1, Juan Carlos Leo n1, The patient was stable in terms of respiration and hemodynema, but her renal function
Cesar Sanchez1, Ander Vergara1, Sheila Bermejo1, Marıa José Soler1, worsened and progressed well under hydration. In addition, she presented with a
Daniel Seron Micas1, Irene Agraz1 slippage syndrome and she was died
1
Hospital Universitario Vall d’ Hebron, Nephrology, Barcelona, Spain, 2Hospital CONCLUSION: The natural history of CV is not predictable and strongly depends on
Universitario Vall d’ Hebron, Pathological Anatomy, Barcelona, Spain and 3Hospital concomitant diseases and complications and response to treatment. The SARS Cov2
Universitario Vall d’ Hebron, Immunology, Barcelona, Spain infection can complicate its evolution. There is no association has been described
between them to our knowledge
BACKGROUND AND AIMS: IgA nephropathy (IgAN) is the most common
glomerulonephritis. The presence of ANCAs in this pathology represents a rare
coincidence. However, it is not clear if the presence of IgA or IgG ANCAs in these
patients could have clinical significance.
We aim to describe the presence of IgA and IgG ANCAs in patients diagnosed with
IgAN with crescents, and its possible clinical implications.
METHOD: Retrospective study from 2013 to 2020, it included all patients diagnosed
by kidney biopsy of IgAN with extracapillary proliferation. Outpatient follow-up time
was up to 24 months. Demographics and clinicopathologic data, ANCAs subtype,
characteristics of the biopsy and treatment at the time of diagnosis/follow up was
recollected.
RESULTS: From 2013 to 2020, 17 adults were diagnosed with IgAN and extracapillary
proliferation. 5 patients presented ANCAs, 3 (17%) were IgA ANCAs and 2 (11%)
were IgG ANCAs. At diagnosis, the median age was 48 years old (27-75 years, sd. 15),
with 9 women (52%). At the time of diagnosis, the most common clinical presentation
was hypertension (71%). The laboratory analysis showed that median hemoglobin was
11.7 mg/dl (8.4-14.9 mg/dL, sd. 1.5), median creatinine was 2.2 mg/dL (0.55-5.7 mg/
dL, sd. 1.4) and median proteinuria was 3.5 g/mgCr (0.1-12 g/mgCr, sd. 3.5). 7 patients
(41%) presented extracapillary proliferation less than 25%, 7 patients presented it
between 25% and 50%, and 3 patients (17%) had it in more than 50%. 5 (30%) patients
presented fibrinoid necrosis. 1 (6%) patient needed renal replacement therapy upon
admission. In terms of treatment, all patients with ANCAs IgAN received endovenous
steroids and cyclophosphamide. The mean follow-up time was 6 months. Oral steroids
(59%) and mycophenolate (41%) were the most frequent treatments. At six months,
the median creatinine was 1.9 mg/dL (0.4-7, sd. 1.78) and the median proteinuria was
1.45 g/gCr (0.12-5.9, sd. 1.84 g/gCr). 3 patients developed end-stage chronic kidney
disease and requiring substitute renal therapy; 4 patients died. Statistical analysis did
not show differences in clinical characteristics, demographics, kidney function,
MO310 LIPID DISORDERS IN NEPHROTIC SYNDROME
proteinuria, need for renal therapy replacement or mortality according to the presence
or subtype of ANCA. ANCA negative patients presented less than 25% of
extracapillary proliferation in renal biopsy (p = 0.04). ANCA positive patients
presented more fibrinoid necrosis than ANCA negative patients (p=0.01). Jose Maria Pen ~a Porta1, José Antonio Ferreras Gasco 1, Almudena Castellano
CONCLUSION: Given the limited size of our sample, our results do not allow us to be Calvo1, Ana Coscojuela Otto1, Paula Juarez Mayor1, Rafael Alvarez Lipe1
1
conclusive, showing no significant differences between the ANCA subtypes. However, Hospital Clinico Universitario Lozano Blesa, Nephrology, Zaragoza, Spain
from the point of renal biopsy, it is observed that patients with negative ANCAs
present less extracapillary proliferation; and that patients ANCA positive presented BACKGROUND AND AIMS: Lipid disorders are a characteristic manifestation that
more fibrinoid necrosis. accompanies the presentation of nephrotic syndrome (NS). The pathophysiology
underlying its origin is debated in the literature. It is important to collect large series of
patients to accurately characterize these manifestations.
MO309 SARS COV2 INFECTION COMPLICATING The aim of this study was to carry out an analysis of the lipid alterations detected in the
CRYOGLOBULINEMIC VASCULITIS WITH RENAL presentation of NS, as well as its evolution, in a large cohort of patients treated in the
INVOLVEMENT Nephrology Service of a tertiary referral hospital.
METHOD: 111 NS outbreaks corresponding to 71 patients seen in the last 12 years
Hanene Bouafif1,2, Hajji Mariem3, Samia Barbouch2, Hedri Hafedh1, were analyzed.
Imen Gorsane1, Fethi Ben Hmida1,4, Taieb Ben abdallah1 RESULTS: 53 patients had a single outbreak. 18 patients (25.35%) had 2 or more
1 outbreaks. 63.1% of the outbreaks affected males. Mean age 54.76 6 18.46 years (17-
Tunis, internal medecine, Tunis, Tunisia, 2Department of medecine A. Laboratory of
85). Charlson comorbidity index 2.62 6 2.43 points (0-8). The mean of drugs ingested
renal pathology LR00SP0, 3Tunis, Department of medecine A. Laboratory of renal path-
daily prior to NS was 4 6 3.88 (0-13) There were no significant differences between
ology LR00SP0, Tunis, Tunisia and 4Department of medecine A. Laboratory of renal
men and women regarding these three parameters. A renal biopsy was performed in
pathology LR00SP0, Tunisia
the first outbreak in 67 patients with the result of: 21 membranous nephropathy, 11
minimal change nephropathy, 17 mesangial glomerulonephritis, 8 focal segmental
BACKGROUND AND AIMS: Cryoglobulinaemic vasculitis (CV) leading to clinically glomerulosclerosis, 2 IgA nephropathy, 5 AA amyloidosis, 3 AL amyloidosis.
apparent skin lesions, and in some cases also to internal organ involvement such as 90.1% of the patients had high cholesterol levels (> 200 mg/dL). 73% of the patients
renal involvement. The SARS Cov2 infection in this field is very serious and in the case had high LDL cholesterol (> 160 mg/dL). 72.1% of the patients had triglycerides (TG)
of our patient the outcome was fatal. above normal levels (> 150 mg/dL). 47.75% of the patients had a high atherogenic
index (> 5).

i228 | Abstracts
Nephrology Dialysis Transplantation Abstracts
The mean levels at the presentation of NS were: total cholesterol 338.07 6 111.61 mg/
dL; HDL cholesterol 67.92 6 25.46 mg/dL; LDL cholesterol 227.76 6 99.28 mg/dL; TG
215.48 6 97.27; atherogenic index 5.12 6 2.47. There were no significant differences
regarding these variables and the various glomerular diseases. Patients with prior
dyslipidemia history, showed significantly lower cholesterol levels, 309.69 6 98.08 mg/
dL vs 363.53 6 115.55 mg/dL, perhaps because they were already taking statins (we do
not have this data).
There is a significant correlation between total cholesterol and LDL cholesterol with
serum albumin, but not between total cholesterol or LDL with proteinuria. There is a
correlation between TG with both albumin and proteinuria. There is a significant
inverse correlation between the neutrophil/lymphocyte ratio (NLR) and total
cholesterol and LDL cholesterol. The higher the NLR, the lower the cholesterol. It gives
the impression that the sicker/inflamed the patient is, the lower the ability to synthesize
cholesterol. In our series, patients with acute kidney injury (AKI) or previous chronic
kidney disease (CKD) had significantly lower cholesterol levels. AKI 306.84 6 105.24
mg/dL vs no AKI 354.04 6 110.50 mg/dL. CKD 293 6 124.15 mg/dL vs no CKD
347.07 6 106.27 mg/dL.
In multivariate analysis, the variables associated with the level of total cholesterol and
LDL cholesterol were serum albumin and the Charlson comorbidity index. Regarding
the triglyceride level, the associated variables were serum albumin and proteinuria.
In the evolution of the patients, both total cholesterol and triglycerides improved
significantly after reaching NS remission: final cholesterol 190 mg/dL; Final
triglycerides 141 mg/dL.
CONCLUSION: As in other series, we detected a high prevalence of lipid alterations in
our population of adult patients with NS. Hypoalbuminemia appears as the factor that
is independently associated with cholesterol and triglyceride levels. The lipid MO311 Figure 1: POx concentration in the healthy volunteers and the PGN patients
alterations improve in a parallel way as the NS picture does. stratified by the presence of NS.

MO311 THE ASSOCIATION BETWEEN NEPHROTIC-RANGE


PROTEINURIA AND OXALATE METABOLISM VIOLATION IN
PATIENTS WITH PRIMARY GLOMERULONEPHRITIS

Natalia Stepanova1, Lyudmyla Snisar1, Larysa Lebid1, Svitlana Savchenko1


1
State Institution “Institute of Nephrology of the National Academy of Medical Science
of Ukraine”, Nephrology & Dialysis, Kyiv, Ukraine

BACKGROUND AND AIMS: There is a general lack of scientific research on oxalate


metabolism in primary glomerulonephritis (PGN) patients. The present study aimed to
evaluate plasma oxalic acid (POx) concentration and urinary oxalate (UOx) excretion
in PGN patients and determine the role of nephrotic syndrome in oxalate metabolism,
which has never before been reported.
METHOD: A total of 100 participants were enrolled in this cross-sectional single-
center study, including 76 PGN patients aged 41 6 1.83 years and 24 healthy
volunteers on a free-choice diet who served as a control reference group to evaluate
POx concentration. Among the patients were 53 (69.7 %) patients with nephrotic
syndrome (NS) and biopsy-proven PGN and 23 (30.3 %) patients with a clinical
diagnosis of PGN. All patients were treated according to KDIGO Clinical Practice
Guidelines for Glomerulonephritis.
In addition to routine hematological and biochemical tests, POx concentration and
UOx excretion were found in all study participants. POx was measured MO311 Figure 2: The association between UPE and POx concentrations in the PGN
spectrophotometrically using a commercially available kit (MAK315, Sigma, Spain). patients.
Daily UOx excretion was determined using an oxalate oxidase/peroxidase reagent
(BioSystems, Spain). Urine protein excretion (UPE) was measured in a 24-h urine
collection. The glomerular filtration rate (GFR) was calculated using the CKD-EPI
formula.
The data were presented as the median and the interquartile ranges [Me (Q25-Q75)]
and compared using the Mann-Whitney test. The Spearman correlation test and the
partial correlation coefficient were used to evaluate the association between the
examined markers.
RESULTS: POx concentration was significantly higher in the patients with PGN
compared with the healthy volunteers: 29.9 (14.9-51.7) vs 18.9 (16.2-23.8) mmol/L, p =
0.01. Although the patients with NS demonstrated a statistically higher GFR level
compared with the patients with mild proteinuria [70.5 (47-87) vs 50 (22-76.2) mL/
min/1.73 m2, p = 0.01], these patients also had the highest POx level (Fig. 1).
Moreover, POx concentration was significantly associated with GFR (r = -0.27, p =
0.005), serum phosphate (r = 0.26, p = 0.007) and UPE (Fig. 2) levels. No significant
differences were found in UOx excretions between the groups. However, the higher
level of UPE was, the higher level of UOx was observed in the PGN patients with NS
(Fig. 3). The partial correlation analysis confirmed a strong association between UPE
and POx concentration independently of the patients’ age, gender, GFR and serum
phosphate levels (r = 0.22, p = 0.04).

MO311 Figure 3: The association between urinary protein and oxalate excretions in
the PGN patients with NS.

CONCLUSION: Nephrotic-range proteinuria was significantly associated with the


elevation of POx concentration and UOx excretion in the PGN patients. More research

10.1093/ndt/gfab104 | i229
Abstracts Nephrology Dialysis Transplantation

with a larger cohort is needed to confirm this preliminary evidence and validate NS as a ( Fig. 2).
risk factor for oxalate metabolism violation in PGN patients.

MO312 MAIN TRENDS AND OUTCOMES OF KIDNEY DISEASE IN


GEORGIA: THE FIRST REVIEW OF KIDNEY BIOPSY
DATABASE FROM 2011 TO 2020

Nora Sarishvili1, Irma Tchokhonelidze1, Tamar Tevdoradze1, Tamar Kasradze1,


Dalakishvili Ketevan1, Nona Babutsidze1, Gvantsa Metskhvarishvili1,
Rusudan Rusia1, Nino Buadze1, George Gazdeliani1, Tamar Bagashvili1,
Avtandil Tataradze1, Lela Beglarashvili1, Nino Maglakelidze1, Natia Pachulia1,
Merab Sutidze1
1
Georgia, Georgia

BACKGROUND AND AIMS: Kidney biopsy registry has been established in Georgia
in 2011 by Dialysis, Nephrology and Kidney Transplantation Union of Georgia (DNT
Union) to address the natural history of kidney disease, describe the clinical features,
improve disease understanding and tracking, healthcare planning, patient care and
outcomes. This report is the first review of histological data over a period of 10 years
(2011-2020) covering the entire population of 3.7 million inhabitants and
demonstrates the current data on trends of kidney disease in Georgia.
METHOD: 1267 ultrasound-guided kidney biopsies were performed during the 10
years. Data were extracted from the DNT Union kidney biopsy registry as of 1st of
December 2020. Data on kidney function, urinalysis, treatment options and outcomes
were also included in biopsy registry database. After exclusion of transplant and re-
biopsies, kidney biopsies were analyzed for evaluation main trends in kidney biopsy
rates and diagnosis of glomerular and non-glomerular diseases in two groups divided
in 5-year time frames: the first group 2011-2015 and the second group 2016-2020. The
overall treatment outcome was evaluated as complete remission (CR), partial remission
(PR) and progression to ESRD. MO312 Figure 2: Major trends in outcome among patients with primary
RESULTS: Final cohort consisted of 1089 patients. Mean age was 39 years [SD 13 glomerulonephritis
years]. Fifty five percent of the cohort were male. The average annual biopsy incidence
was 455 biopsies in the first group and 634 cases in the second group. The most
common indication as clinical syndrome for performing the kidney biopsy was a CONCLUSION: The present data are an important contribution to the epidemiology
decrease of glomerular filtration rate GFR (35%), followed by nephrotic syndrome of kidney disease in Georgia. The incidence of glomerulonephritis generally increased
(30%) and nephritic syndrome (21 %) and in lesser degree asymptomatic urinary between 2011 and 2020, that may be related to changes in kidney biopsy policy.
abnormalities (14 %). Substantial decrease in numbers of kidney biopsies were registered in 2020 due to
The frequency of kidney biopsies increased significantly over the years (Fig.1). The pandemic issues. Membranous nephropathy was the most common primary
distribution of major histological groups of kidney disease in both groups is shown in glomerular disease according to the registry database. The prognosis regarding
the Table 1. As for comparison of the major trends among various histological progression to ESRD has improved.
patterns, there was 3,6 times more heredity kidney diseases diagnosed in the second
group, followed by tubulointerstitial nephritis with 3.3 times increase, acute tubular
necrosis 1.5 times increase and glomerulonephritis (primary and secondary) with 1.3
times increase. There was found statistically no changes in the incidence of vascular
kidney disease between two groups (p=0.005).

MO312 Table 1: Distribution of various types of kidney diseases in both time groups

MO312 Figure 1: The number of kidney biopsies by the year


MO313 A CASE OF ALPORT SYNDROME WITH PREGNANCY-
Overall outcome demonstrates some changes during the time. PR was the most RELATED ATYPICAL HEMOLYTIC UREMIC SYNDROME, AND
prevalent outcome in both time groups. However, proportion of PR cases increased CRESCENTIC GLOMERULONEPHRITIS
(45%vs.64%) and proportion of CR (25% vs.17%) and ESRD (30% vs.18%) cases
decreased. This change is statistically significant at p<0.0001. There were no data Ilay Berke Mentese1, Murat Tugcu1, Arzu Velioglu1, Ismail Nazli2, Z.
obtained from 15% (173) of patients. Serhan Tuglular1
The distribution of overall outcome among patients with primary glomerulonephritis
1
Marmara University Research And Education Hospital, Nephrology, _Istanbul, Turkey
(PGN) repeated the same trend. Out of total PGN patients (481 cases) 61% showed PR, and 2Marmara University Research And Education Hospital, Internal Medicine, Istanbul,
24% reached CR and 15% progressed to ESRD. The proportion of patients with PR was Turkey
higher (69%) among patients diagnosed with PGN in the second group compared with
the first (48%). Proportion of patients, who developed ESRD, was lower in the second
group (12% vs.19%).

i230 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO313 Table 1:

Variable Reference Values On Admission At delivery 10 days post-partum 20 days post-partum 6 months post-
admission
Hemoglobulin(g/dl) 12-17 9,2 7,8 6,9 8,2 9,3
Platelet Count (103/ll) 150-440 147 136 84 109 199
Creatinine (mg/dL) 0-1,2 0,78 1,1 3,2 4,81 7,19
Albumin (mg/dL) 3,5-5,4 1,6 1,5 2,4 2,5 4,3
Alanine Aminotransferase (U/L) 10-40 U/L 12 9 14 18 27
Lactate Dehydrogenase (U/L) 0-248 U/L 141 319 376 340 232
Urine protein (mg/day) 0-150 11059 - - 18270 -

BACKGROUND: Thrombotic microangiopathy (TMA) is one of the most important plasma properdin levels were found to show alternative complement activation and
complications in pregnant patients with chronic kidney disease (CKD) causing clinical correlate with disease activity in pauci-immune crescentic GN patients. Few reports
deterioration. However, little is known about the pregnancy course in women with show that anti-complement therapies might be an option in these cases. Although our
Alport syndrome (AS). case’s kidney functions did not improve on eculizumab, we conclude that the
CASE: A 28-week pregnant, 22-year-old woman was admitted to our clinic because of polymorphisms in the complement genes may have induced crescent formation in the
widespread edema. Her medical history was notable only for hearing impairment. On presence of pregnancy and abnormal glomerular structure due to AS.
examination, vital signs were normal except for the blood pressure (150/90 mmHg). CONCLUSION: Here we presented a case with AS complicated by aHUS and
There were diffuse crackles at the lung bases, and 3þ pitting edema in both legs. Lab crescentic GN. Given this complex combination of rare causes of acute kidney injury,
results revealed heavy proteinuria with 11 gr/day and isomorphic erythrocytes with detailed clinical evaluation is of great importance in the evaluation of acute kidney
granular casts in microscopic urine examination. An emergency c-section was injury during pregnancy.
performed due to severe preeclampsia at 30 weeks’ gestation.
After delivery, her edema did not improve, serum creatinine and lactate dehydrogenase
levels elevated, anemia and thrombocytopenia developed (Table 1). Additional tests
MO314 ANA POSITIVITY IN IGA NEPHROPATHY: IS SYSTEMIC
revealed negative Coombs test, schistocytes on peripheral smear and normal
LUPUS ERYTHEMATOSUS COMING UP?
ADAMTS13 level. There was no pathology in serological studies.
She received four sessions of plasmapheresis therapy, and with the diagnosis of aHUS, Fausta Catapano1, Benedetta Fabbrizio2, Elena Mancini1
eculizumab therapy was started. Despite improving thrombocytopenia and anemia, 1
Nephrology, Dialysis and Hypertension Unit, Policlinico S. Orsola, Bologna, Italy and
serum creatinine levels continued to rise and her urine output decreased. A kidney 2
Department of Pathology, Policlinico S. Orsola, Italy
biopsy was performed (Figure 1). In the light microscopy, 11 of 15 glomeruli had
circumferential cellular crescents and 4 had partial cellular crescents. The sample had
no findings consistent with TMA. No staining was seen with IgG, IgA, IgM, C3, C1q, j BACKGROUND AND AIM.: IgA nephropathy (IgAN) is the most common chronic
and k in immunofluorescence. primary glomerulonephritis leading to progressive renal failure in 1/3 of patients.
Although it is a limited non-systemic renal disease, many systemic diseases, such as
Systemic Lupus Erythematosus (SLE), are sporadically associated with mesangial IgA
deposits. We investigate frequency and meaning of ANA positivity in IgAN.
METHODS.: All biopsy-proven IgAN patients followed in our Unit with ANA
positivity were selected. Data are compared by non parametric test (Wilcoxon signed-
rank test).
RESULTS.: 15/68 (22%) IgAN patients resulted ANAþ during a 9-year median follow-
up. 10 were females and five were male. Mean age was low. Renal function was normal
in 9/15. 24 h Proteinuria was non nephrotic in 15/16. In 10 patients there was low C3.
Patient characteristics are summarized in Table 1. At follow-up, renal function did not
change significantly (p=NS), however mean 24h-Uprot reduced (p=0.075) Table 2.
One male developed SLE, one female a lupus-like Mixed Connective Tissue Disease.

MO314 Table 1. Patient Characheristics at onset (kidney biopsy) in 15 IgA plus


ANAþ patients.

N. SEX Race Age (years) sCr(mg/dl) Uprot (g/


day)
1 F Italy 30 0.8 0.9
2 M Italy 16 0.8 0.3
3 F Philippines 32 1.6 0.9
4 F Italy 39 0.9 6
5 F Italy 23 0.8 0.2
6 M Italy 39 3 1
Further evaluation of hearing impairment revealed bilateral sensorineural hearing loss.
A homozygous mutation was identified on COLA4 gene, while homozygous 7 F Japan 47 0.7 0.3
polymorphism on complement factor H (CFH) c.1204C>T and heterozygotic 8 M Italy 29 0.9 0.3
polymorphisms on CFH c.2808G>T and c.3148A>T were revealed.
9 M Italy 32 1.2 0.8
After discharge, her kidney function remained poor requiring maintenance
hemodialysis despite 6 months of eculizumab therapy. 10 F Philippines 48 1.1 1
DISCUSSION: Alport syndrome is a genetic disease with the triad of hematuria, 11 M Italy 37 1.8 6
sensorineural hearing loss, and ocular symptoms due to the defect in the synthesis of
a3, a4 and a5 chains of Type 4 collagen. The increase in proteinuria, hypertension and 12 F Italy 33 0.8 1.6
the presence of CKD are shown as poor prognostic factors for both maternal and fetal 13 F Italy 27 0.9 0.5
health in pregnant women with AS. 14 F Italy 17 0.7 0.4
However, crescentic glomerulonephritis is not the classical biopsy finding of AS. In a
few studies, crescents in AS have been reported to correlate with rapid disease 15 F Italy 28 1.1 1.5
progression. 1.1460.63 1.4961.96
There is increasing knowledge that the complement system is involved in the
pathogenesis of pauci-immune crescentic GN. High plasma c3a, c5a, c5b-9, Bb and low

10.1093/ndt/gfab104 | i231
Abstracts Nephrology Dialysis Transplantation

The majority of patients received supportive treatment (87,9%, N= 29), mainly with
MO314 Table 2. Follow-up data in 15 IgA plus ANAþ patients. ACEi/ARB (N=31) and omega (15,2%, N=5). Immunosuppressive treatment included
mainly corticosteroids (51,5%, N=17), with other options being (12,1% N=4):
cyclophosphamide (N=2), ciclosporin (N=1) and MMF (N=1).
N. Therapy Follow-up (years) sCr (mg/dl) Uprot (g/ From the group of low/intermediate risk patients, only two (28,5%) received
immunosuppressive treatment with either oral or intravenous corticosteroids. On the
day) other hand, from the high-risk group, more than one third of patients (38,4%, N=10)
1 NONE 11 0.7 0.1 did not receive immunosuppressive treatment.
CONCLUSION: A better prediction of kidney outcomes and consequent better patient
2 STEROIDS 5 1 0.7
selection for IS therapy may be challenging in IgA nephropathy. In spite of the existent
3 STEROIDSþMMF 7 1.9 0.3 tools, it is still difficult to determine which patients benefit from immunosuppressive
4 STEROIDS 10 1 0.1 treatment. In this case series we stratified our patients by using the IgANPT identifying
who was at higher risk of progression to ESKD, in whom, a more aggressive treatment
5 ACE-I 15 0.8 0.1 could have potentially benefit avoiding kidney disease progression. It was also
6 STEROIDSþMMF 3 2.7 0.3 important to stratify patients at low-risk, in whom immunosuppressive treatment
7 ARB 3 0.7 0.8 could carry risk of adverse events with no additional advantage in kidney outcomes.
8 ACE-I 3 0.8 0.4
9 STEROIDS 11 1.1 0.4 MO316 RITUXIMAB IN GLOMERULAR DISEASES: A COHORT
10 STEROIDSþAZA 12 0.8 0.3 ANALYSIS AND A LITERATURE REVIEW
11 STEROIDSþMMF 4 0.8 0.5
^s Duarte1, Jo~
Ine ao Oliveira1, Cristina Outerelo1, Iolanda Godinho1, Marta
12 ACE-I 1 0.8 1.1 Sofia Henriques Pereira1, Paulo Fernandes1, Sofia Jorge1, Joana Gameiro1
13 ACE-I 20 1 0.1 1
Centro Hospitalar Universit
ario Lisboa Norte, Nephrology and Renal Transplantation,
14 STEROIDS 38 0.6 0.1 Lisbon, Portugal
15 STEROIDS 9 1.1 0.2
BACKGROUND AND AIMS: Glomerular diseases (GD) account for about 20% of
9 (1-38) 1.0960.55 0.3960.30 chronic kidney disease causes. They are a heterogeneous group of diseases and current
MMF=Mophetil Mycophenolate; AZA= Azatioprine; ACE-i= ACE- treatment is still inadequate. Rituximab (RTX) is a chimeric antibody which binds
specifically to the B-cell surface antigen CD20 and has been applied in the treatment of
inhibitors; ARB, angiotensin II receptor blocker different GD. The authors present the single center experience of the use of RTX for
the treatment of GD as well as a literature review.
CONCLUSIONS.: Our data suggest that 1) in 22% of IgAN patients ANA positivity METHOD: We performed a retrospective analysis of all patients with biopsy-proven
could be detected; 2) ANAþ IgAN patients are mostly women with normal renal GD treated with RTX as first or second-line therapy between January 2010 and March
function and non nephrotic proteinuria; 3) after a median 9-year follow-up, ANAþ 2020. The protocol used was RTX 375 mg/m2 once a week for 4 weeks. Infusions were
IgAN patients, on therapy, presented a stable renal function and a reduced proteinuria; preceded by adequate premedication.
4) ANAþ IgAN patients could develop SLE. More clinical observations and studies are RESULTS: Nineteen patients with biopsy-proven GD received RTX therapy. Seven
needed for supporting the hypothesis that IgANþANA positivity could be part of a patients had membranous nephropathy (MN) (36.8%), 4 patients had focal segmental
new clinical entity of SLE patients. glomerulosclerosis (FSGS), 4 patients had lupus nephritis (LN) and 4 patients had
vasculitis (25.0% each). Five patients (26.3%) received RTX as first-line therapy and 14
patients (73.7%) as second-line therapy, namely long-term prednisolone (Pd) (n=15,
78.9%), calcineurin inhibitors (CNI) (n=6, 31.6%), cyclophosphamide (Cp) (n=7,
MO315 CLINICAL AND PATHOLOGICAL FEATURES OF IGA 36.8%), mycophenolate mofetil (MMF) (n=5, 26.3%) and methotrexate (MTX) (n=1,
NEPHROPATHY: A REPORT FROM A SINGLE CENTER 5.3%). Serum creatinine at diagnosis was 1.5 6 1.7mg/dL and the 24-h urine protein at
diagnosis was 4.9 6 4.5g. Mean follow-up time was 7.7 6 7.2 years. In MN, 2 patients
Anna Lima1, Afonso Santos1, Catarina Br as1, Rita Manso1, Pedro Campos1, (28.6%) had CR, 2 patients (28.6%) had PR and 3 patients (42.9%) had no response. In
Patrıcia Carrilho1, Miriam Karina Soto Rios1 FSGS, 2 patients (50.0%) presented CR, 1 patient (25.0%) had no response and the
1
Hospital Fernando Fonseca, Amadora, Portugal other one had renal deterioration. Two patients (50.0%) had a LN class IV with a CR
after RTX, 1 patient with LN class IIIC/V had no response and 1 patient with LN class
BACKGROUND AND AIMS: IgA nephropathy (IgAN) is one of the most prevalent II had renal deterioration. In vasculitis, 3 patients (75.0%) presented CR and 1 patient
glomerulopathies worldwide with broad variable clinical presentation and extremely had PR. Mean serum creatinine after RTX was 1.6 6 1.4mg/dL and the mean 24-h
heterogeneous risk of progressive CKD and ESKD. It was recommended risk stratifying urine protein was 1.9 6 3.1g. Two patients (10.5%) presented infusion reactions and
patients in order to target immunosuppressive treatment to high-risk patients. The one patient had multiple respiratory infections. This patient had received previous
OXFORD MEST classification and, more recently, a new international risk-prediction immunosuppression with cyclophosphamide.
tool for IgAN (IgANPT) help to predict kidney outcomes and stratify patient risk, CONCLUSIONS: A total of 19 patients with biopsy-proven GD received RTX therapy
eventually aiding in treatment decision. Here, we analyzed a single center cohort of and 12 patients (63.2%) presented a complete or partial remission suggesting the
IgAN to investigate if treatment decisions were accurately accomplished using efficacy of RTX in different types of GD. In MN, our response rate was similar to
individualized risk from the IgANPT. studies such as GEMRITUX and MENTOR trial, which have shown remission in 60–
METHOD: A retrospective analysis of all kidney biopsies performed from January 70% of patients. In FSGS, 50% of patients had a stable and complete remission with
2010 to December 2019 in a Nephrology Department was performed and adult RTX therapy similar with a meta-analysis of five studies with 51 patients with FSGS.
patients with IgAN diagnosis were selected. The presence of IgA vasculitis and Two patients had refractory LN class IV and both had complete remission (50% of
Henoch-Schönlein purpura as well as lack of follow-up data were exclusion criteria. patients with LN). This is in line with a systematic review of case reports and case series
Clinical, laboratorial and pathological data were collected, including treatment and that reported sustained complete and partial response rates of 67% in LN class IV. In
kidney outcome. Risk of kidney progression decline was assessed by using the on-line our cohort, patients with vasculitis received RTX as first-line therapy and complete
web-based calculator of the IgANPT. remission was achieved in 75% of cases, which is in line with the results found in
RESULTS: A total of 33 patients met the study criteria, with median age at diagnosis of RITUXVAS and RAVE trial. Rituximab was safe and effective in achieving remission
58 (IQR 38 - 68) years-old, mostly male (84,8%, N=28) and all Caucasian. At biopsy in different types of immune-mediated glomerular diseases.
time 60,6% (N=20) had hypertension, only 15,5% (N=5) diabetes mellitus and 57,6%
(N=19) were under ACE inhibitors/ARBs. Median GFR at biopsy time was 57 (IQR 20
- 78,5) ml/min/1.73m2. More than half of the patients (57,6%, N=19) had GFR <60ml/ MO317 DETERMINANTS OF LENGHT OF HOSPITAL STAY (LOS) IN
min/1.73m2. All patients had proteinuria (UACR > 300mg/g), with 18,2% (N=6) in the NEPHROTIC SYNDROME PATIENTS
nephrotic range. Hematuria was present in almost all patients.
Overall MEST classification was: 51,5% (N= 17) with M1 score, 39,4% (N=13) E1, Simone Accarino1, Marco Colucci1, Ettore Pasquinucci1, Giuseppe Sileno1,
66,7% (N=22) S1 and 45,5% (N=15) had T 1 score (2 patients with T2). Crescents Vittoria Esposito1, MARTA ARAZZI1, Eleonora Cristini2, Ciro Esposito3
were present in 27,3% of the biopsies (N=9). Near one-half of the patients (45,5%, 1
ICS Maugeri, Nephrology and Dialysis Unit, Pavia, Italy, 2University of Pavia, Internal
N=15) presented IgA deposits on both mesangium and capillary wall.
Medicine and Medical Therapy, Pavia, Italy and 3ICS Maugeri, University of Pavia,
Around one-third of patients (30,3%, N=10) progressed to ESKD during follow up.
Nephrology and Dialysis Unit, Pavia, Italy
According to the risk of kidney disease progression in 60-months calculated with
IgANPT, patients were stratified into low/intermediate risk in 21,2% (N=7) of cases
(mean predicted risk < 4,7%) and high risk in 78,8% (N=26) of cases (mean predicted BACKGROUND AND AIMS: Generalized edema, non responsive to oral diuretics, is
risk > 4,7%). Using the chi-squared test the high-risk group was associated with one of the main causes of hospital admission for nephrotic syndrome patients.
progression to ESKD(p=0,019). On the contrary none of the low-risk group progressed Although hospital length of stay (LOS) may vary widely, in 2017 the average LOS in
to ESKD. acute-care hospitals was lower than 8 days in OECD countries. The aim of the present

i232 | Abstracts
Nephrology Dialysis Transplantation Abstracts
study was to determine the factors commonly associated with a longer LOS in patients MO319 BEDSIDE URINE SEDIMENT EXAMINATION IN
admitted for edema due to nephrotic syndrome in the Nephrology Unit of ICS IMMUNOGLOBULIN A NEPHROPATHY PATIENTS
Maugeri, Pavia, Italy PERFORMED BY NEPHROLOGISTS
METHOD: In this retrospective study we reviewed the medical records of all patients
admitted for nephrotic syndrome between 2012-2020 in the Nephrology Unit of ICS Anna Popova1,2,3, Karlis Racenis1,2, Anna Jana Saulite1,2, Aiga Vasilvolfa1,2,3,
Maugeri. Inclusion criteria were the following: age between 18-85 years of age; severe Aivars Petersons1,2, Harijs Cernevskis1,2, Viktorija Kuzema1,2
1
edema non responsive to oral, low dose diuretics; patients with heart failure, serum Pauls Stradins Clinical University Hospital, Nephrology department, Riga, Latvia, 2Riga
creatinine > 3.5 g/dl or on dialysis treatment were excluded from the study. Patients Stradiņs University, Riga, Latvia and 3University of Latvia, Riga, Latvia
were divided into two groups according to the length of stay:  7 days or  8 days.
Age, gender, serum protein concentration, creatinine, and hemoglobin; serum BACKGROUND AND AIMS: Urine sediment microscopy is mostly abandoned by
cholesterol and tryglicerides, urinary protein excretion rate; types of glomerular nephrologists nowadays, however it is an important diagnostic tool in kidney and
disease, weight loss were recorded. Student T tests and one-way Anova were performed urinary tract diseases. The aim of this study is to emphasize the benefits of urine
to evaluate the differences between the means. microscopy performed by a nephrologist.
RESULTS: 60 patients (42 male, 18 female) with a total number of hospital accesses of METHOD: A prospective cohort study at Pauls Stradins Clinical University Hospital
93 were enrolled in the study. Mean age was 66.8 6 13.07 years. Average LOS was 9.02 Nephrology center included patients with histologically confirmed diagnosis of IgA
6 7.4 days. Protein excretion rate was 6.7 6 3.6 g/24 hours at the admission and was nephropathy from 1st January 2020 till December 2020. Appropriately collected urine
not statistically changed at discharge. Mean total serum protein and creatinine samples were examined using manual microscopy within an hour after sample
concentration at the admission were 4.7 6 0.8 g/dl and 1.8 6 1.1 mg/dl respectively. collection and by automated urinalysis. Samples were centrifuged at 4000 rpm for 4
Patients with LOS < 7 days were younger (64 6 11.9 vs 69 6 13.6 years, p <0.05), had minutes, the supernatant urine was carefully decanted, 1 - 1,5 ml of the left urine was
a lower serum creatinine (1.55 6 0.92 vs 2.08 6 1.2 mg/dl, p>0.001) and a significantly mixed by gentle agitation and placed on a standard glass slide with a cover slip. Sample
higher total serum protein concentration (5.02 6 0.77 vs 4.65 6 0.76 g/dl, p< 0.001) examination was performed using low (magnification x10) and high power
and haemoglobin (12.6 6 1.8 vs 11.4 6 1.8 g/dl, p< 0.05) compared to patients with (magnification x40) using brightfield microscopy with a minimum of 10 fields.
longer LOS. Proteinuria was not significantly different between the two groups (6.27 6 RESULTS: A total of 37 patients (24 men, mean age 42.7 6 10.9 years) were included
3.36 vs 7.1 6 3.9 g/24 hours, p= NS). While serum cholesterol and tryglicerides were in the study. 59.5 % of patients (n = 22) had hematuria based on automated urine
higher in the group of patients with longer LOS, weight loss was similar in the two sediment analysis and 62.2 % (n = 23) of patients had hematuria based on manual
groups at discharge. Although the difference was not significant, the group with longer urine microscopy. 45.9 % of patients (n=17) had dysmorphic erythrocytes, 13.5 % of
hospitalization had a greater number of patients with a diagnosis of focal segmental patients (n = 5) had isomorphic red blood cells (RBC) and 40.5 % of patients (n = 15)
glomerulosclerosis (FSGS) did not have RBC in urine samples by manual urine microscopy. 54.2 % (13/24) of men
CONCLUSION: Our results demonstrate that age, total serum protein concentration, and 30.8 % (4/13) of women had dysmorphic RBC in urine.
serum creatinine, higher lipids and probably the diagnosis of FSGS may affect the CONCLUSION: Manual urine sediment examination was more sensitive than
hospital length of stay of patients with nephrotic syndrome admitted for severe edema. automated analysis. Majority of IgA nephropathy patients have active urine sediment
A more aggressive diuretic treatment may be needed in elderly nephrotic syndrome with hematuria and dysmorphic RBC. Manual microscopy remains an effective and
patients with lower GFR and total serum protein concentration. reliable method that can be easily and quickly performed by nephrologists.

MO318 END-STAGE RENAL DISEASE RELATED FACTORS IN ANCA- MO320 LUPUS FLARE MIMICKING COVID-19 INFECTION: A CASE
ASSOCIATED VASCULITIS REPORT

Guillermo Ferrer Garcıa1, Esperanza Moral Berrio1, Maria Paz Castro Fern andez1, Meryem Sabah1, Fatimzahra Jabrane1, Hiba El oury1, Mohamed
Luis Guillermo Piccone Saponara1, Agustın Carren ~o Parrilla1, Amine Khalfaoui1, Nasreddine Chehab1, Ghizlaine Medkouri1
Alberto Martınez Calero1, Minerva Arambarri Segura1, Diego Sidel Tambo1, 1
Mohamed VI University of health sciences, Nephrology, Casablanca, Morocco
Patricia Sanchez Escudero1, Carmen Vozmediano Poyatos1
1
Hospital General Universitario Ciudad Real, Nephrology, Ciudad Real, Spain BACKGROUND AND AIMS: The world is in midst of the coronavirus disease 2019
(COVID-19) pandemic.
BACKGROUND AND AIMS: Management of ANCA-Associated Vasculitis (AAV) is METHOD: Studies of the COVID-19 pathophysiology show that its defining character
in constant update. The aim of the study is to describe our experience as a territorial is an overt inflammatory response, similar to cytokine release syndrome, causing a
reference center with this systemic disease and to analyze which factors have a dysregulated immune response. Systemic lupus erythematosus (SLE) is also a disease of
significant influence on the development of end-stage renal disease (ESRD). immune dysregulation contributing to multisystem compromise. There is very little
METHOD: Retrospective observational study. All the patients who developed AAV in literature to suggest that COVID-19 could potentially mimick SLE presentation. We
our center between 2010 and 2019 were included. Demographic variables (age, sex), describe the case of a female patient who presented with typical Covid19 clinical
renal function, other vasculitis related symptoms, induction and maintenance therapy, features, later diagnosed as a new-onset SLE.
response degree and follow-up were collected. Categorical variables are expressed as RESULTS: A 51-year-old female presented with fever, dyspnea, cough and
percentages and compared using Chi2 test. Quantitative variables are expressed as desaturation at the emergency room. Chest computed tomography scan showed
mean 6 standard deviation and compared using Mann-Whitney U test. Cox bilateral areas of ground-glass opacities in a peripheral distribution. She was admitted
regression was performed to determine independent predictors of ESRD. Kaplan- in a Covid-19 ICU. She then progressed to severe acute respiratory distress syndrome,
Meier was used to estimate ESRD-free survival. Statistical significance for a value of p< and worsening renal function with proteinuria and hematuria. Further investigations
0,05. Statistical analysis was performed with SPSS 25.0. showed bilateral pleural effusions, ascites, leukopenia and thrombocytopenia, positive
RESULTS: 45 patients were analyzed, with an average age of 70 6 11 years. 62.2% were antinuclear and anti-double-stranded DNA antibodies, and low levels of C3 and C4.
men. Mean time of follow-up 36 6 31.6 months. 37.8% presented c-ANCA SARS-Cov-2 PCR was negative twice. After the establishment of the diagnosis, the
autoantibodies and 57.8% p-ANCA. Mean baseline serum creatinine level was 5.51 6 patient was transferred to the internal medicine department where she received
3.65 mg/dl and proteinuria 2.82 6 2.48 g/24h. 77.8% received cyclophosphamide as decongestive therapy, intravenous (IV) pulses of methylprednisolone, along with
induction immunosuppressive treatment whereas 13.3% rituximab. 50% received hydroxychloroquine. She improved sustainably and was discharged after two weeks.
azathioprine, 36.1% mycophenolate and 13.9% rituximab as maintenance treatment. CONCLUSION: A patient with new-onset lupus presented with clinical features
37.8% patients underwent plasma exchange therapy and 44.4% hemodialysis. typically seen in COVID-19 patients. The adequate management of the patient was
Complete remission was achieved by 13.3% of patients, while 57.8% partial remission. delayed due to the misguided diagnosis.
28.9% had absence of remission. 28.9% achieved ESRD. ESRD was associated with
undergoing hemodialysis (69.2% vs 30.8% p=0.033), to the type of response (complete
7.7% vs partial 23.1% vs no response 69.2%), baseline creatinine level (8.36 6 5.44 vs
4.35 6 1.64 mg/dl p=0.011), creatinine 6 months after induction treatment (4.3 6 2.05 MO321 THE USE OF INTRAVENOUS CYCLOPHOSPHAMIDE AND
vs 2.04 6 0.77 mg/dl p=0.001) and at the end of follow-up (6.33 6 2.47 mg/dl vs 2.2 6 ORAL STEROIDS IN PRIMARY MEMBRANOUS
1.29 mg/dl p=0.001) and also to baseline proteinuria (4.21 6 3.12 vs 2.25 6 1.96 NEPHROPATHY WITH ADVANCED KIDNEY DISEASE
p=0.003), proteinuria 6 months after induction treatment (1.4 6 1.46 vs 0.58 6 0.73 g/
24h p=0.014) and at the end of follow-up (2.48 6 1.9 vs 1.12 6 1.64 p=0.001). Logistic Omar Ragy1, Patrick Hamilton2, Durga Kanigicherla3
1
regression only showed end of follow up serum creatinine level as an independent risk Manchester Royal Infirmary, Manchester, United Kingdom, 2Manchester Royal
factor of ESRD (OR3.74 IC 95% 1.01-13.75 p=0.047). ESRD-free survival chance after 5 Infirmary, Renal, United Kingdom and 3Manchester Royal Infirmary, Renal, Manchester,
of follow-up was 67%. United Kingdom
CONCLUSION: Only serum creatinine level at the end of follow-up could be found as
an associated factor with ESRD. Greater number of patients would be needed in order BACKGROUND AND AIMS: International guidelines do not recommend specific
to obtain other factors leading to ESRD in patients with AAV. use of immunosuppression treatment in membranous nephropathy patients presenting
with an estimated glomerular filtration rate of <30ml/min/1.73m2. This is due to the
scant published evidence of effectiveness and uncertainty around toxic effects at this
stage. In this study, we sought to examine the safety and effectiveness of combined

10.1093/ndt/gfab104 | i233
Abstracts Nephrology Dialysis Transplantation

cyclophosphamide and steroids in primary membranous nephropathy with advanced


kidney disease.
METHOD: This is a retrospective study of 18 patients with a biopsy confirmed
membranous nephropathy who received combination therapy between 2004 and 2019.
The mean age was 66.5 with a 5:1 male: female ratio. The immunosuppression regime
included monthly intravenous pulse cyclophosphamide and daily oral steroids. All
patients had an initial eGFR of < or = 30 ml/min/1.73 m2 at time of treatment. Clinical
parameters are serially monitored as part of clinical care and anti-PLA2R antibody
levels were measured at the time of and 1-year post immunosuppression treatment
where available.
The primary outcome was the achievement of partial remission as per standard criteria.
Secondary outcomes were immunological response defined by following the anti-
PLA2R antibody levels at the time of presentation and 1-year post, need for renal
replacement therapy, outcomes including hospital admission, infections, malignancy,
and death.
RESULTS: Partial Remission was achieved in 16 out of 18 (88%) patients.7 patients
(39%) reached complete remission, with none of them requiring dialysis over an
average follow-up of 5 years. The average increase in eGFR was 12.5 ml/min/1.73m2
from the time of immunosuppression till the latest follow up.
2 out of 18 (11%) patients were refractory to treatment and required initiation of
dialysis 1 and 8 years post immunosuppression. Results for the anti-PLA2R antibody
test were available for 12 (66.6%) patients at presentation all shown to be positive. Of MO322 Figure: Abdominal Angio-TC first (A) and after treatment with heparin (B)
these, 7 (58%) achieved both immunological and clinical remission. 4 patients
developed 4 different cancers (Bladder, mesothelioma, skin SCC and sigmoid) during
follow-up; 2 patients required hospital admission for episodes of infections. Both were
managed with antibiotics, and patients were discharged home safely. 5 patients died at
the end of the follow-up period (27.7%).
MO323 MEDICATION INDUCED RELAPSE OF FGSG
CONCLUSION: Here we show that the combination of intravenous pulse
cyclophosphamide and steroid is well tolerated and effective in achieving remission in
primary membranous nephropathy with advanced renal disease. Both immunological Evamaria Anvari1, Julie Barnes1
and clinical responses could be achieved in this cohort. Longer-term risk in such 1
Cleveland Clinic Main Campus, Nephrology, Cleveland, United States of America
patients includes malignancy and infections. This study provides reassurance that this
cohort of patients can be considered for immunosuppressive treatment, although
prospective studies are required to provide further robust evidence. BACKGROUND AND AIMS: 31-year-old female with past medical history of
Multiple Sclerosis diagnosed with Minimal Change Disease (MCD) in 2011. At
diagnosis she had proteinuria that exceeded 7 g per day. She was treated with steroids
and went into complete remission. In 2017 presented again with nephrotic syndrome
MO322 VENOUS THROMBOEMBOLISM AND NEPHROTIC SYDROME: and on repeat biopsy she was diagnosed with Focal Segmental Glomerulosclerosis
A FAMOUS BUT STILL SURPRISING COUPLE (FSGS). She was restarted on steroids and had some improvement but despite 20 weeks
of high dose steroids did not achieve remission. After every attempt of tapering, she
Carolina Ruosi1, Michele Cavasso1, Francesca Caprio1, Sofia Giuliana1, would relapse.
Alessandro Perna1, Giuseppe Orefice1, Alessandra Perna1, Mariadelina Simeoni1 METHOD: Other treatments tried without success were tacrolimus,
1
University of Campania “ Luigi Vanvitelli”, department of Translational Medical cyclophosphamide and rituximab. Mild improvement with tacrolimus but stopped
Sciences, NAPOLI, Italy after a grand mal seizure. The lowest achievable steroid dose was 20mg daily. She was
started on combination therapy tacrolimus and mycophenolate mofetil and was able to
BACKGROUND: Venous thromboembolism (VTE) is a multifactorial disorder, come off steroids and went into remission.
accounting for high morbidity and mortality rates, due to a complex interplay of RESULTS: After a few months of remission, she began to relapse. It was noted after
several variables classifiable as inherited (mutated Leiden V factor, prothrombin, extensive investigation that she had been placed on cabergolin for hyperprolactinemia
protein C, protein S and antithrombin) and acquired (lupus anticoagulants, pregnancy, by her endocrinologist at the time she began to relapse. Cabergolin was stopped and
major surgery procedures, cancer and inflammatory diseases) risk factors. she went into remission again. We present the first case of FSGS relapse due to
The association of VTE with the nephrotic syndrome, particularly deep vein and renal cabergolin.
vein thrombosis (DVT and RVT, respectively) is tightly established. This risk is CONCLUSION: Cabergoline is metabolized by hydrolysis and has limited cytochrome
particularly high in patients with idiopathic membranous nephropathy. In fact, P450 (CYP) metabolism. Despite limited CYP metabolism, cabergoline does have an
thromboembolic events occur with a frequency between <10% and 45% in this disease. interaction with clarithromycin, a known inhibitor of CYP and p-glycoprotein. One rat
The reason(s) underlying the hypercoagulable status in nephrotic patients are not study suggest that mycophenolate is a substrate for p-glycoprotein, so it is possible that
clearly understood. Multiple hemostatic abnormalities have been described, including there is some competitive inhibition. This would explain why the patient relapsed while
decreased levels of antithrombin and plasminogen (due to urinary losses), increased on cabergoline and in remission after stopping it.
platelet activation, reduced plasminogen activation, overproduction of fibrinogen and
factors V and VIII as a compensatory response to hypoalbuminemia. The risk of
thrombosis seems to be related to the severity and duration of the nephrotic status and MO324 A RARE CASE OF GRANULOMATOSIS WITH POLYANGIITIS
seems to be particularly increased with serum albumin concentrations 2.0 g/dl (20 g/ ASSOCIATED WITH FACTOR II DEFICIENCY
L).
CASE REPORT: We report the case of a 28 year-old male with nephrotic syndrome Yosra Elouaer1, Dorsaf Zellama1, Salma Toumi1, Mohamed Riadh Troudi1,
due to membranous nephropathy positive for serum anti-phospholipase-A2 receptor Rahma Guesmi2, Yosra Guedri1, Sanda Mrabet1, Wissal Sahtout1,
antibody. The patient was asymptomatic for VTE, but abdominal ultrasound showed Awatef Azzabi1, Asma Fradi1, Zohra Jlali2, Abdellatif Achour1
endoluminal obstruction of both renal veins. Abdominal Computer Tomography 1
SAHLOUL UNIVERSITY HOSPITAL, NEPHROLOGY, DIALYSIS AND TRANSPLANTATION,
confirmed the extensive bilateral renal vein thrombosis and also revealed an extension
SOUSSE, Tunisia and 2SIDI BOUZID REGIONAL HOSPITAL, NEPHROLOGY AND DIALYSIS,
of the thrombosis to the inferior cava vein and the left common iliac vein. He was
SIDI BOUZID, Tunisia
treated with low-molecular weight heparin for six months. According to our internal
protocol, a complete Thrombophilia Molecular Study was performed and showed a
normal Leiden V factor, but a rare homozygous mutation of the G20210A gene BACKGROUND AND AIMS: Granulomatosis with polyangiitis (GPA) (formerly
encoding for prothrombin. The prevalence of this is less than 5% in the general called Wegener’s) is a systemic disorder that is characterized by necrotizing vasculitis
population, but is highly variable with ethnicity. The G20210A mutation confers a of small arteries and veins. The kidney damage is severe. We report an observation of a
mildly increased thrombotic risk that is amplified by the presence of other risk factors, young patient whose exploration of rapidly progressive renal failure revealed GPA with
such as nephrotic syndrome. an original association with factor II deficiency.
CONCLUSIONS: In our case report, the association of a nephrotic syndrome METHOD: This a case report of a patient who was admitted to the nephrology,
secondary to a primitive membranous glomerulonephritis and the mutation in dialysis and transplantation in the sahloul university hospital in Tunisia. She was
homozygous of the G20210A prothrombin, a rare mutation associated with a high transferred from the regional hospital of sidi bouzid.
thrombotic risk, led to a severe VTE in an still asymptomatic 28-year-old patient. RESULTS: This a case of a 19-year-old patient. She had the only a history of allergic
Based on this experience, we would highlight the importance of the genetic screening rhinitis. She presented recently epistaxis and headache. The explorations reported a
for polymorphisms associated with inherited thrombophilia in nephrotic patients kidney failure with level of creatinine at 5.6 mg/dl. On examination: The blood
complicated with VTE. pressure was normal (120/70 mmHg), she had signs of acute sinusitis and edema in

i234 | Abstracts
Nephrology Dialysis Transplantation Abstracts
both lower limbs and she developed anuria. For the biology: creatinine = 11.3 mg/dl MO326 CORTICOSTEROIDS FOR THE TREATMENT OF
(clearance = 4.6 ml/min), urea = 50 mmol/l, Proteinuria = 2.5 g/24h and Hematuria = AUTOIMMUNE DISEASE: A SYSTEMATIC REVIEW AND
100/mm3. The cANCA type PR3 was positive. The diagnosis of rapidly progressive META-ANALYSIS OF REPORTED ADVERSE EVENTS IN
glomerulonephritis (RPGN) was suspected. RANDOMISED CONTROLLED TRIALS
She had microcytic hypochromic anemia of 6.9 g/dL and a low Prothrombin time (PT)
of 54%. The exploration concluded to an isolated Factor II deficiency (59%). Rupert Major1, Robert Grant2, Keith Nockels2, Mrinal Das2, Jürgen Floege3,
The Ear, Nose and throat (ENT) examination revealed nasal inflammation, sinusitis Jonathan Barratt2
1
and nasal crusting. The kidney ultrasound showed two kidneys of normal size. The University of Leicester, Health Sciences, Leicester, United Kingdom, 2University of
computed tomography showed bilateral maxillary sinusitis and there were no intra- Leicester, Leicester, United Kingdom and 3University Hospital, Aachen, Nephrology and
alveolar hemorrhage. The Kidney biopsy could not be performed initially due to the Clinical Immunology, Germany
risk of bleeding.
On hospitalization, the patient presented a generalized tonic clonic seizures. The BACKGROUND AND AIMS: Systemic corticosteroids are commonly used to treat
exploration by a cerebral Magnetic resonance imaging (MRI) showed signs of cerebral autoimmune diseases such as immunoglobulin A (IgA) nephropathy. Corticosteroids
vasculitis and the electroencephalography (EEG) showed no focal abnormalities. The are associated with increased risk of adverse events such as weight gain,
association of ENT involvement, the cerebrovascular disease, the rapid evolution of the hyperglycaemia, hypertension, infection and bone fracture occur frequently and affect
creatinine, the positivity of the cANCA, the diagnosis of granulomatosis with safe long-term use. Adverse events of corticosteroids in clinical trials may have been
polyangiitis was established. historically under-reported. We aimed to perform a systematic review and meta-
The therapeutic management was to start symptomatic treatment: diuretics, antibiotic analysis of reported adverse events of corticosteroids in autoimmune diseases, with a
therapy, transfusions, hemodialysis initially and antiepileptic therapy. The particular focus on kidney pathologies.
immunosuppressive treatment was based on pulses of methylprednisolone followed by METHOD: Pre-registered protocol systematic review (Prospero ID:
full dose corticosteroid therapy, cyclophosphamide intravenous and sessions of plasma CRD42020206650). The following databases were searched from 1980 to 2020:
exchange.
The evolution was characterized by clinical and biological improvement with OVID MEDLINE
creatinine = 1.3 mg/dl, a PT at 100% and a factor II at 70 % stable after stopping the Cochrane Library database of controlled trials (CENTRAL), to include:
plasma exchange in favor of the immunological cause of this deficit. NIH Clinical Trials Database (ClinicalTrials.gov)
CONCLUSION: The early diagnosis and treatment of RPGN is important even if the WHO International Clinical Trials Registry Platform (who.int/ictrp/en)
biopsy cannot be performed. We reported a rare association between granulomatosis EU Clinical Trials Registry (clinicaltrialsregister.eu)
with polyangiitis and factor II deficiency. The normalization of the factor II after the Placebo-controlled trials in adults with any form of autoimmune disease receiving intravenous
treatment is in favor of the immunological cause of this deficit. or oral corticosteroids were included in the systematic review. Trial protocol major adverse
events and all-cause mortality were included as the current study’s main outcome.
RESULTS: After exclusion of duplicates between databases, 4490 OVID MEDLINE
and 4987 Cochrane abstracts were reviewed. In total, 110 published clinical trials were
MO325 YOU CAN BE DIAGNOSED AND CURED FOR LUPUS identified for inclusion in the study: 14 clinical trials were in kidney autoimmune
CYSTITIS AND LUPUS PODOCYTOPATHY DESPITE BEING A diseases, including 8 in IgA nephropathy. Results of their published adverse events,
POOR, VILLAGE TEENAGE GIRL IN ALBANIA including where appropriate meta-analysis, will be presented. Specific results of those
studies of kidney pathologies such as IgA nephropathy will be presented.
Erjola Likaj1, Myftar Barbullushi2, Larisa Shehaj2 CONCLUSION: This systematic review with a pre-registered protocol identified 110
1
UHC Mother Theresa, Tirana, Albania, Tirane, Albania and 2UHC Mother Theresa, clinical trials examining systemic corticosteroid use versus placebo in autoimmune
Tirana, Albania, Nephrology Dialysis Transplantation diseases. These results will help to understand whether the risks of systemic
corticosteroids for autoimmune disease has been historically under-reported in the
BACKGROUND AND AIMS: We present the case of a 16 years old girl who was medical literature and whether a clear risk and benefit profile of corticosteroids in
admitted to our Emergency Unit in May 2019 for diarrhea, nausea, dysuria, foamy autoimmune disease can be assessed.
urine, urinary incontinence, malnutrition, polyserositis, and hypertension. Her medical
history started 8 months ago with diarrhea and urinary incontinence for which first
was hospitalized in the Gastroenterology unit and then in the Infectious Disease Unit. MO327 LUPUS NEPHRITIS IN MALES: PROSPECTIVE STUDY IN
There she was completed with colonoscopy, contrast CT scan and then was discharged SOUTH MOROCCO
with the diagnosis of Gastrocolitis. In January 2019 due to the persistence of symptoms
they did a specialized consultation in Athens, Greece. After a series of examinations the Sara Allibou1, Wadi Ouhamou1, Ramia Benhamou1, Meriem Chettati1,
patient was diagnosed with Anorexia Nervosa and antidepressant therapy was started. Wafaa Fadili1, Inass Laouad1
In February 2019, the patient was rehospitalized with nephritic grade proteinuria and 1
Mohammed VI University Hospital Center of Marrakesh, Cadi Ayyad University,
the kidney ultrasound showed stage four bilateral hydronephrosis and urinary bladder
Nephrology, marrakech, Morocco
with thick and trabecular walls. To exclude urological problems, an MRI was
performed which results in no obstructive problems. Arterial hypertension and lower
extremities edema were present. She was then transferred to our University Hospital BACKGROUND AND AIMS: Male systemic lupus erythematosus is rare and known
“Mother Teresa”, Nephrology Department for further examinations. During to have a poor prognosis. Renal involvement is one of its most severe and frequent
hospitalization her blood investigation showed severe anemia (HGB = 6.7gr / dl), manifestations, which can progress to end-stage renal disease.
kidney failure (creatinine = 1.5mg / dl, urea = 83mg / dl), elevated liver enzymes The aim of our study is to search for the clinical, biological, histological and therapeutic
(Alt:162u/ml, Ast:101u/ml), albuminemia: 2.9 g / dl, total proteinemia: 5.9g / dl. The parameters that predict a poor outcome in kidney patients followed for LN.
lipid profile showed cholesterolemia: 300mg / dl, triglyceridemia: 170mg / dl. METHOD: It’s a prospective descriptive study over 6 years from January 2014 to
Electrolytes were within normal limits. Coombs test resulted positive. Urinalysis December 2019 of renal nephritis in male patients, biopsied and followed up at the
showed microscopic hematuria with leukocyturia and grave albuminuria around16gr/ nephrology service in Mohamed VI University Hospital of Marrakech.
24 hours. Immunologic workup showed: AntiDna = 383.5U / ml, Ena profile SSA poz, RESULTS: We collected 10 male patients with LN. The mean age at diagnosis was 35 6 16.8
ANA þþþþ, C3 101, C4 18. Tumoral markers and hepatitis resulted in negativ. years. NL was inaugural in 87.5% of cases. The circumstances of discovery of NL were
METHOD: Renal biopsy was performed which resulted: Lupus Podocytopathy edematous syndrome with proteinuria in all of our patients. At the time of initial
RESULTS: The patient was diagnosed with a case of lupus cystitis with lupus presentation, 62.5% were hypertensive, 87.5% had microscopic hematuria, 62.5% had
podocytopathy. She was treated with methylprednisolone, immunosuppressive nephrotic syndrome, and 75% of patients had renal failure with a GFR of 55.87 6 43, 4 ml /
therapy, and Plaquenil. It was started with intravenous methylprednisolone 0.5 g / day min / 1.73m2 .
for 3 days and then switched to oral methylprednisolone 0.5 mg /kg /day. Antinuclear antibodies were positive in all our patients, anti DNA antibodies were positive
Mycophenolate mofetil was started with 1 gr increased to 2 grams. After 6 months of in 50% of cases, C3 hypocomplementemia was noted in 75% of cases. Anemia and
therapy Hydroureteronephrosis completely disappeared and 24 h urinary protein lymphopenia were found in 87.5% and 75% of patients, respectively.
became normal. The dose of therapy was tapered and switch to maintenance doses, Histologic examination of kidney revealed class IVA in 90% of cases, class V NL in 10% of
methylprednisolone 8 mg, MMF 500gr, and Plaquenil. Laboratory examinations Hgb: cases and a mixed class NL (IV -V) in one patient. Nine patients were treated with the
12gr / dl, Urea: 36mg / dl, Creatine: 0.6mg / dl, Alt: 23u / l, Ast: 26u / l. Urinalysis: combination of IV corticosteroid therapy and IV cyclophosphamide (NIH protocol). Only
albumin trace, RBC: 0, Wbc 8 / field. The autoimmune workup was normalized, one patient was treated with MMF as an attack treatment. The evolution was marked after a
AntiDna; C3, C4, Ana. In a realized ultrasound hydronephrosis was gone, kidney mean follow-up of 3 years by remission in only 37.5% of cases, deterioration of GFR in
structure was in normal parameters and bladder wall was in a normal structure. 62.5% of cases with end-stage renal desease in 37.5% of cases.
CONCLUSION: Disseminated Eritematous Lupus and its rare forms like Lupus A relapse was found in 50% of patients with recourse to rituximab in 2 patients with
Cystitis and Lupus Podocytopathies can be diagnosed, cured successfully, and followed refractory lupus nephritis. We identified during bivariate analysis proliferative
up in the best way despite you are a simple teenager in a village of Albania or a noticed histological class as predictor of poor renal evolution (p <0.05).
and famous actor or singer in the USA. CONCLUSION: The severity of the clinical, histopathological and prognostic picture in
lupus glomerulonephritis in males was confirmed by our study. The renal prognosis remains
poor, which could explain the need for intensive immunosuppressive therapy in these patients.

10.1093/ndt/gfab104 | i235
Nephrology Dialysis Transplantation 36 (Supplement 1): i236–i243, 2021
10.1093/ndt/gfab084

AKI. EXPERIMENTAL

MO329 THE GENETIC DELETION OF THE DUAL SPECIFICITY


MO328 ASYMPTOMATIC HYPERURICEMIA ACTS AS ANTIOXIDANT PHOSPHATASE 3 (DUSP3) ATTENUATES KIDNEY DAMAGE
DURING ACUTE KIDNEY INJURY AND DISEASE* FOLLOWING ISCHEMIA/REPERFUSION INJURY IN MOUSE

Qiuyue Ma1, Viviane Gnemmi2, Anders Hans-Joachim1, Stefanie Steiger1 Badr Khbouz1, Pascal Rowart1, Laurence Poma1, Martina Bottner2,
1
LMU Hospital, Department of Medicine IV, Division of Nephrology, Munich, Germany Géraldine Bolen3, Souad Rahmouni4, Franziska Theilig2, François Jouret1
and 2CHU Lille, Centre de Biologie Pathologique, Service d’Anatomie Pathologique, Lille, 1
GIGA Cardiovascular sciences, Liege University , Nephrology unit , Liege, Belgium,
2
France University of Kiel, Anatomisches Institut, Kiel, Germany, 3University of Liège, FARAH,
department of Clinical Sciences, Liège, Belgium and 4GIGA Medical genomics, Liege
BACKGROUND AND AIMS: Acute kidney injury (AKI) and disease (AKD) are University
major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common
in patients with impaired kidney function. While there is no doubt that crystalline uric BACKGROUND AND AIMS: Dual Specificity Phosphatase 3 (DUSP3) is a positive
acid (UA) causes acute and chronic UA nephropathy, urolithiasis and kidney stone regulator of the innate immune response in case of sepsis, but its role in the ischemic
disease, the pathogenesis of asymptomatic HU in AKI/AKD is incompletely damage is unknown. Here, we study (i) whether and where DUSP3 is expressed in the
understood. In animal studies, elevated serum UA levels may lead to endothelial renal parenchyma, and (ii) whether its genetic deletion in Dusp3 systemic knock-out
dysfunction, renin-angiotensin system activation and oxidative stress. However, such (Dusp3-/-) mice attenuates the I/R-associated inflammation and injury.
models do not mimic human HU. To overcome this issue, we established a model of METHOD: Experiment 1: Ten C57BL/6 male WT and Dusp3-/- mice underwent right
AKI/AKD with clinically relevant serum UA levels and hypothesized that nephrectomy and left renal ischemia for 30 minutes followed by a reperfusion of 48
asymptomatic HU improves the outcomes after AKI/AKD by restoring metabolic hours. Blood and kidneys were collected. Renal function was assessed upon I/R
activity and mitochondrial biogenesis in macrophages and tubular epithelial cells. biomarkers, i.e. blood urea nitrogen (BUN) and creatinine (SCr). Expressions of
METHOD: Alb-creERT2;Glut9lox/lox and Glut9lox/lox control mice were injected with inflammatory and immune markers were comparatively quantified at both mRNA
tamoxifen and placed on a chow diet enriched with inosine. Hyperuricemic mice (real-time qPCR) and protein (immuno-blotting and –staining) levels in ischemic vs.
(serum UA 7 mg/dL) and mice without HU (serum UA 4-5 mg/dL) underwent non-ischemic kidneys in Dusp3 WT vs. KO mice.
uninephrectomy followed by unilateral ischemia-reperfusion (IR) to induce AKI/AKD. Experiment 2: Ten C57BL/6 male WT and Dusp3-/- mice were anesthetized. Renal
Serum and kidneys were collected on day 3 and 14 after AKI/AKD, and kidney Doppler ultrasound was performed to assess the renal resistivity index (RRI). The
function, tubular injury, inflammation, mitochondrial dysfunction, metabolic activity expression of CD31 and VEGF vascular markers was quantified by the means of real-
(fatty acid oxidation) and macrophage infiltration were quantified using GFR time qPCR and and immuno-staining (FiJi software).
measurement, immunohistochemistry, colorimetric assays, electron microscopy, RT- RESULTS: Experiment 1: An immuno-reactive signal for DUSP3 was detected in the
PCR and flow cytometry. glomeruli (in co-localization with nephrin) and in Meca-32-positive endothelial cells of
RESULTS: We observed an increase in serum UA levels from 7 to 10 mg/dL in both outer and inner medulla of mouse non-ischemic WT kidneys. No significant
hyperuricemic mice on day 3 after IR-induced AKI/AKD that returned to 7 mg/dL immunoreactivity for DUSP3 was detected in Dusp3-/- kidneys. Following renal I/R, the
after 14 days (Figure left). While there was no difference in GFR between mRNA level of Dusp3 was increased 1.8-fold compared to baseline (p<0.001).
hyperuricemic and mice without HU with AKI/AKD on day 3, we found an improved Immunoblot quantifications showed a 77-fold increased expression of DUSP3 post
kidney function in hyperuricemic mice on day 14 (Figure middle). This was associated renal I/R. Serum levels of I/R biomarkers were significantly lower in Dusp3-/- compared
with significantly less tubular injury and inflammation as well as an increase in the to WT mice following renal I/R (BUN: 78.4633.7 vs. 258.96162.9mg/dL; SCr:
number of infiltrating anti-inflammatory M2-like macrophages as compared to mice 0.160.07 vs. 0.860.9 mg/dL; p<0.01). At mRNA levels, Dusp3-/- ischemic kidneys
without HU. Intrarenal mRNA expression level of the pro-oxidant heme-oxygenase-1 showed a significantly decreased expression level of CD11b, TNF-a, KIM-1, IL-6, IL-1b
was reduced in hyperuricemic mice. However, the expression of anti-oxidant enzymes and caspase-3 compared to controls. The numbers of PCNA-, F4-80- and CD11b-
(Nrf-1 and Sod) and metabolic genes associated with fatty acid oxidation (Cpt1, Pparg, positive cells were significantly reduced in Dusp3-/- vs WT renal parenchyma post I/R.
and Pgc1b) significantly increased as compared to mice without HU 14 days after AKI/ Experiment 2: The RRI non-invasively measured by ultrasound was lower in Dusp3-/-
AKD. In addition, HU increased the number of phospho-Histone-3 and intact group compared to controls (0.566 0.03 vs. 0.6660.02; p<0.001). The Dusp3-/- non-
proximal tubules and restored tubular mitochondrial morphology as indicated by an ischemic kidneys were characterized by a 1.8-fold increased surface of CD31-positive
increased mitochondrial aspect ratio (Figure right). cells compared to WT kidneys (p<0.001). At mRNA levels, the Dusp3-/- kidneys
CONCLUSION: Our data imply that asymptomatic HU improves kidney outcomes showed significantly increased basal levels of CD31 and VEGF compared to controls.
after IR-induced AKI/AKD because HU attenuates tubular injury and inflammation. CONCLUSION: The genetic deletion of DUSP3 is associated with (i) increased renal
In addition, we found that HU enhances the metabolic activity and anti-inflammatory vascular density, (ii) decreased RRI and (iii) nephroprotection against renal I/R injury.
M2-like macrophage polarization as well as restores mitochondrial biogenesis in
tubular epithelial cells, suggesting that HU acts as antioxidant by improving kidney
recovery after AKI/AKD.
MO330 ACTIVATION OF B2 ADRENERGIC RECEPTOR SIGNALING IN
MACROPHAGES BLOCKS SYSTEMIC INFLAMMATION AND
PROTECTS AGAINST RENAL ISCHEMIA/REPERFUSION
INJURY

Sho Hasegawa1, Tsuyoshi Inoue2, Masaomi Nangaku1, Reiko Inagi3


1
The University of Tokyo, Division of Nephrology and Endocrinology, Tokyo, Japan,
2
Nagasaki University, Department of Physiology of Visceral Function and Body Fluid,
Japan and 3The University of Tokyo, Division of CKD pathophysiology, Tokyo, Japan

BACKGROUND AND AIMS: The sympathetic nervous system regulates immune cell
dynamics. However, the detailed role of sympathetic signaling in inflammatory
diseases is still unclear because it varies according to the disease situation and
responsible cell types. Here, we focused on sympathetic signaling in macrophages and
sought to determine its detailed roles in lipopolysaccharide (LPS)-induced systemic
inflammation and renal ischemia/reperfusion injury (IRI).
METHOD: In vitro, RAW 264.7 cells and murine peritoneal macrophages were used to
determine the effects of b2 adrenergic receptor (Adrb2) signaling on LPS-induced
proinflammatory cytokine (tumor necrosis factor-a; TNF-a) production. We also
identified the critical gene that mediates the anti-inflammatory effect of Adrb2
signaling by RNA-sequencing.
In vivo, we examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-
induced systemic inflammation and renal IRI. The involvement of macrophage Adrb2
signaling was confirmed by macrophage-specific Adrb2 conditional knockout (cKO)

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
mice and adoptive transfer of salbutamol-treated macrophages. We also performed CONCLUSION: Our study provides gene expression patterns specifically in STCs
single-cell RNA sequencing of renal tissue to analyze the renoprotective role of upon injury and repair at multiple time points and suggests that the STC phenotype is
salbutamol-treated macrophages in detail. a transient and reversible phenotype triggered by injury.
RESULTS: In vitro, norepinephrine, a sympathetic neurotransmitter, suppressed LPS-
induced TNF-a production in macrophages. This anti-inflammatory effect was also
induced by salbutamol and reversed by butoxamine (a selective Adrb2 antagonist) in a
MO332 THE IRRADIATION-INDUCED RENAL ISCHEMIC
dose-dependent manner, indicating the importance of Adrb2 in this process.
PRECONDITIONING IS BLUNTED BY THE ORAL
RNA sequencing of these macrophages revealed that T-cell immunoglobulin and
ADMINISTRATION OF THE ANTI-ANGIOGENIC AGENT,
mucin-3 (Tim3) expressions were upregulated by the activation of Adrb2 signaling,
SUNITINIB
which partially mediated the anti-inflammatory phenotypic alteration in macrophages.
In vivo, salbutamol administration mitigated LPS-induced systemic inflammation and
Badr Khbouz1, François Lallemand2, Pascal Rowart1, Laurence Poma1,
protected against renal IRI; this protection was mitigated in macrophage-specific
Agnès Noel3, Jean-Marie Krzesinski4, Nor Eddine Sounni3, François Jouret1,4
Adrb2 cKO mice. Adoptive transfer of salbutamol-treated macrophages also protected 1
against renal IRI (Figure 1). Single-cell RNA sequencing revealed that this protection GIGA - Research Center, Cardiovascular Sciences - University of Liège, Liège, Belgium,
2
was associated with the accumulation of Tim3-expressing macrophages in the renal Chu De Liège, Radiotherapy unit, Liège, Belgium, 3GIGA - Research Center, GIGA
tissue. Cancer, Liège, Belgium and 4Chu De Liège, Nephrology unit, Liège, Belgium
CONCLUSION: The activation of b2 adrenergic receptor signaling in macrophages
induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 BACKGROUND AND AIMS: Whole-body irradiation has been suggested to induce
expressions, which blocks LPS-induced systemic inflammation and protects against renal ischemic preconditioning (RIP) in rodent models, possibly via neo-angiogenesis.
renal IRI. First, we comprehensively investigate the pathways involved in kidney-centered
irradiation. Next, we assess the functional and structural impact of kidney-centered
irradiation applied before ischemia/reperfusion (I/R) injury. Finally, we test whether
Sunitinib-mediated inhibition of the neo-angiogenesis prevents irradiation-associated
RIP.
METHOD: Experiment 1: Unilateral irradiation of the left kidney (8.56 Gy) was
performed in male 10-week-old wild-type C57bl/6 mice (n=10). One month later, total
kidney RNA was extracted from irradiated and control (n=5) mice for comparative
high-throughput RNA-Seq (using BaseSpace Sequence Hub Illumina). Functional
enrichment analysis was performed using Database for Annotation, Visualization and
Integrated Discovery (DAVID).
Experiment 2: Two x-ray beams (225Kv, 13mA) specifically targeted both kidneys for a
total dose of 8.56Gy. The right kidneys were removed and harvested, and the left
kidneys undergo 30-minute ischemia followed by 48-hour reperfusion (n=8) at Days 7-
14-21-28 post irradiation.
Experiment 3: Following the same protocol of renal I/R at Day14, 3 groups of male 10-
week-old wild-type C57bl/6 mice were compared (n=8 per group):
1/ bilateral pre-irradiation;
2/ bilateral pre-irradiation and gavage with Sunitinib from Day2 to Day13;
3/ control group without irradiation or gavage.
RESULTS: Experiment 1: Comparative transcriptomics showed a significant up-
regulation of various signaling pathways, including angiogenesis (HMOX1) and stress
response (HSPA1A, HSPA1B). Expressions of angiogenesis markers (CD31, TGFb1,
HMOX1) showed an increase at both mRNA (real-time qPCR) and protein (immuno-
staining) levels in irradiated kidneys compared to controls (p<0.01).
Experiment 2: Following I/R, the blood urea nitrogen (BUN) and serum creatinine
(SCr) levels were significantly lower in the irradiated animals compared to controls:
(BUN: 86.266.8 vs. 454.5627.2mg/dl; SCr: 0.160.01 vs. 1.760.2mg/dl, p<0.01). The
renal infiltration by CD11b-positive cells (187632 vs. 477620/mm2) and F4-80
macrophages (110622 vs. 212625/mm2) was significantly reduced in the irradiated
group. The real-time qPCR mRNA levels of the angiogenic markers, TGFb1 and CD31,
MO331 LINEAGE TRACING OF REGENERATING PROXIMAL TUBULE were significantly increased in the irradiated group compared to controls (p<0,01).
CELLS (STC) BY SINGLE CELL PROFILING IN ACUTE KIDNEY The CD31-immunostating (quantified by FiJi) was increased in irradiated mice
INJURY. compared to controls (p<0.01).
Experiment 3: One-way analysis of variance followed by Tukey’s test showed that,
Eleni Stamellou1,2, Mingbo Cheng3, Viktor Sterzer1, Katja Leuchtle1, following I/R, the serum levels of BUN and SCr were lower in irradiated group
Thiago Strieder1, Peter Boor2, Jürgen Floege1, Ivan G. Costa3, Marcus compared to controls (BUN: 106.1633.6 vs. 352.2654.3mg/dl; SCr: 0.360.13 vs.
Johannes Möller1 160.2mg/dl), and in irradiated group compared to the irradiated-exposed group to
1 Sunitinib (BUN: 106.1633.6 vs. 408.4654.9mg/dl; SCr: 0.360.12 vs. 1.560.3mg/dl;
Division of Nephrology and Clinical Immunology, RWTH University of Aachen, Aachen, p<0.01). No difference was observed between the irradiated-exposed mice to Sunitinib
Germany, 2Institute of Pathology and Electron Microscopy Facility, RWTH University of and the controls.
Aachen, Aachen, Germany and 3Institute for Computational Genomics, Faculty of CONCLUSION: Renal irradiation induces the activation of signaling pathways
Medicine, RWTH Aachen University, Aachen, Germany involved in angiogenesis in mice. Renal pre-irradiation leads to RIP, with preserved
renal function and attenuated inflammation post I/R. Exposure to the anti-angiogenic
BACKGROUND AND AIMS: Acute tubular injury accounts for the most common drug Sunitinib post-irradiation prevents the irradiation-induced RIP.
intrinsic cause for acute kidney injury (AKI). The scattered tubular cell (STC)
phenotype was discovered as a uniform reaction of tubule cells triggered by injury. Our
group was the first to identify an inducible transgenic mouse (PEC-rtTA-mouse)
specifically labeling STCs with eGFP. Analysis of the transcriptional factors and MO333 TARGETING HIGH MOBILITY GROUP BOX 1 WITH
associated signaling pathways might reveal the function and role of STCs in AKI. INHIBITORS ATTENUATE ACUTE KIDNEY INJURY IN
METHOD: Here, we performed single-cell RNA sequencing of unilateral ischemia- POSTISCHEMIC KIDNEYS
reperfusion murine model of AKI 8, 24, 48 hours and 6 and 12 days after AKI
induction. Zhibo Zhao1, Julian Aurelio Marschner1, Chenyu Li1, Anders Hans-Joachim1
1
RESULTS: Genes expressing proximal tubular proteins and transporters were University Hospital of the Ludwig Maximilians University, Renal Division, Department
markedly downregulated during transition into the STC phenotype upon injury; but of Medicine IV, Munich, Germany
expression recovered over time and upon resolution and tubular cells re-differentiated
into proximal tubule cells. This provides evidence for the first time that the STC BACKGROUND AND AIMS: HMGB1 (high mobility group box 1) is released from
phenotype is a transient and reversible phenotype triggered by injury. Among cells in dying cells and hence works as a danger signal, which amplifies necroinflammation in
the STC phenotype, we could identify 2 sub-clusters; a highly proliferating sub-cluster postischemic acute kidney injury. If and to what extend small molecule HMGB1
that in the cell cycle analysis showed the highest proportion of cycling cells. The second inhibitors are capable to ameliorate the acute kidney injury is still unknown.
eGFP-positive cluster appeared very early after AKI and expressed a distinct set of METHOD: Mice underwent 17 min unilateral renal ischemia followed by reperfusion
genes (defined by 7 anchor genes). Some of the highly up-regulated genes are known (IR) for 4 or 7 days and were administered either 50 mg/kg glycyrrhizic acid, 80 mg/kg
markers of STCs hence confirming the specificity of our transgenic mouse line. ethyl pyruvate, or PBS i.p. 1h before surgery and once daily until day 7.
RESULTS: Administration of HMGB1 inhibitors consistently increased the glomerular
infiltration rate at day 4 and day 7, in parallel with a reduction of plasma creatinine and

10.1093/ndt/gfab084 | i237
Abstracts Nephrology Dialysis Transplantation

circulating HMGB1 at day 7 of reperfusion. Histopathological analysis confirmed that MO335 URINARY CYTOKINES REFLECT THE ONGOING RENAL
HMGB1 inhibitors consistently attenuated tubule injury. In vitro, HMGB1 inhibitors INFLAMMATION IN THE DIAGNOSTIC OF ACUTE
protected primary murine tubular epithelial cells against H2O2-induced cell death. TUBULOINTERSTITIAL NEPHRITIS: RESULTS OF A
CONCLUSION: Our data indicate that the treatment with glycyrrhizic acid or ethyl MULTIPLEX BEAD-BASED ASSAY ASSESSMENT
pyruvate ameliorates post-ischemic renal injury. This serves as a rationale to further
study the role of extracellular HMGB1 and its inhibition in different models of acute Laura Martinez Valenzuela1, Juliana Draibe1, Xavier Fulladosa1, Francisco Gomez
kidney injury. Preciado1, Ernest Nadal2, Maria Jove2, Oriol Bestard1, Josep Cruzado1,
Joan Torras1
1
Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain and 2Institut Catal
a
d‘Oncologia - L’Hospitalet de Llobregat, L’Hospitalet de Llobregat, Spain

BACKGROUND AND AIMS: Acute tubulointerstitial nephritis (ATIN) diagnostic


lays on the kidney biopsy given the absence of non-invasive biomarkers for disease
demonstration and follow-up. The aim of this study was to evaluate the accuracy of ten
urinary inflammatory-related cytokines in the diagnostic of ATIN and its clinical
distinction from acute tubular necrosis (ATN).
METHOD: Observational prospective study including 21 ATIN and 12 ATN patients,
and 6 healthy controls. We determined the urinary levels of 10 inflammation-related
cytokines using a multiplex bead-based Luminex assay. We registered clinical,
analytical and histological data from the medical records.
RESULTS: Urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFa and MCP-1 were
higher in ATIN compared to healthy controls. In contrast, healthy controls exhibited
higher EGF urinary levels compared to ATIN patients. Follow-up samples available
from 11/21 ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/
CXCL9 and CXCL10 levels. Urinary levels of I-TAC/CXCL11, IL-6 and MCP-1 were
significantly higher in ATIN compared to ATN patients, with I-TAC/CXCL11 as the
best discriminatory biomarker based on its higher AUC in the ROC curve and
likelihood ratio. The combinatory model of the three cytokines increased the sensitivity
of the individual biomarkers in the distinction of ATIN/ATN but the best results were
obtained when blood eosinophil count and leukocyturia were added to the model. We
found a positive correlation of the extent of the tubulointerstitial infiltrate in kidney
biopsies with the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10,
IL17, IFNa, MCP1 and EGF, indicating the potential renal source of the cytokines
CONCLUSION: the higher cytokine levels in ATIN compared to ATN patients and
healthy controls, the significant decline after treatment and the positive correlation of
the cytokines with the grade of the inflammatory infiltrate allows us to propose I-TAC/
MO333 Figure: Targeting HMGB1 with inhibitory molecules protects against acute
CXCL11, CXCL10, IL6 and MCP-1 as candidate biomarkers in this disease.
kidney injury in postischemic kidneys. a. Glomerular infiltration rate. Gly
(Glycyrrhizic Acid) and EP (Ethyl pyruvate) b. Plasma creatinine level and HMGB1
concentration at day 7. c. Tubular damage was quantified upon staining with periodic
acid-Schiff (PAS). Images are the magnification of 200x. d. Quantification of PAS
staining. e. Renal primary tubular cells were treated with different dose of HMGB1
antagonists upon H2O2 stimulation.

MO334 ERYTHROPOIETIN-STIMULATED HUMAN ENDOTHELIAL


PROGENITOR CELLS AMELIORATE INFLAMMATION AND
FIBROSIS VIA INFLAMMASOME IN ISCHEMIA/
REPERFUSION-INDUCED ACUTE KIDNEY INJURY

Ha Nee Jang1,2, Jin Hyun Kim2,3, Seunghye Lee1, Sehyun Jung1, Se-
Ho Chang1,2, Hyun-Jung Kim1,2
1
College of Medicine, Gyeongsang National University and Gyeongsang National
University Hospital, Division of Nephrology, Department of Internal Medicine, Jinju,
Korea, Rep. of South, 2Gyeongsang National University, Institute of Health Sciences, MO335 Figure: Decision trees. Classificatory models of patients into ATN or ATIN
Jinju, Korea, Rep. of South and 3Gyeongsang National University Hospital, Biomedical based on the combination of the proposed biomarkers. Panel A shows Model 1,
Research Institute, Jinju, Korea, Rep. of South combining the urinary concentration of MCP1, CXCL11 and IL6. Panel B shows
Model 2, composed by the combination of the novel biomarkers with the blood
BACKGROUND AND AIMS: Ischemia/reperfusion-induced AKI (IR-AKI) is a eosinophil count and the leukocyte urinary count.
major cause of AKI and progress to chronic kidney disease. But an effective therapeutic
intervention for IR-AKI is not established yet. Erythropoietin (EPO) is a potent
stimulator of erythroid progenitor cells and is significantly upregulated during hypoxia.
Endothelial progenitor cells (EPCs) are derived from the bone marrow or tissue-
resident cells and play major roles in the maintenance of vascular integrity and the MO336 RENAL CONTRAST-ENHANCED ULTRASOUND (CEUS) TO
repair of endothelial damage. So, we investigated if EPO-stimulated human EPCs could EVALUATE EARLY AND CHRONIC MODIFICATIONS OF
have the renoprotective effects in an IR-AKI mouse model. RENAL PERFUSION AND TO PREDICT RENAL DYSFUNCTION
METHOD: EPCs originated from human peripheral blood were cultured with EPO AFTER RENAL ISCHEMIA-REPERFUSION IN MICE
(10 IU/mL). Mice were assigned to sham, IR only groups, IR with EPC, and IR with
EPO-treated EPC. EPCs (5x105 cells, tail vein) were administered twice at 30 min prior Maxime Schleef1,2, Delphine Baetz1, Christelle Leon1, Bruno Pillot1,
to bilateral renal artery occlusion, and 5 min before reperfusion, with all mice sacrificed Gabriel Bidaux1, Laurent Juillard1,2, Fitsum Guebre-Egziabher1,2,
24 h after IR-AKI. Sandrine Lemoine1,2
RESULTS: Both EPCs and EPO-treated EPCs significantly attenuated the renal
dysfunction associated with IR-AKI, as well as tissue injury. Apoptotic cell death and
1
B13 Opera / Inserm U1060 Carmen, Bron, France and 2Hospital Edouard Herriot,
oxidative stress were significantly reduced in EPC and EPO-treated EPC mice. Nephrology Department, Lyon, France
Expression of PCNA, ICAM-1, MCP-1 and a-SMA were also significantly reduced in
EPC and EPO-treated EPC mice. Furthermore, the expression of NLRP3 and caspase-1 BACKGROUND AND AIMS: Renal ischemia-reperfusion can lead to acute kidney
via the activation of NF-jB signaling pathways were significantly reduced in EPC and injury (AKI), increasing the risk of developing chronic kidney disease (CKD) through
EPO-treated EPC mice. These results show more effective in EPO-treated EPC than inflammation and vascular lesions. Serum urea or creatinine level routinely used as
EPC alone and suggest EPO might be involved in the development of EPC. diagnostic indices of renal function are always delayed from the onset of the disease.
CONCLUSION: This study provides that inflammasome-mediated inflammation and Therefore, we currently lack reliable markers to early detect AKI, especially in animals.
fibrosis might be a potential target of EPC as a treatment for IR-AKI.

i238 | Abstracts
Nephrology Dialysis Transplantation Abstracts
We aimed to show that non-invasive renal contrast-enhanced ultrasound (CEUS) an important risk factor for the development of chronic kidney disease (CKD). A
could be a reliable tool to assess early and chronic changes of renal perfusion after renal crucial aspect for successful renal recovery after AKI is an efficient proliferative
ischemia-reperfusion. response of surviving tubular epithelial cells (TECs). Recently, we established a murine
METHOD: Male C57BL6 mice underwent 15 minutes of unilateral renal ischemia by model in which the functional and histological recovery of a single kidney, injured by
clamping of the left renal vascular pedicle (n = 7), or a sham procedure (n = 3), under ischemia, is enhanced by removal of the unharmed contralateral kidney; a
inhaled general anesthesia by Sevoflurane. A renal ultrasound was performed on the phenomenon termed nephrectomy-induced recovery. The renal epithelial reparative
left ischemic kidney at baseline 1 week before the surgery, then, 20 minutes after response in this unique physiological model has not been investigated, yet can provide
reperfusion to assess early modifications of renal perfusion, and 1 month after new insights in unlocking the inherent regenerative potential of the renal epithelium.
reperfusion to follow chronic modifications. CEUS was performed in supine position METHOD: AKI was induced in R26RtdTomato and PAX2/Confetti mice by left
by using a high-resolution ultrasonic imaging system (VEVO 3100 Fujifilm unilateral ischemia/reperfusion (UIRI) for 21 min at 34 C, after which either right
Visualsonics, Toronto, Canada) with a MX550D probe fixed in place with an iron nephrectomy (Nx) or no Nx was performed 3 days later. Mice were euthanized 6 weeks
support, ensuring the constant imaging plane throughout acquisition. First, a and 28 days after UIRI, respectively. At week 6, kidneys were weighted and renal
continuous infusion of microbubbles (VS-11913, Fujifilm Visualsonics, Toronto, function was assessed by serum creatinine. At 28 days, renal tissue of Pax2/Confetti
Canada) was done through the tail vein, then a high mechanical index burst was given mice was collected to perform renal progenitor cell lineage tracing experiments by
to destroy microbubbles when the contrast enhancement had reached a steady state, immunofluorescence and confocal microscopy.
and finally, low mechanical-index imaging mode was used until, and 30 sec after the RESULTS: When nephrectomy was performed after UIRI, left kidney-to-body weight
contrast agent concentration reached the plateau. Images were recorded and were ratio did not change significantly over time, whereas, when no nephrectomy was
analyzed using the “destruction-replenishment” fitting model of the Vevo LAB performed, left kidney-to-body weight ratio gradually declined from 7,84 6 0,48 mg/dl
software (Fujifilm Visualsonics, Toronto, Canada). Renal perfusion was estimated by at day 3 till 3,26 6 0,51 mg/dl at week 6, indicating severe atrophy in the injured left
the total renal Blood Volume (rBV) parameter and was expressed as percentage of the kidney. This loss of renal mass was associated with a significant increase in serum
baseline value for each animal. Renal function was also assessed by serum urea creatinine (1,76 6 0,13 mg/dl) as compared to control (0,21 6 0,12 mg/dl), whereas
concentration 1 month after reperfusion, and the long axis lengths of both the kidneys with nephrectomy, renal function fully restored. Clonal analysis in PAX2/Confetti
were measured ex vivo after the mice were euthanized. mice revealed that nephrectomy after UIRI led to a significant increase in proliferating
RESULTS: Renal perfusion of the ischemic kidney measured by CEUS was (i.e. clonogenic) Pax2þ progenitor cells, resulting in more multicellular clones as
significantly decreased as soon as 20 minutes of reperfusion compared to baseline compared to un-nephrectomized controls.
(median 28,8% of baseline value; interquartiles [20,1 – 69,8%]). 1 month after CONCLUSION: Nephrectomy after UIRI overcomes chronic loss of renal mass and
reperfusion, renal perfusion recovered partially but was still significantly decreased function within the investigated 6-week time frame. This study is the first to
compared to baseline (median 79,9% of baseline value; interquartiles [52,8 – 99,9%]) demonstrate that nephrectomy stimulates clonal expansion of renal progenitor cells in
(Figure A). In sham operated mice, renal perfusion did not differ from baseline at 20 an injured kidney, beyond that observed for spontaneous repair after UIRI. Insight in
minutes or 1 month (p > 0.05). the signaling mechanisms may reveal new therapeutic approaches to incite the inherent
The renal function, assessed by serum urea, was mildly but significantly impaired 1 renal regeneration potential.
month after ischemia-reperfusion compared with sham (median serum urea 9,8 vs. 7,6
mmol/L) (p = 0.02), and this was consistent with the observed kidney atrophy in the
ischemic group when compared to the contralateral kidney (median long axis length
MO338 INCREASED INFLAMMATORY RESPONSE IS A HALLMARK
7,5 vs 10,8 mm) (p = 0.03).
OF AGE-RELATED AGGRAVATION OF EXPERIMENTAL AKI
Moreover, the decrease of renal perfusion 20 minutes after reperfusion was
significantly correlated with the impairment of renal perfusion 1 month after
Laura Marquez-Exposito1,2, Lucia Tejedor1,2, Laura Santos-Sanchez1,2, Floris
reperfusion (Pearson r = 0.836, p = 0.005) and with the serum urea level at 1 month
A. Valentijn3, Elena Cantero-Navarro1,2, Sandra Rayego-Mateos1,2,
(Pearson r = -0.710, p = 0.03) (Figure B-C).
Raul Rodrigues Diez1,2, Antonio Tejera-Mun ~oz1,2, Vanessa Marchant1,2,
CONCLUSION: Renal CEUS was able to detect early impairment of renal perfusion as
Ana Sanz2,4, Alberto Ortiz2,4, Roel Goldschmeding3, Marta Ruiz-Ortega1,2
soon as 20 minutes after 15 minutes of renal ischemia in mice, and perfusion was still 1
decreased 1 month after reperfusion, compared to baseline. This early impairment of IIS-Fundaci
on Jiménez Dıaz-Universidad Autonoma Madrid, Cellular Biology in Renal
perfusion was correlated with the chronic decrease of renal perfusion and renal Diseases Laboratory, Madrid, Spain, 2Red de Investigacion Renal (REDinREN), Madrid,
function 1 month after reperfusion. This was also associated with a significant kidney Spain, 3University Medical Center Utrecht, Department of Pathology, Utrecht, The
atrophy. CEUS is an interesting non-invasive tool to assess renal lesions dynamically Netherlands and 4IIS-Fundaci on Jiménez Dıaz-Universidad Aut
onoma Madrid, Division
after ischemia-reperfusion. of Nephrology and Hypertension, Madrid, Spain

BACKGROUND AND AIMS: Acute kidney injury (AKI) is associated with elevated
mortality and morbidity presenting higher frequency in aged patients. Different
mechanisms are activated in AKI, including tubular epithelial cell death (apoptosis and
regulated necrosis), inflammatory cell infiltration, impaired mitochondrial function,
and prolonged cell-cycle arrest (or cellular senescence). There is a strong connection
between pathways activated in AKI and development of cellular senescence, a process
implicated in regeneration failure and progression to fibrosis. However, the molecular
mechanisms in ageing-associated mortality are not completely understood. Our aim
was to investigate age-related molecular mechanisms of AKI.
METHOD: Experimental nephropathy by folic acid administration (FA, 125mg/kg)
was induced in young (3 months) and old (12 months) mice. Renal lesions and
mechanisms were evaluated at 48 hours (AKI acute phase).
RESULTS: AKI mortality was higher in old (50 %) than in young (15%) mice 4 days
after FA injection (pilot study). Tubular damage score (PAS evaluation) and KIM-1
tubular expression (renal damage biomarker) were also higher in old than in young
FA-injected mice after 48h. The number of infiltrating immune cells (mainly
neutrophils and macrophages) and gene expression levels of proinflammatory genes
(Lcn-2 and ccl2) were significantly higher in FA kidneys of old as compared to young
mice. Regulated necrosis (necroptosis), contrary to apoptosis, induces an inflammatory
response and necroinflammation, being macrophages the key effector immune cells of
this cell death pathway. Among some of the key necroptosis mediators, MLKL and
RIPK3 were higher in old FA kidneys. These data could indicate a magnification of the
inflammatory response to AKI in older mice. In contrast, expression of protective
factors was dramatically downregulated in old FA mice, including the mitochondrial
MO337 UNILATERAL NEPHRECTOMY OVERCOMES PROGRESSION
biogenesis driver PGC-1a, and the antiaging factor Klotho. Cellular senescence was
TO CHRONIC KIDNEY DISEASE AFTER ACUTE INJURY IN
induced in FA kidneys, as indicated by increased levels of cyclin-dependent kinase
MICE BY STIMULATING PROLIFERATION OF RENAL
inhibitors p16ink4a and p21cip1, and of the DNA Damage Response marker yH2AX.
PROGENITOR CELLS
Importantly, p21 mRNA expression and nuclear staining for p21 and yH2AX were
increased in FA kidneys, and the fold increase was significantly higher in old than in
Lies Moonen1, Elena Lazzeri2, Anna Julie Peired2, Carolina Conte2,
young mice. Also, the expression of senescence-associated secretory phenotype (SASP)
Patrick D’Haese1, Paola Romagnani2,3, Benjamin Vervaet1
1
components (Tgfb1, Il-6, and Serpine-1) was significantly higher in old FA mouse
University of Antwerp, Laboratory of Pathophysiology, Wilrijk, Belgium, 2University of Florence, kidneys. Interestingly, also some infiltrating immune cells were p21/yH2AX positive,
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, Florence, suggesting molecular senescence in the immune cells (“immunesenescence”) and
Italy and 3Meyer Children’s University Hospital, Nephrology Unit, Florence, Italy inflammation in the ageing kidney (“inflammaging”) are involved in the aggravated
AKI response to FA in old mice.
BACKGROUND AND AIMS: Acute kidney injury (AKI) is a global health concern CONCLUSION: Our data indicate that in advanced age, exposure to toxic compounds
with an incidence of 13.3 million patients per year, and increasing. AKI is recognized as results in a more severe AKI response that might relate to an early inflammatory

10.1093/ndt/gfab084 | i239
Abstracts Nephrology Dialysis Transplantation

response characterize by more extensive necroptosis and activation of pathways related microscope, including unclear boundaries, damaged membrane structures,
to cellular senescence of resident kidney cells and infiltrating inflammatory cells. disappeared mitochondrial cristae, and fragmented mitochondria or abnormal giant
mitochondria in PT cells. The expression of cytochrome b was reduced by 52.0%
(P<0.0001), indicating the damages of mitochondrial respiratory chain. ATP levels
which reflected mitochondrial functions were also decreased after TDF treatment in
MO339 KIDNEY DERIVED APOM AND ITS ROLE IN ACUTE KIDNEY
HK-2 cells with a time- and dose-dependent relationship.
INJURY.
CONCLUSION: TDF may down-regulate Npt expression, leading to decreased
intracellular phosphorus concentrations, mitochondrial dysfunctions, and finally
Line Stattau Bisgaard1,2, Pernille M Christensen1,2, Ernst-Martin Füchtbauer3,
kidney injury.
Lars Bo Nielsen4, Christina Christoffersen1,2
1
Copenhagen University Hospital, Rigshospitalet, Department of Clinical Biochemistry,
Copenhagen, Denmark, 2Copenhagen University, Department of Biomedical Sciences,
Copenhagen, Denmark, 3Aarhus University, Department of Molecular Biology and
Genetics, Aarhus, Denmark and 4Aarhus University, The Faculty of Health Sciences,
Aarhus, Denmark

BACKGROUND AND AIMS: Acute kidney injury is a severe disease with detrimental
outcomes. The underlying ethiology is still elusive and besides dialysis, treatment
options are poor.
Apolipoprotein M (apoM) is mainly expressed in liver and in proximal tubular
epithelial cells in the kidney. In plasma, apoM associates with HDL particles via a
retained signal peptide. ApoM is a carrier of sphingosine-1-phosphate (S1P), a small
bioactive lipid involved in e.g. angiogenesis, lymphocyte trafficking, and vascular
barrier function. Recently, it was shown that apoM/S1P protects against development
of liver and lung fibrosis. In urine, apoM is normally undetectable in both wild type
mice and healthy humans. However, lack of megalin receptors in proximal tubuli
induces loss of apoM into the urine. The biological function of kidney-derived apoM is
unknown, but it has been hypothesized that apoM might be secreted to the pre-urine to
sequester molecules, such as S1P, from secretion.
The aim of this study was to unravel the role of apoM in kidney biology and in acute
kidney injury.
METHOD: A novel kidney specific human apoM transgenic mouse (RPTEC-
hapoMTG), was generated by expressing human apoM under the control of the
proximal tubular epithelial cell specific Sglt2 promoter. The effect of kidney specific
apoM overexpression on acute kidney injury was accessed by inducing either cisplatin
or ischemia/reperfusion injury. Further, a stable cell line of HK-2 cells overexpressing
hapoM (HK-2hapoM-TG) was generated and the cells were cultured on transwells to
assess the secretion of apoM to respectively the apical and basolateral site.
RESULTS: hapoM was present in plasma from RPTEC-hapoMTG mice (mean 0.18
lM), indicating that kidney-derived apoM can be secreted to plasma. When assessing
the secretion of hapoM from proximal tubular epithelial cells in vitro, studies support MO340 Figure 1: Representative light micrographs and electron micrographs of
that apoM can be secreted to both the apical (urine) and basolateral (blood) mice kidney. (A1-C1) Renal cortex of a control mouse and TDF treated mice. The
compartment. No differences in kidney injury markers (plasma urea and creatinine) proximal convoluted tubules were edematous and their lining epithelium was
between RPTEC-hapoMTG and wild type (WT) mice subjected to cisplatin injections, destroyed (yellow arrow, H & E, X 200). Some glomeruli were shrunken. (A2-C2)
or in kidney injury score determined by histological evaluation was found. Similar, we Brush border cilia of proximal tubule epithelial cells (original magnification  15000).
could not detect any histological difference between RPTEC-hapoMTG and WT mice (A3-C3) Mitochondrial structure in the renal tubules (original magnification  30000).
after ischemia/reperfusion injury, and overexpression of hapoM did not affect kidney Disruption of mitochondrial cristae in the renal tubules of TDF treated mice was
gene expression of inflammatory markers (i.e. IL6, MCP-1) compared to WT mice. detected.
CONCLUSION: Our study suggests that apoM can be secreted to both the apical and
basolateral compartment, supporting a role for apoM in sequestering molecules from
secretion in urine.
Transgenic overexpression of apoM in proximal tubular epithelial cells of mice did not
protect against acute kidney injury.

MO340 THE EFFECT OF NA+/PI COTRANSPORTER IN TENOFOVIR


INDUCED NEPHROTOXITY BY REGULATING
INTRACELLULAR PHOSPHORUS BALANCE AND
MITOCHONDRIAL FUNCTION

Tiantian Ma1, Xiaoxiao Shi1, Bingbin Zhao1, Jiaying Li1, Peili Ji1, Limeng Chen1
1
Peking Union Medical College Hospital, Department of Nephrology, Beijing, P.R. China

BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF), a reverse


transcriptase inhibitor used to treat virus infections, could cause proximal tubular (PT)
dysfunctions and eGFR decline with mitochondria damages. PDZ domain containing 1
(PDZK1), PDZK1-interacting protein 1 (PDZK1IP1), and Naþ/Hþ exchanger
regulatory factor 1 (NHERF1) are scaffold proteins or membrane-associated proteins
that influence the localization and function of membrane proteins. We tried to
investigate the changes of both proximal tubular transporters and membrane-
associated proteins in TDF induced nephrotoxic model.
METHOD: C57/BL6 mice (n = 8) were gavaged daily with 10mg/kg/d, 50mg/kg/d of MO340 Figure 2: The changes of intracellular inorganic phosphorus concentration
TDF for 8 weeks. The human renal tubular epithelial cells (HK-2) were grown and in HK-2 cells treated with tenofovir for 72h. After TDF treatment of HK-2 cells, the
received 24 to 72 h exposure to 0–128 mM TDF or vehicle. intracellular inorganic phosphorus concentration significantly decreased, and as the
RESULTS: Chronic TDF administration to mice and HK-2 cells resulted in PT TDF treatment time prolonged and the concentration increased, the intracellular
damages including swollen and exfoliated tubular epithelial cells, brush border cilia inorganic phosphorus concentration further decreased. *P<0.05, **P<0.01,
lodging and dissolving, and serum creatinine elevation (P<0.05, mean 10.2362.683 vs. ***P<0.001, ****P<0.0001.
27.18618.41) compared to the control group. The Naþ/Pi cotransporter (Npt) and
sodium-glucose cotransporter type 2 (SGLT-2) were decreased in the kidneys of TDF
treated mice and HK-2 cells. The intracellular phosphorus concentrations decreased
with the increase of TDF concentration and the extension of TDF treatment time,
which were in line with down-regulated Npt expressions. Mitochondrial
morphological changes were seen in TDF treated mice and HK-2 cells by electron

i240 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO341 VALUE OF THE CELL CYCLE ARREST BIOMARKERS IN THE AM might delay pathogenesis and progression of CKD. Here we focused on AKI as a
DIAGNOSIS OF PREGNANCY RELATED ACUTE KIDNEY promoter of CKD progression in order to examine the effects of AM histologically and
INURY histochemically in mice.
METHOD: Here we used two groups of female C57BL/6 mice: one that was aged 12
Hesham Kamal Habeeb Keryakos1, Osama El-Minshawy1, Mahmoud Khedr1, weeks and one that was aged 52 weeks. After the first blood collection (of
Ayman Yousuf2, Moustafa Abo Elela3, Fatma Kamel1 approximately 0.2 ml), the two age groups of mice were administered AM powder
1
Faculty Of Medicine - Minia University, Internal Medicine and Nephrology Department, mixed with sterilized 0.5% methylcellulose 400 (w/v) (the AM-administered group) or
El-Minya, Egypt, 2Faculty Of Medicine - Minia University, Obstetrics and Gynecology, El- sterilized 0.5% methylcellulose 400 (the control group), respectively. Two hours after
Minya, Egypt and 3Faculty Of Medicine - Minia University, Clinical Pathology the administration, 0.5 mg/ml cisplatin (20 mg/kg or 14 mg/kg) or 0.9% NaCl were
Department, El-Minya, Egypt injected intraperitoneally. Three days after injection, blood was collected and kidneys
were harvested. We measured blood urea nitrogen (BUN) and creatinine (CRE) to
BACKGROUND AND AIMS: Pregnancy related acute kidney injury (PRAKI) is still a detect AKI, and assessed histological change in dissected kidney sections stained with
common serious problem in developing countries. Insulin-like growth factor-binding Hematoxylin-Eosin and Periodic acid-Schiff and histochemical change in sections
protein 7 (IGFBP7) and tissue inhibitor metalloproteinases-2 (TIMP-2) can identify stained with anti-CD3 and anti-CD68 antibodies. Generally, 20 mg/kg cisplatin was
critically ill patients at risk for the development of severe AKI. Aims: To identify main used to induce AKI in the experimental model.
causes and timing of PRAKI and to study the G1 cell cycle arrest biomarkers in cases RESULTS: Injection with 20 mg/kg cisplatin was shown to induce AKI pathology in
diagnosed with (PRAKI) as a diagnostic tool. young mice and shorten survival in old mice, and AM administration was unable to
METHOD: 80 pregnant women diagnosed with PRAKI were recruited from a single improve AKI pathology in young mice or survival in old mice. Next, we injected mice
hospital as well as 30 age-matched pregnant women with normal pregnancy in both age groups with 14 mg/kg cisplatin. We found that this dose significantly
participated in this study. A urine specimen was collected from all study participants increased serum BUN or CRE and caused histological damage in renal tubule epithelial
with established AKI within 24 hours of ICU admission to measure [TIMP- cells and glomeruli in old mice but not in young mice, which showed no pathological
2]*[IGFBP7]. change. And Astragalus treatment in advance almost totally prevented these
RESULTS: The incidence of PRAKI was 1.1%. The most common cause of PRAKI is pathological changes in old mice. The AKI generated in old mice with 14 mg/kg of
preeclampsia/eclampsia spectrum (61%). Most of the cases occur in the third trimester cisplatin was significantly normalized by pretreatment with AM. Next, histochemical
(60%) and postpartum period (23%). At a cutoff 0.33 ng/mL, the estimated sensitivity analysis of renal CD3- and CD68-positive cells revealed both were increased in the
and specificity of urinary [TIMP-2]*[IGFBP7] in predicting PRAKI is 100% (95% CI) murine AKI model induced by injection with 20 mg/kg cisplatin. Interestingly, in old
with NPV and PPV are 100%. mice, 14 mg/kg cisplatin-AKI increased CD3-positive cells but not CD68-positive cells.
CONCLUSION: Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific These findings suggest that AM may improve daily minor disturbances, such as AKI,
biomarker in the diagnosis of PRAKI. that cause pathogenesis and progression of CKD especially in old age.
CONCLUSION: AM administration, at least in part, can reduce day-to-day AKI
occurrence, but is ineffective in young kidneys. However, sustained use of AM could
play a critical role in prolonging the activity of aged kidneys.
ACKNOWLEDGMENTS: We thank the Education and Research Support Center,
Tokai University, for technical assistance. This work was supported by a grant from the
Japan Society for Promotion of Science JSPS KAKENHI KIBAN-C (Grant Number
16K09259) and by Tokai university general research organization grant.

MO343 SERUM RESPONSE FACTOR, A NOVEL EARLY DIAGNOSTIC


BIOMARKER OF ACUTE KIDNEY INJURY

Long Zhao1, Yan Xu1


1
The Affiliated Hospital of Qingdao University, Nephrology, Qingdao, P.R. China

BACKGROUND AND AIMS: Studies have shown that serum response factor (SRF) is
increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic
nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic
value of SRF in acute kidney injury (AKI).
METHOD: AKI-related microarray data were analyzed, and the expression and
location of SRF were investigated in the early phase of AKI.
RESULTS: Bioinformatics results demonstrated that SRF was dramatically elevated 2-4
h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly
expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at
1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC
curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum
creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively.
CONCLUSION: SRF is remarkably upregulated in early (before 24 h) AKI and can
replace Scr as a potential new early diagnostic biomarker of AKI.

MO342 ADMINISTRATION OF ASTRAGALUS MEMBRANACEUS


PREVENTED CISPLATIN-INDUCED AKI, ESPECIALLY IN OLD
MICE
MO343 Figure 1: Analysis of the microarray results from bilateral I/R mice
Kagemasa Kajiwara1, Makoto Arai2, Tatsuya Nogami2, Yoshinobu Nakada2,
Go Nagashima1, Kyoka Tashiro1, Takaaki Kinue4
1
Tokai University School of Medicine, Division of Basic Molecular Science and Molecular
Medicine, Isehara, Japan, 2Tokai University Hospital, Department of Kampo Medicine,
Isehara, Japan and 4Tokai University School of Medicine, Department of Community
Health, Isehara, Japan

BACKGROUND AND AIMS: Recent findings suggest that acute kidney injury (AKI),
which occurs frequently but is believed to be completely reversible, is an important
factor driving chronic kidney disease (CKD) pathogenesis or progression. We have
investigated Astragalus membranaceus (AM), which has been shown to have various
pharmacological effects on several organs (see http://nccih.nih.gov/health/astragalus).
However, up to now, little evidence of its effectiveness against CKD has been provided.
We hypothesized that AM could target AKI and that sustainable prevention of AKI by

10.1093/ndt/gfab084 | i241
Abstracts Nephrology Dialysis Transplantation

MO343 Figure 2:SRF was upregulated and localized in TECs in I/R rats

MO343 Figure 5:The ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF,
serum SRF and Scr in early (before 24 h) AKI.

MO343 Figure 3:Scr level and renal SRF mRNA expression in I/R rats

MO343 Figure 6:SRF protein and mRNA expression was upregulated with the
extension of renal pedicles occlusion time.

MO344 INCIDENCE AND RISK FACTORS FOR ACUTE


POSTOPERATIVE RENAL FAILURE

Imane Failal1, Sanae Ezzaki1, Rania Elafifi1, Mohamed Zamd1, Naoufal Mtioui1,
Salma Elkhayat1, Ghizlaine Medkouri1, Mohamed Benghanem1,
Benyounes Ramdani1
1
CHU ibn rochd, nephrology, casablanca, Morocco

MO343 Figure 4:The protein level of SRF in kidney, urine and serum in vivo BACKGROUND AND AIMS: Postoperative acute renal failure (AKI) is a particular
form of acute failure with several triggers. Decreased renal blood flow and the resulting
ischemia seem to be the most common cause of kidney damage. The objective was to
study the incidence and risk factors associated with post-operative AKI.
METHOD: It was a retrospective, descriptive study spanning a 3-year period from
January 1, 2017 to December 31, 2019. The patients in this series were admitted to the
various surgical departments.
RESULTS: Our study included 618 cases of AKI. The incidence of postoperative AKI
was 8.73%. The average age of our patients was 40.4 þ/- 12.3 years, a male
predominance with a sex ratio of 1.2. The main history was diabetes found in 39%,
hypertension in 27.5% and an injection of contrast product a few days before the
intervention in 14.5%. General surgery topped the list in 49.5% of our patients,
followed by trauma in 25%, gyneco-obstetrics in 14.5%, and 11% for the rest of the
surgeries. The associated risk factors were: hypovolemic shock, diabetes, severe sepsis.
CONCLUSION: The occurrence of acute renal failure in the postoperative period
results from factors related to the field and surgery. Hence the need for early
identification of risk situations, in order to reduce the incidence of renal damage during
the perioperative period.

i242 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO345 LIFESAVING BIOMARKERS IN CONTRAST-INDUCED ACUTE MO346 NEPHROPROTECTIVE EFFECT OF A METHANOLIC EXTRACT
KIDNEY INJURY IN ADULT CRITICAL ICU PATIENTS OF TWO GANODERMA SPECIES AND THEIR ASSOCIATION
IN AN IN VITRO MODEL OF CISPLATIN INDUCED
Ravi Mishra1, HARSHIT SINGH2, Saurabh Chaturvedi3, Durga P Mishra3, TUBULOTOXICITY
Vikas Agarwal3, Mohan Gurjar4
1
Sanjay Gandhi Post Graduate Institute of Medical Science, Lucknow India, Depatment Sébastien Sinaeve1, Cécile Husson2, Marie-Hélène Antoine2, Stéphane Welti3,
of clinical Immunology, Lucknow, India, 2Sanjay Gandhi Post Graduate Institute of Cony Decock4, Caroline Stevigny1, Joelle Nortier2
1
Medical Science, Lucknow India, Depatment of nephrology, Lucknow, India, 3Sanjay Université libre de Bruxelles-Faculty of Pharmacy, RD3-Pharmacognosy, Bioanalysis
Gandhi Post Graduate Institute of Medical Science, Lucknow India, Depatment of and Drug Discovery Unit, Brussels, Belgium, 2Université libre de Bruxelles-Faculty of
clinical immunology, Lucknow, India and 4Sanjay Gandhi Post Graduate Institute of Medicine, Laboratory of Experimental Nephrology, Brussels, Belgium, 3Université Lille 2-
Medical Science, Lucknow India, Depatment of Critical Care Medicine, Lucknow, India UFR Pharmacie, Laboratoire des Sciences Végétales et Fongiques, Lille, France and
4
Université Catholique de Louvain, BCCM/MUCL, Louvain-la-Neuve, Belgium
BACKGROUND : -: Intravenous administration of radiocontrast media is referred to
as contrast-induced kidney injury (CI-AKI).CI-AKI is described as the third most BACKGROUND AND AIMS: Cisplatin is currently used as a first-line cancer
common cause of new AKI in hospitalized patients. The occurrence of CI-AKI is treatment, such as testicular, ovarian or pulmonary cancers. Their nephrotoxicity
reported up to 55% in these high-risk patients.: NGAL (Neutrophil gelatinase- remains a real problem. Acute kidney injury induced by cisplatin is located on
associated Lipocalin)and Cystatin C have been found an early and sensitive marker of proximal tubular cells, causing necrosis and possibly subsequent interstitial fibrosis and
acute kidney injury (AKI). chronic dysfunction. These severe side effects can lead to a cessation of the patient’s
AIMS: To evaluate biomarkers in plasma (P) and urine (U) after intravenous contrast treatment. Currently, there is no effective prophylactic action to reduce cisplatin
in adult ICU patients. nephrotoxicity, beside hyperhydration of the patient [1].
METHOD: Total of 36 patients recruited as per inclusion criteria. ICU patients who The aim of the present work is therefore to identify new prophylactic therapy. For this,
were >18 years with radiographic contrast for diagnostic or interventional computed natural products can be studied, in this case, the interest of potential new medicinal
tomography (CT scan), were included. After ethical approval, samples of 5 ml blood mushrooms extracts. Among 13 mushroom extracts, the methanolic extracts of
and 5 ml urine were collected before contrast exposure and at 4 h, 24 h, and 48 h after Ganoderma parvigibbosum Welti & Courtecuisse, Ganoderma tuberculosum Murrill
contrast exposure. NGAL and Cystatin C assay was done by ELISA, and urinary levels and their association were selected to study their effects on human proximal tubular
were normalized as per urine creatinine (UCr) values for each sample. In the present cells (HK-2) intoxicated with cisplatin.
study, CI-AKI is defined as a rise in SCr of 0.3 mg/dl within 48 hrs. Data presented in METHOD: HK-2 cells are grown in 75cm2 sterile flasks using DMEM low glucose
a mean or median analysis performed. (1mg/mL), supplemented with FBS (10%), L-Glutamin and a mix of Penicillin/
RESULTS: In this study, 30 CT scan episodes requiring intravenous contrast in 25 ICU Streptomycin. Dried mushrooms were grounded and extracted 3 times by methanol,
patients were included. Median age was 36 yrs and 13 (43%) were male. On day of evaporated extracts are stored at -20 C. A viability assay allowed to determine the work
inclusion, median SOFA score was 3; 16% In patients having CI-AKI, mean values concentration of extracts range have been done. After that, tests were performed after a
changes from pre-contrast to at 4 h, 24 h and 48 h after contrast are presented..Kinetics pretreatment of 1h with the extracts before adding cisplatin at a concentration of 20
of plasma (P) and urine (U) NGAL and Cystatin C levels (Mean6SD) with p value mM. Viability assays (CCK-8) and antioxidant activity (DPPH) were done in 96-well.
among patients having CI-AKI P NGAL (ng/ml), Before Contrast(BC)( The intracellular concentration of b-catenin and calcium, Caspase-3, p53, cytochrome
708.56201.76) , 04hrC(851.56332.05, p=0.07), 24hrC(1093.256225.03, p=0.02), C, IL-6, NFjB, the membranal expression of KIM-1 and finally the ROS production
48hrC(7886323.4, p=0.21), UNGAL (ng/mg of U Cr)BC(67.63648.09) , (H2DCFDA) were studied by flow cytometry.
04hrC(39.69619.79, p=0.07) , 24hrC(101.97690, p=0.12) , 48hrC(59.87656.85, RESULTS: Tests have shown that methanolic extracts of G. parvigibbosum and G.
p=0.73) , P Cystatin C (ng/ml) BC(4698.856574.71), 04hrC(4704.5761144.87) , tuberculosum (10 mg/mL) and their association (5 þ 5 mg/mL) prevented the loss of
p=0.02) , 24hrC(4428.8561135.73, p=0.03), 48hrC(4288.856435.8, p=0.17), U viability after a 24h incubation. They also have prevented the increase of cytochrome C
Cystatin C (ng/mg of UCr) BC(3 46.066224.7), 04hrC(219.66672.18, p=0.91), 24hrC and p53 after 24h. G. parvigibbosum and the association of the two mushrooms
(470.216536.28, p=0.99), 48hrC(633.616811.77, p=0.23). extracts have also prevented the increase of caspase-3 and intracellular b-catenin.
CONCLUSION: ROC curve analysis during pre-contrast exposure: NGAL, and Finally, G. parvigibbosum was the only to prevent the ROS overproduction. None of
Cystatin C), both plasma and urine level AUC was significantly higher in patients who them showed a scavenger activity, nor a prevention in the increase of IL-6 and NFjB or
develop CI-AKI and Post-contrast exposure Plasma levels AUC significantly higher the membrane expression of KIM-1.
than Urine levels. CONCLUSION: Ganoderma parvigibbosum appears to be therefore more beneficial
than Ganoderma tuberculosum and the association of the two mushrooms extracts by
acting also on the ROS overproduction. In conclusion, in this study, the extracts have
shown a significant activity on the prevention of the pro-apoptosis pathway rather than
a pro-inflammatory prevention. Further investigation will be performed to identify the
precise activity and chemical content of these extracts.
Reference
[1]. Bunel V. et al, Pharm Biol. 2015

10.1093/ndt/gfab084 | i243
Nephrology Dialysis Transplantation 36 (Supplement 1): i244–i269, 2021
10.1093/ndt/gfab082

AKI. CLINICAL. EPIDEMIOLOGY AND OUTCOME CONCLUSION: There was considerable centre-variation in LOS for patients with
HA-AKI across England. Further interrogation of patient and centre-level factors
underlying the observed variation is now necessary to better understand why this
variation exists and to inform development of future targeted quality improvement
MO347 CENTER VARIATION IN LENGTH OF STAY FOR PATIENTS interventions to address this.
WITH HOSPITAL-ACQUIRED ACUTE KIDNEY INJURY IN
ENGLAND*

Javeria Peracha1,2, David Pitcher1, Shalini Santhakumaran1, Jamie Day3,


Margaretha Steenkamp1, James Medcalf1,4, Graham Lipkin2, William McKane5
1
The Renal Association, UK Renal Registry, Filton, United Kingdom, 2Queen Elizabeth
MO348 CLINICAL TRAJECTORIES AND IMPACT OF ACUTE KIDNEY
Hospital Birmingham, Department of Renal Medicine, United Kingdom, 3NHS
DISEASE AFTER ACUTE KIDNEY INJURY IN INTENSIVE
Improvement and Royal National Orthopaedic Hospital, Getting it Right First Time,
CARE UNIT: A 5-YEAR SINGLE-CENTER COHORT STUDY
United Kingdom, 4Leicester General Hospital, John Walls Renal Unit, United Kingdom
and 5Northern General Hospital Sheffield Kidney Institute, United Kingdom
Arthur Orieux1, Mathilde Prezelin-Reydit2, Christian Combe3, Renaud Prevel1,
Alexandre Boyer1, Sébastien Rubin3
BACKGROUND AND AIMS: Acute kidney injury (AKI) is a common and serious 1
Groupe hospitalier Pellegrin, Medical Intensive Care Unit, Bordeaux, France, 2Aurad
condition associated with longer length of hospital stay (LOS) for affected patients;
Aquitaine, Gradignan, France and 3Groupe hospitalier Pellegrin, Néphrologie,
leading to increased morbidity, emotional distress and higher healthcare costs.
Transplantation, Dialyse et Aphérèses, Bordeaux, France
Implementation of AKI care quality improvement interventions have consistently been
shown to reduce patient LOS, suggesting its measurement may serve as a valuable AKI
care quality indicator for hospitals. In this study, we set out to explore, for the first BACKGROUND AND AIMS: Acute kidney injury (AKI) is observed in more than
time, unwarranted centre variation in case-mix adjusted LOS for patients who develop 50% of patients admitted in intensive care units (ICU) and more than 10% of them
hospital acquired AKI (HA-AKI) across England. require renal replacement therapy (RRT) Acute kidney disease (AKD) has been
METHOD: Analysis was undertaken using a routinely collected national database of recently proposed to describe a highly vulnerable period with pathophysiological
patients with biochemically detected AKI, linked with hospitals administrative data. process following AKI during which the patient could experience a decline in
250,504 HA-AKI episodes were studied in total, across 103 hospitals between 01/01/ glomerular filtration and finally developed CKD. Patients suffering from AKI in ICU
2017 – 31/12/2018. LOS was defined as the number of days between first AKI alert and could have various renal trajectories and outcomes (early, late, or absence of recovery;
discharge. A negative binomial model was used to generate predicted LOS for patients early or late relapse; acute kidney disease (AKD); or chronic kidney disease (CKD))
with HA-AKI at each hospital trust using age, sex, diagnosis group, comorbidity score, after discharge. No cohort study described them accurately. Aims were to assess the
AKI severity, admission method, month of AKI alert and critical care attendance. various clinical trajectories after AKI in ICU and to determine risk factors for
Variation in “observed LOS – predicted LOS” values across centres were then developing CKD taking into account the new concept of AKD and to assess the long-
compared using a funnel plot. Additional analyses were undertaken to investigate term incidence of CKD.
potential associations between centre LOS and readmission rates as well as variation in METHOD: We conducted a prospective five-year follow-up study in a medical ICU in
LOS amongst patients in the most common diagnosis groups. Bordeaux University Hospital (France). The patients who received invasive mechanical
RESULTS: The overall median LOS following HA-AKI alert was 8 days (Interquartile ventilation, catecholamine infusion or both and developed an AKI (defined by KDIGO
range, 3-17). There was significant variation seen in “observed - predicted LOS” values criteria) from September 2013 to May 2015 were included. We excluded the patients
across hospitals, with 55/103 trusts classed as outliers (99.8% control limits). When with a previous estimated glomerular filtration rate (eGFR) of <90mL/min/1.73m2.
analysis was limited to patients with more severe AKI (stages 2 or 3) at presentation AKD was defined as a condition wherein the criteria for AKI stage 1 or greater persists
this number fell to 10/103 (99.8% control limits). Risk factors for longer LOS included 7 days after exposure. CKD was defined by an eGFR of <60ml/min/1.73m2 at least
male sex, advancing age, higher comorbidity score, more severe AKI at presentation, 90 days after the AKI. Renal recovery was defined by serum creatinine 125% of serum
emergency admission and critical care attendance. Patients admitted due to fracture basal creatinine. Using the Aalen-Johansen estimator to account for competing risks,
neck of femur were at highest risk of longer LOS and exhibited considerably more we estimated the cumulative incidence of CKD. To estimate adjusted hazard ratios
variation in “observed - predicted LOS” values compared to patients with congestive (HRs) we used standard Cox proportional hazard models adjusted for age, sex,
heart failure, pneumonia or septicaemia. Just over 1/5 of patients with HA-AKI went hypertension, diabetes, cardiovascular history, SOFA and AKI stage. Proportional
on to have an emergency re-admission within 30 days of discharge, with no association hazard assumptions were checked using Schoenfeld residuals. Violation of
observed between a trusts “observed – predicted LOS” values and readmission rates proportional hazard assumption for AKD was handled by using appropriate
(Figure). interaction terms with time, resulting in time-dependent HR.
RESULTS: 232 patients were enrolled. The age was 62 6 16 years, 142/232 (61%) were
male.
AKI stage 1 was present in 62/232 (27%) patients, AKI stage 2 in 50/232 (21%), and
AKI stage 3 in 120/232 (52%). Among patients with AKI, 65/232 (28%) recovered
before day 7. At day 7, 106/232 (46%) had been progressing to AKD. AKD also
developed secondary in 3/65 because of a second episode of AKI without recovery.
Among the AKD patients, 21/109 (19%) recovered before day 90, 41/109 (38%) dead
and 47/109 (43%) progressed to CKD (figure). The cumulative incidence of CKD was
17 [12-21]% at 1-year follow-up and 30 [24-36] % at 5-years follow-up. This incidence
was higher in AKD-patients (44 [35-54]%, and 48 [39-58]%) than in non-AKD
patients (9 [1-16]% and 22 [10-34]%) after 1 and 5 years of follow-up, respectively
(p=6.10-5). The risk of developing CKD in AKD-patients was increased up to six
months compared to those without AKD (HR 27.1 [7.9-93.5]; p<0.0001). Six months
after AKI, the risk of progression to CKD was not statistically different between AKD
patients and non-AKD patients (HR 2.45 [0.68 – 8.85]; p = 0.17). In this model only
gender (male sex: HR 0.5 [0.3-0.9]; p= 0.02) was also significantly associated with CKD.
CONCLUSION: There were many clinical trajectories after AKI in ICU. Risk for
developing CKD remained during the 5 years of follow-up. AKD was the main risk
factors for developing CKD only in the first 6 months. After, the risk was similar in
AKD or non-AKD patients. Female gender was associated with CKD during all the
follow-up. These patients need a specific follow-up after ICU discharge.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
BACKGROUND AND AIMS: Initial WHO guidance advised cautious fluid
administration for patients with COVID-19 due to concern about the development of
acute respiratory distress syndrome (ARDS). However, as the pandemic unfolded it
became apparent that patients who were admitted to hospital had high rates of AKI
and this initiated a change in local clinical guidelines during early April 2020. We
aimed to ascertain the impact of judicious intravenous fluid use on mortality, length of
hospitalisation and AKI.
METHOD: An observational cohort study of 158 adults admitted with confirmed
SARS-Cov-2 between 18th March and 9th May 2020 was conducted in a teaching
hospital and designated centre for infectious diseases, London, UK. Key clinical and
demographic data collected included clinical severity markers on admission,
biochemical and haematological parameters as well as radiological findings. Primary
outcomes were inpatient mortality, mortality at 6-weeks post discharge, length of
hospitalisation and intensive care (ICU) admission. We also measured requirement for
kidney replacement therapy (KRT) and AKI recovery rate at discharge. Using tests of
difference, we compared key outcomes between patients treated with varying fluid
regimens and then identified risk factors for AKI and mortality using multivariate
logistic regression with results expressed as odds ratios (OR) with corresponding 95%
MO349 IMPACT OF EARLY FLUID ADMINISTRATION ON INPATIENT
confidence interval (CI).
MORTALITY AND ACUTE KIDNEY INJURY IN PATIENTS WITH
RESULTS: The median age was 74.4 (IQR 59.90 - 84.35) years, 66% were male, 53%
COVID-19 DISEASE
white with hypertension and diabetes being the commonest co-morbidities. The
median duration of illness prior to admission was 7 days (IQR 2 – 10) with respiratory
Heidy Hendra1,2, Dinesha Sudusinghe1, James Greenan-Barrett3,
Melissa Chowdhury4, David Mathew1, Muhammad Umaid Rauf1, Efthimia Karra5, symptoms and fever most prevalent. The people who presented with AKI on admission
Umaira Aziz5, Ioannis D. Kostakis6, Tara Sood3, Lucy Lamb4,7, Philip Masson1,2, were more likely to receive fluids (34% vs 15%, p=0.02).
118 patients (75%) received fluids within 24-hours of admission with no difference in
Sally Hamour1,2
1
volume administered after local guidance change (p=0.78). Comparing patients
Royal Free London NHS Foundation Trust, Renal Unit, London, United Kingdom, receiving fluids with those who did not, we observed no difference in mortality
2
Royal Free Hospital, University College London Department of Renal Medicine, (p=0.97), duration of hospital stays (p=0.26) or requirement for ICU admission
London, United Kingdom, 3Royal Free London NHS Foundation Trust, Emergency (p=0.70). 18% died as an inpatient, and 52 patients were either admitted with or
Medicine Department, London, United Kingdom, 4Royal Free London NHS Foundation developed AKI.
Trust, Department of Infectious Diseases, London, United Kingdom, 5Royal Free London Of these 52 patients, 43 received fluids and 9 did not with no difference in KRT
NHS Foundation Trust, Department of Diabetes and Endocrinology, London, United requirement (p=0.34), mortality (p=0.50) or AKI recovery (p=0.63). Peak AKI stage
Kingdom, 6Royal Free London NHS Foundation Trust,, Department of Hepatobiliary was greater among participants who received fluids though stage of AKI at
Surgery and Liver Transplantation, London, United Kingdom and 7Royal Centre for presentation was also greater (p=0.04). Mortality rate in patients with an AKI is higher
Defence Medicine, Academic Department of Military Medicine, Birmingham, United compared to overall inpatient mortality (31% vs 18%). Of the 36 patients with AKI
Kingdom

10.1093/ndt/gfab082 | i245
Abstracts Nephrology Dialysis Transplantation

who were discharged home, 25 patients (69.4%) had renal recovery by the time of MO351 CENTRE VARIATION IN MORTALITY FOLLOWING HOSPITAL-
discharge. ACQUIRED ACUTE KIDNEY INJURY IN ENGLAND
Increasing age and clinical severity on admission were associated with higher mortality
(see Figure 1). Older age was associated with 34 - 53 times higher risk of death Javeria Peracha1,2, David Pitcher1, Shalini Santhakumaran1, Jamie Day3,
compared with those aged  65 years (age 76 - 85 years: OR 34.26, 95% CI: 3.94 - James Fotheringham4, Retha Steenkamp1, James Medcalf1,5,
297.48, p=0.001; age > 85 years: OR 53.07, 95% CI: 5.23 - 539.03, p=0.001). Patients Dorothea Nitsch1,6,7, Graham Lipkin2, William McKane4
1
with NEWS2 >4 on admission has 5-fold increased risk of death than those with a UK Renal Registry, Bristol, United Kingdom, 2Queen Elizabeth Hospital Birmingham,
score 4 (OR 5.26, 95% CI: 1.32 - 20.92). Black ethnicity was associated with a 16-fold Department of Renal Medicine, Birmingham, United Kingdom, 3Getting It Right First
increased risk of developing AKI (OR 15.86, 95% CI: 1.67 - 150.99). Time, NHS Improvement and Royal National Orthopaedic Hospital, London, United
CONCLUSION: To our knowledge, this is the first study to examine the impact of Kingdom, 4Northern General Hospital Sheffield Kidney Institute, Sheffield, United
fluid management on inpatient mortality as well as on renal-associated outcomes of Kingdom, 5Leicester General Hospital, John Walls Renal Unit, United Kingdom,
6
COVID-19 admission. Fluid administration regimen did not have an impact on University College Hospital, London, United Kingdom and 7London School of Hygiene
mortality, length of hospitalisation or ICU admission, nor did it affect renal outcomes. & Tropical Medicine, London, United Kingdom
Given the high rates of AKI and KRT in COVID-19 disease, early fluid administration
is likely to be an important cornerstone of future management. Further adequately BACKGROUND AND AIMS: Routine monitoring of outcomes for patients with
powered prospective studies are required to identify whether early fluid administration Acute Kidney Injury (AKI) is necessary to drive quality improvement in AKI care. In
can reduce renal injury. this study, we describe development of a case-mix adjusted 30-day mortality indicator
for patients with hospital acquired AKI (H-AKI), to facilitate identification of
unwarranted variation in outcomes across hospitals in England.
MO350 ACUTE KIDNEY INJURY RELATED TO ENDOSCOPIC METHOD: We utilised a routinely collected national dataset of biochemically defined
RETROGRADE COLANGIO-PANCREATOGRAPHY IS AKI cases, linked with hospitals administrative and mortality data. 250,504 H-AKI
ASSOCIATED WITH INCREASED INCIDENCE OF IN- episodes were studied in total, across 103 hospitals between January 2017 - December
HOSPITAL MORTALITY 2018. Standardised mortality ratios were calculated for each hospital using logistic
regression; adjusting for age, sex, primary diagnosis, comorbidity score, AKI severity,
Florica Gadalean1, Parv Florina2, Adalbert Schiller3, Flaviu Bob3, month of AKI, and admission method.
Cristina Gluhovschi3, Milas Oana3, Adelina Mihaescu3, Anca Simulescu3, RESULTS: Mean 30-day mortality rate was high at 28.6% and varied considerably
Alina Golea-Secara3, Lazar Chisavu3, Iulia Dana Grosu3, Luciana Marc3, between hospitals (22.3%-35.5%), with 23/103 trusts classed as outliers (95% control
Iulia Ratiu3, Adrian Goldis3, Bogdan Miutescu3, Andrei Riza3, Ligia Petrica3 limits). Patients with H-AKI had mortality rates more than 5 times higher than the
1 overall hospitalized population in 90/136 diagnosis groups and over 10 times higher in
University of Medicine and Pharmacy “Victor Babes” Timisoara, Nephrology,
60/136 groups. Increasing age, male sex, deprivation, higher comorbidity burden, more
Timis, oara, Romania, 2University of Medicine and Pharmacy “Victor Babes” Timisoara,
severe AKI stage at detection, emergency admission and admission during winter
Cardiology, Timis, oara, Romania and 3University of Medicine and Pharmacy “Victor
months were all associated with a higher risk of death Presentation at hospitals with
Babes” Timisoara, Gastroenterology, Timis, oara, Romania
on-site specialist nephrology services and Asian or Black ethnicity, however, were
linked to a lower risk of death.
BACKGROUND AND AIMS: To date, endoscopic retrograde colangio- CONCLUSION: This is the largest multi-centre analysis of mortality for patients with
pancreatography (ERCP) represents a major advance in gastro-intestinal biochemically ascertained H-AKI to date, once again highlighting development of AKI
endoscopy. The ERCP is a safe and minimally invasive therapy for pancreatic-biliary as an important patient safety concern across hospital settings. Centres identified as
diseases. Adverse events (AEs) associated to ERCP are well described. However, little is having poor outcomes will need to carefully interrogate their AKI care pathways to
known about acute kidney injury (AKI) associated to ERCP. The aim of this study was understand and explore reasons underlying the observed variation to guide future
to evaluate the incidence of post-ERCP AKI and the risk factors for AKI development. quality improvement interventions.
The prognostic implication of ERCP-associated AKI in in-hospital mortality has been
also assessed.
METHOD: In this prospective observational study, we evaluated 396 patients who
underwent ERCP, from the 3rd January 2019 through the 27th January 2020. AKI was
defined as an increase in serum creatinine (SCr)  0.3 mg/dl or an increase in SCr 
50% and/or by a decrease in urine output to 0.5 ml/kg/hour for 6 hours, in the first 48
hours following ERCP. Logistic uni- and multivariable regression methods were used
to determine predictors of AKI and in-hospital mortality. A two-tailed value <0.05 was
considered significant.
RESULTS: In the studied group, median age was 69 years, interquartile range [IQ
=17], 183 (46.21%) patients being males. ERCP-associated AKI was detected in 103
patients (26%). Univariable regression analysis showed that AKI was associated with
baseline eGFR (r=0.246, P<0.001), age (r=0.108, P=0.04), Charlson Comorbidity Index
(CCI) (r=0.239, P<0.001), and with the following pre-ERCP parameters: systemic
inflammatory response syndrome (SIRS) (r=0.125, P=0.012), serum albumin (r= -
0.232, P<0.001), C-reactive protein (r=0.246, P<0.001), hematocrit (r= -0.130,
P=0.009), platelet count (r=-0.155, P=0.001), total bilirubin level (r=0.230; P<0.001),
alaninamino transferase level (r= -0.101, P=0.044), and alcaline phosphatase level
(r=0.286, P<0.001). In the multivariable regression analysis, the independent
predictors of AKI were: baseline eGFR (adjusted odds ratio (OR) 0.941, 95%
confidence interval (CI): 0.927–0.956, P<0.001), CCI score (OR=1.17, 95%CI: 1.05-
1.32, P=0.005), SIRS (OR=2.02, 95%CI: 1.009-4.036, P=0.047), total bilirubin
(OR=1.08, 95%CI: 1.036-1.123, P<0.001), and alcaline phosphatase (OR=1.002,
95%CI:1.001-1.002, P<0.001). AKI was associated with increased in-hospital mortality
(7.76 % versus 0.34 %, P<0.001). In our group, AKI was an independent predictor of
in-hospital mortality (OR=9.98 , 95% CI: 1.19-83.26, P=0.03).
CONCLUSION: In patients undergoing ERCP, AKI was a common complication and
an independent risk factor for in-hospital mortality. These findings highlight the
importance of early AKI and AKI-related risk factors recognition, in order to
minimise the risk for ERCP-associated AKI and to improve the post-ERCP outcome of
patients. MO352 RENAL DYSFUNCTION AS A MAJOR PREDICTOR OF
CLINICAL OUTCOMES IN ANTERIOR STEMI PATIENTS

Florence Sens1,2, Camille Amaz3, Laurent Juillard1,2,4, Michel Ovize3,


Fitsum Guebre-Egziabher1,2,4
1
Hospices Civils de Lyon, Service de Néphrologie et D’Explorations Fonctionnelles
Rénales - Hôpital Edouard Herriot, Lyon, France, 2FCRIN INI-CRCT, Nancy, France,
3
Hospices Civils de Lyon, Hôpital Louis Pradel, Centre d’Investigation Clinique (CIC) 1407
de Lyon, Lyon, France and 4Université Claude Bernard Lyon 1, CARMEN UMR INSERM
1060, Lyon, France

BACKGROUND AND AIMS: Among ST-segment elevation myocardial infarction


(STEMI) patients, the respective impact of the baseline renal function, of the

i246 | Abstracts
Nephrology Dialysis Transplantation Abstracts
development of acute kidney injury (AKI), and of their combination, on the long-term
cardiovascular outcomes, remain unclear.
METHOD: The present study was based on a post hoc analysis of the CIRCUS trial
database, a multicentre randomized study which gathered 969 patients with
anterior STEMI treated by primary percutaneous intervention (PPCI) within 12 hours
of symptoms onset. Uni and multivariate regressions were performed to identify if the
estimated glomerular filtration rate (eGFR) at admission and the development of AKI
were associated with (1) cardiovascular death and heart failure (HF) at one year and (2)
sub-optimal treatment prescription at discharge.
RESULTS: A total of 822 patients were included. The mean baseline eGFR was 86 6
19 mL/min/1.73m2. AKI occurred in 97 patients (11.8%). Baseline eGFR <60mL/min/
1.73m2 was associated with HF (40.0 vs 16.8%, p<0.001) and with a sub-optimal
treatment at discharge (35.9 vs 18.9%, p=0.001). AKI was associated with
cardiovascular death (12.4 vs 2.8%, p<0.001), HF (50.5 vs 14.9%, p<0.001), and sub-
optimal treatment (35.8 vs 18.5%, p<0.001). The multivariate analysis showed that
AKI (OR=4.88, CI=2.89-8.27) and a lower baseline eGFR (OR=1.29 per 10mL/min/
1.73m2 decrease, CI=1.11-1.50) are independent predictors of cardiovascular death or
HF after anterior STEMI.
CONCLUSION: In anterior STEMI patients undergoing PPCI, the development of
AKI was the strongest independent predictor of poor clinical outcome at one year. The
study suggests the need for a tailored monitoring of STEMI patients with AKI or
baseline kidney dysfunction.

MO354 PRELIMINARY EVIDENCE OF RIVASTIGMINE EFFICACY IN


CKD RELATED MILD COGNITIVE IMPAIRMENT

Pasquale Mone1,2, Antonella Pansini3, Giovambattista Capasso 2 ,


Davide Viggiano 2
1
University of Campania “L. Vanvitelli”, Naples, Italy, Dept. Of Translational Medicine,
Naples, Italy and 3ASL Avellino, Elderly Assistance, Avellino, Italy

MO352 Figure: Forest plot for independent predictors of death or heart failure BACKGROUND AND AIMS: Mild Cognitive Impairment (MCI) is a common
event finding in chronic kidney disease (CKD) patients. Indeed, CKD represents a relevant
Abbreviations: AKI, Acute kidney injury; CK, Creatinine kinase; GFR, estimated risk factor for developing dementia and MCI. Cholinesterase inhibitors, such as
glomerular Filtration Rate; TIMI, Thrombolysis In Myocardial Infarction score. rivastigmine, are among the few drugs approved for the treatment of dementia and
MCI. Rivastigmine is also used to treat vascular dementia because it protects
subcortical brain structures. Data are scanty regarding the use of rivastigmine in CKD
patients with MCI and are much needed to guide the therapy for MCI in this cohort of
patients.
METHOD: This retrospective case-control study compared the effects of rivastigmine
on cognitive functions in MCI patients with CKD (stage III-IV; n= 20) and without
CKD (n=21, control group), comparable for the extent of cognitive impairment
MO353 MACHINE LEARNING-BASED PREDICTION OF ACUTE (indexed by Montreal Cognitive Assessment, MoCA), age (range 18-65 years), gender,
KIDNEY INJURY AFTER NEPHRECTOMY IN PATIENTS WITH weight, and comorbidities. Patients under treatment with rivastigmine and with a
RENAL CELL CARCINOMA baseline MoCA score available were included in the study. Exclusion criteria were ictus,
psychiatric or other neurological conditions, heart failure, liver failure, severe obesity,
Sejoong Kim1, Yeonhee Lee2, Seung Seok Han2 anemia, electrolyte disorders, cancer, dialysis, and other severe comorbidities.
1
Seoul National University Bundang Hospital, Internal Medicine, Seongnam-si, Korea, Laboratory test data (glycemia, cholesterol, hemoglobin, proteinuria, creatinine) were
Rep. of South and 2Seoul National University College of Medicine, Internal Medicine, used to characterize the two populations. MCI was defined as a MoCA score between
Seoul, Korea, Rep. of South 21-26. The cognitive screening was available at baseline (before treatment) and during
a follow-up in a range of three-six months after the start of the treatment. CKD was
BACKGROUND AND AIMS: The precise prediction of acute kidney injury (AKI) defined by eGFR < 60 mL/min/1.73m2.
after nephrectomy for renal cell carcinoma (RCC) is an important issue because of its RESULTS: The follow-up timing for cognitive screening was not statistically different
relationship with subsequent kidney dysfunction and high mortality. Herein we between the two cohorts. The control group (MCI without CKD) showed a small,
addressed whether machine learning algorithms could predict postoperative AKI risk significant improvement in the MoCA score after treatment (baseline MoCA:
better than conventional logistic regression (LR) models. 22.960.5, follow-up MoCA: 23.560.5, p=0.02, t-test for paired data).
METHOD: A total of 4,104 RCC patients who had undergone unilateral nephrectomy At variance, the MCI-CKD group showed a significant improvement in the MoCA
from January 2003 to December 2017 were reviewed. Machine learning models such as score (baseline MoCA=2360.4, follow-up MoCA=24.360.4, p<0.05).
support vector machine, random forest, extreme gradient boosting, and light gradient Accordingly, the extent of improvement of MoCA score after rivastigmine was
boosting machine (LightGBM) were developed, and their performance based on the inversely correlated to the eGFR (r = -0.23).
area under the receiver operating characteristic curve, accuracy, and F1 score was CONCLUSION: A significant improvement in MoCA score accompanied treatment
compared with that of the LR-based scoring model. with rivastigmine in the CKD group. More extensive population studies are needed to
RESULTS: Postoperative AKI developed in 1,167 patients (28.4%). All the machine verify the greater efficacy of Acetylcholinesterase inhibitors in this population.
learning models had higher performance index values than the LR-based scoring
model. Among them, the LightGBM model had the highest value of 0.810 (0.783–
0.837). The decision curve analysis demonstrated a greater net benefit of the machine MO355 ACUTE KIDNEY INJURY INCREASES THE RISK FOR
learning models than the LR-based scoring model over all the ranges of threshold SUBSEQUENT HEART FAILURE HOSPITALIZATIONS
probabilities. The LightGBM and random forest models, but not others, were well
calibrated. Matthias Diebold1, Tobias Zimmermann2, Ivo Strebel2, Desiree Wussler2,
CONCLUSION: The application of machine learning algorithms improves the Stefano Bassetti3, Christian Mueller2, Tobias Breidthardt3
predictability of AKI after nephrectomy for RCC, and these models perform better 1
University Hospital Basel, Clinic for Transplantation Immunology and Nephrology,
than conventional LR-based models.
Basel, Switzerland, 2University Hospital Basel, Cardiovascular Research Institute Basel,
Basel, Switzerland and 3University Hospital Basel, Division of Internal Medicine, Basel,
Switzerland

BACKGROUND AND AIMS: Acute kidney injury (AKI) is common and associated
with increased mortality and morbidity. The impact of AKI on subsequent heart failure
remains largely unknown.

10.1093/ndt/gfab082 | i247
Abstracts Nephrology Dialysis Transplantation

METHOD: The Basics in Acute Shortness of Breath Evaluation Study (BaselV) one year after initial AKI-episode patients with suspected infection at the emergency
prospectively enrolled patients presenting the emergency department with acute department.
dyspnea. Two independent specialists adjudicated the final cause of dyspnea. Serum METHOD: We used data from the SPACE-cohort (SePsis in the ACutely ill patients in
creatinine concentrations were prospectively assessed throughout the hospitalization. the Emergency department), which consisted of all consecutive patients that presented
AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical to the emergency department of the internal medicine with suspected infection in the
practice guideline. AKI adjudication occurred blinded to the cause of dyspnea. period between 2016 and 2018 at the University Medical Center Utrecht. Clinical and
Mortality and rehospitalizations were prospectively assessed during follow-up laboratory data were prospectively collected of all patients. AKI was defined according
(median:768 days [IQR:290-950]. Renal recovery was defined as a discharge to the Kidney Disease: Improving Global Outcomes criteria. Outcomes were 1-year all-
creatinine<1.25x baseline creatinine. cause mortality and renal function. Hazards ratios were assessed using Cox regression
RESULTS: AKI occurred in 809 (40%) of 2021 patients and was associated with to investigate the association between AKI, 1-year mortality and renal function decline
increased all-cause (adjusted Hazard Ratio [aHR] 1.33, 95%CI 1.13-1.55; p<0.01) and after AKI. HRs were adjusted for potential confounders including age, gender,
cardiovascular mortality (aHR 1.43, 95%CI 1.16-1.75; p<0.01). However, the impact of Charlson Comorbidity Index, immune status, smoking status, medication use
AKI on mortality was time-dependent with the highest impact on early 30-day (diuretics, proton-pump inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs)
mortality (aHR 2.47, 95%CI 1.62-3.76; p<0.01) (Figure 1A). AKI was not associated and angiotensin converting enzyme inhibitors (ACEi)), disease severity, diagnosis in
with all-cause or cardiovascular mortality in patients achieving renal recovery (p=0.10 the emergency department. Decline of renal function after AKI episode at emergency
and p=0.30). In contrast, AKI displayed a time-independent association with department visit was defined as Serum Creatinine (SCr) level 30% above baseline.
subsequent hospitalisations for heart failure (hHF) (aHR 1.49, 95%CI 1.15-1.94; Survival in patients with and without AKI was assessed using Kaplan-Meier analyses.
p<0.01) (Figure 1B). The association with hHF was stronger for higher degrees of AKI RESULTS: Of the 3105 patients in the SPACE-cohort with suspected infection, we
(stage 2/3 aHR: 1.89; 95%CI 1.33-2.83; p<0.01). This association with hHF persisted in included 1716, who fulfilled the inclusion criteria and had a baseline SCr measurement.
patients with non-cardiac dyspnea (aHR 2.43, 95%CI 1.05-5.59; p=0.04), even after Patients without SCr at baseline (401 patients), at emergence department visit (113
renal recovery (aHR 2.56, 95%CI 1.00-6.54; p=0.05). Again, in patients with non- patients), during follow-up (33 patients), on renal replacement therapy (66 patients) or
cardiac dyspnea the association of advanced AKI (stage 2/3) with hHF was even had a repeated emergency department visit (776 patients) were excluded. Of the 1716
stronger (aHR 4.25, 95%CI 1.59-11.36; p<0.01).

CONCLUSION: AKI independently increases the risk of hHF by almost 50%. This patients presenting with suspected infection patients (median age 62y, 52.9% male),
association persists in patients with non-cardiac dyspnea, even after renal recovery by 185 patients (10.8%) had an AKI episode. Mortality was 23.8% for the AKI group and
discharge. This suggests AKI to be a novel risk-factor for the development of clinically 20.4% for the non-AKI group. The adjusted HR for all-cause mortality at 1-year after
significant HF. presentation at the emergency department in AKI patients was 2.1 (95% CI 1.5 – 3.1).
Moreover, the cumulative incidence of renal function decline was 69.8% for patients
with AKI and 39.3% for patients without AKI. Patients with an episode of AKI had
MO356 THE INCIDENCE, MORTALITY AND RENAL OUTCOMES OF higher risks of developing renal function decline (adjusted HR 3.3, 95% CI 2.4-4.5) at
ACUTE KIDNEY INJURY IN PATIENTS WITH SUSPECTED one year after initial AKI-episode at the emergency department.
INFECTION AT THE EMERGENCY DEPARTMENT CONCLUSION: Acute kidney injury is common in patients with suspected infection
in the emergency department and is significantly associated with mortality and renal
Meriem Khairoun1, Jan Willem Uffen2, Gurbey Ocak3, Romy Koopsen2, function decline one year after AKI.
Saskia Haitjema4, Jan Jelrik Oosterheert2, Ronald Gansevoort5, Karin Kaasjager1
1
, Department of Nephrology and Hypertension, University Medical Center Utrecht,
Utrecht University, Utrecht, 2, Department of Internal Medicine, Infectious Diseases,
University Medical Center Utrecht, Utrecht University, Utrecht, 3, Department of Internal
Medicine and Nephrology, Sint Antonius Hospital, Nieuwegein, Nieuwegein, The
Netherlands, 4, Department of Central Diagnostic Laboratory, University Medical Center
Utrecht, Utrecht, University, Utrecht and 5, Department of Internal Medicine and
Nephrology, University Medical Center Groningen, Groningen

BACKGROUND AND AIMS: Acute kidney injury (AKI) is a major health problem
associated with considerable mortality and morbidity. The epidemiology of AKI in
hospitalized and critically ill patients at the Intensive Care Unit with severe infection
and sepsis has been well described, however data on mortality and clinical outcomes of
AKI at the emergency department in patients with suspected infection are scarce. In
this study, we investigated the incidence, mortality and renal outcomes after AKI up to

i248 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO357 ACUTE KIDNEY INJURY IN HOSPITALIZED COVID-19 Nephrology, Kayseri, Turkey, 34Health Science University, Kocaeli Derince Education and
PATIENTS: A MULTICENTRE STUDY BY TURKISH SOCIETY Research Hospital, Division of Nephrology, Kocaeli, Turkey and 35Recep Uzmanı Tayyip
OF NEPHROLOGY Erdogan University, Faculty of Medicine, Deparment of Internal Medicine, Division of
Nephrology, Rize, Turkey
_Izzet Hakkı Arıkan1, Savas Ozturk2, Bulent Tokgoz3, Belda Dursun4,
Nurhan Seyahi5, Sinan Trablus5, Mahmud Islam6, Yavuz Ayar7, Numan Gorgulu8, BACKGROUND AND AIMS: Acute kidney injury (AKI) is common in coronavirus
Serhat Karadag2, Mahmut Gok9, Esra Akcali10, Feyza Bora11, Zeki Aydin12, disease-2019 (COVID-19) and the severity of AKI is linked to adverse outcomes. In
Eda Altun13, Elbis Ahbap Dal14, Mehmet Polat15, Zeki Soypacaci16, Ebru Gok this study, we investigated the factors associated with in-hospital outcomes among
Oguz17, Sumeyra Koyuncu3, Hulya Colak18, _Idris Sahin19, Murside hospitalized patients with COVID-19 and AKI.

Esra Dolarslan20, Ozant Helvacı21, Ilhan Kurultak22, Zehra Eren23, Hamad Dheir24, METHOD: In this multicenter retrospective observational study, we evaluated the
MELIKE BETUL OGUTMEN25, Dilek Guven Taymez26, Dilek Gibyeli Genek27, characteristics and in-hospital renal and patient outcomes of 578 patients with
Sultan Ozkurt28, Elif Ari Bakir29, Enver Yuksel30, Tuncay Sahutoglu31, Ozgur confirmed COVID-19 and AKI. Data were collected from 34 hospitals in Turkey from
Akin Oto32, Gulsah Boz33, Sengul Erkan34, Ekrem Kara35, Z. Serhan Tuglular1 March 11 to June 30, 2020. AKI definition and staging were based on the Kidney
1
Marmara University School of Medicine, Deparment of Internal Medicine, Division of Disease Improving Global Outcomes criteria. Patients with end-stage kidney disease or
Nephrology, Istanbul, Turkey, 2Haseki Training and Research Hospital, Department of with a kidney transplant were excluded. Renal outcomes were identified only in
Nephrology, Istanbul, Turkey, 3Erciyes University School of Medicine, Deparment of discharged patients.
Internal Medicine, Division of Nephrology, Kayseri, Turkey, 4Pamukkale University RESULTS: The median age of the patients was 69 years, and 60.9% were males. The
Medical School, Deparment of Internal Medicine, Division of Nephrology, Denizli, most frequent comorbid conditions were hypertension (70.5%), diabetes mellitus
Turkey, 5Istanbul University, Cerrahpasa Medical Faculty, Department of Nephrology, (43.8%), and chronic kidney disease (41.5%). The proportions of AKI stages 1, 2, and 3
Istanbul, Turkey, 6Zonguldak Ataturk State Hospital, Division of Nephrology, Zonguldak, were 54.0%, 24.7%, and 21.3%, respectively. 291 patients (50.3%) were admitted to the
Turkey, 7University of Health Science. Faculty of Medicine, Bursa City Hospital, Division intensive care unit. Renal improvement was complete in 80.7% and partial in 17% of
of Nephrology, Bursa, Turkey, 8University of Health Sciences, Istanbul Bagcilar Training the patients who were discharged. Renal outcomes were worse in patients with AKI
and Research Hospital, Department of Nephrology, Istanbul, Turkey, 9Sultan 2. stage 3 or baseline CKD. The overall in-hospital mortality in patients with AKI was
Abdulhamid Han Training and Research Hospital, Department of Nephrology, Istanbul, 38.9%. By multivariate Cox regression analysis, age (hazard ratio [HR] [95%
Turkey, 10Mersin University Faculty of Medicine, Department of Nephrology, Mersin, confidence interval (95%CI)]: 1.01 [1.0-1.03], p = 0.035], male gender (HR [95%CI]:
Turkey, 11Akdeniz University Faculty of Medicine, Deparment of Internal Medicine, 1.47 [1.04-2.09], p = 0.029), diabetes mellitus (HR [95%CI]: 1.51 [1.06-2.17], p = 0.022)
Division of Nephrology, Antalya, Turkey, 12University of Health Sciences, Kocaeli Darica and cerebrovascular disease (HR [95%CI]: 1.82 [1.08-3.07], p = 0.023), serum lactate
Farabi Training and Research Hospital, Department of Nephrology, Kocaeli, Turkey, dehydrogenase (greater than two-fold increase) (HR [95%CI]: 1.55 [1.05-2.30],
13
Golcuk Necati Celik State Hospital, Division of Nephrology, Kocaeli, Turkey, 14Sisli p = 0.027) and AKI stage 2 (HR [95%CI]: 1.98 [1.25-3.14], p = 0.003) and stage 3 (HR
Hamidiye Etfal Education and Research Hospital, Department of Nephrology, Istanbul, [95%CI]: 2.25 [1.44-3.51], p = 0.0001) were independent predictors of in-hospital
Turkey, 15Nevsehir State Hospital, Division of Nephrology, Nevsehir, Turkey, 16University mortality. The in-hospital mortality rates across AKI stages by age, gender, and
of Katip Celebi, Ataturk Training and Research Hospital, Department of Nephrology, diabetes mellitus were shown in the Figure.
Izmir, Turkey, 17University of Health Sciences, Diskapi Yildirim Beyazit Education and CONCLUSION: Advanced-stage AKI is associated with extremely high mortality
Research Hospital, Department of Nephrology, Ankara, Turkey, 18University of Health among hospitalized COVID-19 patients. Age, male gender, comorbidities, which are
Sciences, Tepecik Education and Research Hospital, Division of Nephrology, Izmir, risk factors for mortality in patients with COVID-19 in the general population, are also
Turkey, 19Inonu University Faculty of Medicine, Deparment of Internal Medicine, related to in-hospital mortality in patients with AKI. Renal problems continue in a
Division of Nephrology, Malatya, Turkey, 20University of Health Sciences,Trabzon Kanuni significant portion of the patients who were discharged.
Education and Research Hospital, Division of Nephrology, Trabzon, Turkey, 21Yildirim
Beyazit University Yenimahalle Research and Training Hospital, Division of Nephrology,
Ankara, Turkey, 22Trakya University Faculty of Medicine, Department of Nephrology,
MO358 ACUTE KIDNEY INJURY AND MORTALITY RISK IN OLDER
Edirne, Turkey, 23Alanya Alaaddin Keykubat University School of Medicine, Deparment
ADULTS WITH AND WITHOUT COVID-19: DATA FROM
of Internal Medicine, Division of Nephrology, Antalya, Turkey, 24Sakarya University
GEROCOVID STUDY
Medical Faculty Education and Research Hospital, Deparment of Internal Medicine,
Division of Nephrology, Sakarya, Turkey, 25University of Health Sciences, Haydarpasa
Hong Xu1, Sara Garcia-Ptacek2, Martin Annetorp3, Annette Bruchfeld3,
Numune Education and Research Hospital, Division of Nephrology, Istanbul, Turkey,
26 Tommy Cederholm4, Peter Johnson5, Miia Kivipelto3, Carina Metzner3,
Kocaeli State Hospital, Nephrology and Dialysis Department, Kocaeli, Turkey, 27Mugla
Dorota Religa3, Maria Eriksdotter2
Sıtkı Kocman University, Faculty of Medicine, Department of Nephrology, Mugla, 1
Turkey, 28Eskisehir Osmangazi University Faculty of Medicine, Department of Karolinska Institutet, Division of Clinical Geriatrics, Huddinge, Sweden, 2Karolinska
Nephrology, Eskisehir, Turkey, 29Bahcesehir University Hospital, Department of Institutet, 3Karolinska University Hospital, 4Uppsala University and 5Capio Geriatrik
Nephrology, Istanbul, Turkey, 30University of Health Sciences, Gaziyaşargil Training and Nacka AB
Research Hospital, Department of Nephrology, Diyarbakir, Turkey, 31Sanliurfa Mehmet
Akif Inan Training and Research Hospital, Nephrology Unit, Sanliurfa, Turkey, 32Istanbul BACKGROUND AND AIMS: Research regarding COVID-19 and acute kidney injury
University Istanbul Medical Faculty, Deparment of Internal Medicine, Division of (AKI) in older adults is scarce. We evaluated the risk factors and outcomes of AKI in
Nephrology, Istanbul, Turkey, 33Kayseri City Training and Research Hospital, Division of hospitalized older adults with and without COVID-19.

MO357 Figure: The in-hospital mortality rate across acute kidney injury (AKI) stages by age (A), gender (B), and diabetes mellitus (C)

10.1093/ndt/gfab082 | i249
Abstracts Nephrology Dialysis Transplantation

METHOD: Observational study of patients admitted to two geriatric clinics in the In the prediction of AKI, machine learning (ML) techniques have been demonstrated
Stockholm Region of Sweden during the first wave of the COVID-19 pandemic from to improve on the predictive ability of existing models that rely on more conventional
March 1st to June 15th 2020. The difference in incidence, risk factors and adverse statistical methods. ML is a broad term which refers to various types of models:
outcomes for AKI between patients with or without COVID-19 were examined. Odds Parametric models, such as linear or logistic regression use a pre-specified model form
ratios (ORs) for AKI were obtained from logistic regressions. The hazard ratios (HRs) which is believed to fit the data, and its parameters are estimated. Non-parametric
for the risk of in-hospital death were calculated from Cox proportional hazard models, such as decision trees, random forests, and neural networks may have varying
regression models. complexity (e.g. the depth of a classification tree model) based on the data. Deep
RESULTS: We analyzed 316 older patients hospitalized for COVID-19 and 876 learning neural network models exploit temporal or spatial arrangements in the data to
patients for non-COVID-19 diagnoses. The mean age was 8369 years, 57% were deal with complex predictors.
women, and mean baseline kidney function as depicted by estimated glomerular Given the rapid growth and development of ML methods and models for AKI
filtration rate (eGFR) was 62623 ml/min/1.73m2. AKI occurred in 92 (29%) of patients prediction over the past years, in this systematic review, we aim to appraise the current
with COVID-19 vs. 159 (18%) without COVID-19. The severity of AKI was state-of-the-art regarding ML models for the prediction of AKI. To this end, we focus
significantly worse in patients with COVID-19 compared with non-COVID patients. on model performance, model development methods, model evaluation, and
The odds for developing AKI were higher in patients with COVID-19 (adjusted OR, methodological limitations.
1.70; 95% CI, 1.04-2.76), low baseline kidney function [4.19 (2.48-7.05), for eGFR 30  METHOD: We searched the PubMed and ArXiv digital libraries, and selected studies
<60 ml/min/1.73m2, and 20.3 (9.95-41.3) for eGFR <30ml/min/1.73m2], and higher that develop or validate an AKI-related multivariable ML prediction model. We
C-reactive protein (CRP) level (OR 1.81(1.11-2.95)). The risk of in-hospital death was extracted data using a data extraction form based on the TRIPOD (transparent
highest in patients with COVID-19 and AKI [adjusted HR 23.5, 95% CI (8.75-63.0)], reporting of a multivariable prediction model for individual prognosis or diagnosis)
followed by COVID-19 without AKI [9.10 (3.52-23.6)] and by patients without and CHARMS (critical appraisal and data extraction for systematic reviews of
COVID-19 and with AKI [6.38 (2.28-17.9)] after adjusting for patient demographics, prediction modelling studies) checklists.
vital signs, baseline kidney function and medications and using non-COVID patients RESULTS: Overall, 2,875 titles were screened and thirty-four studies were included. Of
with no AKI as reference. those, thirteen studies focussed on intensive care, for which the US derived MIMIC
CONCLUSION: Geriatric patients hospitalized with COVID-19 had a higher dataset was commonly used; thirty-one studies both developed and validated a model;
incidence of AKI compared with patients hospitalized with other diagnoses. AKI and twenty-one studies used single-centre data. Non-parametric ML methods were used
COVID-19 were associated with in-hospital death. Optimal management of AKI may more often than regression and deep learning. Random forests was the most popular
improve the outcome of COVID-19 in geriatric patients. method, and often performed best in model comparisons. Deep learning was typically
used (and also effective) when complex features were included (e.g., with text or time
series). Internal validation was often applied, and the performance of ML models was
usually compared against logistic regression. However, the simple training/test split
MO359 ASSOCIATIONS BETWEEN RENAL FUNCTION
was often used, which does not account for the variability of the training and test
TRAJECTORIES AFTER 3 MONTHS ACUTE KIDNEY INJURY
samples. Calibration, external validation, and interpretability of results were rarely
AND LONG-TERM RENAL OUTCOMES
considered. Comparisons of model performance against medical scores or clinicians
were also rare. Reproducibility was limited, as data and code were usually unavailable.
Chien-Ning Hsu1, You-Lin Tain2
1
CONCLUSION: There is an increasing number of ML models for AKI, which are
Kaohsiung Chang Gung Memorial Hospital, Deaprtment of Pharmacy, Kaohsiung, mostly developed in the intensive care environment largely due to the availability of the
Taiwan, R.O.C. and 2Kaohsiung Chang Gung Memorial Hospital, Department of MIMIC dataset. Most studies are single-centre, and lack a prospective design. More
Pediatrics, Kaohsiung, Taiwan, R.O.C. complex models based on deep learning are emerging, with the potential to improve
predictions for complex data, such as time-series, but with the disadvantage of being
BACKGROUND AND AIMS: Renal function recovery after acute kidney injury less interpretable. Future studies should pay attention to using calibration measures,
(AKI) is associated with patient outcomes. The study objectives were to assess the external validation, and on improving model interpretability, in order to improve
patterns of AKI recovery within 6 months following discharge for AKI and subsequent uptake in clinical practice. Finally, sharing data and code could improve reproducibility
incidence of chronic dialysis. of study findings.
METHOD: A retrospective cohort of 234,867 hospitalized adult patients was examined
for AKI between January 1, 2010, and December 31, 2017 in the largest healthcare
delivery system in Taiwan. Renal function recovery at 3- and 6-month post discharge,
MO361 INCIDENCE AND RISK FACTORS OF INFECTION AFTER AN
incident chronic kidney disease and chronic dialysis initiation were analyzed over 7
EPISODE OF ACUTE KIDNEY INJURY DURING
years of follow-up. Renal recovery was defined by < 1.5 baseline SCr (prior to the
HOSPITALIZATION
hospitalization). Independent associations between renal function recovery patterns
and renal outcomes was assessed by Cox proportional hazard model controlling for
Ana Sanchez1, Alicia Cabrera1, Laura Salanova Villanueva1, Patricia Mun
~oz
potential confounders, and subdistribution hazard ratio (SHR) with [95% CI] was
Ramos1, Pablo Ruano1, Borja Quiroga1
analysed for competing risk of early death. 1
RESULTS: Among 3 months AKI survivors (n=24,132), 14.28% (n=3,430) did not HOSPITAL DE LA PRINCESA, NEPHROLOGY, MADRID, Spain
recovery back to baseline, and 16% of recovery did not sustain. Three distinct renal
function recovery continuums at 6 months post hospital discharge were: persistent BACKGROUND AND AIMS: Acute kidney injury (AKI) is a major risk factor for
non-recovery (10.18%), non-recovery (14.33%), and recovery (75.5%). Comparing to development and progression to chronic kidney disease (CKD). The aim of the present
survivors without AKI (n=50,387), the impact of renal recovery continuum on chronic study is to assess the incidence of infections after an admission for AKI.
dialysis initiation varied by patient’s baseline renal disease (SHR was 2.82 [95%CI, METHOD: In this retrospective study all patients who developed AKI during
2.42-3.28] in CKD, and 0.8 [95%CI, 0.27-2.38] for non-CKD. Persistent non-recovery hospitalization and were discharged from 2013 to 2014 were included. Factors
was significantly associated with a greater increased risk of chronic dialysis than non- associated to infections were evaluated. The mean follow-up after discharge was 39630
recovery in any patients with AKI. Comparing to patients with sustained AKI recovery, months.
risk of CKD onset increased 5-fold in persistent non-recovery and 3-fold risk in non- RESULTS: We included 1255 patients with a mean age of 75613 years, of which 692
recovery. (55%) were men. At baseline, 944 (75%) patients presented with hypertension, 379
CONCLUSION: The continuum of AKI recovery post 6 months is associated with (30%) with diabetes, 560 (44%) with hypercholesterolemia and 543 (43%) with CKD.
increased risk of chronic dialysis, particularly in patients with baseline CKD. These Mean baseline creatinine was 1,361,8 mg/dl (glomerular filtration rate [eGFR]
study results suggested that patients ever with AKI should receive close renal function estimated by CKD-EPI was 55625 ml/min/1,73m2). The peak level of creatinine
monitoring for post-discharge management. reached during AKI was 2,4761,97 mg/dl (eGFR 30618 ml/min/1,73m2). At
discharge, creatinine was 1,62 mg/dL and eGFR 53627 ml/min/1,73m2. Seven
hundred and seventy-three (62%) patients presented an eGFR inferior to 60 ml/min/
1,73m2.
MO360 MACHINE LEARNING MODELS FOR PREDICTING ACUTE
During follow-up, 681(54%) patients presented an infectious event. Urinary tract
KIDNEY INJURY: A SYSTEMATIC REVIEW
infection was the most frequent infection (286 patients, 23%) followed by respiratory
infection (214 patients, 17%). Factors associated with infection were age (p<0,001),
Iacopo Vagliano1, Nicholas Chesnaye1,2,3, Jan Hendrik Leopold1, Kitty
hypertension (p=0,03), atrial fibrillation (p=0,014), functional dependence measured
J Jager1,2,3, Ameen Abu Hanna1, Martijn C. Schut1
1
by Barthel index (p=0,03), previous diagnosis of CKD (p=0,01), baseline eGFR
Amsterdam UMC, University of Amsterdam, Dept. of Medical Informatics, Amsterdam, (p>0,001) and eGFR at discharge (p=0,002). Survival analysis using Kaplan-Meier
The Netherlands, 2ERA-EDTA Registry, Amsterdam, The Netherlands and 3Amsterdam demonstrated an existing association between eGFR inferior to 60 ml/min/1,73m2 and
Public Health research Institute, Amsterdam, The Netherlands infections (LogRank 12,2, p<0,001, figure 1).

BACKGROUND AND AIMS: Acute kidney injury (AKI) has a substantial impact on
global disease burden of Chronic Kidney Disease. To assist physicians with the timely
diagnosis of AKI, several prognostic models have been developed to improve early
recognition across various patient populations with varying degrees of predictive
performance.

i250 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO363 CHECKPOINT-INHIBITOR-ASSOCIATED ACUTE KIDNEY
INJURY AND MORTALITY: AN OBSERVATIONAL STUDY

Marije Koks1, Gurbey Ocak2, Britt Suelmann3, Cornelia Hulsbergen-Veelken4,5,


Saskia Haitjema5, Marieke Vianen6, Marianne Verhaar1, Karin Kaasjager1,
Meriem Khairoun1
1
, Department of Nephrology and Hypertension, University Medical Center Utrecht,
Utrecht University, Utrecht, the The Netherlands, 2, Department of Internal Medicine
and Nephrology, Sint Antonius Hospital, Nieuwegein, the The Netherlands, 3,
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University,
Utrecht, The Netherlands, 4, Central Diagnostic Laboratory, University Medical Center
Utrecht, Utrecht University, Utrecht, the Netherlands, 5, Department of Central
Diagnostic Laboratory, University Medical Center Utrecht, Utrecht, University, Utrecht,
The Netherlands and 6, Department of Internal Medicine and Dermatology, University
Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

BACKGROUND AND AIMS: Immune checkpoint inhibitors, approved for the


treatment of various types of cancer, are known to cause a unique spectrum of
autoimmune-related side effects, including acute kidney injury (AKI). The aim of this
study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI
in patients receiving checkpoint inhibitors.
METHOD: Patients receiving checkpoint inhibitors between January 2013 and May
2020 were identified using the Utrecht Patient Oriented Database. AKI was defined as
an increase in creatinine of 1.5 times the baseline value. Cox proportional hazard
regression analysis was used to assess risk factors for AKI and to evaluate the
MO361 Figure 1: Survival curve for time to first infection among patients with relationship between AKI and mortality. Persistent kidney injury was diagnosed in AKI
eGFR <60ml/min (green) and >60ml/min (blue) at hospital discharge. patients with a final creatinine measurement of >1.3 times the baseline value.
RESULTS: Out of 676 patients receiving checkpoint inhibitors, AKI occurred in 96
(14.2%) patients. Chart review showed that AKI was checkpoint inhibitor-associated in
32 (4.7%) patients. Baseline variables associated with AKI were a primary gynecological
Adjusted multivariable analysis demonstrated that age (HR 1,01 [CI95% 1,00-1,02],
malignancy (HR 3.91, 95% CI 1.55 to 9.85), treatment with checkpoint inhibitor
p=0,009) and the presence of eGFR inferior to 60 ml/min/1,73 m2 (HR 1,45 [CI95%
ipilimumab (HR 2.31, 95% CI 1.03 to 5.20), and pre-existent use of a diuretic (HR 2.61,
1,04-2,02], p=0,02) were independent predictors of infection after AKI episode.
95% CI 1.21 to 5.60), an angiotensin-converting enzyme inhibitor or angiotensin-
CONCLUSION: The existence of eGFR inferior to 60 ml/min/1,73 m2 after an
receptor blocker (HR 2.49, 95% CI 1.10 to 5.60), and a proton pump inhibitor (HR
hospitalization with AKI shows an independent association with presenting an
1.69, 95% CI 1.04 to 2.75). In 35.4% of the patients who had developed AKI, persistent
infection afterwards.
kidney dysfunction was observed at the end of follow-up. Patients who developed AKI
had a 2.13-fold (95% CI 1.58 to 2.87) increased mortality risk compared to patients
who did not develop AKI. Mortality risk was not increased by checkpoint inhibitor-
MO362 CHECK- POINT INHIBITORS AND THEIR KIDNEY associated AKI (HR 1.11, 95% CI 0.64 to 1.92), but only by AKI related to other causes
INVOLVEMENT (HR 2.87, 95% CI 2.04 to 4.04).
CONCLUSION: Patients receiving checkpoint inhibitors frequently develop AKI,
however, checkpoint inhibitor-associated AKI does not seem to increase mortality.
Tania Villagrasa1, José Luis Garcia1, Sonia Cleofe Jimenez Mendoza1, Mario Lado
Fuentes1, Paloma Livianos Arias-Camiso n1, Maria Giovanna Dangelo1, Maria
Antonia Munar Vila1, Aitor Azkarate2, Barbara Boyeras3, Gonzalo Gomez
Marques1 MO364 ASSOCIATION OF AKI-EVENT DEFINED BY DIFFERENT
1
Hospital Universitari Son Espases, Nephrology, Palma, Spain, 2Hospital Son Espases, DEFINITIONS WITH IN-HOSPITAL MORTALITY
Oncology, Palma de Mallorca, Spain and 3Hospital Universitari Son Espases, Pharmacy,
Palma, Spain Fateme Nateghi1,2, Konstantinos Makris3, Pierre Delanaye4, Hans Pottel1
1
KU Leuven, Campus KULAK , Department of Public Health and Primary Care, Kortrijk,
BACKGROUND AND AIMS: Monotherapy immunotherapy with “check-point Belgium, 2ITEC - imec and KU Leuven, Kortrijk, Belgium, 3KAT General Hospital, Clinical
inhibitors” (anti PD-1, Anti PD-L1) is an effective therapy to advanced-stage cancer biochemistry Department, Athens, Greece and 4University of Liège, Department of
patients. Little is known about our experience and its renal implication, although it is Nephrology, Dialysis, Hypertension, Transplantation, Liège, Belgium
related to fluid and electrolyte disorders or acute kidney failure (AKI).
To evaluate changes in natremia or acute renal impairment (primary endpoints) in IV BACKGROUND AND AIMS: Studies have shown that millions of hospitalized
stage cancer patients with lung, bladder or melanoma neoplasm who have received patients suffer from Acute Kidney Injury (AKI) per year which increases mortality risk
monotherapy with pembrolizumab (PEM), atezolizumab (ATZ) or nivolumab (NIV). for these patients. Different definitions for AKI have been proposed during the past
At the same time, analyze if there are differences between drug administered, years such as RIFLE (2002) and AKIN (2004). In 2012, KDIGO published a clinical
underlying disease or having received cisplatin previously (secondary outcomes). practice guideline harmonizing AKIN and RIFLE into one general guideline which
METHOD: single-center retrospective analysis. Inclusion period: January 2015 to classifies AKI into 3 stages, where stage 1 is defined as an absolute increase of SCr  0.3
September 2020. Dose administered: PEM 2mcg/kg/21 days; ATZ 1200mg/21 days; mg/dl over 48 hours or a relative increase in SCr  50% from baseline within the
NIV 3mg/kg/ 21 days. Changes in natremia and GFR (CDK-EPI) were evaluated in previous 7 days. A recent study [Sparrow et al., 2019] evaluated the impact of further
0,1,3 months of follow-up. Patients with combined chemotherapy were excluded. categorizing AKI stage 1 into 2 stages based on SCr criteria. The study separates
RESULTS: 137 patients were included. Mean age: 64 years. Men: 71.6%. Neoplasm: KDIGO AKI stage 1 and AKIN stage 1 into 2 stages (KDIGO-4 and AKIN-4) based on
lung (76.8%), bladder (7.2%), melanoma (15.9%). Patients received 27.5% PEM; 26.1% the different SCr criteria. Having different AKI definitions makes it challenging to
ATZ; 46.4% NIV. Between all of them, 76% had received platinum previously. Up to analyze AKI incidence and associated outcomes among studies. The present study
13.6% developed hyponatremia and 12.40% AKI 3 months later. The decrease in GFR aimed to investigate the incidence of AKI events defined by 4 different definitions
was significantly greater in bladder neoplasm (mean GFR 42ml / min / m2 p <0.01) at (standard AKIN and KDIGO, and modified AKIN-4 and KDIGO-4) and its
three months. Bladder cancer was also the most frequent (but not significant) in association with in-hospital mortality.
reduced natremia (mean Na 135mEq / L p = 0.08). There were no differences METHOD: Retrospective clinical data available for all adult (18 years old) hospital
according to drug administration or having received platinum previously. 61% were admissions to a local health district in Athens, Greece between October 1999 and
death, but none of them due to a renal event. March 2019 was used in the analysis. We excluded patients whose time between
CONCLUSION: admission and discharge was less than 7 days. Also, patients with less than 5 Scr
measurements were omitted from the analysis resulting in the final cohort of 7242
• The longer follow-up period, the greater kidney disorders were observed. admissions. We used the AKIN, KDIGO, AKIN-4, and KDIGO-4 definitions to check
• The most significantly associated neoplasm with reduced GFR was the bladder the incidence of AKI. As our second goal, we assessed associations of AKI-events with
one. in-hospital mortality, adjusted for characteristics (age, sex, AKI staging) using
multivariable logistic regression.
• There are no significant differences in receiving cisplatin previously or the kind of
RESULTS: The incidence of in-hospital AKI using the modified KDIGO-4 was 6.72%
drug administered in both, natremia and GFR.
for stage 1a, 15.71% for stage 1b, 8.06% for stage 2, and 2.97% for stage 3; however,
these percentages for AKIN-4 were 11.5%, 5.83%,1.75%, and 0.33% for stage 1a, stage
1b, stage 2, and stage 3, respectively. Using the standard KDIGO and AKIN definition,
19.08 and 14.05 % developed stage 1, respectively. To find the association between AKI
stages and in-hospital mortality, we considered the most severe stage of AKI reached

10.1093/ndt/gfab082 | i251
Abstracts Nephrology Dialysis Transplantation

by a patient. Results of logistic regression models show that in-hospital mortality quickly (19 vs 48 days, log-rank test; p=0.01). In patients with uMCP-1 >1354 pg/mg-Cr,
increased as the stage of AKI events increased for both KDIGO-4 and AKIN-4 (Table they also died more quickly, but with no significance (25 vs 48 days, log-rank test; p=0.08).
1). Table 2 shows the same results using the original KDIGO and AKIN definitions. CONCLUSION: Urinary biomarkers NGAL and MCP-1 quantified at hospital
CONCLUSION: The results of both definitions (AKIN-4 and KDIGO-4) show a admission were associated with poor outcomes, mostly with needed of invasive
significant association with mortality, but KDIGO-4 has a larger odds ratio meaning respiratory support in ICU. Prediction cut-off values for invasive respiratory support
that AKI classification based on KDIGO-4 has a stronger association with mortality was useful to determine the survival prognosis.
than AKI classification based on AKIN-4. However, based on our results, splitting stage
1 to stage 1a and stage 1b does not seem to make a difference; hence, using KDIGO-4
as a replacement for KDIGO would not have a significant impact on capturing AKI
MO366 CONCORDANCE BETWEEN FIVE CLASSIFICATION
events.
SYSTEMS OF COMMUNITY-ACQUIRED ACUTE KIDNEY
INJURY
MO364 Table 1 Association between AKI-stages using KDIGO-4 and AKIN-4 and
in-hospital mortality Jose Maria Pen ~a Porta1, José Antonio Ferreras Gasco 1, Almudena Castellano
Calvo1, Ana Coscojuela Otto1, Paula Juarez Mayor1, Rafael Alvarez Lipe1
1
KDIGO-4 AKIN-4 Hospital Clinico Universitario Lozano Blesa, Nephrology, Zaragoza, Spain
Odds ratio 95% CI Odds ratio 95% CI
BACKGROUND AND AIMS: In recent years, up to five classification systems have
Intercept 0.018 0.010 - 0.030 0.027 0.016 - 0.044 appeared according to the severity of acute kidney injury (AKI), some based on relative
Age 1.006 0.999 - 1.013 1.006 1.000 - 1.013 increases in creatinine (RIFLE, AKIN, KDIGO) and others in absolute increases: the
Sex (Male) 1.272 1.042 - 1.552 1.298 1.075 - 1.567 kinetic method of creatinine (KC) and delta creatinine (DC) method. It is discussed in
the literature which methodology offers better diagnostic performance.
Stage 1a 4.689 2.978 – 7.156 10.381 8.254 – 13.049 The aim of this study was to analyze the concordance using the Kappa index of the 5
Stage 1b 11.863 9.284 – 15.179 22.753 17.780 – 29.178 classification systems in a cohort of patients with community-acquired AKI (CA-AKI)
treated in the Nephrology Service of a tertiary hospital.
Stage 2 39.794 30.614 – 51.956 24.281 16.536 – 35.821
METHOD: All the CA-AKI cases admitted to our service in the period: January 2010 -
Stage 3 62.884 45.227 – 88.237 37.448 16.062 – 94.035 December 2016 were analyzed.
RESULTS: 536 patients (59,9% male) of 73.13 6 13,6 years of age. Etiology of AKI:
prerenal 72.8%; renal 20.5%; obstructive 6.7%. 69.6% of patients were carriers of
MO364 Table 2 Association between AKI-stages using KDIGO and AKIN and previous chronic kidney disease (CKD-EPI glomerular filtration <60 ml/min). The
in-hospital mortality. table shows the Kappa index among the various classification systems. Agreement was
absolute (Kappa = 1) between the three systems based on percentage increase in
creatinine. When comparing KDIGO with CK and DC, the agreement was much lower
KDIGO AKIN (Kappa 0.35). Concordance between CK and DC was good (Kappa = 0.84). These last
Odds ratio 95% CI Odds ratio 95% CI two systems classify a greater number of stage 3 cases compared to KDIGO, while
Intercept 0.019 0.011 - 0.032 0.031 0.019 - 0.050 KDIGO classifies more cases as stage 1 (Stage 1: KDIGO 89, KC 27; DC 19; Stage 2:
KDIGO 56, KC 56; DC 54; Stage 3: KDIGO 391, CK 453; DC 463)
Age 1.006 0.999 - 1.012 1.005 0.999 - 1.011
Sex (Male) 1.22 1.002 - 1.486 1.248 1.036 – 1.504
Stage 1 9.725 7.702 – 12.30 14.671 12.144 – 17.759
Stage 2 39.72 30.548 – 51.865 24.482 16.677 - 36.112 RIFLE AKIN KDIGO Kinet. Creat. Delta
Stage 3 62.675 45.143 – 87.801 37.593 16.139 - 94.327 Creat.
RIFLE - 1 1 0,406 0,351
AKIN 1 - 1 0,406 0,351
MO365 URINARY BIOMARKERS AND POOR OUTCOMES IN KDIGO 1 1 - 0,406 0,351
PATIENTS WITH COVID-19 ADMITTED TO A REFERENCE Kinet. Creat 0,406 0,406 0,406 - 0,841
HOSPITAL IN NORTHEAST BRAZIL
Delta Creat 0,351 0,351 0,351 0,841 -
Gdayllon Cavalcante Meneses1, Gabriela Freire Bezerra1, Lana Andrade Lucena
Lima1, Izabel Cristina Justino Bandeira1, Nicole Coelho Lopes1, Ma rcia
Maria Pinheiro Dantas2, Sandra Maria Brasileiro Mota2, Polianna Lemos Moura
Moreira Albuquerque2,3, Alice Maria Costa Martins1, Elizabeth De Francesco
Daher1, Geraldo Bezerra da Silva Junior3
1
a, Fortaleza, Brazil, 2Toxicological Assistance Center,
Federal University of Cear
Instituto Dr Jose Frota Hospital, Fortaleza, Brazil and 3University of Fortaleza, Fortaleza,
Brazil

BACKGROUND AND AIMS: Kidney biomarkers improve early and specific AKI
detection and also poor outcomes in different clinical contexts. Kidney disease is an
important risk factor for poor outcomes in COVID-19. The aim of this study was to
evaluate association of early levels of kidney biomarkers with poor outcomes in
hospitalized patients with COVID-19.
METHOD: This is a prospective study conducted at the Instituto Dr. Jose Frota
Hospital, an important public reference hospital for COVID-19 in northeast Brazil.
Medical records with clinical, epidemiologic, laboratory and outcomes were collected.
The urinary NGAL, KIM-1, MCP-1 and nephrin were the kidney biomarkers
quantified at hospital admission. ELISA assays were used for analysis and biomarkers
urinary concentrations were adjusted for urinary creatinine. Data were expressed as
mean6 standard deviation or median.
RESULTS: A total of 69 patients collected urine and were included in this study. Male
gender was predominant (65%) and mean age was 56619 years. Regarding outcomes, the
group had 62% of death, 92% of ICU admission and 65% of invasive respiratory support in
ICU. Urinary NGAL and MCP-1 were significantly elevated in patients that needed invasive
respiratory support in comparison with non-invasive support: uNGAL (median=104
[IQR=74-153] vs 71 [31-79] ng/mg-Cr, p=0.013), and uMCP-1 (3055 [1127-5008] vs 1315
[574-2127] pg/mg-Cr, p=0.027). Urinary nephrin and KIM-1 was also elevated, however
with no statistical significance. Moreover, all urinary biomarkers were higher in ICU
admission group and death group, but with p>0.05. In ROC curve analysis for prediction of
invasive respiratory support, uNGAL had AUC=0.696 (0.565-0.827),p=0.012 and cut-off=78
ng/mg-Cr; uMCP-1 had AUC=0.676 (0.539-0.813), p=0.023 and cut-off=1354 pg/mg-Cr. In
survival analysis, patients with uNGAL >78 ng/mg-Cr had worse prognosis and died more

i252 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: KDIGO system is valid as a reference system with respect to AKIN were evaluated with the univariate and multivariate analyses.
and RIFLE. Systems based on absolute increases in creatinine tend to classify fewer RESULTS: A total of 147 patients were included in the analyses. Median age was 61
cases as mild and more cases as severe than systems based on relative increases in [interquartile range (IQR) 51-67], and 69.4% of the patients were male. Patients were
creatinine. It remains to be seen what is the practical significance of these discrepancies given a median of 8 (IQR 5-17) ICI cycles. Patients with melanoma (24.5%), non-small
in the clinical management of AKI patients. cell lung cancer (15%), and renal cell carcinoma (25.9%) comprised almost 2/3 of the
cohort and 72.8% of the patients were treated with nivolumab. Hypertension was the
most common comorbidity (38.1%), followed by chronic kidney disease (21.2%) and
type 2 diabetes (19.7%). Median Charlson Comorbidity Index (CCI) was 8 (7-9).
MO367 USEFULNESS OF ECHOCARDIOGRAPHIC PARAMETERS IN
Median follow-up was 10.3 (IQR 6.3-19.4) months, and patients had median 9 (IQR 5-
LONG - TERM CARDIOVASCULAR EVENTS AFTER AN
18) serum creatinine measurements. During the follow-up, 28 patients (19%) had at
ACUTE KIDNEY INJURY EPISODE
least one AKI episode with multiple AKI episodes in 3 patients (10.7%). The median
time to AKI development was 2.53 (IQR 1.39-6.19) months. Almost all AKI events
Alicia Cabrera1, Laura Salanova Villanueva1, Ana Sanchez1, Patricia Mun
~oz
were mild (grade 1 or 2 in 27/28) and reversible (25/28). In univariate analyses,
Ramos1, Pablo Ruano1, Borja Quiroga1
1
coronary artery disease (CAD) (p=<0.001), chronic kidney disease (CKD) (p=0.002),
Hospital de La Princesa, Nephrology department, Madrid, Spain previous nephrectomy (p=0.015), iodinated contrast exposure in the week before
immunotherapy (p=0.035), the use of renin-angiotensin-aldosterone system inhibitors
BACKGROUND AND AIMS: Acute kidney injury (AKI), a frequent condition during (p=0.046) or proton pump inhibitors (PPI) (p=0.041) was associated with an increased
hospitalizations, leads to an increase morbidity and mortality. Cardiovascular events AKI risk. The association between diabetes (p=0.067), higher CCI (9 vs. 9, p=0.107),
are one of the most post-AKI studied complications, but the role of the baseline baseline lactate dehydrogenase levels (p=0.177), and performance status (ECOG 0 vs.
functional and structural cardiac alterations on prognosis has not been widely studied. 1, p=0.235) and AKI risk did not reach statistical significance. In multivariate
The aim of the present study is to evaluate the prognostic value of echocardiographic analyses, patients with CKD (OR: 3.719, 95% CI: 1.375- 10.057, p=0.010) or CAD (OR:
parameters in the incidence of cardiovascular events (CVE) after a hospitalization- 4.774, 95% CI: 1.803- 12.641, p=0.002) had increased AKI risk. Additionally, regular
acquire AKI. PPI use (OR: 2.734, 95% CI: .991- 7.542, p=0.052) had borderline statistical significance
METHOD: In this is retrospective observational cohort study 1255 patients who for AKI development. The development of AKI was not associated with decreased
presented AKI from 2013 to 2014 at our center were included. Baseline epidemiological survival (HR: 0.726, 95% CI: 0.409-1.291, p=0.276).
data, comorbidities and echocardiographic parameters were collected. After discharge, CONCLUSION: In this study, we observed AKI development under ICIs in almost
patients were followed (mean 49628 months) and post-AKI CVE were registered. In one in five cancer patients. The increased AKI rates in patients with CAD, CKD, or
addition, new performed echocardiograms after discharge were collected. Associated regular PPI use pointed out the need for better onco-nephrology collaboration in all
factors to CVE and the predictive role of echocardiographic parameters were analyzed. ICI-treated patients, with a particular emphasis in these high-risk patients.
RESULTS: Among the 1255 included patients, 676 (54%) had a registered
echocardiogram in the six months before the AKI episode. Of them, 231 patients
(38%) had left ventricle hypertrophy (LVH), 178 (30%) pulmonary hypertension
MO369 ACUTE KIDNEY INJURY IS ASSOCIATED WITH ELEVATED
(PHT), 178 (30%) diastolic dysfunction and 138 (21%) systolic dysfunction. After
AMINOTRANSFERASES AT ADMISSION IN HOSPITALIZED
discharge (and prior to post-AKI CVE), 248 (20%) patients had a new echocardiogram
PATIENTS WITH COVID-19
that revealed LVH in 108 patients (45%), diastolic dysfunction in 96 (42%), PHT in 68
(32%) and systolic dysfunction in 47 (19%).
Yulia Khruleva1, Olga Arisheva1, Elena Troitskaya1, Marina Efremovtseva1,
During follow-up, 484 (39%) patients had CVE. The presence of diastolic dysfunction,
Zhanna Kobalava1
systolic dysfunction, PHT and LVH in any moment were associated factors to the 1
incidence of CVE. An adjusted multivariate model showed that systolic dysfunction Peoples’ Friendship University of Russia, Internal Medicine, Moskva, Russia
(hazard ratio [HR] 1.44, 95% confidence interval [95%CI] 1.073-1.943, p=0.015), age
(HR 1.018, 95%CI 1.003-1.030, p=0.02), diabetes mellitus (HR 1.373, 95%CI 1.041- BACKGROUND AND AIMS: Initial reports indicate a high incidence of abnormal
1.811, p=0.025), atrial fibrillation (HR 1.397, 95%CI 1.055-1.851, p=0.020) and diuretic liver tests and acute kidney injury (AKI) in the novel coronavirus infection (COVID-
intake (HR 1.580, 95%CI 1.171-2.131, p=0.003) were independent predictors of post- 19). However, outcomes in hospitalized patients with COVID-19 and elevated
AKI CVE. aspartate transaminase (AST) and alanine transaminase (ALT) levels at admission and
CONCLUSION: The evaluation of cardiac structure and functionality valued by their associations with AKI are not well understood.
echocardiographic parameters can be a useful tool for stratifying CVE risk after an The aim of the study was to investigate the incidence of cytolysis at admission and its
AKI. Systolic dysfunction is an independent predictor of post-AKI CVE. contribution to the development of AKI, severity of COVID-19 and outcomes.
METHOD: A retrospective analysis of the register of patients hospitalized with
COVID-19 was performed (n=481). COVID-19 was defined as the laboratory-
confirmed infection and/or presence of the typical computer tomography (CT) picture.
MO368 THE INCIDENCE AND RISK FACTORS FOR ACUTE KIDNEY
We excluded patients with previously known liver disease, re-hospitalization, acute
INJURY IN PATIENTS TREATED WITH IMMUNE
surgical pathology, single serum creatinine measurement during hospitalization.
CHECKPOINT INHIBITORS: A REAL-LIFE STUDY
Abnormality in aminotransferases was defined as ALT and/or AST >40 U/L.
Definition of AKI was based on KDIGO criteria. P value <0.05 was considered
Deniz Can Güven1, Deniz Aral Ozbek2, Taha Koray Sahin2, Melek Seren Aksun2,
statistically significant.
Gozde Kavgaci2, Cebrayil Cebrayilov3, Tolga Yildirim3, Omer Dizdar1,
RESULTS: 462 patients were included (50.4% males, mean age 63616 years, mean
Sercan Aksoy1, Saadettin Kilickap1, Suayib Yalcin1, Mustafa Erman1,
Charlson index 362.4, 67% with hypertension, 48% with obesity, 25% with diabetes
MUSTAFA ARICI3
1
mellitus). 26,4% (122) of patients were hospitalized in the intensive care unit (ICU),
Hacettepe University Cancer Institute, Department of Medical Oncology, Ankara, 71,3% (87) of them were treated with mechanical ventilation. The median length of
Turkey, 2Hacettepe University Faculty of Medicine, Department of Internal Medicine, stay was 11 [9;15] days, in the ICU – 4 [2;9] days. 20% (92) of patients died.
Ankara, Turkey and 3Hacettepe University Faculty of Medicine, Department of At admission 43% (200) of the patients had abnormal level of aminotransferases.
Nephrology Elevated AST was more common than ALT, (39% (178) vs 29% (132)). The median
levels of AST and ALT at admission were 54.5[44;72] and 45.9[34;66] U/L in the group
BACKGROUND AND AIMS: The immune checkpoint inhibitors (ICIs) became a with cytolysis and 26[19;33] and 19[11;27] U/L in the group without it, respectively.
vital part of cancer treatment. The ICIs seem to be safer than chemotherapy for kidneys The AKI incidence in the register was 24.8%. The 1st stage of AKI was observed in the
in clinical trials. However, recent observational studies from high-resource settings majority of the patients (46% - 1st stage, 36% - 2nd stage, 18% - 3rd stage. Patients in
pointed out the possible underreporting of renal adverse events like acute kidney injury ICU compared to non-ICU patients more often had AKI (50% vs 13%, p<0.001). In-
(AKI) in the clinical trials due to focusing only to the renal immune-related adverse hospital mortality was significantly higher in the group with AKI (54% vs 10% for
events. Additionally, clinical trials generally enroll a fitter population with lesser patients with and without AKI development, respectively, p<0.001).
comorbidities and include mostly treatment-naive patients making studies in real-life Groups with and without aminotransferases elevation were similar in age, gender,
cohorts imperative for evaluating the AKI rates during ICI treatment. From these presence of comorbidities, coagulation status, statins and frequency of antibiotic intake
points, we aimed to evaluate the AKI rates and predisposing factors in ICI-treated before admission. Increase in AST and/or ALT levels at admission showed no
patients. association with AKI severity. The higher incidence of elevated ALT or/and AST was
METHOD: This retrospective study has evaluated the data of adult metastatic cancer observed in ICU compared with non-ICU patients (59% vs 37%, p<0.001). Patients
patients treated with ICIs in Hacettepe University Cancer Center from 01.2014 to with elevation of aminotransferases at admission compared to patients without it had
12.2019. All patients other than the ones treated within the context of clinical trials or more severe lung injury by CT scan (22.4% vs 18.6%, with 50-75% lung injury; 5.5% vs
followed in other institutions after the first dose of ICIs were included. Baseline 0.4% with 75-90% lung injury, p=0.008 for the trend), higher ferritin (598[404;715] vs
demographics, cancer types, patient weight and heights, ICI type and the number of 391[189;587] mkg/l, p=0.03) and serum creatinine levels (91[78;118] vs 86[74;109]
cycles, serum creatinine and the estimated GFR values under treatment, regular mmol/l, p=0.008), higher rate of AKI development (29% vs 18%, p=0.005) and in-
medications, and comorbidities were recorded. AKI was defined by Kidney Disease hospital mortality (26% vs 15,4%, p=0.005). Elevated ALT and/or AST at admission
Improving Global Outcomes criteria. The predisposing factors to AKI development were the independent predictors for the development of AKI (OR 1.87 95%CI 1.17-

10.1093/ndt/gfab082 | i253
Abstracts Nephrology Dialysis Transplantation

2.92, p=0.005) and in-hospital mortality (OR 1.89 95%CI 1.17-3.08, p=0.006). day. Early AKI was related to pre-renal causes and had a milder course. However, later
CONCLUSION: Syndrome of cytolysis is common among hospitalized patients with AKIs were more related to immunologic response and had significantly higher
COVID-19. Development of AKI and disease severity were associated with elevated mortality. Patients who died had significantly higher ferritin and d-dimer levels upon
levels of aminotransferases at admission, and are predictors for AKI development and their hospital admissions (p=0,000). Electrolyte disturbances, metabolic acidosis and
in-hospital mortality in this population. mortality were also higher in patients who developed AKI later. Hypernatremia (OR:
6,5, 95% CI: 3 – 13,9) and phosphorus disturbances (both hyperphosphatemia (OR:
3,3; 95%CI: 1,6 – 6,9) and hypophosphatemia (OR: 3,9; 95% CI: 2,0-7,9)) were related
to mortality.
MO370 PREGNANCY-RELATED ACUTE KIDNEY INJURY IN TUNISIA:
CONCLUSION: Findings of this study suggest that AKI in COVID-19 is not of one
A CLINICAL CHALLENGE
kind. When developed, AKI should be evaluated in conjunction with the disease stage
and possible etiologies
Menel Msehli1, Hela Jbali1, Mami Ikram1, Badreddine Ben kaab1, Fethi Ben
hamida2, Lamia Rais1, LILIA BEN FATMA1, ZOUAGHI KARIM1
1
Rabta Hospital, Department of Nephrology, Tunis, Tunisia and 2Charles Nicolle
Hospital, Laboratory Research of Kidney Pathology, tunis, Tunisia MO372 IN-HOSPITAL MORTALITY IN ACUTE CARDIAC DISEASES IS
ASSOIATED WITH CERTAIN PHENOTYPES OF ACUTE
KIDNEY INJURY
BACKGROUND AND AIMS: Acute kidney injury (AKI) is a complex disorder that
occurs in several clinical settings. During pregnancy, there are additional unique
Marina Efremovtseva1,2, Svetlana Avdoshina1,3, Zhanna Kobalava3
conditions that contribute to AKI. The clinical manifestations of Pregnancy related 1
acute kidney injury(PRAKI) range from a minimal elevation in serum creatinine to Moscow, Department of Internal Medicine, Moscow, Russia and 2Peoples’ Friendship
severe renal failure requiring renal replacement therapy and may be associated with University of Russia (RUDN University), Department of Internal Medicine, Moscow,
significant morbidity and mortality in young healthy women. This study aims to Russia
describe epidemiologic features, study clinical profile and outcomes of women with
PRAKI and identify risk factors related to requiring hemodialysis among patients. BACKGROUND AND AIMS: Impaired renal function is a common finding in
METHOD: We performed a retrospective study over a 5-year period (2015–2019) in a patients with cardiac diseases and confers an adverse prognosis in this population. To
Tunisian intensive care unit. All patients presenting PRAKI were included. evaluate the incidence, phenotypes and prognostic value of cardiorenal interrelations in
RESULTS: Ninety-six cases of PRAKI were listed. The rate of AKI during pregnancy- patients with acute decompensated heart failure (ADHF) and non-ST-elevation acute
related hospitalizations was 16% .the average age was 31 6 5 years. coronary syndrome (NSTE-ACS).
Most women were from urban areas (62%) but with insufficient prenatal care METHOD: we examined 278 patients with ADHF (85.3% had anamnesis of
(57%).Seventy-eight percent underwent cesarean section delivery. symptomatic HF with frequent hospitalizations, 20.1% had ejection fraction <35%)
PRAKI occurred in the postpartum in 79%of the cases. Oligo-anuria was the most and 288 with NSTE-ACS (64.9% developed myocardial infarction (MI)). In ADHF
common clinical feature of PRAKI, noted in 82% of our patients. group in comparison with NSTE-ACS the patients were younger (69.7610.2 vs
The leading etiological causes were pre eclampsia, eclampsia, postpartum haemorrhage 72612.1 years, p<0.01), there were more males (55.4 vs 36.5%, p<0.001), smokers and
and sepsis respectively, in 49%, 38%, and 24% of the cases. alcohol abusers (47.8 and 30.6% vs 8 and 5.6%, p<0.001). The comorbidities were
Hemodialysis was required in 23% of cases. In the adjusted regression analysis, factors more typical for ADHF group: atrial fibrillation 46 vs 24% (p<0.001), obesity 55.8 vs
associated with dialysis were insufficient prenatal care (p=0,010 ; O Ra=24,113), 30.9% (p<0.001), anemia 40.6 vs 25.3% (p<0.001), diabetes mellitus 33.1 vs 23.3%
HELLP syndrome (p=0,003 ; ORa=35,129), disseminated intravascular coagulation (p<0.01).
(p=0,007 ; OR=11,854), average duration of oliguria (p=0,001; ORa=3,025) , Failure Chronic kidney disease (CKD) and acute kidney injury (AKI) were diagnosed
stage of RIFLE criteria while admitted (p=0,009; ORa=2,09) and length of ICU stay according to KDIGO 2012 Guidelines. AKI phenotypes were identified depending on
(p=0,042 ; ORa=1,118). time of development (community- or hospital-acquired), persistency (transient or
Renal outcome was favorable, with a complete renal function recovery for 72 patients persistent), history of CKD (AKI de novo or AKI on CKD).
(75%). Only four patients (4%) developed chronic renal failure. Mortality rate was 13%. RESULTS: Incidence of CKD in patients with ADHF and NSTE-ACS was 45 and
CONCLUSION: PRAKI is a dreaded complication of pregnancy with high morbidity 46.5%, CKD was first diagnosed on admission in 57.6 and 64.2% of patients
and mortality. Prevention of PRAKI requires an improvement of the sanitary respectively. In 7.6% cases of ADHF and 14.2% of NSTE-ACS groups the duration of
infrastructures with the implementation of an obligatory prenatal consultation in order impaired kidney function was unknown. No associations of existing CKD and in-
to prompt management of the underlying risk factors hospital mortality were detected.
Incidence of AKI in ADHF and NSTE-ACS groups was 43.5 and 37.2%. The hospital-
acquired AKI, AKI on CKD and persistent AKI were found in 52.9, 47.9 and 46.3% of
ADHF patients, and in 57.9, 58.9 and 50.5% in NSTE-ACS group respectively. In-
MO371 TIME AND THE ETIOLOGY OF ACUTE KIDNEY INJURY
hospital mortality was higher in patients with AKI in ADHF and NSTE-ACS groups
DEFINE PROGNOSIS IN THE COURSE OF COVID-19
(12.4 vs 5%, p<0.01 and 17.8 vs 3.3%, p<0.001). Mortality in patients with ADHF and
hospital-acquired persistent AKI de novo and community-acquired persistent AKI on
Ahmet Murt1, Mevlut Tamer Dincer1, Cebrail Karaca1, Sinan Trabulus1,
CKD was 41 and 29%, and in community-acquired transient AKI on CKD in the
Nurhan Seyahi1, Mehmet Riza Altiparmak1
1
NSTE-ACS group – 29%.
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Nephrology, Istanbul, CONCLUSION: Different cardiorenal interrelations were revealed in 75.2% of patients
Turkey with ADHF and in 61.8% with NSTE-ACS. In patients with acute cardiac diseases high
in-hospital mortality is tightly associated with phenotypes of hospital-acquired
BACKGROUND AND AIMS: Kidneys are among the affected organs in COVID-19 persistent AKI de novo and community-acquired persistent AKI on CKD in ADHF,
and there may be different etiologies resulting in acute kidney injury (AKI) in different and in community-acquired transient AKI on CKD in the NSTE-ACS.
stages of the disease. There have been previous studies focusing on incidence and
mortality of AKI in COVID-19 but none has made in depth analysis in relation to the
background pathophysiology. Based on previous observations, we hypothesized that all
MO373 EXPERIENCE OF EXTRACORPOREAL BLOOD PURIFICATION
AKIs seen in COVID-19 are not uniform and we aimed to analyze the etiologies and
METHODS APPLICATION TO PATIENTS WITH SEVERE
prognosis of AKI among hospitalized COVID-19 patients in relation to the time of
COVID - 19
AKI during different phases of the disease.
METHOD: A total of 1056 patients were admitted to the designated COVID-19 clinics
Nilufar Jabayeva1, Aidyn Kuanyshbek2, Timur Kapyshev2, Timur Lesbekov3,
from March to July in 2020. 77 Patients who were younger than 18 years old and 7
Bolat Bekishev1, Tatyana Li2
kidney transplant patients were excluded from the study. 427 of the remaining patients 1
were confirmed by real time polymerase chain reaction (RT-PCR) test.). As eGFR National Research Cardiac Surgery Center, laborotory of extracorporeal hemocorrec-
below 60 mL/min/1,73 m2 was already shown to be related to mortality, these patients tion, Nur-Sultan, Kazakhstan, 2National Research Cardiac Surgery Center, ICU, Nur-
(44) were also excluded. As immunologic response is generally accepted to start with Sultan, Kazakhstan and 3National Research Cardiac Surgery Center, head of cardiac
the second week of COVID-19 course, patients were classified into three groups, those surgery, Nur-Sultan, Kazakhstan
who had AKI on admission, those who developed AKI in the first week and those who
developed AKI starting from 7th day. Initial lymphocyte counts, creatinine levels, BACKGROUND AND AIMS: In the rapidly changing conditions of life due to the
electrolytes, acid-base status and changes in the inflammatory markers were compared COVID - 19 pandemic, the medical society around the world have faced with the
between the groups. A comparison between patients who survived and who died was question of treatment previously unknown, multi-faceted and insidious infection. The
also performed. coronavirus infection has forced doctors to reconsider the tactics of intensive care
RESULTS: 89 of the 383 included COVID-19 patients developed AKI. 24% of those patients in critical condition. To date, overall mortality rate from COVID – 19 varied
who developed AKI died. Patients who developed AKI later had higher peak CRP and from 8.11 to 120.85 per 100.000 population (Johns Hopkins University mortality
D-dimer levels with lower nadir lymphocyte counts (p=0,000, 0,004 and 0,003 analyses). Mortality rate in extremely severe cases exceeds 60% - 78% (Yang et al.,
respectively). Additionally, patients who died had higher initial inflammatory marker Lancet Respiratory Medicine, 2020. Zhou et al., Lancet, 2020).
levels and lower lymphocyte counts than those who survived. Mortality of patients who We would like to share our clinical experience of extracorporeal blood purification
had AKI on hospital admission (13%) was similar to the overall COVID-19 mortality methods application to patients in ICU with various clinical manifestations, as well as
for inpatients, however it was as high as 44% for those who developed AKI after 7th the presence of comorbid pathology.

i254 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: We conducted a retrospective analysis of 239 medical records of patients
hospitalized in the ICU of JSC NRCSC Nur-Sultan, Kazakhstan because of severe
course of COVID 19. Period of hospitalization from 16.06.2020 to 29.09.2020, the total
number of beds - 97, in the ICU - 25. Laboratory Before After After After p
RESULTS: The total number of patients with COVID -19 - 239 patients. In ICU -67
patients. Patients required in renal replacement therapy (RRT) – 31 patients. data blood the 1st the 2nd the 3d value
Among patients on RRT males-28 (90.3%) - female-3 (9.67%). purification procedure procedure procedure
Mean age-60 years.
Distribution of the comorbid pathology.
Leukocyte 15.30 13.31 10.68 8.23 0.01
CRP 17.91 16.12 14.10 13.02 0.02
Il - 6 260.77 205.82 201.188 188.9 0.027
PCT 26.58 12.13 4.34 5.56 0.01
Creat 2.33 1.77 1.89 1.34 0.01
NO Comorbid pathology N = 31 Presepsin 2420.24 2788.81 1783.56 2063.41 0.18
Diabetes insipidus 10 (32,2%) General Mortality – 37 from 239 (15.5%)
Sepsis 5 (16.1%) Mortality in ICU – 37 from 67 (55.2%)
MODS 6 (19.3%) According to literature review, the mortality rate of patients with severe COVID - 19 in
the ICU (Fawad Rahim et al, Cureus . 2020 Oct 12;12(10):e10906. doi: 10.7759/
Acute kidney damage 2 (KDIGO 2018) 9 (29%) cureus.10906.) without the use of CRRT exceeds 70-77%.)
Acute kidney damage 3 (KDIGO 2018) 5 (16.1%) CONCLUSION: Our analysis had showed a positive effect of early use (1 day of
hospitalization) of extracorporeal methods of blood purification, on a decreasing of
Anuria 11 (35.48%)
inflammation indicators, as well as positive survival rate of patients with severe
Acute respiratory failure 3 24 (77.4%) COVID-19 course in ICU conditions.
ARDS 19 (61.29%)
Artificial lung ventilation 28 (90.32%)
MO374 DISCLOSURE OF THE RESULTS OF A 40-YEARS RESEARCH
COPD 3 (9.67%)
OF UPPER TRACT UROTHELILAL CANCER AND BALKAN
Hypertension 9 (29%) ENDEMIC NEPHROPATHY
Ischemic heart disease 6 (19.3%)
Stevan Glogovac1, Zorica Dimitrijevic1, Miomir Stojanovic1, Danijela Tasic1,
Obesity 9 (29%) Karolina Paunovic1, Miomir Prokopovic2, Stanimir Ljubenovic1,
Cytokine storm 19 (61.29%) Branislav Apostolovic3, Milan Pertovic2, Branka Mitic1
1
ECMO 15 (48.38%) Clinical Center Nis, Nephrology, Nis, Serbia, 2General Hospital, Nephrology, Leskovac,
Serbia and 3KBC Zemun, Nephrology, Beograd-Zemun, Serbia
LVAD 1 (3.22%)
Gastric ulcer 1 (3.22%) BACKGROUND AND AIMS: The general significance of Balkan endemic
nephropathy (BEN) is the association with upper tract urtohelial cancer (UTUC). In
Indications for RRT: acute respiratory failure in the absence of heart failure or fluid published papers studying these two entities, there is large difference between the
overload; presence of diffuse alveolar damage (DAD) (detected by high-resolution CT); obtained results. By UTUC research, obtained results are the most diverse in relation to
PaO2 / FiO2  300 mm Hg Duration:> 6-24 hours per column with a blood flow rate the period and region of research.
of 80-120 ml/min. In addition, indications for the urgent start of extracorporeal The aim of the research is to show the discrepancy between the results of the research
treatment are: of UTUC of Jablanica district in relation to the observation period and the type of
settlement.
• signs of severe coronavirus infection (respiratory rate  30 per minute and / or METHOD: The research period lasted from 1978-2017. During the analysis of the
blood oxygen saturation  93% and / or PO2/FiO2 index  200 mmHg; frequency of UTUC, we used the operative material of Urology Department, Health
• detection of lung lesion progression using one of the imaging methods 10% per Care Center, Leskovac , and Urology Clinic, Clinical Center, Nis, Clinical Center, Nis.
day; For practical reasons, this period was devided into two periods, the first (1978-1997)
and the second (1998-2017). In order to make classification of settlements we used the
• progressive increase in the level of inflammatory markers (CRP, IL-6, etc.).
data of the Institute of Nephrology and Hemodialysis in Nis (A-endemic regions, B-
hypo-endemic, C-non-endemic urban, D-non-endemic rural regions). Data on the
The duration of hospitalization in the ICU – 12.54 days. total number of Jablanica region population were obtained on the basis of the censuses
Combinations and duration of the procedures. from 1991 and 2011. The average annual incidence rate (AAIR) was calculated per 100
000 people. Finally, we jointly observed groups A and B (endemic areas) C and D (non-
endemic areas) for UTUC.
RESULTS: The average annual incidence rate (AAIR) in the period of 1978-2017 in
endemic settlements of Jablanica region was (11.82), while in hypo-endemic was (4.49)
and non-endemic (0.83). The data demonstrated that inhabitants of endemic
Name of the procedure (n) Duration (in settlements has 14.24 times higher UTUC frequency in comparison to non-endemic
settlements in time span of research.
hour)
Our research in Jablanica region also demonstrated unexpectedly high frequency of on
HP HA330 þ CVVHF/CVVHDF 2þ1þ1 (n=33) > 1224 x UTUC not only in endemic settlements with BEN (Kutles village- 1 tumor per 99.63
HP Cytosorb̀ þ CVVHF/CVVHDF 1þ1þ1(n=5) > 24 x and AAIR 40.15), but also in some of the non-endemic area (Brejanovac village-1
tumour per 98.75 people and AAIR of 40.50; Rudare village-1 tumour per 139.50
HP HA330IIþ CVVHF/CVVHDF 2þ1þ1 (n=31) > 1224 x people and AAIR of 28.67; Bogojevce village-1 tumour per 187.63 people and AAIR
PE þ CVVHF/CVVHDF 2þ1þ1(n=7) > 624 x 21.32). This occurrence of UTUC frequency in some non-endemic settlements refers to
HP 2þ1þ1(n=14) > 3-6 x the first observed period until no occurrence was recorded in the second observed
period.
There is a higher UTUC frequency in endemic settlements of 11.37 in the first period
Footnote: combinations and duration of use are in accordance with the (A- AAIR 21.95), while in hypo-endemic (B-AAIR 11.82) is 3.64 higher incedence. In
recommendations of Ronco C. et al. (2020). non-endemic settlements (C,D-AAIR 1.09) there is 1.63 higher incidence in
comparison to the second period.
Laboratory data - Leukocyte, CRP, Interleukine, procalcitonin, Creatinin, presepsin in Observing the periods, there is a higher UTUC frequency of five times in endemic
dynamics. settlements (A, B) of Jablanica region in the first period comparing to the second.
The linear trend of UTUC in the 40-year period demonstrates a slow decrease (y= -
0.0797x þ 4.2846; r2 = 0.2028) in Jablanica region. In the same observed period, linear
trend of BEN is in corelation of decreased linear trend of UTUC (y= -0.164xþ6.0669;
r2 =0.748).
CONCLUSION: A forty-year study of UTUC in the Jablanica region showed a
discrepancy between the results in relation to the observation period and the type of
settlement, which coincides with the generally accepted view that epidemiology is the
most fascinating part of BEN.

10.1093/ndt/gfab082 | i255
Abstracts Nephrology Dialysis Transplantation

In endemic settlements, in the second observed period, the frequency of UTUC was In a multivariable logistic regression model, baseline CKD (eGFR<60mL/min/
registered five times lower than in the first, which coincides with the decrease in the 1.732m2; odds ratio, 95%CI: 5.32,1.72-15.90), Prolonged bypass time (1.73,1.21-2.48;
frequency of BEN in these settlements. per hour), intraoperative PRBC transfusion (2.33,1.08-5.03) and elevated 24-hour post-
operative Neutrophil/Lymphocyte ratio>18 (3.00, 1.07-8.35) were associated with an
increased risk of AKI.
AKI after CPB resulted in greater hospital (23.6 versus 14.6 days, p<0.001) and ICU
stay (8.1 versus 3.3 days, p<0.001) and a 6-fold increase in 30-day mortality after
adjusting for age and sex (HR, 95 CI: 6.40, 2.38-17.25). (see Figure 1 Kaplan Meier
survival estimates for AKI)
CONCLUSION: The occurrence of AKI following CPB is comparable to that reported
in the literature and is associated with poor short-term outcomes. Larger multicentre
prospective studies to predict risk, identify interventions to reduce mortality and assess
long term complications of AKI following CPB in Caribbean countries are needed.

MO376 CLINICAL OUTCOMES OF ACUTE KIDNEY INJURY


FOLLOWING SNAKE BITE INJURIES

Weerakit Naweera1, Thapat Wannarong2


1
King Narai Hospital, Nephrology Division, Department of Internal Medicine, Lopburi,
Thailand and 2Neurological Institute, University Hospitals Cleveland Medical Center,
Case Western Reserve University School of Medicine, Department of Neurology,
Cleveland, OH, United States of America

BACKGROUND AND AIMS: Snakebite is a common animal bite injury in tropical


countries. Acute kidney injury (AKI) is an important complication in snakebite
MO375 EPIDEMIOLOGY AND PREDICTORS OF CARDIAC BYPASS patients. This study aimed to comprehensively investigate the clinical profiles and
ASSOCIATED AKI IN A MIDDLE-INCOME CARIBBEAN outcomes of patients following hematotoxin-related snakebite associated with kidney
COUNTRY impairment.
METHOD: We conducted a hospital-based, cross-sectional study of 238 patients with
Lori-Ann Fisher1, Sunil Stephenson2, Marshall Tulloch-Reid1, Simon Anderson3 hematotoxin-related snakebite injuries. Data were retrieved from the King Narai
1
The University Of The West Indies - Mona, Medicine, Kingston, Jamaica, 2The University Hospital Registry from October 2014 to August 2020. The prevalence of complications
Of The West Indies - Mona, Surgery, Radiology and Anaesthesia , Kingston, Jamaica associated with snakebite injuries, including acute kidney injury (AKI) and its severity,
and 3University of the West Indies - Cave Hill Campus, Wanstead, Barbados was determined. Univariate and Multivariate predictors of AKI diagnosis were
evaluated using binary logistic regression analysis
RESULTS: A total of 238 patients, with 63.4% men, median (IQR) age 49.8 (39-61)
BACKGROUND AND AIMS: AKI is a common and resource intensive complication
years and median duration from injury to a hospital arrival of 1 hour (0.5-2) hours,
of cardiopulmonary bypass surgery (CPB) in high income-countries occurring in up to
were injured by Green pit viper (85.7%), Russell’s viper (12.6%) and Malayan pit viper
one third of surgeries performed. However, little is known of its incidence and impact
(1.7%). AKI mostly occurred in Russell’s viper group 66.7%. An AKI was reported in
in the small island developing states of the Caribbean. We describe the incidence, risk
thirty (12.6%, 95% CI: 8.7 % - 17.5%) patients, with the severity of 66.7% stage one,
factors and outcomes of AKI following CPB at a referral cardiac centre in Jamaica.
6.7% stage two, 26.6% stage three by KDIGO classifications, and 13.3% requiring
METHOD: A review of the Medical Records of adult patients (aged  18 years) with
hemodialysis. Complete renal recovery was seen in twenty-two patients (73.3%), while
no prior ESRD or dialysis requirement undergoing CPB at the University Hospital of
partial renal recovery was 23.3%. Other complications included 84.4 % limb cellulitis,
the West Indies, Mona between January 1, 2016 to June 30, 2019 inclusive was
4.6% significantly bleeding, 2.5% hypotension, 25.6% prolonged venous clotting time
undertaken. Demographics, pre-operative status, intraoperative and post-operative
(VCT), 46.7% prolonged prothrombin time (PT), and 14.3% prolonged partial
data were abstracted. The primary outcome was all-cause 30-day mortality. AKI was
thromboplastin time (PTT). Of total patients, 60.1% were treated with anti-venom.
defined as meeting the KDIGO criteria based on the peak serum creatinine
Mortality was relatively low (0.4%). In multivariable logistic regression analyses, AKI
measurement obtained within 72 hours post-operatively. Multivariable logistic
was significantly associated with time to hospital arrival more than 3 hours (p = 0.04),
regression was used to examine the risk factors for and impact of AKI on all-cause
Russell’s viper bitten (p = 0.01), clinical bleeding (p = 0.01), and prolonged PT (p <
mortality.
0.01).
RESULTS: Of the 259 persons who underwent CPB in the study period, 211 (58%
CONCLUSION: The prevalence of AKI in patients bitten by hematotoxin snakes was
men, mean age 58.1612.9 years, median6 IQR Euro-score II of 1.4 6 1.4) met
12.6%, mostly from Russell’s viper. Factors associated with AKI outcomes were time to
inclusion criteria. AKI occurred in 37.3 % (80) of patients with 43.8% (35) KDIGO I,
hospital arrival more than 3 hours, Russell’s viper bitten, clinical bleeding, and
32.5% (26) KDIGO II and (19) 23.7% KDIGO III. Renal replacement therapy was
prolonged PT. Besides, one-fourth of AKI patients turned to chronic kidney disease.
required in 3.2% (7) of patients.

MO377 HOW THE ITALIAN COVID-19 LOCKDOWN AFFECTED


NEFROLOGICAL ACTIVITY IN A LOMBARD CENTER

Paolo Albrizio1, Silvano Costa1, Annalisa Foschi1, Ivo Angelo Antonio Milani1,
Stefano Rindi1, Manuela Zucchi1, Fabio Milanesi1
1
Voghera Hospital - ASST Pavia, Nephrology and Dialysis Unit, Voghera, Italy

BACKGROUND AND AIMS: Italy and Lombard hospitals particularly, were hard
affected by Covid-19 pandemic, mostly during spring and autumn, seasons
characterized by two lockdown periods which were however, partly different as rules.
During first lockdown in fact, by hospital decision, all ambulatorial activity was closed,
including nephrological one. This did not happen during second lockdown period.
How the different choices about hospital activity affected nephrological patients is the
aim of this study.
METHOD: we evaluated all nephrological advices requested by first aid units of our 3
hospitals, all located in Lombardy, to our Nephrology Unit, splitting out data in 3
periods (I lockdown, summer and II lockdown) and comparing with 2019. Data
collected were: number of advices requested by day, age, sex, previous regular
nephrological follow-up, Covid-19 diagnosis, nephrological diagnosis after
nephrological advice and outcome.
MO375 Figure 1: Kaplan-Meier survival estimates for AKI RESULTS: as shown in table 1, during I lockdown period, with hospital decision of
suspending our nephrological ambulatorial activity, we suffered an incremented rate of
patients approaching local first aid units compared to 2019 same period with an
increased rate of acute kidney injury, mostly for dehydration, and with a higher rate of
patients requiring hospitalization. All these differences resulted statistically significant
vs 2019 same period (figure 1). On the other side, no statically significant difference

i256 | Abstracts
Nephrology Dialysis Transplantation Abstracts
was found during the other two examined periods, including the II lockdown, while all MO379 EVALUATION OF NEUTROPHIL-LYMPHOCYTE RATIO IN
our ambulatories were fully operating. PROGNOSIS OF SEVERE ACUTE RENAL INJURY
CONCLUSION: Covid-19 pandemic affected also the nephrological population with
an increased rate of first aid units’ accesses, acute kidney injury events and Lei Chen1, Limin Wei1
1
hospitalization comparing to 2019. However, these differences were detectable only the First Affiliated Hospital of Xi‘an Jiaotong University, Dialysis Department of
during the I lockdown period characterized by the suspension of all ambulatorial Nephrology Hospital, Xi’an, P.R. China
activity, including our Unit. The absence of statistically significant differences during
summer and primarily during II lockdown period demonstrates the importance of BACKGROUND AND AIMS: Recently, more and more attention has been paid to
nephrological ambulatorial activity in management of renal diseases and in prevention the predictive value of neutrophil to lymphocyte ratio (NLR) in various diseases. As a
of acute events. novel marker for inflammatory response, NLR has been proved to be useful for the

diagnosis and prognosis evaluation of inflammatory diseases such as tumor, diabetes,


MO378 WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE
atherosclerosis and other disease. It is well known that inflammatory response plays an
KIDNEY INJURY
important role in the occurrence and development of AKI. Previous studies have
shown that NLR has a great value in the diagnosis of AKI, but its value in the prognosis
Hernando Trujillo1, Justo Sandino Pérez1, Teresa Cavero Escribano1,
evaluation in AKI patients, especially in critical ill patients with AKI, remains unclear.
Eduardo Gutierrez1, Angel Sevillano1, Manuel Praga1,2,3
1
This study aimed at investigating the predictive value of neutrophil-lymphocyte ratio
Hospital Universitario 12 de Octubre, Nephrology, Madrid, Spain, 2Instituto de (NLR) on the risk of 90-day mortality in critically ill patients with acute kidney injury
Investigacion Hospital 12 de octubre (i+12), Madrid, Spain and 3Universidad (AKI), so as to provide a simple, feasible, and valuable tool for the prognosis
Complutense de Madrid, Medicine, Madrid, Spain assessment of such patients.
METHOD: The data of 802 critically ill patients with AKI admitted to the intensive
BACKGROUND AND AIMS: Acute kidney injury (AKI) secondary to glomerular care unit of the First Affiliated Hospital of Xi’an Jiaotong University from January 2015
hemorrhage in the context of overanticoagulation, commonly known as anticoagulant- to December 2019 were retrospectively analyzed. According to the initial NLR level at
related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or admission, they were divided into a low NLR group (NLR9) and a high NLR group
underlying kidney disease seems to be a predisposing factor; however, few studies have (NLR>9). Differences in comorbidities, the initial Sequential Organ Failure
described histologic findings in patients with ARN. We aimed to examine underlying Assessment (SOFA) score, white blood cell (WBC), neutrophil percentage (Neu%),
kidney pathology in patients on oral anticoagulation who presented an episode of AKI hemoglobin (Hb), platelet (PLT), lactic acid (Lac), pH, blood glucose (Glu), creatine
with hematuria in whom a kidney biopsy was performed. kinase (CK), and all-cause mortality at 90-day were compared between groups. Binary
METHOD: Spanish retrospective observational multicenter case study in patients Logistic regression model was used to analyze the risk factors for 90-day mortality in
treated with oral anticoagulants who developed macroscopic or intense hematuria critically ill patients with AKI, and the receiver operating characteristic (ROC) curve
followed by AKI. Only patients with available kidney biopsy specimens were included. was computed to evaluate the predictive value of NLR for the risk of 90-day mortality
Histologic findings and clinical data throughout follow-up were analyzed. The main in such patients.
outcome was to describe pathologic findings in kidney biopsy specimens of patients RESULTS: There were no statistically significant differences in age, sex, and Glu
with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes between the two groups. The SOFA score, WBC, Hb, Plt, Lac, CK, SC, BUN and
during follow-up. NEU%of patients in the high NLR group were higher than those in the low NLR group,
RESULTS: Twenty-four patients were included with a median age of 76 years while the BMI and pH value was lower in the high NLR group than that in the low
(interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) NLR group. The 90-day mortality rate was significantly higher in the high NLR group
months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most than that in the low NLR group (36.2% vs 16%, P < 0.001). Binary Logistic regression
cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of showed that NLR was an independent risk factor for 90-day mortality in critically ill
cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and patients with AKI (OR=2.402, 95% CI:1.633-3.533,ı̈1=4 <0.001), even after adjusting for
a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and age, gender, BMI, comorbidities, SOFA score, and AKI stages. The area under the ROC
11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except curve (AUC) of NLR predicting 90-day mortality was 0.613 with a highest prognostic
one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], cut-off point of 8. The sensitivity was 65.77%, and the specificity was 54.78%.
probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and CONCLUSION: NLR has a predictive value on risk of the 90-day mortality in critically
idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell ill patients with AKI. As a simple and easily available clinical indicator, NLR could be
casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. applied as a valuable tool in guiding the initial treatment of such patients.
Management included anticoagulation withdrawal in 14 cases (58.3%) and
immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic
acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had >50% decrease in
SCr (with respect to peak SCr), 6 had <50% decrease and 5 were on chronic dialysis.
CONCLUSION: IgA nephropathy was the most common underlying kidney disease in
our biopsy-proven series of ARN, in which a significant percentage of patients did not
achieve kidney function recovery.

10.1093/ndt/gfab082 | i257
Abstracts Nephrology Dialysis Transplantation

MO379 Figure 1: ROC Curve

MO380 INCREASED PREVALENCE OF ACUTE KIDNEY INJURY AND 52.5 ml/min for stage 3. Mean serum creatinine at admission was 1.17 mg/dl in NO
MORTALITY IN COVID-19 HOSPITALIZED PATIENTS AKI group, 1.43 mg/dl for total AKI group divided in1.22 mg/dl for stage 1, 1.4 mg/dl
for stage 2 and 2.25 mg/dl for stage 3.
Umberto Maria Morosini1, Greta Rosso1, Guido Merlotti1, Andrea Colombatto1, Among evaluated comorbidities, only diabetes (p=0,048) and cognitive impairment
Angelo Nappo1, Marco Quaglia1, Gabriele Guglielmetti1, Danila Azzolina2, (p=0,001) were associated with a significant increased risk for AKI development.
MARITA MARENGO3, Giuseppe Castellano4, Vincenzo Cantaluppi1 ICU admission rate was 5% for NO AKI group and 18% for total AKI group divided in
1
University Hospital Maggiore della Carita, Nephrology and Kidney Transplantation 14% for stage 1, 22% for stage 2 and 44% for stage 3.
Unit, Novara, Italy, 2University of Eastern Piedmont, Department of Translational Mean length of hospital stay for NO AKI group was 7.22 days vs 15.08 days for total
Medicine, Vercelli, Italy, 3ASL CN 1, Nephrology and Dialysis Unit, Cuneo, Italy and AKI group divided in 13.67 for stage 1, 15.83 for stage 2 and 21.82 for stage 3.
4
Universita degli studi di Foggia, Nephrology, Dialysis and Kidney Transplantation Unit, Of note, all different therapies administered to COVID-19 patients did not correlate
Foggia, Italy with AKI incidence.
Mean eGFR at discharge was 76 ml/min for NO AKI group vs 66 ml/min for total AKI
group divided in 68.7 ml/min for stage 1, 59.3 ml/min for stage 2 and 59.3 ml/min for
BACKGROUND AND AIMS: In 2020, SARS-CoV-2 pandemic had a devastating stage 3. Mean serum creatinine at discharge was 1.14 mg/dl for NO AKI group vs 1.45
impact on individuals and on national health systems worldwide. Although being mg/dl for total AKI group divided in 1.28 mg/dl for stage 1, 1.58 mg/dl for stage 2 and
primarily a lung disease, COVID-19-associated systemic inflammation and activation 2.05 mg/dl for stage 3.
of coagulation/complement cascades lead to multiple organ dysfunction including
Acute Kidney Injury (AKI).
Our aim is to evaluate AKI prevalence and mortality in hospitalized patients during
COVID-19 pandemic in a 500-bed University Hospital.
METHOD: Observational study on 945 COVID-19 patients (March-May 2020). Data
collection from Board Hospital Discharge and serum creatinine (Lab database). AKI
stratification in accordance to KDIGO criteria and evaluation of outcome in the
different subgroups. The same methodology was adopted to assess AKI prevalence and
outcome in 2018-2019.
RESULTS: 351/945 (37.14%) of all hospital admissions for COVID-19 showed AKI
further sub-classified as follows: 173 (18.3%) stage 1, 112 (11.9%) stage 2 and 66 (6.9%)
stage 3: the control NO AKI group was 594/945 (62.86%). COVID-associated AKI
prevalence was higher than that observed in 2018 (total AKI 17.9%, stage 1 10.7%, stage
2 4.5%, stage 3 2.7%) and 2019 (total AKI 17.2%, stage 1 10.1%, stage 2 4.5%, stage 3
2.6%).
During COVID-19 pandemic, in-hospital mortality was 27% for NO AKI group, 28%
for total AKI group, further subdivided 24% for stage 1, 45% for stage 2 and 42% for
stage 3 group, respectively. Mortality was different from that observed during 2018
(NO AKI 3.77%, total AKI 15.2%, stage 1 9.69%, stage 2 17.24%, stage 3 18.9%) and
2019 (NO AKI 3.56%, total AKI 18.35%, stage 1 10.6%, stage 2 20.1%, stage 3 24.3%).
In COVID-19 patients, mean age of NO AKI group was 64.6 ys vs. 71.7 ys of total AKI
group divided in 71.6 ys for stage 1, 74.3 ys for stage 2 and 67.9 ys for stage 3,
respectively. Mean eGFR at admission was 74.2 ml/min for NO AKI group, 61.3 ml/
min for total AKI group divided in 64.3 ml/min for stage 1, 57.8 ml/min for stage 2 and

i258 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: COVID-19 pandemic is associated with an increased AKI prevalence RESULTS: Median age was 80 years (IQR: 70-86). 58.8% of patients were males. The
in hospitalized patients (2-fold increase in all KDIGO stages). AKI associated with an most common symptom on admission was fever (68.8%), followed by cough (57.7%).
increased risk of mortality: of note, AKI stage2-3 had a strong impact on mortality in The majority of subjects presented with severe COVID-19 on admission (75.7%).
comparison to NO AKI group (OR 2.59 and 2.11, respectively). The presence of eGFR During 28-day follow-up, 87 patients (32%) developed Stage 1 AKI, 17 subjects (6.3%)
>60 ml/min and serum creatinine < 1.2 mg/dl at admission were associated with a developed Stage 2 AKI and 12 patients (4.4%) developed Stage 3 AKI.
lower risk of AKI development: reduced eGFR levels were observed at discharge AKI was more frequent (61 vs 24.3%) and more severe (Stage 2 AKI: 10.3 vs 2.2%;
particularly in AKI stage 2-3. The length of hospital stay and risk of ICU admission Stage 3 AKI: 6.6 vs 2.2%) among CKD patients. In adjusted logistic regression analysis,
depended on AKI incidence and severity. only disease severity and baseline eGFR were independent predictors for AKI in
COVID-19 lead to an increased burden for Nephrologists due to increased AKI COVID-19 patients that required hospitalization.
prevalence: a nephrological follow-up is needed to avoid progression from AKI to CONCLUSION: CKD patients suffer AKI more frequently and of higher severity
chronic kidney disease (CKD). during COVID-19. Baseline eGFR, along with COVID-19 severity, are strong predictor
factors of AKI in this setting.

MO381 RISK FACTORS FOR AKI DURING COVID-19 AMONG NON-


DIALYSIS CKD PATIENTS MO382 POTASSIUM DISTURBANCES AND CHARACTERISTICS OF
RENAL RECOVERY IN 1519 CONSECUTIVE PATIENTS WITH
1 2 3
Armando Coca , Carla Burballa , Francisco Javier Centellas Pérez , ACUTE KIDNEY INJURY
Isabel Acosta-Ochoa1, Juan Pérez Martınez3, Eva Rodriguez2, Veronica Fidalgo1,
Agustin Ortega Cerrato3, Marta Crespo2 Christina Montgomerie1, Jonas Spaak2, Marie Evans3, Stefan H. Jacobson1
1
Hospital Clinico Universitario de Valladolid, Nephrology, Valladolid, Spain, 2Hospital 1
Karolinska Institutet, Danderyd University Hospital, Dept of clinical sciences, division of
del Mar, Nephrology, Barcelona, Spain and 3Complejo Hospitalario Universitario de Nephrology, Stockholm, Sweden, 2Karolinska Institutet and Danderyd University
Albacete, Nephrology, Albacete, Spain Hospital, Dept of Clinical Sciences, division of Cardiology, Stockholm, Sweden and
3
Karolinska Institutet, Karolinska University Hospital, CLINTEC and Dept of Renal
BACKGROUND AND AIMS: AKI is a strong risk factor for adverse outcomes during Medicine, Stockholm, Sweden
Coronavirus disease (COVID-19) in the general population. CKD has been correlated
with increased risk of AKI both in the outpatient and inpatient settings. We aimed to BACKGROUND AND AIMS: Acute kidney injury (AKI) is a common condition
define potential risk factors for AKI among patients with non-dialysis CKD admitted occurring in about 15% of hospitalized patients, often complicated by hyperkalemia
due to COVID-19. causing increased risk for adverse cardiovascular events. The level of AKI (prerenal,
METHOD: Multicenter, observational cohort study including 136 adult patients with renal or postrenal), is of importance as both pathophysiology and prognosis differ.
CKDand 136 age- and sex-matched controls who required admission for COVID-19 in Although early recovery from AKI is associated with less morbidity and mortality,
three academic hospitals. Viral infection was confirmed by real-time RT-qPCR and/or patients with a history of AKI have a higher long-term risk of end-stage kidney disease
serologic testing in all cases. Disease severity on admission was classified according to and death. Most AKI studies include critically ill patients treated at intensive care units;
the WHO—China Joint Mission Report on COVID-19; briefly subjects with COVID- less is known about AKI patients in general. The aim of this large single-center study
19 were divided into mild (laboratory confirmed, without pneumonia), moderate was to report potassium disturbances and short-term hospital outcomes in 1519
(laboratory confirmed with pneumonia), severe (dyspnea and/or lung infiltrates >50% consecutive patients with AKI admitted to a nephrology department.
of the lung field within 24–48 h) and critical (respiratory failure requiring mechanical METHODS: All patients diagnosed with AKI between 2009 and 2018 and admitted to
ventilation, shock, or other organ failure that requires intensive care). AKI was defined the nephrology department at Danderyd University Hospital, Stockholm, Sweden,
using the 2012 KDIGO classification. CKD was defined as sustained eGFR <60 and were screened. Patients who fulfilled the KDIGO 2012 definition of AKI, a sCreatinine
>15 ml/min/1.73m2 within the 6 months prior to COVID-19 hospitalization. Baseline (sCr) >1.5 times baseline or increase by >0.3 mg/dL (>26.5 mmol/L), were included.
eGFR was calculated using the CKD-EPI equation. Demographic and clinical data were Potassium levels at admission were classified into hypokalemia (<3.5 mmol/L),
gathered from medical records. Outcomes were recorded during the following 28 days normokalemia (3.5-4.9 mmol/L), mild hyperkalemia (5-5.4 mmol/L), moderate (5.5-
after admission. We applied logistic regression analysis to describe potential predictors 5.9 mmol/L) and severe hyperkalemia (6 mmol/L). Partial recovery was defined as an
for AKI. in-hospital sCr decrease by at least 30% while modest recovery was defined as s sCr

10.1093/ndt/gfab082 | i259
Abstracts Nephrology Dialysis Transplantation

decrease by at least 50%. Using logistic regression with conditional backward selection, MO383 COVID - 19 AND AKUTE KIDNEY INJURY- A SINGLE CENTER
we determined which variables that were associated with a partial recovery or a EXPERIENCE
hyperkalemia (>5 mmol/L). Patients on dialysis treatment were excluded. Patients
were followed until either discharge or death, whichever came first. Ana Bulatovic1,2, Jelena Bjedov1,2, Vesna Maslarevic Radovic1, Nada Dimkovic1,
RESULTS: In 1519 patients with AKI, the majority (n=687 (45%)) had prerenal AKI, Radomir Naumovic1,2
1
followed by AKI on chronic (defined as chronic kidney disease combined with any type KBC“ZVEZDARA”, Nephrology, Beograd, Serbia and 2University of Belgrade - Faculty of
of AKI) (n=536 (35%)), renal (n=166 (11%)) and postrenal AKI (n=130 (9%)). At Medicine, Beograd, Serbia
admission, 30% of patients had any hyperkalemia, whereas 7% had severe
hyperkalemia. Normokalemia was seen in 60% of the patients while 10.5% had BACKGROUND AND AIMS: The new coronavirus disease (COVID 19) has become
hypokalemia. The more hyperkalemia, the higher level of sCr at admission, the more a worldwide health emergency with a wide spectrum of clinical presentation, from
acidosis and the less proteinuria. Proteinuria was most pronounced in patients with common cold symptoms to multiorgan failure. A great number of medical centers have
mild hyperkalemia and normokalemia. In-hospital partial renal recovery was seen in reported that patients with COVID-19 have developed acute kidney injury. The kidney
63% of the patients, while 38% had a modest recovery. Mortality during hospitalization is a target organ for SARS - COV2 because of ACE2 receptor, the binding site for this
was 4%; most of these patients had normokalemia (58%), followed by mild (18%) and virus, is expressed in kidney tissue. The potential mechanisms for kidney injury are
moderate hyperkalemia (15%). In the prerenal and postrenal groups, most patients had direct kidney injury, inflammation, activation of coagulation and complement
a partial renal recovery (76% and 73% respectively). In patients with renal and AKI on cascades. Data from centers worldwide reported a wide range of AKI incidence, from
chronic the proportions were lower (40% and 51%, respectively). 0,5% in China to 46% in USA. The aim of this study was to analyze incidence, risk
CONCLUSION: This study provides data from a large, contemporary AKI patient factors and outcomes of AKI in hospitalized patients with COVID 19 who were treated
cohort under nephrology care. Severe potassium disturbances are common and short- from 01.04. to 01.06.2020. at Nephrology Department of University Clinical Center
term outcomes differ substantially in patients of variable AKI level and etiology. These Zvezdara, which was at the time transformed into COVID hospital.
findings have important implications for prognostic evaluation upon admission and METHOD: This retrospective observational study included 51 patients who had
further resource planning. normal kidney function before the infection with SARS COV2, and 7 of them
developed dialysis non-dependent AKI. Analysis included data collection from the
patients’ history including demographic, clinical and administrative data. Statistical
analysis has been performed using SPSS software version 20 (IBM Corporation, New
York, USA).
Hyperkalemia Renal recovery RESULTS: Out of 51 patients 7 (13.7%) developed AKI, mean age was 59 þ 16 years
(K5 mmol/L) (30% sCr decrease) and 53% were male. Diabetes mellitus was present in 27 of patients with AKI,
hypertension in 6/7, obesity in 3/7, coronary artery disease in 1/7 and 1 of 7 patients
P-value OR 95% CI P-value OR 95% CI
was smoker. These risk factors except obesity (p= 0.05) didn’t vary significantly
Upper Lower Upper Lower between two groups (AKI and non AKI patients with COVID-19). Our results showed
Age <0.001 1.022 1.012 1.032 <0.05 1.010 1.002 1.018 significant correlation between AKI development and obesity (p= 0.05, OR 4.75),
Charlston index score (p=0.01), D dimer score (p=0.01), and CT COVID score
sCr <0.001 1.001 1.001 1.002 <0.001 1.001 1.001 1.002 (p=0.03). Regarding the outcome, COVID 19 patients with AKI showed 7-fold higher
admission risk for fatal outcome (p= 0.046).
CRP <0.001 0.997 0.995 0.999 <0.05 1.002 1.000 1.003 CONCLUSION: Obesity, higher D dimer values, worse CT findings and higher
Charlston comorbidity score index were associated with acute kidney injury in patients
ACR 0.088 1.000 1.000 1.001 <0.01 0.999 0.999 1.000 with COVID 19. AKI proved to be significant risk factor for fatal outcome in patients
Prerenal <0.01 0.629 0.466 0.849 <0.001 3.256 2.436 4.352 with SARS COV2 infection.
AKI (ref)
Renal AKI 0.085 0.633 0.376 1.065 - - - -
MO384 ERYTHROCYTURIAAT ADMISSION IS A PREDICTOR OF
Postrenal - - - - <0.01 2.370 1.406 3.997 ACUTE KIDNEY INJURY AND IN-HOSPITAL MORTALITY IN
AKI HOSPITALIZED PATIENTS WITH COVID-19

Yulia Khruleva1, Elena Troitskaya1, Marina Efremovtseva1,


Tapiwa Mubayazvamba1, Zhanna Kobalava1
1
Peoples’ Friendship University of Russia, Internal Medicine, Moskva, Russia

BACKGROUND AND AIMS: Acute kidney injury (AKI) is common among patients
with coronavirus disease (COVID-19) and a major risk factor associated with mortality
in hospitalized patients. Previously abnormal urine tests were reported to have a high
incidence in COVID-19. We aimed to investigate the prevalence of urine tests changes
and their impact on the outcomes in patients hospitalized with COVID-19.
METHOD: A retrospective analysis of the register of patients with COVID-19 was
performed. COVID-19 was defined as the laboratory-confirmed infection and/or
presence of the typical computer tomography (CT) picture with typical clinical signs.
We excluded patients with re-hospitalizations, urinary tract infection, and single serum
creatinine (SCr) measurement during hospitalization. Urine tests were performed
within the first 24 h after hospitalization. Erythrocyturia was defined as the presence of
>3 red blood cells (RBC) per high-power field. Definition of acute kidney injury (AKI)
was based on KDIGO criteria. Patients were identified as having in-hospital AKI, if
AKI developed during hospitalization. P value <0.05 was considered statistically
significant.
RESULTS: In final analysis we included 495 patients. Mean age was 64 [53;74], 51%
(244) were males, mean Charlson index 3 [1;3], 66% with hypertension, 48% with
obesity, 24% with diabetes mellitus (DM) and 6% with chronic kidney disease (CKD).
MO382 Figure: Logistic regression with conditional backward selection showing 25% of patients were hospitalized in the intensive care unit (ICU), 17.8% (88) were
variables that were associated with a hyperkalemia and renal recovery. treated with mechanical ventilation at some point during hospitalization. Patients were
hospitalized on the 664 day of illness at mean. The mean length of stay was 11 [9;14]
days, in the ICU - 4 [2;7] days. 19.4% patients died in hospital. The incidence of AKI
was 22%, 47% patients had the 1st stage of AKI, 41% - the 2nd and 20% - the 3rd. In-
hospital AKI was observed in 8.3% (41) of patients. Among discharged patients AKI
was registered in 13%, of those who died in 60% (p<0.0001).
52% (256) of patients had erythrocyturia and/or proteinuria and/or leukocyturia in
urine test and admission: 35% of patients had proteinuria, 17% - hematuria and 19% -
leukocyturia. The most prognostically significant associations of urinalysis changes
were identified for erythrocyturia, which was present in 82 patients at admission, their
mean RBC count in urine was 18.5 [7;52]. The presence of erythrocyturia at admission
was independent of age, gender, presence of hypertension, DM, obesity, blood test
changes, pre-admission drug intake, included oral anticoagulants. Patients with
erythrocyturia at admission had higher level of SCr at admission (101[83;140] vs
88[74;109] mmol/l, p=0.003), were more likely to develop AKI compared to patients

i260 | Abstracts
Nephrology Dialysis Transplantation Abstracts
without AKI (31.2% vs 12.4%, p<0.001, respectively), had higher prevalence of in- MO386 MASS SCREENING AND THE LOW RATES OF ACUTE KIDNEY
hospital AKI (17% vs 6.5%, p=0.002) and more severe course of AKI (the 1st stage – INJURY AMONG COVID-19 PATIENTS IN HONG KONG
31% vs 54%, the 2nd - 43% vs 32%, the 3rd – 26% vs 14%, p=0.02). They also more
often had CKD (13,4% vs 4.4%, p=0.001), more severe lung injury by CT scan during Kam Wa Chan1, Ivan Fan-Ngai Hung2, Owen Tak-Yin Tsang3, Tak Chiu Wu4,
hospitalization (15.6% vs 5.5% with 75-90% lung injury, p=0.005, for the trend), were Eugene Yuk-Keung Tso5, Kwok Cheung Lung6, Chung Man Lam3, Gary Chi
more frequently hospitalized in ICU (39% vs 22%, p=0.001), and had higher level of in- Wang Chan1, Sunny Sze-Ho Wong5, Kam Yan Yu2, Johnny Wai-Man Chan4,
hospital mortality (32% vs 17%, p=0.002). Sydney Tang1
1
Erythrocyturia at admission was predictor for development of in-hospital AKI (odds The University of Hong Kong, Department of Medicine, Hong Kong, Hong Kong, P.R.
ratio (OR) 2.94 with a 95% confidence interval (CI) of 1.35 to 6.15, p=0.002) and in- China, 2The University of Hong Kong, Department of Medicine, Hong Kong, P.R. China,
3
hospital mortality (OR 2.28, 95% CI of 1.28 to 3.97, p=0.002). Princess Margaret Hospital, Department of Medicine & Geriatrics, Hong Kong, P.R.
CONCLUSION: Erythrocyturia at admission is a common finding in hospitalized China, 4Queen Elizabeth Hospital, Department of Medicine, Hong Kong, P.R. China,
5
patients with COVID-19, and is associated with severity of disease and adverse United Christian Hospital, Department of Medicine, Hong Kong, P.R. China and
6
outcomes in this population. Pamela Youde Nethersole Eastern Hospital, Department of Medicine, Hong Kong, P.R.
China

MO385 THE IMPACT OF SARS-COV-2 INFECTION ON MORTALITY IN BACKGROUND AND AIMS: Renal involvement in COVID-19 under vigilant public
CKD PATIENTS – A SINGLE-CENTER PILOT STUDY health surveillance, including mass screening and early hospitalization is less well-
characterized. We assessed renal involvement of COVID-19 patients in Hong Kong,
Ileana Peride1,2, Andrei Niculae1,3, Corina Adriana Balas3, Ana-Maria Nechita2, including the association with risk factors, length of hospitalization, critical
Ionel Alexandru Checherita1 presentation and mortality.
1 METHOD: Linked electronic records of all confirmed patients from 5 major
Carol Davila University of Medicine and Pharmacy, Nephrology, Bucures, ti, Romania, designated hospitals were extracted. Primary outcome was the incidence of in-hospital
2
Sf. Ioan Clinical Emergency Hospital, Nephrology, Bucures, ti, Romania and 3Sf. Ioan AKI. Secondary outcomes were AKI-associated mortality, incident RRT, intensive care
Clinical Emergency Hospital, Bucures, ti, Romania admission, prolonged hospitalization and disease course (defined as >90th percentile
of hospitalization duration and duration from symptom onset to discharge,
BACKGROUND AND AIMS: Since the beginning of 2019, once COVID-19 respectively), and change of eGFR. Patients were further stratified into being
pandemic was declared, there is a keen interest in understanding the impact of SARS- symptomatic or asymptomatic.
CoV-2 infection on chronic kidney disease (CKD) patients, regarding the influence on RESULTS: Patients were characterized by young age (median:38.4, IQR:28.4-55.8 years
CKD progression and the suitable therapy options, as most of the indicated old) and short time (Median:5, IQR:2-9 days) from symptom onset to admission.
medications are contraindicated for a glomerular filtration rate (GFR) below 30 ml/ Among the 591 patients, 22 (3.72%) developed AKI and 4 (0.68%) required RRT. AKI
min, and, in addition, there is a little experience in dialyzed patients. The aim of our increased the odds of prolonged hospitalization and disease course by 2.0 and 3.5 folds,
single-center pilot study is to determine the influence of SARS-CoV-2 infection on respectively. Estimated GFR 24 weeks post-discharge reduced by 7.51 and 1.06 ml/min/
CKD patients’ (dialyzed or not) outcome and hospitalization rate. 1.73m2 versus baseline (at admission) in the AKI and non-AKI groups, respectively.
METHOD: We evaluated the patients diagnosed with COVID-19, admitted in our The incidence of AKI was comparable between asymptomatic (4.8%) and symptomatic
Department between October and December 2020. The inclusion criteria were: age > (3.7%) patients.
18 years old, diagnosis of CKD – predialysis and hemodialyzed patients. The exclusion CONCLUSION: The overall rate of AKI among COVID-19 patients in Hong Kong is
criteria were: patients without pre-existing CKD. All included subjects signed the low, which could be attributable to a vigilant screening program and early
patients’ consent. To all included patients we performed the following tests: total blood hospitalization. Among patients who developed in-hospital AKI, the duration of
count, erythrocyte sedimentation rate, C-reactive protein, fibrinogen, ferritin, serum hospitalization is prolonged and kidney function impairment can persist for up to 6
free iron, serum creatinine, urea, uric acid, calcemia, total proteins, electrolytes and months post-discharge. Mass surveillance for COVID-19 is warranted in identifying
acid-base balance, urinary exams (including urine culture), coagulation and lipid asymptomatic subjects for earlier AKI management.
profile, quantitative D-dimer, IL-6, procalcitonin, and imaging tests (CT, pulmonary
Rx, abdominal ultrasonography). The patients were monitored by the infectious
disease medical team that adjusted the therapy according to the patients’ lab and
imagistic results. The specific treatment for SARS-CoV-2 infection included primary MO387 CLINICAL PERFORMANCE, HEMOCOMPATIBILITY AND
anti-interleukin receptor monoclonal antibody drugs (such as Anakinra, Tocilizumab), SAFETY OF A NEW DIALYZER WITH A MODIFIED
corticotherapy (dexamethasone), anti-retroviral therapy (remdesivir, favipiravir) only POLYSULFONE MEMBRANE
in hemodialyzed patients or in those presenting an eGFR > 30 mL/min, antibiotics,
antifungal drugs, and oxygen-therapy. Usually, anti-interleukin receptor monoclonal Manuela Kempkes-Koch1, Manuela Stauss-Grabo2, Ansgar Erlenkötter3,
antibody consisted in 7 doses, administrated every 48 hours. The dose of all other Lena Rauber3, James Kennedy3, Adelheid Gauly2, Hans Schmidt-Gürtler4
1
recommended drugs was adapted according to the patients’ eGFR. PHV-Dialysis Center, Goslar, Germany, 2Fresenius Medical Care, Global Medical Office,
RESULTS: A total of 63 patients were admitted in our Department and were under our Bad Homburg, Germany, 3Fresenius Medical Care, Global Research & Development, St.
care, presenting medium or severe forms of SARS-CoV-2 infection. After applying the Wendel, Germany and 4Zentrum für Nieren-, Hochdruck- und
inclusion and exclusion criteria, only 38 patients were considered eligible: 21 male Stoffwechselerkrankungen, Hannover,
patients (mean age 63.52 6 13.82 years), and 17 female patients (mean age 67.24 6
12.83 years). 31.57% represented the percentage of death during the hospitalization BACKGROUND AND AIMS: Hemodialyzers containing membranes made from a blend
(due to the severity of the disease, 4 patients died within 24 hours) in patients of polysulfone and polyvinylpyrrolidone (PVP) are widely used. PVP makes the membrane
presenting heterogenous comorbidities, such as diabetes mellitus, hypertension, pre- material more hydrophilic to reduce interactions with plasma proteins and platelets. A
existing glomerulonephritis and/or oncological pathologies; we also noticed that female modified spinning technique has been established to stabilize the PVP on the blood-side
gender represented 58.33% of the deceased patients. The mean hospitalization period surface in the polysulfone dialysis membrane in the new dialyzer FX CorAL 600.
in the deceased patients was 6.42 6 5.38 days – 4 6 3.21 days in female gender, and 9.8 The objective of the present study was to prove for this new dialyzer non-inferiority of
6 6.30 days in male gender. performance in comparison to established dialyzers. Further, hemocompatibility and
CONCLUSION: Most of our patients, although diagnosed with medium and severe safety of the dialyzers were explored.
forms of SARS-CoV-2 infection, presented a favorable evolution, and an adequate METHOD: In a multicenter, prospective, randomized, crossover study adult patients
response to the specific medication. We observed that most of the deceased cases were on online hemodiafiltration (HDF) were enrolled. They were treated for one week each
female patients, and compared to the male deceased subject, female deceased patients with on-line HDF in post-dilution mode, and in randomized order with the dialyzers
presented a lower period of hospitalization. Therefore, probably female CKD patients FX CorAL 600, FX 600, and FX CorDiax 600 (all Fresenius Medical Care, Bad
with comorbidities and diagnosed with COVID-19 are more predisposed to an Homburg, Germany). Blood samples were taken on the midweek session before start,
unfavorable prognosis. Further and larger clinical trials are necessary to validate the at the end to analyze removal rate and at 60 min to determine clearance of ß2-
impact of SARS-CoV-2 infection on mortality in CKD patients. microglobulin, myoglobin, urea, creatinine and phosphate. Further a pattern of
hemocompatibility parameters and safety was evaluated. Assuming no carry over
effect, linear mixed models were used for statistical analysis.
RESULTS: The mean age of the 49 enrolled patients was 66.3613.6 years, 76% were
male. Treatments were performed in post-dilution mode with a mean blood flow > 300
mL/min and a substitution volume >19 L.
The removal rate of ß2-microglobulin was 74.4, 70.4, and 73.1% for the FX CorAL 600,
FX 600, and FX CorDiax 600 dialyzer, respectively. FX CorAL 600 proved to be
statistically significantly non-inferior to FX 600 (p=0.0006) and to FX CorDiax 600
(p=0.036). The removal rate of FX CorAL 600 was by 4.0% (confidence interval 0.4 –
7.5%) significantly higher than with FX 600. The difference to FX CorDiax 600 was not
significant. The clearance of ß2-microglobulin and myoglobin and the removal rate of
myoglobin were significantly higher with the new dialyzer FX CorAL 600 than with the
FX 600, and comparable to the FX CorDiax 600. Performance for small molecules was
similar for all dialyzers.

10.1093/ndt/gfab082 | i261
Abstracts Nephrology Dialysis Transplantation

The complement factors C3a and C5a increased early in the treatment with a peak at 15 MO389 PREDICTORS OF COMMUNITY-ACQUIRED ACUTE KIDNEY
min, without differences between the three dialyzers for C3a, and for C5a with significantly INJURY IN PATIENTS WITH ACUTE CARDIAC DISEASES
lower increase at 15 min with FX CorAL 600 than for FX 600 (p=0.007); the difference of
increase between FX CorAL 600 and FX CorDiax 600 was not significant (p=0.515). The Marina Efremovtseva1, Svetlana Avdoshina1, Maria Markova1, Zhanna Kobalava1
1
course of sC5b9 was similar for all three dialyzers, with significantly lower increase at 15 min Peoples’ Friendship University of Russia (RUDN University), Department of Internal
for both FX CorAL 600 (p=0.009) and FX CorDiax 600 (p=0.026) as compared to FX 600 Medicine, Moscow, Russia
and similar increase at 60 min for both FX CorAL 600 (p=0.573) and FX CorDiax 600
(p=0.386) as compared to FX 600. The area-under-the-curve for the course of sC5b-9 with BACKGROUND AND AIMS: Acute kidney injury (AKI) is a common and serious
FX CorAL 600 was significantly lower than with FX 600 (p=0.044) and comparable to FX problem associated with poor prognosis. The aim of the study was to reveal the
CorDiax 600 (p=0.092). The leukocyte count showed a decrease in the first 15 min of the prevalence and predictors of community-acquired AKI in patients with acute cardiac
treatment, which recovered afterwards, similarly for all treatment phases with the different diseases.
dialyzers. Further, the dialyzers did not differ with respect to adverse events. METHOD: 566 patients (278 with acute decompensated heart failure (ADHF), 288
CONCLUSION: All three dialyzers showed good performance, with higher removal with non-ST-elevation acute coronary syndrome (NSTE-ACS), 46% male, 71611 years
rates for middle molecules with the new dialyzer FX CorAL 600 compared to the FX (M6SD), smokers 26%, arterial hypertension 91%, previous myocardial infarction
600. Hemocompatibility profiles were mostly similar, with lower activation of C5a and (MI) 45%, diabetes mellitus (DM) 28%, atrial fibrillation 35%, chronic kidney disease
of sC5b9 with FX CorAL 600 compared to FX 600. The new dialyzer provides (CKD) 46%, previous hospitalization with ADHF 36%, ejection fraction (EF) <35%
comparable performance levels capable of delivering adequate treatment and good 15%, blood pressure (BP) 142630/83616 mmHg) were examined. AKI was diagnosed
tolerability for the patient. according 2012 KDIGO Guidelines. Community-acquired AKI was identified in
patients with elevated serum creatinine levels on admission, which decreased during
hospitalization.
MO388 DEVELOPMENT OF ACUTE KIDNEY INJURY DURING A RESULTS: : Incidence of AKI in all patients, patients with ADHF and NSTE-ACS was
RHABDOMYOLYSIS EPISODE: DIFFERENCES IN LONG- 40, 43.5 and 37.2%. In-hospital mortality in patients with AKI was higher than in those
TERM KIDNEY FUNCTION with stable kidney function (14.9 vs 3.6%, p<0.001). Community-acquired AKI was
present in 18% of patients (20.5 and 15.6% in ADHF and NSTE-ACS respectively), in-
Sara Nun~ez Delgado1, Miren Iriarte-Abril1, Ju
lia Farrera-Nu
n~ez1, Sergi Pascual- hospital mortality was 16.7% (10.5 and 24.4% respectively). The risk assessment scale
Sanchez1, Laia Sans-Atxer1, Adriana Sierra-Ochoa1, Clara Barrios-Barrera1, M for community-acquired AKI was developed based on independent predictors of AKI,
Dolores Arenas-Jiménez1, Julio Pascual1, Eva Rodrıguez Garcıa1 using binary logistic regression and ROC analysis (AUC 0.860, 95% CI 0.821-0.898).
1 Independent variables included in the model, and the corresponding points (pts) are
Hospital del Mar, Nephrology Department, Barcelona, Spain
listed below: clinical and demographic characteristics (male gender - 6 pts, alcohol
abuse - 7 pts, DM - 1 pt), present on admission (MI - 5 pts, AHF/ADHF - 9 pts, systolic
BACKGROUND AND AIMS: Acute renal failure (AKI) associated to rhabdomyolysis BP <120 - 10 pts, <110 - 15 pts, <90 mmHg - 27 pts; state of kidney function on
conditions a worse prognosis in short-term, its implication in the long-term renal admission: serum creatinine >98 and >128 mkmol/L - 14 and 22 pts, GFRCKD-EPI <45
function has been less evaluated. and <15 ml/min/1.73 m2 - 7 and 14 pts; glucose level >7 mmol/L - 4 pts), outpatient
METHOD: Retrospective analysis of patients diagnosed with rhabdomyolysis defined intake of ACE inhibitors - 4 pts, absence of spironolactone in outpatient therapy - 1 pt.
by creatinine kinase > 5000 IU/L between 2015-2019. Basal and 12-month renal Diagnostically significant risk score for predicting AKI was >30 pts, the risk prediction
function was evaluated. AKI was classified as either non-severe (AKI-KDIGO 1/2) or model showed sensitivity 89%, specificity 66%.
severe (AKI-KDIGO 3). CONCLUSION: Community-acquired AKI is common in patients in acute
RESULTS: Eighty-seven patients were included, 25 (28.74%) had some degree of chronic cardiovascular events, is associated with high mortality, and often is underdiagnosed.
kidney disease (CKD) on admission. 56 (64.37%) had AKI on admission, 17 of which were Usage of risk assessment scale in clinical practice may help to detect patients with high-
severe (6 required hemodialysis). The patients with AKI had more cardiovascular disease risk of AKI on admission. Baseline kidney function and blood pressure level are main
(CVD) and worse analytical parameters on admission (table). Patients with severe AKI predictors of AKI in patients admitted with acute cardiac diseases.
showed no difference in CVD from those with non-severe AKI but were younger and had
more hyperkalemia. There were no significant differences between patients with severe AKI
who required hemodialysis and those who did not. Inpatient mortality was 8%, higher in
patients with AKI but without differences according to severity. MO390 THE RISK FACTORS AND CLINICAL OUTCOMES
In 45 patients kidney function was available 12 months after the episode, loss of eGF ASSOCIATED WITH ACUTE KIDNEY INJURY IN PATIENTS
was -4.90 6 14.35 ml/min-1.73m2 (p=0.007). There was no difference between WITH COVID-19
patients who developed AKI and those who did not (-4.10 6 14.4 vs. -5.39 6 14.57 ml/
min-1.73m2; p=0.67), nor between non-severe and severe AKI (-5.50 6 14.76 vs. -5.12 Hormat Rahimzadeh Eshkalak1, Hossein Farrokhpour2, Sina Kazemian2,
6 15.08ml/min-1.73m2; p=0.98). Of the 33 patients without previous CKD, 5 Maryam Rahbar3, Mahnaz Montazeri4, Samira Kafan5, Ahmad Salimzadeh6,
developed CKD, with greater decrease in eGF than those who did not (-22.69 6 6.04 Mohammad Talebpour7, Fazeleh Majidi8, Atefeh Gannatalipour9,
vs. -2.63 6 13.92 ml/min-1.73m2; p=0.003). Female sex (60% vs. 12%; p=0.031) and Effat Razeghi10,11
1
previous basal eGF (72.22 6 4.37 vs. 95.6619.97 ml/min-1.72m2; p=0.016) were Tehran University of Medical Sciences, Tehran, Iran, Department of Nephrology
related to this deterioration. Disease, Sina Hospital, Tehran, Iran, 2Tehran University of Medical Sciences, Tehran,
CONCLUSION: After an episode of rhabdomyolysis, the loss of eGF is similar in Iran, Students’ Scientific Research Center (SSRC), Tehran, Iran, 3Tehran University of
patients who develop AKI compared to those who do not. Medical Sciences, Tehran, Iran, Department of Nephrology Disease, Tehran, Iran,
4
Tehran University of Medical Sciences, Tehran, Iran, Department of Infectious Diseases,
Tehran, Iran, 5Tehran University of Medical Sciences, Tehran, Iran, Department of
Pulmonary Diseases, Tehran, Iran, 6Tehran University of Medical Sciences, Tehran, Iran,
Rheumatology Research Center, Tehran, Iran, 7Tehran University of Medical Sciences,
Tehran, Iran, Department of Surgery, Tehran, Iran, 8Tehran University of Medical
Sciences, Tehran, Iran, Research Development Center, Tehran, Iran, 9Tehran University
of Medical Sciences, Tehran, Iran, Research Development Center, 10Tehran University of
Medical Sciences, Tehran, Iran, Nephrology Research Center, Center of Excellence in
Nephrology, Tehran, Iran and 11Tehran University of Medical Sciences, Tehran, Iran,
Department of Nephrology Disease,Sina Hospital

BACKGROUND AND AIMS: Kidney involvement, ranging from mild hematuria and
proteinuria to acute kidney injury (AKI) in patients with coronavirus disease-2019
(COVID-19), is a recent finding with various incidence rates reported among
hospitalized patients with COVID-19. Current evidence on AKI rate in patients
hospitalized with COVID-19 and its associated risk factors is limited, especially in Iran.
METHOD: In this retrospective cohort study, we enrolled adult patients referred to the
Sina hospital, Iran, from 20 February to 14 May 2020, with either a positive PCR test or
a highly susceptible chest computed tomography features (CT) consistent with
COVID-19 diagnosis. AKI was defined according to the kidney disease improving
global outcomes (KDIGO) criteria, and patients were stratified based on their AKI
staging. We evaluated the risk indicators associated with AKI during hospitalization
besides in-hospital outcomes and recovery rate at the time of discharge.
RESULTS: : We evaluated 516 patients with a mean age of 57.6616.1 years and a male
to female ratio of 1.69 who were admitted with the COVID-19 diagnosis. AKI
development was observed among 194 (37.6%) patients, comprised of 61.9% patients
in stage 1, 18.0% in stage 2, and 20.1% in stage 3. Out of all patients, AKI occurred in
58 (11.2%) patients during the hospital course, and 136 (26.3%) patients arrived with

i262 | Abstracts
Nephrology Dialysis Transplantation Abstracts
AKI upon admission. AKI development was positively associated with all of the in- Table-2. Mean PNI of the patients who survived was higher than patients who were
hospital outcomes, including intensive care unit admissions, need for invasive exitus.
ventilation, acute respiratory distress syndrome (ARDS), acute cardiac injury, acute CONCLUSION: AKI in hospitalized patients with COVID-19 was associated with
liver injury, multi-organ damage, and mortality. Patients with stage 3 AKI showed a high mortality. Of all patients with AKI, only 18.4% survived.
significantly higher mortality rate, ARDS, and need for invasive ventilation than other
stages. After multivariable analysis, male sex (odds ratio (OR):11.27), chronic kidney
disease (OR: 6.89), history of hypertension (OR:1.69), disease severity (OR; 2.27), and
high urea levels (OR: 1.04) on admission were independent risk indicators of AKI
development. Among 117 (28.1%) patients who experienced AKI and survived, only 33 Dischargedn= 9 Deadn=40 p
(28.2%) patients made a recovery from the AKI, and 84 (71.8%) patients did not Age 78.366.6 74.8613.4 0.451
exhibit full recovery at the time of discharge.
CONCLUSION: We found that male sex, history of chronic kidney disease, Gender (male/female) 5/4 23/17 1.000
hypertension, disease severity, and high serum urea were independent risk factors PNI 32.467.2 25.266.3 0.049
associated with AKI in patients with COVID-19. Also, higher stages of AKI were
WBC 10.465.6 16.8610.4 0.017
associated with increased risk of mortality and in-hospital complications. Our results
indicate a necessity for more precise care and monitoring for AKI during Neutrophil 8.365.8 14.369.2 0.011
hospitalization in patients with COVID-19, and lack of AKI recovery at the time of Lymphocyte 1.26 (0.55-1.80) 0.64 (0.40-1.33) 0.159
discharge is a common complication in such patients.
NLR (Neutrophil/ 5.59 (3.48-10.47) 19.7 (10.5-28) 0.025
Lymphocyte Ratio)
MO391 RISK FACTORS OF ACUTE KIDNEY INJURY IN SEVERE Hemoglobin (g/dL) 10.661.8 10.862.3 0.877
ACUTE RESPIRATORY ILLNESS DURING CORONAVIRUS Creatinine 2.1560.96 2.1961.53 0.597
DISEASE 2019 PANDEMIC
LDH 213 (164-312) 683 (293-1379) <0,001
Wee Leng Gan1, Boon Huei Kong1 AST 16 (12-34) 43 (26-87) 0.012
1
Hospital Bukit Mertajam., Department of General Medicine., Penang., Malaysia Troponin T 0.042 (0.024-0.078) 0.109 (0.056-0.0583 0.050
Procalcytonin 0.195 (0.145-0.253) 0.945 (0.310-2.448) 0.070
BACKGROUND AND AIMS: Acute Kidney Injury (AKI) is associated with poor
outcome in severe acute respiratory illness (SARI) during Coronavirus Disease 2019 Ferritin 240 (99-872) 690 (456-1238) 0.048
(COVID 19) pandemic. This study aim at detetction of risk factors for AKI among D-dimer 604 (425-1895) 4083 (1898-6376) 0.003
patients admitted for SARI at our Center for COVID 19 screening. CRP 19.3 (14.2-35.7) 142.0 (85.6-259.3) <0.001
METHOD: Restrospective study by reviewing admission notes from March 2020 until
December 2020 at our district center. Patient aged more than 18 year old who admitted
for SARI as defined by World Health Organisation and AKI as defined by Kidney
Disease Improving Global Outcome (KDIGO) guideline were included. Chronic
kidney disease and End stage Renal Failure as defined by KDIGO were excluded.
RESULTS: A total 230 ( 56%) patients out of 410 patients with SARI had AKI during
hospitalisation. The mean age was 72 years old (SD 13.8), 130 (56.5%) were male and
100 ( 43.5%) were female. SARI patients with AKI took mean 5 days ( SD 0.9) to be Before treatment After treatment p
admitted at our center from the first day of illness. The mean body mass index (BMI) PNI 32.167.2 25.266.3 <0.0001
was 27.2 kg/m2 . The mean arterial pressure was 52.1 ( SD 3.7) mmhg upon admission.
The mean neutrophils lymphocytes ratio ( NLR ) was 22.4 (SD 2.4). The independant WBC 12.368.5 16.8610.4 0.011
Risk factors for AKI in SARI are Male gender ( OR 0.95; 95% CI 0.35-2.6), smoking ( Neutrophil 10.167.7 14.369.2 0.012
OR 0.72 ;95% CI 0.23- 2.3), ischaemic heart disease (OR 0.48; 95% CI 0.06-3.8),
Lymphocyte 0.80(0.51-1.41) 0.64(0.40-1.33) 0.973
diabetes mellitus ( OR 1.15; 95% CI 0.39-3.38) and hypertension ( OR 1.58; 95% CI
0.58-4.25). Hemoglobin (g/dL) 11.462.47 10.862.3 0.008
CONCLUSION: Non modifiable risk factors for AKI in SARI include male gender and NLR 11.2(4.3-19.2) 19.7 (10.5-28) 0.013
advance age. The modifiable risk factors for AKI in SARI are over weight, smoking,
ischemic heart disease, diabetes mellitus and hypertension. NLR play a role in CRP (mg/dL) 110.5 (35.8-147.9) 142(85.6-259.3) 0.009
predicting AKI among SARI patients. Delay hospitalisation and hypoperfusion Creatinin (mg/dL) 1.4961.21 2.1961.53 0.033
predispose to AKI in SARI. Early recognition of risk factors is crucial in preventing LDH 398 (282-592) 683 (293-1379) 0.011
deterioration of kidney function in SARI patients during the inital screening for
COVID 19 infection. Troponin T 0.057(0.021-0.234) 0.109 (0.056-0.583) 0.004
Procalcitonin 0.275 (0.140-2.220) 0.945 (0.310-2.448) 0.327
Ferritin 514 (239-1210) 690 (456-1238) 0.026
MO392 ACUTE KIDNEY INJURY IN HOSPITALIZED PATIENTS WITH D-dimer 2451 (997-4955) 4083 (1898-6376) 0.045
COVID-19: A SINGLE-CENTER EXPERIENCE

Tulin Akagun1, Arzu Ayraler2, Murat Usta3, Süleyman Baylan4, Ahmet


Cumhur Dulger5
1
Giresun University Faculty of Medicine, Nephrology, Giresun, Turkey, 2Giresun
University Faculty of Medicine, Family Medicine, Turkey, 3Giresun University Faculty of
Medicine, Biochemistry, Turkey, 4Giresun University Faculty of Medicine, Internal
Medicine, Turkey and 5Giresun University Faculty of Medicine, Gastroenterology, Turkey

BACKGROUND AND AIMS: Preliminary reports indicate that AKI (acute kidney
injury) seem to be associated with coronavirus disease 2019 (COVID-19) severity
and outcomes. Although the reported incidence of AKI among hospitalized
patients with COVID-19 varies widely, AKI among hospitalized patients is
associated with poor prognosis. The aim of this study was to evaluate the clinical
characteristics and outcomes in our COVID-19 patients who developed AKI during
intensive care unit hospitalization.
METHOD: In our retrospective, observational study COVID-19 PCR positive 49
patients who were hospitalized with COVID-19 pnumoniae in intensive care unit and
developed AKI were evaluated with demographics, laboratory data, treatment and
outcome. The prognostic nutritional index (PNI), which is calculated using the serum
albumin concentration and total lymphocytic count were also evaluated. All patients
were treated with favipiravirþlow molecular weight heparin; laboratory tests were
recorded before and after favipiravir treatment.
RESULTS: Of 49 patients; 28 were male. A total of 9/49 (18.4%) patients survived. All
patients were treated with favipiravir; laboratory tests were recorded before and after MO392 Figure 1: Clinical and laboratory findings of patients after favipiravir treatment.
favipiravir treatment. The clinical parameters of patients are shown in Table-1 and

10.1093/ndt/gfab082 | i263
Abstracts Nephrology Dialysis Transplantation

MO392 Figure 2: Laboratory findings of the non-survived patients before and after
favipiravir treatment (n=40).

MO393 ACUTE RENAL REPLACEMENT THERAPY IN CRITICAL ILL constant production rate by roughly 100 mmol/l every day. This rise leads to the
OCTOGENARIAN OR OLDER PATIENTS: PROGNOSTIC corresponding bisection of the estimated eGFR nearly every day (100 => 50 => 25 =>
FACTORS AND RENAL OUTCOMES 13 => . . . ml/min). The curvilinear eGFR decline will never become zero even after >
2 weeks. The new kinetGFR can identify a complete anuria already after one day (24 h).
Jimena Del Risco1, Joaquim Casals1, Evelyn Hermida-Lama1, Luis F. Quintana1,
Miquel Blasco1, Gaston Pin ~eiro1, Esteban Poch1, Ali-cia Molina Andujar1
1 100  50
Hospital Clınic de Barcelona, Nephrology, Barcelona, Spain kinetGFR ¼ 50   24 ¼ 0:0 ml=min
24  0
BACKGROUND AND AIMS: a growing number of octogenarians or older patients
are being admitted to the intensive care unit (ICU). The aim of this study was to assess This is already at the critical day (t2).
factors associated with acute renal replacement therapy (ARRT) requirement in these RESULTS: The retrospective look at the anonymized data from 20 patients with AKD
patients and the impact of ARRT on the 90-day ICU mortality. Also we aimed to allowed for comparing the former KeGFR with the new two-point kinetGFR estimate.
identify prognostic factors associated with mortality risk in the group of patients that For worsening kidney function, the average eGFR2 was 18 ml/min (þ 12) and the
required ARRT. KeGFR estimate was not different with 19 ml/min (þ 17). The new 2-point kinetGFR,
METHOD: retrospective study of octogenarian or older patients admitted to the ICUs however, was 13 ml/min (þ 11) and 28 % less than eGFR2 at the critical day (t2). For
of Hospital Clınic de Barcelona from June 2007 to April 2019. Patients on chronic improving kidney function, the eGFR2 was 15 ml/min (þ 4) and the KeGFR was
dialysis treatment or kidney transplant, and patients with limitation of therapeutic already much higher at 27 ml/min (þ 3). The new 2-point estimate of the kinetGFR
support or admitted for less than 48 hours were excluded. was in between at 21 ml/min (þ 7).
RESULTS: 217 patients were included in the study, of which 36.4% required ARRT. CONCLUSION: In AKD, the difference between eGFR and presumably true GFR was
Use of vasoactive drugs and Sequential Organ Failure Assessment (SOFA) score on the higher the more rapidly kidney function declined. The new kinetGFR estimate
admission were higher in ARRT patients (p=0.009 and <0.001). Basal estimated appears clinically more plausible than the former KeGFR estimates.
glomerular filtration rate (eGFR) was lower in the ARRT cohort (p<0.001). Hospital
and ICU length of stay were longer in the ARRT cohort (p<0.001). Ninety-day
mortality was 58.2% in the ARRT cohort and 55.8% in the control cohort, without
MO395 EPIDEMIOLOGY AND OUTCOME OF PATIENTS WITH ACUTE
statistical differences. In the survival analysis, only female sex and non-renal SOFA
KIDNEY INJURY REQUIRING DIALYSIS: ABOUT 230 CASES
6.5 were significantly associated with mortality (p= 0.005 and 0.002 respectively) in
the ARRT cohort.
Yosra Elouaer1, Yosra Guedri1, Mohamed Riadh Troudi1, Awatef Azzabi1,
CONCLUSION: mortality was not significatively increased in the octogenarian
Sanda Mrabet1, Wissal Sahtout1, Asma Fradi1, Narjes Ben Aicha1,
population that required and got ARRT respect to those who did not require it. Scores
Dorsaf Zellama1, Abdellatif Achour1
like SOFA can help in the process of decision making about initiation of ARRT. 1
SAHLOUL UNIVERSITY HOSPITAL, NEPHROLOGY, DIALYSIS AND TRANSPLANTATION,
SOUSSE, Tunisia

MO394 TWO POINT ESTIMATE OF KINETIC GFR IN ACUTE KIDNEY


BACKGROUND AND AIMS: Acute renal injury (ARI) is a frequent pathology. Rarer
DISEASE
are the studies dedicated specifically to the subgroup requiring dialysis. The objective of
our study is to identify: The epidemiological profiles of patients with ARI requiring
Frieder Keller1
1
dialysis. The course of the dialysis sessions to determine the dialysis’ prescription and
University Hospital of Ulm, Internal Medicine 1, Nephrology, Ulm, Germany the different accidents.
METHOD: This is a descriptive cross-sectional study including patients admitted to
BACKGROUND AND AIMS: When anuria suddenly occurs, the rise in creatinine the different departments of Sousse University Hospitals in Tunisia who presented an
and consequently the decrease in the estimated glomerular filtration rate (eGFR) will ARI requiring emergency dialysis. Our study was conducted from February 2015 until
always be delayed. Thus, the drug dose could be selected too high in the progressive August 2018. The data collected were analysed by the SPSS software.
phase whereas it could be adjusted too low in the restitution phase of acute kidney RESULTS: During three and a half years, 230 patients presented ARI requiring
disease (AKD). Sheldon Chen proposed a solution for changing kidney function with dialysis. The average age was 60 6 16 years old. The sex ratio was 1.61. A history of
the kinetic GFR (KeGFR). A simplified but also more general solution (kinetGFR) hypertension, diabetes, heart disease, dyslipidaemia, hyperuricemia, uropathy and
might even facilitate the automatic implementation into lab systems. neoplasia was noted in respectively 34.9%, 27.1%, 21.6%, 22.7%, 25.5%, 22.7% and
METHOD: Deterioration of kidney function is diagnosed when the creatinine 14.3% cases. The causes of ARI were dominated by organic, obstructive and functional
increases within a definite time interval (D t) and the estimated eGFR declines (D causes in 66.2%, 21.7% and 7.4% of cases, respectively. For organic causes, we noted
eGFR). The new 2-point estimate of the kinetGFR can be derived when the prospective acute tubular necrosis in 70.4% of cases, a glomerular cause in 14.5% of cases, an
eGFRtþ24 predicted for the next day (tþ24) will be set equal to the present true GFR at interstitial cause in 7.9% of cases and a vascular cause in 7.2% of cases. Dialysis
critical day (t2). indications were dominated by severe acidosis, pulmonary oedema, uremic syndrome
and hyperkalaemia in 27.4%, 24.3%, 16.5% and 14.3% of cases, respectively. Among
our patients, 26.7% presented a hemodynamic instability with catecholamine use in
eGFR1  eGFR2 16.8% of cases and the use of isovolumic connection at the beginning of the session in
kinetGFR ¼ eGFR2   tþ24 h 21.2% of cases. The median ultrafiltration was 444 ml / hour IQR [166, 67-750] with
t2  t1
extremes of 0 to 1333 ml/hour. The median blood flow was 250 ml/min IQR [250-280]
with extremes of 180 to 300 ml/min. The median duration of dialysis’ session was 180
The 24 h delay follows from anuria, the most extreme and most relevant case (GFR = minutes IQR [180,240] with extremes of 15 to 360 minutes. We noted dialysis incidents
0). A zero GFR will be associated with a linear rise in creatinine according to the

i264 | Abstracts
Nephrology Dialysis Transplantation Abstracts
in 12% of dialysis’ sessions. These events were dominated by hypotension, occurring in s-AKI was independently associated with an increased hazard of
hypoglycaemia, extracorporeal circuit coagulation, death and chest pain in 13.8%, intrahospital death (HR: 1.36; 95% CI: 1.09–1.51), compared to the non-NOAF group.
4.8%, 2.6%, 2.1% and 0.7% of cases, respectively. The cessation of dialysis sessions was CONCLUSION: A clinically significant number of patients hospitalized for s-AKI
noted in 22 sessions (11.1%). have NOAF, and it is associated with poor hospital outcomes.
Concerning the evolution of patients: 33.1% of patients recovered normal renal
function, 23.9% of patients maintained renal failure, 22.2% of patients died and 20.8%
of patients were lost from seen or the duration of their follow-up was less than three
MO398 DETERIORATION OF RENAL OUTCOMES AND INCREASED
months not making it possible to conclude as to the chronicity of the renal
MORTALITY RISK DUE TO ACUTE KIDNEY INJURY AFTER
insufficiency.
ORTHOTOPIC LIVER TRANSPLANTATION: SYSTEMATIC
CONCLUSION: ARI is a common and serious pathology. Dialysis is an important
REVIEW AND META-ANALYSIS OF COHORT STUDIES
evolutionary step. It is associated with a high risk of progression to chronic renal failure
and mortality. Optimal management of ARI is required.
Boby Pratama Putra1, Felix Nugraha Putra2
1
Medical doctor, Blitar, Indonesia and 2Faculty of Medicine, Universitas Airlangga,
Surabaya, Indonesia
MO396 NOVEL ENDOTHELIAL INFLAMMATION BIOMARKERS IN
SNAKEBITES-ASSOCIATED ACUTE KIDNEY INJURY
BACKGROUND AND AIMS: Orthotopic liver transplantation (OLT) procedure is
increased as incremental end-stage liver disease patients’ prevalence. Acute kidney
Sandra Maria Brasileiro Mota1, Polianna Lemos Moura Moreira Albuquerque1,2,
injury (AKI) is one of most common post-OLT complications that is associated with
Gdayllon Cavalcante Meneses3, Francisco Marcio Tavares Holanda1,
poor renal outcomes and increased mortality risk although the results are still
Mariana Oliveira Brizeno1, Alvaro Rolim Guimaraes3, Alice Maria Costa Martins3,
inconclusive. This study aims to measure the risk of deterioration of renal outcomes
Geraldo Bezerra da Silva Junior2, Elizabeth De Francesco Daher3
1
and mortality risk due to AKI incidence in post-OLT patients.
Toxicological Assistance Center, Instituto Dr Jose Frota Hospital, Fortaleza, Brazil, METHOD: We did comprehensive searching using predefined terms in online
2
University of Fortaleza, Fortaleza, Brazil and 3Federal University of Cear
a, Fortaleza, databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include
Brazil all relevant studies from 2000-2020. We included all cohort studies that reported AKI
incidence in post-OLT patients and accessed the risk of 3-month renal replacement
BACKGROUND AND AIMS: Acute kidney injury (AKI) is a frequent and potentially therapy (RRT) need, 1-year chronic kidney disease (CKD) progression, and 1-year
fatal complications of snakebites. Coagulation disturbances are observed and have a mortality rate. We used The Newcastle-Ottawa Scale for cohort study for accessing bias
high probability to be involved in AKI pathogenesis. Novel endothelial inflammation risk. We conducted analysis to pooled risk ratio (RR) with 95% confidence interval (CI)
biomarkers are capable of predicting disease severity and could be used in the setting of using random-effect heterogeneity test.
snakebites. RESULTS: We included 10 cohort studies met our inclusion criteria. The AKI
METHOD: This is a prospective study conducted at the Instituto Dr. José Frota, a incidence significantly both increases the need of RRT in post-OLT patients (pooled
reference hospital for toxicological assistance in Fortaleza, Northeast Brazil. Blood and RR = 8.41. 95% CI = 2.82 to 25.09, p = 0.0001, I2 = 0%) then leads the CKD progression
urine samples were collected from patients admitted after snakebite accident, without in one year (pooled RR = 6.76. 95% CI = 2.03 to 22.51, p = 0.002, I2 = 84%). The post-
comorbidities, in 3 different time-points post-bite: on admission (until 8h post-bite), OLT patients who suffered from AKI has significant incremental 1-year mortality risk
12 to 16h, and 24-48h. The samples were stored in microtubes, frozen in a freezer (- (pooled RR = 7.27. 95% CI = 4.34 to 12.18, p<0.00001, I2 = 5%).
80 C) until performance of the laboratory tests. To measure the novel biomarkers the CONCLUSION: The incidence of AKI in post-OLT patients significantly increase the
following ELISA kits were used: Angiopoietin-1 (R&D Systems–Duoset DY623), deterioration of renal outcomes and mortality risks. However, further trials are needed
Angiopoietin-2 (R&D Systems–Duoset DY623) and Vascular cell adhesion protein 1 to establish the causalities.
(VCAM-1) (Abcam–ab47355). All procedures were conducted according to the
manufacturer’s guidelines. AKI was defined according to Kidney Disease Improving
Global Outcomes (KDIGO) criteria. Patients were divided in 2 groups: with and
MO399 PROFILE OF ACUTE KIDNEY INJURY IN CRITICAL CARE
without AKI.
PATIENTS
RESULTS: A total of 26 patients were included in the study:23 (88.5%) victims of
Bothrops accident and 3 (11.5%) Crotalus accidents. AKI was observed in 11 cases. The
Jayannan J1, Kevin T John Keeppallil2, Georgi Abraham1
2 groups did not differ in age, gender, electrolytes levels, creatine kinase (CK), 1
hemoglobin and hematocrit levels. There were significant differences regarding the Pondicherry Institute of Medical Sciences, Department of General Medicine,
levels of angiopoietin 1 (16.3968.1 vs 4.3567.36; p=0.0054) and VCAM-1 (12936528 Pondicherry, India and 2Sri Ramachandra Institute of Higher Education and Research,
vs 811.36234; p=0.0175), both in the second sample (12-16h after bite). The analysis of Department of Nephrology, Chennai, India
ROC curve revealed that angiopoietin 1 (AUC: 0.8182, 95% CI0.63–0.99, p=0.0064)
and VCAM-1 (AUC: 0.77, 95% CI0.57–0.97, p=0.0182) presented good accuracy for BACKGROUND AND AIMS: Acute kidney injury is a global health problem. This
AKI prediction in the studied population. study aims to determine the risk factors for poor outcome and to describe the clinical
CONCLUSION: Endothelial inflammation biomarkers (VCAM-1 and angiopoietin 1) profile, etiology & outcomes of patients with Acute Kidney Injury (AKI) admitted to
have good accuracy for snakebites-associated AKI diagnosis. The time 12-16h after the the Critical Care Unit from a tertiary care centre in South India.
bite had the best result in predicting AKI in this setting. METHOD: It was a prospective cohort study conducted in a tertiary care hospital in
South India from December 2016 to Novemeber 2019. All patients in the ICU were
screened for enrolment in AKI using RIFLE criteria with creatinine, GFR and urine
output daily for a period of seven days.
MO397 THE IMPACT OF NEW-ONSET ATRIAL FIBRILLATION ON
RESULTS: A total of 152 patients were taken for final analysis after exclusions. The
ADVERSE OUTCOMES IN PATIENTS WITH SEPSIS-INDUCED
mean age of the subjects was 44.15 years. Majority of the study subjects (55.9%)
ACUTE KIDNEY INJURY
belonged to 26 – 50 years of age. Majority of the study subjects were females (51.3%)
and the rest were males. Sepsis was found to be present in 52% (79) of the study
Zorica Dimitrijevic1, Branka Mitic1, Sonja Salinger2, Goran Paunovic1,
subjects followed by Gastrointestinal loss 36.2% (55), crush injury 9.03% (15), snake
Stevan Glogovac1, Danijela Tasic1
1
bite 3.3% (5), poisoning 4.6% (7) and acute liver failure 1.3% (2). It was found that
Clinical Center Nis, Clinic for nephrology, Nis, Serbia and 2Clinical Center Nis, Clinic for 62.5% (95) of the study subject’s AKI had resolved after appropriate management.
cardiovascular disease, Nis, Serbia Among the rest of the study subjects,27.6% required haemodialysis for recovery, 3.3%
had persistence of AKI, 3.9% progressed to CKD and 2.6% died. The latter three
BACKGROUND AND AIMS: The mortality of septic patients with acute kidney categories were considered as poor outcomes of AKI. In our study, 29.8%people who
injury (s-AKI) prevails high. Atrial fibrillation is commonly observed in the setting of had systemic hypertension and 28.2%people who had diabetes mellitus had poor
systemic inflammation or infection. The study aimed to assess the incidence and outcome. It was found that in our study, sepsis and GI loss both contributes to poor
predictors of new-onset atrial fibrillation (NOAF) in this population and its impact on outcome of AKI in univariate regression analysis whereas Gastrointestinal loss alone
intrahospital mortality. contributes to poor outcome of AKI with multivariate regression analysis.
METHOD: We conducted a retrospective cohort study of 462 patients admitted to our CONCLUSION: In conclusion, even though sepsis is the commonest cause of AKI,
unit for s-AKI between January 2016 and December 2020. NOAF was defined as AF Gastrointestinal loss independently contributes to poor outcome of AKI. Majority of
discovered during hospitalization in patients with sinus rhythm on admission. Subjects the people recovered from AKI spontaneously with conservative management. Few
were classified into NOAF (n=68) and non-NOAF groups (n=364). There were no people required dialysis for recovery of AKI & very few people progressed to CKD.
major differences in sepsis severity between groups, and all patients underwent
intermittent hemodialysis as a renal replacement treatment modality.
RESULTS: The NOAF incidence in the whole s-AKI population was 14.7%. In a
univariate analysis, age (72.4 in patients with NOAF vs. 62.1 years in patients without
NOAF, respectively; p=0.018), male gender (33.5 vs. 14.6%; p= 0.004), history of
coronary disease (23.5 vs. 6.1%; p=0.07) and vasopressor medication use (19.0 vs. 8.2%;
p = 0.002) were associated with NOAF. 116 (25.1%) patients died during the
hospitalization, while 346 patients (74.9%) were discharged from the hospital. NOAF

10.1093/ndt/gfab082 | i265
Abstracts Nephrology Dialysis Transplantation

MO399 Table 1: Association between etiological factors and outcomes of AKI

FACTOR OUTCOME OF AKI TOTAL Adjusted Odds Ratio P Value


RESOLVED AKI POOR OUTCOMES N
N (%) N (%)
Age 0.566
<25 years 8(53.3) 7(46.7) 15
26 – 50 years 56(65.9) 29(34.1) 85
>50 years 31(59.6) 21(40.4) 52
Gender 1.363 0.404
Male 49(66.2) 25(33.8) 74
Female 46(59) 32(41) 78
Acute Liver Failure 1.613 0.528
Present 2(100) 0 2
Absent 93(62) 57(38) 150
Drug History
Absent 95(62.5) 57(37.5) 152
Contrast
Absent 95(62.5) 57(37.5) 152
Snake Bite 0.897 1
Present 3(60) 2(40) 5
Absent 92(62.6) 55(37.4) 147
Poisoning 0.432 0.426
Present 3(42.9) 4(57.1) 7
Absent 92(63.4) 53(36.6) 145
MI/Cardiac Arrhythmia/Shock
Absent 95(62.5) 57(37.5) 152
Diabetes Mellitus 1.748 0.184
Present 28(71.8) 11(28.2) 39
Absent 67(59.3) 46(40.7) 113
Hypertension 1.635 0.209
Present 33(70.2) 14(29.8) 47
Absent 62(59) 43(41) 105
Gastro Intestinal Loss 11.556 0.000
Present 50(90.9) 5(9.1) 55
Absent 45(46.4) 52(53.6) 97
Sepsis 0.228 0.000
Present 37(46.8) 42(53.2) 79
Absent 58(79.5) 15(20.5) 73
Trauma/Road Traffic Accident/Crush Injury 0.36 0.089
Present 6(40) 9(60) 15
Absent 89(65) 48(35) 137

MO400 HISTOPATHOLOGICAL SPECTRUM OF SNAKE- BITE


MO399 Table 2: Univariate and multivariate analysis of the etiological factors INDUCED KIDNEY INJURY IN INDIA: A SYSTEMATIC REVIEW
and outcomes of patients with AKI.
Priti Meena1, Vinant Bhargava2, Soumyadeep Bhaumik3
1
Safdarjung Hospital, Nephrology, Delhi , India, 2Sir ganga ram hospital, Nephrology,
FACTORS UNIVARIATE MULTIVARIATE
NEW DELHI, India and 3The George Institute for Global Health, RESEARCH, Delhi , India
OR (95% CI) p value OR (95% CI) p value
Sepsis 4.389 (2.138 – 9.012) 0.000 0.908 (0.324 – 2.542) 0.854 BACKGROUND AND AIMS: Snakebite is a public health problem leading to about
Gastro 0.087 (0.032 – 0.236) 0.000 0.080 (0.022 – 0.296) 0.000 55,000 deaths every year in India. Kidney injury subsequent to snakebite
envenomation is common ( reported prevalence up to 32%). It is estimated that 3% of
Intestinal total acute kidney injury (AKI) is attributable to snakebites. The current study aims to
Loss elucidate the spectrum of renal histopathology in AKI cases followed by snake bite.
METHOD: We searched seven electronic database studies to identify studies
describing the histopathological findings in the kidney associated with snakebite
envenomation from India. Two reviewers independently conducted titles and abstract
screening as well as full-text evaluation for final inclusion decision. Data were extracted
as per a standardized form and conducted narrative synthesis.
RESULTS: We retrieved 1364 studies and finally included 21 studies involving 961
patients who met the eligibility criteria. Provisional results are presented. Patient ages
ranged from 2.5 years to 80 years. Viper bite was the commonest cause related to AKI.
92 % of the AKI were oliguric and required dialysis. kidney biopsy was usually done
after 3 weeks of AKI onset. Acute tubular necrosis (ATN) was the most common
finding followed by acute interstitial nephritis, acute cortical necrosis, and thrombotic

i266 | Abstracts
Nephrology Dialysis Transplantation Abstracts
microangiopathy (TMA).Vasculitic changes in vessels were rarely reported. A cut-off point of 24 was required for the Best predictive capacity for severe AKI, with
CONCLUSION: Oligo-anuric presentation and prolonged kidney dysfunction were sensitivity, specificity, positive and negative likelihood ratio of 34%, 94%, 5.5 and 0.7
frequent in post snake bite AKI. ATN was the common histological finding respectively.
CONCLUSION: In our population, RAI score requires a cutoff point much higher
than that originally described to predict the development of severe AKI. Losing its
discriminatory capacity.
MO401 RENAL ANGINA INDEX IN ADULT CRITICAL CARE PATIENTS
IN A POPULATION FROM BOGOTA – COLOMBIA

Alejandra Molano-Trivin ~o1,2,3, Eduardo Zu ~iga1,2, José Garcia-Habeych1,2, Juan


n MO402 ACUTE OBSTRUCTIVE RENAL FAILURE IN URGENT
Camilo Castellanos De la Hoz1,2, Noelia Nin ~o Caro1, Juan Pablo Montoya2, HEMODIALYSIS
Laura Gutiérrez Rueda2, Manuel Antonio Pérez Hettinga2, Ana Milena Mejia
Sanjuanelo4, Carlos Mauricio Martinez Montalvo2, Luis Alejandro Castro Imane Failal1, Sanae Ezzaki1, Rania Elafifi1, Mohamed Zamd1, Naoufal Mtioui1,
Durango2, Yilmar Meza Gonza lez4, Claudio Ronco3, Gregorio Romero3, Salma Elkhayat1, Ghizlaine Medkouri1, Mohamed Benghanem1,
Sandra Saumett2, Santiago Baro  n5 Benyounes Ramdani1
1 1
Fundacion Cardio Infantil Instituto De Cardiologia, Nephrology, Bogot a, Colombia, CHU ibn rochd, nephrology, casablanca, Morocco
2
Universidad Del Rosario, Universidad del Rosario escuela de medicina y ciencias de la
salud, Bogota, Colombia, 3Ospedale San Bortolo di Vicenza, International Renal BACKGROUND AND AIMS: Acute obstructive renal failure is secondary to
Research Institute Vicenza, Vicenza, Italy, 4Universidad del Norte, Colombia, Internal obstruction of the upper excretory tract occurring bilaterally or in a single anatomical
medicine, Universidad del Norte., Barranquilla, Colombia and 5Universidad de La or functional kidney. It accounts for 8 to 14% of all acute renal failure in Morocco.
Sabana, Universidad de la Sabana, medicine school, Chıa, Colombia They constitute serious conditions which can jeopardize the functional prognosis of the
kidney .
BACKGROUND AND AIMS: Clinical outcomes of Acute Kidney Injury (AKI) in The objective of our study is to describe the profile of patients on emergency
ICU mainly depend on opportune preventive strategies. Thus, early identification of hemodialysis for acute obstructive renal failure (AKI), the main indications for
AKI is mandatory, and alternative diagnostic strategies become plausible: one of them, hemodialysis and to assess the risk factors for mortality.
Renal Angina Index (RAI), described by Matsuura1, predicts the development of AKI METHOD: It was a 2-year retrospective and descriptive study from January 2018 to
KDIGO 2-3, at 7th day after admission to the intensive care unit according to a cut-off December 2019; performed in the nephrology and hemodialysis department CHU IBN
point >6 on a scale with a “creatinine score” (determined by the difference in serum ROCHD CASABLANCA.
creatinine between that at ICU admission and the first 24 hours in the ICU) and the RESULTS: A total of 118 patients were counted: 43 women, 75 men or 36.4%, 63.5%,
impact of the patients medical history. with an average age of 54.3 years "þ/- 10.3". The circumstances of discovery were:
1
Kidney Int Rep (2018) 3, 677-683. Oligo anuria 51.5%, hematuria 25%, AEG 24%. The obstacle was neoplastic in 67.79%;
Our aim is to describe predictive capacity of the Renal Angina Index (RAI) in adult lithiasis 26.27%; on pregnancy in 0.84%; bladder malformation 0.84%, and unknown
critical care patients in our population. etiologies in 4.2%. The neoplastic origin was cancer of the cervix, followed by the
METHOD: We retrospectively selected from our Critical Care Nephrology database bladder and then the prostate. The average creatinine level was 89.7mg / l. The
adult patients admitted in any of our hospitals ICU between February to August 2020, indication for hemodialysis was: threatening hyperkalemia, uremic syndrome, acidosis
excluding those at admission with diagnosis of AKI, serum creatinine > 2.5 mg/dl, or and acute pulmonary edema in 56%, 25.8%, 9.6% and 10% of cases, respectively
those receiving dialysis (acute or chronic) or kidney transplantation. We defined AKI The total number of hemodialysis sessions was 227 hemodialysis sessions with an
according to KDIGO criteria. The RAI score was defined as the worst condition score average number of 1.91. Obstacle removal was performed by percutaneous
multiplied by the creatinine score. The performance of the RAI score was assessed by nephrostomy in 70.8% of cases, by mounting a double J probe in 10% of cases and by
Receiver Operating Characteristic (ROC) analysis power to detect a difference of 0.2 ureterostomy in 4.2% of cases. The course was good in 77.9% of the cases, 13.5%
between the area under the curve (AUC), under the null hypothesis of AUC = 0.5 (no progressed to the IRCT. Mortality was 8.4%. Risk factors for mortality were: age,
diagnostic accuracy). The optimal cut point was estimated with the Youden method. etiology of neoplasia.
RESULTS: From 1204 new ICU patients, we included 372 patients (women 40.3%), CONCLUSION: A total of 118 patients were counted: 43 women, 75 men or 36.4%,
with mean age 60.9 (18-98) (table 1). Main indication for ICU admission was medical 63.5%, with an average age of 54.3 years "þ/- 10.3". The circumstances of discovery
conditions. Mean APACHE II was 22.9, hemodinamic support was required in 41,1% were: Oligo anuria 51.5%, hematuria 25%, AEG 24%. The obstacle was neoplastic in
patients, mechanical ventilation in 58.6% patients and diabetes mellitus was present in 67.79%; lithiasis 26.27%; on pregnancy in 0.84%; bladder malformation 0.84%, and
21.5% patients. unknown etiologies in 4.2%. The neoplastic origin was cancer of the cervix, followed by
AKI KDIGO 2-3 developed in 26.8% of patients. the bladder and then the prostate. The average creatinine level was 89.7mg / l. The
Mean creatinine at admission was statistically different in patients with AKI (CI 0.95 – indication for hemodialysis was: threatening hyperkalemia, uremic syndrome, acidosis
0.51 - –0.15 mg/dl, p=0.0004). The requirement of hemodynamic (p = 0.003) and and acute pulmonary edema in 56%, 25.8%, 9.6% and 10% of cases, respectively
ventilatory support (p = 0.009), sepsis (p = 0.003), and COVID-19 (p = 0.03) were The total number of hemodialysis sessions was 227 hemodialysis sessions with an
more frequent in patients who developed AKI. Renal replacement therapy was required average number of 1.91. Obstacle removal was performed by percutaneous
in 39 (60%) of patients with severe AKI (incidence 10,5%). nephrostomy in 70.8% of cases, by mounting a double J probe in 10% of cases and by
RAI cutt-off point determined by Youden method in the overall sample was 24, being ureterostomy in 4.2% of cases. The course was good in 77.9% of the cases, 13.5%
significantly higher in patients who developed AKI (16.54 Vs 7.47, CI 0.95 –13.5–4.99, progressed to the IRCT. Mortality was 8.4%. Risk factors for mortality were: age,
p <0.001). etiology of neoplasia.

10.1093/ndt/gfab082 | i267
Abstracts Nephrology Dialysis Transplantation

MO403 ACUTE KIDNEY INJURY IN ELDERLY: EPIDEMIOLOGICAL, inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were
CLINICAL AND ETIOLOGICAL FEATURES negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda
light chains). On the basis of these histological findings, Nivolumab-induced Acute
Mouna Malki abidi1,2, Rajaa Aoudia1,3, Soumaya Chargui1, Imen Gorsane1, Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient
Mouna Jerbi4, Hanen Gaied4, Taieb Ben abdallah1, Rym Goucha4, was treated by steroids and she achieved almost complete renal function recovery
Fethi Ben hamida1,2 (Figure 3).
1
charles nicolle hospital, nephrology, dialysis and renal transplantation department, CONCLUSIONS.: CPIs can induce a long-term Acute Kidney Injury. Histological
tunis, Tunisia, 2research Laboratory LR00SP01, nephrology, dialysis and renal trans- features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve
plantation, tunis, Tunisia, 3 and 4mongi slim hospital, nephrology, dialysis and renal renal outcome. In patients treated with CPIs a multidisciplinary management between
transplantation department, marsa, Tunisia oncologists and nephrologists is desirable for monitoring renal function at basal, after
drug administration and in the long-term follow-up.
BACKGROUND AND AIMS: Acute kidney injury (AKI) is common in the elderly
due to physiologic renal aging and underlying pathologies. Few studies focused on AKI
in Tunisian elderly. The aim of our study was to highlight the epidemiological, clinical, MO405 RISC FACTORS FOR CARDIAC SURGERY-ASSOCIATED
etiological, therapeutic, and progressive characteristics of AKI in elderly. ACUTE KIDNEY INJURY IN A TERTIARY REFERRAL
METHOD: We conducted a descriptive retrospective study of AKI in patients HOSPITAL
admitted to our department over a period of 04 years from 01/01/2014 to 31/12/2017.
RESULTS: We collected 40 patients including 25 women and 15 men with a sex ratio Alvaro Lucas1, Ali-cia Molina Andujar2, Eduard Quintana3, Gaston Pin ~eiro2,
of 1.66. The mean age was 74 [65-87] years. We noted the presence of pre-existing Esteban Poch2
chronic kidney disease in 58% of cases, diabetes in 50% of cases and hypertension in 1
University of Barcelona, Barcelona, 2Nephrology, Barcelona, Spain and 3Cardiac
73% of cases. Polypharmacy was found in 40% of cases. AKI was symptomatic in 80%
surgery, Barcelona, Spain
of cases and found on a routine check-up in 20% of cases. Mean creatinine was 612þ/-
334 mmol/l.
AKI was pre-renal in 37% and parenchymal in 63% of cases. Iatrogenic origin was BACKGROUND AND AIMS: cardiac surgery-associated acute kidney injury (CS-
found in 33% of cases. Renal biopsy was performed for diagnostic purposes in 6 cases. AKI) is a frequent complication that confers significant increase in morbility and
Haemodialysis was necessary in 50% of cases. Etiopathogenic treatment was initiated mortality. It is still unclear how to identify patients at high risk to develop it, in order to
in 73% of cases. Intra-hospital mortality was 10%, recovery of renal function (RF) was apply to them early preventive strategies to avoid AKI. The study aimed to explore risk
partial in 40 % of cases and total in 20 % of cases. Follow-up time was 16 þ/- 23.2 factors associated to CS-AKI.
months. And at the last news, recovery of renal function (RF) was partial in 7 cases and METHOD: to analyze the association between demographic, pre-operative and
total in 10 cases, 6 patients kept a chronic renal failure (CRF), among them 3 cases had intraoperative variables with all grades-AKI, we collected baseline characteristics, type
and end-stage of CRF. of surgery, aortic time of clampage and extracorporeal circulation time, hemodinamic
CONCLUSION: AKI is a frequent pathology in the elderly and its severity is linked to variables during surgery, Euroscore II, Clevelant Clinic Score and Leicester
mortality and the transition to chronicity. Iatrogenic causes are frequent and cardiosurgery score. The post-operative variables included monitorization of the first
preventable in this population, hence the major interest of prevention. 24 h in the Intensive Care Units (ICU), consistent in: use of vasoactive drugs, total
diuresis, use of furosemide, need of transfusions and need and duration of renal
replacement therapy (RRT). Creatinine was collected for all the admision days in order
to calculate the incidence of AKI. Also mortality and need of RRT at 30 th day was
MO404 ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT assessed.
INHIBITORS (CPIS) NEPHROTOXICITY The inclusion criteria were: patients over 18 years old who underwent cardiac surgery
with extracorporeal circulation. Only valve substitution (VS), Coronary Artery Bypass
Fausta Catapano1, Elisa Persici1, Giulia Ubaldi1, Francesca Romani1, Graft (CABG) or a combination of both procedures (not including endocarditis
Elena Mancini1 surgery) were included. Patients who were already in dialysis or suffered an AKI just
1
Nephrology, Dialysis and Hypertension Unit, Bologna, Italy before the surgery were not included in the study.
RESULTS: we included 130 patients who underwent heart surgery intervention in
BACKGROUND AND AIMS: The approved therapeutic indication for immune Hospital Clınic de Barcelona from 1st January to 31 st March 2015. 61,5% were men
checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related and the majority of them was 60 - 75 years old (46.9%), with hypertension (80.8%),
toxicities associated with CPIs can limit its efficacy. without diabetes (68.5%), with stage 2-Chronic Kidney Disease (53.1%). Main surgical
CASE REPORT.: A 52 year-old female diagnosed with left ocular melanoma and procedure was CABG (50.8%), followed by valve substitution (36.1%) and combination
treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute of both (13.1%). 73,1% of the procedures were done electively and 26.9% urgently. Out
Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our of the 130 patients, 60 (46.2%) suffered an AKI (36 AKIN 1, 16 AKIN 2 and 8 AKIN3).
Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical The majority of the episodes (55.2%) started between 24 and 48 hours after the
Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The intervention and 7 patients required RRT. AKI was not associated with mortality or
main damage was interstitial and characterized by tubulitis, tubular necrosis, non- need of renal replacement therapy at 30 days (OR 1.853, p= 0.397).
isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4þ,

MO404 Figure 1: Kidney Biopsy of a patient affected by Nivolumab-induced Acute


Tubulo-Interstitial Nephritis (PAS).

i268 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Regarding risk factors for CS-AKI, basal eGFR <60 ml/min, history of hypertension, acute cardiovascular diseases due to increased risk of severe adverse events associated
age and the clevelant/leicester and euroscore were preoperative risk factors associated with development of cardiorenal syndrome.
with CS-AKI in our cohort (OR 5.571 p=<0.001; OR 2.621 p=0.043; OR 1.036 The aim of the study to explore the role of biomarkers in early diagnosis of AKI and
p<0.001; OR 1.453 p=0.045; OR 1.062 p<0.001; OR 1.351 p=0.006 respectively). their prognostic values in patients with acute cardiac diseases.
Leicester cardiosurgery score >30 was the score who showed the best association with METHOD: 109 patients (51 with acute decompensated heart failure (ADHF), 58 with
AKI (OR 5.167, p<0.001). Intraoperative significant risk factors that were identified non-ST-elevation acute coronary syndrome (NSTE-ACS) were examined. Biomarkers
were: ischaemia time over 70 minutes (OR 2.876, p=0.004), and the need to use of HF (NT-pro BNP in serum) and kidney damage (cystatin C in serum; neutrophil
phenylephrine (3.064, p=0.015); whereas the need to use nitroglycerin was identified as gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and
a protector (OR 0.441, p=0.031). interleukine-18 (IL-18) in the urine) were estimated. Mann-Whitney test and
CONCLUSION: previous eGFR<60 ml/min, age, hypertension, use of phenylephrine multivariate logistic regression analysis were performed, p <0.05 was considered
during surgery and long ischaemia time are the main factors associated with CS-AKI. statistically significant.
Scores like Leicester score can help physicians to identify people at risk and apply RESULTS: Patients with vs without AKI had higher levels of NGAL (3446308.8 vs
preventive strategies. 37.9665.1 ng/ml, p <0.001) and KIM-1 (0.77460.36 vs 0.40260.59 ng/ml, p <0.01) in
all groups. Patients with NSTE-ACS with vs without AKI had higher level of NT-
proBNP (12857.163108.8 vs 1013462479, p<0.001), no difference was detected in
ADHF group. In course of ROC analyses NGAL and KIM-1 showed the best
MO406 ACUTE KIDNEY INJURY AND RENAL REPLACEMENT
prognostic values (AUC value 0.948 and 0.760). The cut points for NGAL >60.1 ng/ml
THERAPY IN HOSPITALIZED PATIENTS: A CROSS
(sensitivity 87%, specificity 92%) and KIM-1 > 0.519 ng/ml (sensitivity 87%,
SECTIONAL STUDY FROM IRAN
specificity 67%) were detected, coefficient of association u was 0,781 and 0,555
respectively. Simultaneous detection of two markers of structural kidney damage
Zohreh Rostami1, Sepehr Shafei1, Eghlim Nemati1, Behzad Einollahi1,
(increase of NGAL and/or KIM-1) in high-risk patients permits to diagnose 95% of
Afsaneh Rostami2
1
AKI cases at admission. Patients with AKI and diagnostically significant levels of
Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, biomarkers had higher prevalence of CKD (p<0.01), acute heart failure, ADHF
Nephrology, Tehran, Iran and 2allameh tabataba’i university, social planning, Tehran, (p<0.05) vs those without increase of biomarkers, in-hospital mortality in this group
Iran was 29,8%.
CONCLUSION: Positive combined biomarker test is an independent and strong
BACKGROUND AND AIMS: Acute kidney injury is an important finding in predictor of AKI in patients with acute cardiac diseases, and its implementation in
COVID-19 patients that can even result in renal replacement therapy. AKI complicates clinical practice improve the early diagnostics of AKI when markers of kidney function
COVID-19 management by making volume management and administering agents are still at normal levels.
with renal clearance challenging tasks. Various reasons have been proposed for the
development of acute kidney injury in COVID-19 patients, including multi-organ
failure and pre-renal causes, drug toxicity, tubular injury, and invasion of proximal
MO408 OBSTRUCTIVE NEPHROPATHY - STILL PREVALENT
tube podocytes by SARS-CoV-2. Although the development of AKI is not uncommon
DISEASE
in COVID-19 patients, several inconsistencies in the literature exist regarding
incidence rate and risk factors of acute kidney injury among hospitalized patients. This
Ana Bulatovic1,2, Verica Todorov Sakic1, Petar Djuric1, Jelena Bjedov1,2,
can be attributed to ethnical variations and methodological differences of studies.
Aleksandar Jankovic1,2, Radomir Naumovic1,2, Nada Dimkovic3
Herein we report AKI incidence in hospitalized COVID-19 patients in Baqiyatallah 1
Hospital in Iran and investigate associate factors that can lead to AKI and renal Zvezdara University Medical Center, Nephrology and Dialysis, Beograd, Serbia,
2
replacement therapy in COVID-19 patients. University School of Medicine, Nephrology and Dialysis, Beograd, Serbia and 3Medical
METHOD: In this cross-sectional study, we investigated medical records and Academy, Serbian Medical Assosiation, Beograd, Serbia
laboratory data of hospitalized COVID-19 patients in Baqiyatallah Hospital in Tehran,
Iran, from September 2020 until the end of November. COVID-19 infection was BACKGROUND AND AIMS: Acute kidney injury (AKI) secondary to urinary
confirmed using polymerase chain reaction (PCR), and only patients with Positive PCR obstruction is a common urological-nephrological problem. In this retrospective study,
for COVID-19 were included. Furthermore, patients with missing data and unknown our goals were to describe the etiology, management and outcomes of patients with
past medical history were excluded from this study, and a total of 459 patients were obstructive nephropathy who were hospitalized at Nephrology Department during
selected. The KDIGO criteria for acute kidney injury were used for evaluating kidney 2019.
injury in COVID-19 patients. ICU admission and dialysis were according to the METHOD: AKI was defined by the RIFLE classification. Diagnosis of obstruction was
Ministry of Health and Medical Education on ICU admission and renal replacement defined by ultrasound imaging, intravenous pyelography and CT scan.
therapy in COVID-19 patients. RESULTS: During 2019 AKI secondary to urinary obstruction was diagnosed to 64
RESULTS: Of 459 patients with the criteria who were admitted to the hospital (244 patients. 73% of them were male, average age 65 6 16 years. About 60% of the patients
male, 213 female, with an average age of 59.57 with SD 14.3), 75 patients (16%) had bilateral hydronephrosis, chronic kidney disease and anuria duration longer than
developed acute kidney injury in the course of the disease. The mortality rate in 24h. The following desobstructive procedures were applied: urinary catheterization to
patients with AKI (44%) was significantly higher than other patients (9%). The 33 patients, percutaneous nephrostomy tube to 14 patients, double-J stent to 7 and
development of the AKI was significantly associated with the risk of ICU admission other procedures to 10 patients. The most common causes of obstruction were
and the severe forms of the disease. Furthermore, it was observed that the patients who malignancy and benign prostatic hyperplasia 60%, calculosis 17%, and other causes
developed AKI was significantly older and male gender, diabetes (DM), Hypertension 20% such as neurogenic bladder and retroperitoneal fibrosis. As many as 30% of
(HTN), and Previous history of Chronic kidney disease(CKD) was also significantly patients required acute hemodialysis treatment, of which 6% remained on a chronic
associated with developing AKI in COVID-19 patients. Chronic heart failure and program in period of three months. Out of all, 30% of patients had a partial recovery of
ischemic heart disease increased the odds of developing AKI, but it was not significant kidney function, while 20% had complete recovery. The most common complication
enough to come up with a conclusion. It was observed that from 75 patients who was infection and bleeding. The univariate logistic regression, adjusted for age and
developed AKI, 22 patients (29%) required renal replacement therapy. Of 22 patients hemodialysis treatment, has shown that significant independent predictors for chronic
who need dialysis, 14 patients did not survive (mortality rate=63%). The previous kidney disease progression were anuria duration >24h (RR 2.21; 95% CI 0.014-1.03;
history of kidney disease increases the risk of dialysis due to AKI, while no significant p=0.05), polyuria duration (RR 2.11; 95% CI 1.112-3.98; p=0.02) and duration of
association was found between age, gender, DM, HTN, and heart disease with the need hospital treatment (RR 9.16; 95% CI 2.102-39.94; p=0.03). The most significant
for dialysis. predictor of death was duration of hospital treatment (RR 9.16; 95% CI 2.102-3.399;
CONCLUSION: Results of our study indicate that acute kidney injury can be a major p=0.003). Multivariate logistic regression did not shown significance any of the above
obstacle in managing COVID-19 patients. Patients with older age, previous history of risk factors.
CKD, HTN, and DM should be admitted to the hospital and monitored closely to CONCLUSION: Given that third of patients with obstructive nephropathy require
prevent unfortunate outcomes of this disease. acute HD, 6% remain in chronic HD, and almost one third require rehospitalization,
close cooperation between a nephrologist and urologist is required. Rapid
desobstructive procedures and careful monitoring after desobstruction is warranted.
Requirement of regular screening remains opened for obstruction in vulnerable
MO407 POSITIVE COMBINED BIOMARKER TEST IS AN
populations.
INDEPENDENT PREDICTOR OF ACUTE KIDNEY INJURY IN
PATIENTS WITH ACUTE CARDIAC DISEASES

Marina Efremovtseva1, Svetlana Avdoshina2, Zhanna Kobalava2


1
Peoples’ Friendship University of Russia (RUDN University), Department of Internal
Medicine, jcrda, and 2Peoples’ Friendship University of Russia (RUDN University),
Department of Internal Medicine, Moscow, Russia

BACKGROUND AND AIMS: Biomarkers are currently considered as an additional


criterion for the diagnosis of AKI. Early diagnosis of AKI is especially important in

10.1093/ndt/gfab082 | i269
Nephrology Dialysis Transplantation 36 (Supplement 1): i270–i278, 2021
10.1093/ndt/gfab083

AKI. CLINICAL. PREVENTION AND TREATMENT RRT. Secondary outcomes were in-hospital mortality and ratio-defined subclinical AKI
characterized by increased odds for AKI-RRT or in-hospital mortality. We compared
biomarkers’ area-under-the-curve of the receiver-operating-characteristic and
performed cross-validated reclassification statistics and regression analysis adjusted to
MO408 OBSTRUCTIVE NEPHROPATHY - STILL PREVALENT Cleveland risk score/EuroScore, cross-clamp time, age and volume of packed red blood
DISEASE cells.
RESULTS: Patients with AKI-RRT (n=13) had 13.7-times higher NGAL and 3.3-times
Ana Bulatovic1,2, Verica Todorov Sakic1, Petar Djuric1, Jelena Bjedov1,2, lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL:hepcidin-25-
Aleksandar Jankovic1,2, Radomir Naumovic1,2, Nada Dimkovic3 ratio early after surgery compared to patients without AKI-RRT (Figure 1). The
1
Zvezdara University Medical Center, Nephrology and Dialysis, Beograd, Serbia, NGAL:hepcidin-25-ratio had higher discriminatory power compared with NGAL for
2
University School of Medicine, Nephrology and Dialysis, Beograd, Serbia and 3Medical risk of AKI-RRT and in-hospital mortality (area-under-the-curve difference 0.087, 95%
Academy, Serbian Medical Assosiation, Beograd, Serbia CI, 0.036 to 0.138, P<0.001; 0.082, 95% CI, 0.018 to 0.146, P=0.012). The
NGAL:hepcidin-25-ratio, but not NGAL, was independently associated with AKI-RRT
(adjusted OR per 1-SD higher lnNGAL:hepcidin-25-ratio, 1.524, 95% CI, 1.046 to
BACKGROUND AND AIMS: Acute kidney injury (AKI) secondary to urinary 2.222, P=0.028). The NGAL:hepcidin-25-ratio increased category-free net-
obstruction is a common urological-nephrological problem. In this retrospective study, reclassification-improvement for AKI-RRT (0.690, 95% CI, 0.146 to 1.234, P=0.013)
our goals were to describe the etiology, management and outcomes of patients with and in-hospital mortality (cfNRI 0.744, 95% CI, 0.201 to 1.288, P=0.007).
obstructive nephropathy who were hospitalized at Nephrology Department during NGAL:hepcidin-25-ratio-positive subclinical AKI was associated with increased AKI-
2019. RRT (OR 10.02, 95% CI, 1.59 to 63.39; P<0.001) and in-hospital mortality rates (OR
METHOD: AKI was defined by the RIFLE classification. Diagnosis of obstruction was 41.07, 95% CI, 4.31 to 391.40; P<0.001).
defined by ultrasound imaging, intravenous pyelography and CT scan.
RESULTS: During 2019 AKI secondary to urinary obstruction was diagnosed to 64
patients. 73% of them were male, average age 65 6 16 years. About 60% of the patients
had bilateral hydronephrosis, chronic kidney disease and anuria duration longer than
24h. The following desobstructive procedures were applied: urinary catheterization to
33 patients, percutaneous nephrostomy tube to 14 patients, double-J stent to 7 and
other procedures to 10 patients. The most common causes of obstruction were
malignancy and benign prostatic hyperplasia 60%, calculosis 17%, and other causes
20% such as neurogenic bladder and retroperitoneal fibrosis. As many as 30% of
patients required acute hemodialysis treatment, of which 6% remained on a chronic
program in period of three months. Out of all, 30% of patients had a partial recovery of
kidney function, while 20% had complete recovery. The most common complication
was infection and bleeding. The univariate logistic regression, adjusted for age and
hemodialysis treatment, has shown that significant independent predictors for chronic
kidney disease progression were anuria duration >24h (RR 2.21; 95% CI 0.014-1.03;
p=0.05), polyuria duration (RR 2.11; 95% CI 1.112-3.98; p=0.02) and duration of
hospital treatment (RR 9.16; 95% CI 2.102-39.94; p=0.03). The most significant
predictor of death was duration of hospital treatment (RR 9.16; 95% CI 2.102-3.399;
p=0.003). Multivariate logistic regression did not shown significance any of the above
risk factors.
CONCLUSION: Given that third of patients with obstructive nephropathy require
MO410 Figure 1: Urinary NGAL:hepcidin-25 ratio over time separated by status of
acute HD, 6% remain in chronic HD, and almost one third require rehospitalization,
acute kidney injury requiring renal replacement therapy
close cooperation between a nephrologist and urologist is required. Rapid
*P<0.001.
desobstructive procedures and careful monitoring after desobstruction is warranted.
NGAL:hepcidin-25 ratio immediately after end of surgery was available in all 198
Requirement of regular screening remains opened for obstruction in vulnerable
patients.
populations.
CONCLUSION: The urinary NGAL:hepcidin-25-ratio appears to early identify high-
risk patients and outperform NGAL after cardiac surgery. Also, the urinary
NGAL:hepcidin-25 ratio can detect subclinical AKI. Confirmation of our findings in
MO410 URINARY NGAL:HEPCIDIN-25 RATIO VERSUS URINARY other cardiac surgery centers is now needed.
NGAL FOR EARLY IDENTIFICATION OF PATIENTS AT RISK
FOR ACUTE RENAL REPLACEMENT THERAPY AND DEATH
AFTER CARDIAC SURGERY
MO411 ACUTE KIDNEY INJURY AFTER PARATHYROIDECTOMY FOR
PRIMARY HYPERPARATHYROIDISM: PREVALENCE,
Saban Elitok1, Anja Haase-Fielitz2, Martin Ernst1, Michael Haase3,4
1
PREDICTORS AND RISK ASSESSEMENT
Hospital Ernst-von-Bergmann, Department of Nephrology, Potsdam, Germany, 2Heart
Center Brandenburg, Department of Cardiology, Bernau, Germany, 3Otto-von-Guericke Ekaterina Parshina1, Aleksei Zulkarnaev2, Pavel Kislyy1, Roman Chernikov3,
University Magdeburg, Medical Faculty, Magdeburg, Germany and 4Diaverum, Kidney Svetlana Mikhailova1
Care Center, Potsdam, Germany 1
Saint-Petersburg State University Hospital, Dialysis department, Saint-Petersburg,
Russia, 2Moscow Regional Research Clinical Institute, Surgical Department of
BACKGROUND AND AIMS: Acute kidney injury requiring renal replacement Transplantology and Dialysis, Moscow, Russia and 3Saint-Petersburg State University
therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery, Hospital, Endocrine surgery department, Saint-Petersburg, Russia
however, options for early identification of patients at high-risk for AKI-RRT are
extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even
BACKGROUND AND AIMS: Surgery is the most effective and the only definitive
of one of the most extensively evaluated novel urinary biomarkers, neutrophil
treatment of primary hyperparathyroidism (PHPT). We aimed to assess the prevalence
gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to
of acute kidney injury (AKI) among patients underwent surgery for PHPT, to
determine whether the discriminatory power and reclassification indices of
determine the possible risk factors.
NGAL:hepcidin-25-ratio (urinary concentrations of NGAL divided by that of
METHOD: A retrospective cohort study included 290 patients who underwent
hepcidin-25) within 60 min after end of surgery compare favorably to NGAL alone for
successful selective parathyroidectomy (PTx) for PHPT. We did not include patients
identification of high-risk patients after cardiac surgery. We also aimed to determine
who underwent re-operative surgeries. AKI was defined according to KDIGO-2012
whether an increased NGAL:hepcidin-25-ratio can detect subclinical AKI (no serum
criteria.
creatinine- or urine output-based criteria for AKI).
RESULTS: In our cohort, 106 patients (36,6%) met AKI criteria after PTx. Most of the
METHOD: This is a prospective substudy of the BICARBONATE trial, a multicenter
patients developed AKI stage 1. In univariate analysis preoperative serum PTH level
parallel-randomized controlled trial comparing perioperative bicarbonate infusion for
(h=0,0004) aa well as degree of its decrease before/after PTx (h<0,0001), preoperative
AKI prevention to usual patient care. At a tertiary referral center, 198 patients at
serum total calcium level (h=0,0158), size of the parathyroid adenoma (h=0,0184),
increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were
presence of proteinuria (RR=1,9 [95%CI: 1,19; 3,54], h=0,0061), hypertension
included into the present study. The primary outcome measure was defined as AKI-
(h=0,019) and anemia (h=0,0313), older age (RR=1,32 [95%CI: 1,03; 1,72], h=0,0265)

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
were significant risk factors of AKI development. In multivariate analysis age (OR 1,05 patients with AKI was much higher than that in patients without AKI (53.3% versus
[95%CI: 1,02; 1,08] per a year, h=0,002), body-mass index (OR 1,07 [95%CI: 1,02; 1,13] 17.5%, P < 0.001). The risk factors of AKI in patients with HLH were
per each kg/m2, h=0,005), anemia (yes/no OR 3,38 [95%CI: 1,38; 8,2], h=0,008), hyperphosphatemia (P<0.001, OR 5.448, 95%CI 2.951-10.059) , vasopressor(P<0.001,
preoperative PTH (OR 1,03 [95%CI: 1,01; 1,05] per each pmol/l, h=0,002), proteinuria OR 3.485, 95%CI 2.114-5.746), heart failure (P=0.044, 0R 2.336, 95%CI 1.022-5.340),
(yes/no OR 3,45 [95%CI: 1,34; 8,93], h=0,011), use of ACE inhibitors/ARBs (yes/no gastrointestinal symptoms (P=0.043, OR 1.877, 95%CI 1.021-3.453), increased heart
OR 2,84 [95%CI: 1,58; 5,12], h=0,001) were discovered as independent predictors of rate (P=0.005, OR 1.017, 95%CI 1.005-1.029), elevated total bilirubin level(P<0.001,
AKI. OR 1.004, 95%CI 1.002-1.007), and hypoproteinemia (P=0.034, OR 0.939, 95%CI
Considering the most significant risk factors we developed two regression models for 0.886-0.995).
AKI risk assessment: the model 1 for patients with preserved kidney function CONCLUSION: The incidence of AKI was higher in patients with HLH, and the risk
(estimated glomerular filtration rate (eGFR 60 ml/min/1,73 m2) and the model 2 for of death was significantly higher in HLH patients with AKI. A variety of risk factors are
those with decreased kidney function (eGFR less than 60 ml/min/1,73 m2) – tab. 1 and related to the occurrence of HLH-induced AKI. Identifying and correcting them early
2. Both models were statistically significant: v2=25,39, df=5, h<0,001, RN2=0,341 for in clinical diagnosis and treatment may reduce the incidence of AKI in patients with
the model 1, v2=19,355, df=3, h<0,001, RN2=0,428 for the model 2. The proposed HLH and improve the prognosis of them.
models had good discrimination to predict AKI with area under the receiver operating
characteristic curves (AUC-ROC) of 0,792 [95%CI: 0,691; 0,894], h<0,001 for the
model 1 (normal kidney function) and 0,84 [95%CI: 0,73; 0,951], h<0,001 for the
model 2 (decreased kidney function). Optimal cut-off values for predicted probability
of AKI to define high-risk individuals were > 0,57 (Youden’s index 0,525) for the Variables B SE Wald P OR 95%CI
model 1 and > 0,439 (Youden’s index 0,589) for the model 2. Vasopressor 1.249 0.255 23.959 <0.001 3.485 2.114-5.746
CONCLUSION: We observed high prevalence of AKI in patients after PTx for
primary HPT. Developed risk models predict AKI with adequate accuracy. Risk factors Heart failure 0.849 0.422 4.049 0.044 2.336 1.022-5.340
of AKI should be considered when planning PTx, special attention should be paid to Edema 0.226 0.231 0.961 0.327 1.254 0.798-1.971
modifiable ones.
Gastrointestinal 0.630 0.311 4.103 0.043 1.877 1.021-3.453
symptoms
DIC 0.535 0.309 3.003 0.083 1.708 0.932-3.129
Admission heart rate 0.017 0.006 8.020 0.005 1.017 1.005-1.029
PLT ( 109/L) -0.010 0.005 3.421 0.064 0.990 0.980-1.001
WBC ( 109/L) -0.052 0.076 0.463 0.496 0.950 0.818-1.102
Baseline Scr (umol/L) 0.004 0.005 0.481 0.488 1.004 0.993-1.014
Cys-C mg/L -0.183 0.288 0.404 0.525 0.833 0.473-1.465
Phosphorus (mmol/L) 1.695 0.313 29.367 <0.001 5.448 2.951-10.059
Potassium (mmol/L) -0.246 0.182 1.814 0.178 0.782 0.547-1.118
Total bilirubin (umol/L) 0.004 0.001 15.183 <0.001 1.004 1.002-1.007
Albumin (g/L) -0.063 0.030 4.492 0.034 0.939 0.886-0.995
Triglyceride (mmol / L) 0.029 0.034 0.724 0.395 1.029 0.963-1.099
Sodium (mmol/L) -0.029 0.021 1.898 0.168 0.972 0.933-1.012
APTTs 0.002 0.004 0.373 0.542 1.002 0.995-1.009
Fibrinogen (g / L) 0.093 0.133 0.492 0.483 1.098 0.846-1.424
PCT ng/ml 0.015 0.013 1.438 0.230 1.015 0.990-1.041
Urine protein 3.792 0.435
þ- 0.027 0.391 0.005 0.945 1.028 0.477-2.213
þ -0.060 0.352 0.029 0.865 0.942 0.472-1.878
þþ 0.254 0.425 0.357 0.550 1.289 0.560-2.967
þþþ 1.289 0.801 2.587 0.108 3.629 0.755-17.453

PLT, platelet; WBC, white blood cell; Scr, serum creatinine; Cys-C, cysta-
tin C; APTT, activated partial prothrombin time ;PCT, procalcitonin; B:
Partial regression coefficient; SE: Standard error; OR: Odds ratio; CI:
Confidence interval
MO412 THE RISK FACTORS OF ACUTE KIDNEY INJURY CAUSED BY
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Siwen Wang1, Jia Yang1, Chen Xuelian1, Jiaojiao Zhou1, Lichuan Yang1
1
West China Hospital of Sichuan University, Division of Nephrology, Chengdu, P.R. MO413 EFFECTS OF CHRONIC, LONG-TERM ACE-INHIBITOR
China TREATMENT ON CYTOKINE STORM AND RENAL FUNCTION
AFTER CARDIO-PULMONARY BYPASS: A PROSPECTIVE
OBSERVATIONAL STUDY
BACKGROUND AND AIMS: Hemophagocytic lymphohistiocytosis (HLH) is a
syndrome characterized by overproduction of proinflammatory cytokines and
Pierangela Presta1, Davide Bolignano1, Giuseppe Coppolino1,
hemophagocytosis. Acute kidney injury (AKI) is the most common complication of
Mariateresa Zicarelli1, Filiberto Serraino2, Pasquale Mastroroberto2,
HLH in the kidney, which is a strong predictor of poor prognosis. In this retrospective
Giorgio Fuiano1, Michele Andreucci1
study, we aimed to find the risk factors of AKI in patients with HLH. 1
METHOD: We screened all adult patients with HLH admitted to West China Hospital Nephrology and Dialysis Unit, “Magna Graecia” University of Catanzaro, Catanzaro,
of Sichuan University from January 2009 to June 2019. Patients in this study were Italy and 2Cardiac Surgery Unit, “Magna Graecia” University of Catanzaro, Catanzaro,
secondary HLH according to the HLH diagnostic criteria revised by the Histocyte Italy
Society in 2004. Patients with HLH were excluded from the study if they had a
functioning kidney transplant, received renal replacement therapy (RRT) in the past BACKGROUND AND AIMS: Cardiopulmonary bypass (CPB) may trigger organs
month, suffered from end-stage renal disease (ESRD), or had the renal malignant damage, including kidney injury, due to a massive cytokine release. In this
tumor. We collected basic information, clinical manifestations, and laboratory data of observational, prospective study, we have analyzed the possible impact of chronic
patients from electronic medical records. treatment with ACE-Inhibitors (ACE-I) on the inflammatory response and renal
RESULTS: A total of 600 patients with confirmed diagnosis of secondary HLH are function after CPB.
included in our analysis. There are 199(33.2%)HLH-induced AKI patients, among METHOD: Sixty-nine patients undergoing major cardiac surgery with CPB were
whom 37.2%, 32.7%, and 30.2% are classified as AKI I, II, and III, respectively, enrolled. Patients were stratified according to long-term (>6 mo.) ACE-I use (n=38) or
according to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) not (n=31). The primary endpoint was to analyze the changes in their IL-1 alpha, IL-
guideline. Overall hospital mortality is 176(29.3%), and the number of deaths in 1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF alpha, EGF and VEGF plasma levels.

10.1093/ndt/gfab083 | i271
Abstracts Nephrology Dialysis Transplantation

Secondary (renal) endpoints were: postoperative acute kidney injury (AKI), recovery of PHPT group (41,5 [Q1-Q3: 30; 51] years vs 59 [Q1-Q3: 50,8; 67] years, respectively,
baseline GFR values and the absolute changes in renal function indexes. p<0,0001), had higher mean baseline estimated glomerular filtration rate (eGFR) (91,1
RESULTS: After CPB, IL-1alpha, IL-1beta, IL-4 and TNF-alpha remained stable 6 18 vs 78,8 6 18,6 ml/min/1,73 m2 respectively, p=0,0001) and had less comorbidity
overtime, while a significant decrease in IL-2 plasma levels was noticed in the ACE-I index (p<0,0001). Hypertension encountered much more often in PHPT group vs
group (p=0.01). IL-6 and IL-8 plasma levels increased after surgery and tended to thyroid group (69% and 22,5%, respectively, v2 p<0,0001). Duration of surgery also
decrease after 48h. IL-10 plasma levels showed a similar variation, but both their rise differed between groups: 25 min [Q1-Q3: 20; 40] min in PHPT group vs 50 [Q1-Q3: 31;
and decrease were more pronounced in patients under ACE-I treatment (p=0.007). 62,5] min in thyroid group, p<0,0001.
Finally, VEGF and EGF showed a marked initial decrease with a tendency to
normalization 10 days after surgery (p for trend ranging from 0.01 to 0.001) (Figure 1-
2).

MO414 Figure 1: Change of serum creatinine level before/after surgery in two


groups. Repeated measures ANOVA.

The occurrence of AKI within 2 days after surgery, the rate of GFR recovery and the
absolute changes in renal function indexes were not statistically different between
groups (Figure 3).
CONCLUSION: Chronic, long-term ACE-I treatment may influence the
inflammatory response following CPB. On the other hand, this drug class apparently
has neutral impact on perioperative renal outcomes.

MO414 ACUTE KIDNEY INJURY AFTER ELECTIVE ENDOCRINE


SURGERY: ARE PATIENTS WITH PRIMARY
HYPERPARATHYROIDISM AT RISK? MO414 Figure 2: Fraction of patients with or without AKI in PHPT group and
thyroid surgery group.We hypothesized that acute decline of parathyroid hormone
Ekaterina Parshina1, Aleksei Zulkarnaev2, Roman Chernikov3, Pavel Kislyy1 after PTx increases risk of AKI in the PHPT group. To evaluate whether type of surgery
1
Saint-Petersburg State University Hospital, Dialysis department, Saint-Petersburg, (PTx/thyroid surgery) is independently associated with risk of AKI, we used 1:1
Russia, 2Moscow Regional Research Clinical Institute, Surgical Department of pseudorandomization (Propensity Score Matching, “matchit” package, “nearest”
Transplantology and Dialysis, Moscow, Russia and 3Saint-Petersburg State University method in R) to balance the baseline characteristics (age, BMI, comorbidity, baseline
Hospital, Endocrine surgery department, Saint-Petersburg, Russia eGFR, duration of surgery, presence of hypertension). The 40 patients in the thyroid
surgery group were matched to 40 patients in the PHPT group according to these
confounders. After PSM the prevalence of AKI remained significantly higher in the
BACKGROUND AND AIMS: Development of acute kidney injury (AKI) after
PHPT group than in the thyroid surgery group (30% vs. 5%, respectively, RR=6
elective endocrine surgery is underreported. We aimed to assess the prevalence of AKI
[95%CI: 1,7; 23,1], p=0,006), confirming that PTx is the independent risk factor of
among patients underwent surgery for primary hyperparathyroidism (PHPT) and
AKI.
thyroid surgery and compare risk of AKI between these cohorts.
CONCLUSION: We observed higher prevalence of AKI after PTx for PHPT
METHOD: A retrospective cohort study included 299 patients who underwent
comparing with patients after thyroid surgery. Our data suggests that PTx itself is the
successful selective parathyroidectomy (PTx) for PHPT, and 40 patients after thyroid
main risk factor of AKI development after elective endocrine surgery.
surgery with comparable scope of the intervention (thyroid follicular cells tumor, non-
invasive papillary thyroid carcinoma). AKI was defined according to KDIGO-2012
criteria.
RESULTS: Change of serum creatinine before/after surgery differed significantly
between PHPT and thyroid surgery group: type of surgery*time interaction p<0,0001
(repeated measures ANOVA after Box-Cox transformation) – fig.1. 109 patients
(36,5%) in the PHPT group and 2 patients (5%) in the thyroid group met AKI criteria
after PTx. Most of the patients developed AKI stage 1. Risk of AKI was significantly
higher in the PHPT patients: RR=7,3 [2,19; 26,6], OR=10,9 [2,82; 46,6], h<0,0001.
Patients in the thyroid surgery group were significantly younger than those in the

i272 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO415 DOES LOW CONTRAST VOLUMES REDUCE RATES OF MO417 NEPHROLOGIST INTERVENTION TO AVOID KIDNEY
CONTRAST-INDUCED NEPHROPATHY IN PATIENTS REPLACEMENT THERAPY IN ACUTE KIDNEY INJURY
UNDERGOING CORONARY ANGIOGRAPHY?
Jonathan Cha vez1, Pablo Maggiani-Aguilera1, Andres De la Torre-Quiroga1,
Emna Chaabouni1, Hela Jbali1, Najjar Mariem2, Mzoughi Khadija3, Alejandro Martınez-Gallardo Gonzalez1, Ramo n Medina-Gonza lez1, Andrea Luna-
Zouaghi Mohamed karim1 Ramos2, Luz Alcantar-Vallin1, Guillermo Garcıa-Garcıa1
1
La Rabta, Nephrology, Tunis, Tunisia, 2Charles Nicolle Hospital, Nephrology Charles 1
Hospital Civil de Guadalajara Fray Antonio Alcalde, Universidad de Guadalajara
Nicolle, Tunis, Tunisia and 3Habib Thameur Hospital, cardiology, Tunis, Tunisia Centro Universitario de Ciencias de la Salud CUCS, Nefrologıa, GUADALAJARA, Mexico
and 2Hospital Civil de Guadalajara Fray Antonio Alcalde, Universidad de Guadalajara
BACKGROUND AND AIMS: Coronary angiography (CAG) necessitates Centro Universitario de Ciencias de la Salud CUCS, Nefrologıa, Guadalajara, Mexico
administration of iodinated contrast, which may precipitate an acute deterioration in
renal function (contrast-induced nephropathy). BACKGROUND AND AIMS: Based on the pathophysiology of acute kidney injury
Previous work on contrast-induced nephropathy (CIN) has identified contrast volume (AKI) it is plausible that certain early interventions by the nephrologist could influence
as a risk factor and suggested that there is a toxic contrast dose above which the risk of its trajectory. In this study, we investigated the impact of 5 early nephrology
CIN is markedly increased. interventions on starting kidney replacement therapy (KRT), AKI progression and
The focus of this study is to provide a critical appraisal of this modifiable risk factor. death.
METHOD: We prospectively enrolled 158 patients who CAG with or without METHOD: In a prospective cohort at Hospital Civil of Guadalajara, we followed-up
percutaneous coronary intervention from December 2017 to February 2018 at a for 10 days AKI patients in whom a nephrology consultation was requested. We
cardiology department . analyzed 5 early interventions of the nephrology team (fluid adjustment, nephrotoxic
CIN was defined as an increase in serum creatinine level >25% or 0.5 mg/dL after 48 withdrawal, antibiotic dose adjustment, nutritional adjustment and removal of
hours postcardiac catheterization. hyperchloremic solutions) after propensity score and multivariate analysis for the risk
Toxic contrast dose was defined as a ratio volume of contrast media to estimated of starting KRT (primary objective), AKI progression to stage 3 and death (secondary
glomerular filtration rate (V/eGFR) > 2 . Multivariable regression was conducted to objectives).
evaluate the effect of exceeding the toxic contrast dose on CIN. RESULTS: From 2017 to 2020 we analyzed 288 AKI patients. The mean age was 55.3
RESULTS: Of 158 patients (females = 36.1%, mean age 60.0 6 11 years) who years, 60.7% were male, AKI KDIGO stage 3 was present in 50.5% of them, sepsis was
underwent CAG , 15 (9,5%) developed CIN . the main etiology 50.3%, and 72 (25%) patients started KRT. The overall survival was
The volume administered of contrast was not related to the existence of postprocedure 84.4%. Fluid adjustment was the only intervention associated with a decreased risk for
CIN (96,6635,9 ml vs 102,5633,7ml , p=0,16). However , it was associated with a starting KRT (OR 0.58, 95% CI 0.48-0.70, p = <0.001) and AKI progression to stage 3
higher incidence of CIN in patients with chronic renal failure (90619,1 ml vs (OR 0.59, 95% CI 0.49-0.71, p = <0.001). Receiving vasopressors and KRT were
116,6673,7ml , p=0,008) . associated with mortality, but neither of these interventions reduced these risks.
The mean V/eGFR value was 1,260,7.Nine percent of patients exceeded the toxic CONCLUSION: In this prospective cohort study of AKI patients, we found for the first
contrast dose. time that early nephrologist intervention and fluid prescription adjustment was
After adjusting for other known predictors of CIN, a V/eGFR ratio > 2 remained associated with a reduction in the risk of starting KRT and progression to AKI stage 3.
significantly associated with CIN (odds ratio 4.7, 95% confidence interval 1.28-17.7,
P=0,02).
CONCLUSION: Low incidences of CIN suggest that a reduced dose of contrast agent
is safe in high-risk patients with impaired renal function. A ratio volume of contrast
media to estimated glomerular filtration rate > 2 is a significant and independent
predictor of CIN after CAG.

MO416 PREDICTORS OF CONTRAST-INDUCED NEPHROPATHY AND


THE APPLICABILITY OF THE MEHRAN RISK SCORE IN
PATIENTS UNDERGOING CORONARY ANGIOGRAPHY

Emna Chaabouni1, Hela Jbali1, Najjar Mariem2, Mzoughi Khadija3,


Zouaghi Mohamed karim1
1
La Rabta, Nephrology, Tunis, Tunisia, 2Charles Nicolle Hospital, Nephrology, Tunis,
Tunisia and 3Habib Thameur Hospital, cardiology, Tunis, Tunisia
MO417 Figure: Forest plot of early nephrologist intervention associated with KRT
BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN) after coronary and death.
angiography (CAG) is associated with poor outcomes. The purpose of our study was to
identify predictors of CIN in patients undergoing CAG and to evaluate the applicability
of the Mehran Risk Score (MRS) in the prediction of CIN in our population.
METHOD: We prospectively enrolled 158 patients who underwent coronary MO418 CONTINUOUS RENAL REPLACEMENT THERAPY WITH
angiography with or without percutaneous coronary intervention from December 2017 REGIONAL CITRATE ANTICOAGULATION VERSUS NON-
to February 2018 at a cardiology department . ANTICOAGULATION REGIME IN CRITICALLY ILL PATIENTS
CIN was defined as an increase in serum creatinine level >25% or 0.5 mg/dL after 48 WITH ACUTE KIDNEY INJURY AND A HIGH RISK OF
hours postcardiac catheterization. BLEEDING
The patients who developed CIN were then analysed for the presence of specific risk
factors. The patients were categorized into the 4 risk groups based on the MRS. Violeta Knezevic1,2, Tijana Azasevac1,2, Gordana Strazmester Majstorovic1,2,
RESULTS: The incidence of CIN was 9,5%. On multivariate analysis, the presence of Mira Markovic1, Igor Mitic1,2
1
anemia (p = 0.043), toxic contrast dose (as defined by ratio volume of contrast media to Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad,
estimated glomerular filtration rate (V/eGFR) > 2) (p = 0.02) and chronic renal failure Serbia and 2University of Novi Sad, Faculty of medicine Novi Sad, Novi Sad, Serbia
(p = 0.026) were independently found to confer a significant risk of CIN. In patients
belonging to the high Mehran risk group (MRS10- 15) the risk of CIN was 3,7 fold BACKGROUND AND AIMS: Critically ill patients with acute renal impairment
(OR: 3.7, 95% CI: 0,88–15,6, p = 0.036) higher when compared to intermediate and low (AKI) with a high risk of bleeding require treatment with one of the methods of
risk patients (MRS <10). continuous renal replacement (CRRT) with regional citrate anticoagulation (RCA) or
CONCLUSION: Mehran risk score is as a good score for predicting CIN in patients without anticoagulation (NA). The aim of the study was to compare CRRT with RCA
who underwent coronary angiography. According to this, we support its use in order to using calcium with CRRT in NA regimen.
identify the ones at risk, and to optimize CIN prophylactic therapy prior to and after METHOD: A clinical trial included 55 surgical and non-surgical patients with acute
catheterization. kidney injury and an episode of acute kidney injury in chronic kidney disease who were
admitted to the Intensive Care Unit (ICU) during 2020. The patients were divided into
two groups, RCA- CRRT with 39 and NA-CRRT with 16 patients. Demographic,
clinical and lab data before and after CRRT, treatment parameters CRRT and
outcomes were analyzed.
RESULTS: RCA vs NA group did not differ significantly by gender (small, 71.79% vs
56.25%, p = 0.106) and age (56.53 6 17.55 vs 45.75 6 13.3, p = 0.220). The NA group
had a significantly higher prevalence of liver disease as a reason for the ICU admission
when compared to the other group (12.5% vs 0.00%, p = 0.024). The RCA group before
CRRT had significantly higher mean values of CRP (173.68 6 122.06 vs 86.33 6 51.05,
p = 0.01) and significantly lower mean values of total bilirubin (16.78 6 4.31 vs 40.02
6 9.22, p = 0.005) and creatinine (463.97 6 36.24 vs 486.0 6 36.25, p = 0.001), while

10.1093/ndt/gfab083 | i273
Abstracts Nephrology Dialysis Transplantation

after CRRT it had significantly higher average values of total calcium (2.12 6 0.016 vs MO419 THE ROLE OF SHORT-TERM, HIGH-DOSE ATORVASTATIN
2.11 6 0.017, p = 0.023) and lower average values of pH (7.29 6 0.02 vs 7.32 6 0.015, p FOR PREVENTION OF CONTRAST-INDUCED ACUTE KIDNEY
= 0.040) and creatinine (463.97 6 36.24 vs 486.0 6 36.25, p = 0.001) in relation to the INJURY (CI-AKI) IN PATIENTS WITH CARDIOVASCULAR
NA group. No significant difference was found in relation to invasive mechanical DISEASES UNDERGOING COMPUTED TOMOGRAPHY WITH
ventilation, vasopressors therapy, SAPS II score, oliguria / anuria, recovery of renal INTRAVENOUS CONTRAST ADMINISTRATION
function, the length of hospital stay and mortality (p> 0.05) (Table 1). Compared to
treatment parameters, the RCA group had a significantly lower number of procedures Andrey Vasin1, Olga Mironova1, Viktor Fomin1
1
(4.33 6 2.80 vs 5.81 6 1.28, p = 0.027) and ultrafiltration rate (2.79 6 0.19 vs 3.14 6 I. M. Sechenov First Moscow State Medical University (Sechenov University), Russia
0.33, p = 0.015) and significantly longer hemofilter lifespan compared to NA group
(24.64 6 0.48 vs 18.10 6 0.58, p = 0.000). Although the prevalence of bleeding was BACKGROUND AND AIMS: Computed tomography with intravenous contrast
higher in the NA group, no significant difference was found between the groups (37.5% media is widely used in hospitals. The incidence of CI-AKI due to intravenous contrast
vs 28.20%, p = 0.498), as well as in the infusion of red blood cell (33.3% vs 37.5%, p = media administration in high-risk patients remains not studied as well as CI-AKI after
0.768), fresh frozen plasma (28.2% vs 50%, p = 0.742) and platelets (35.89 vs 31.25, p = intraarterial contrast media administration is. According to other researchers, the use
0.123). The overall citrate accumulation (CA> 2.25) rate was 5.12% in the RCA group of statins in the prevention of AKI after intra-arterial administration of a contrast agent
(Table 2). The Kaplan-Meier survival analysis using the log-rank test (Mantel-Cox test) is currently considered an efficient preventive measure. The aim of our study is to
for comparing the hemofilter lifespan between RCA and NA regime found a significant assess the incidence of contrast-induced acute kidney injury in patients with
difference in survival between the groups (v2 = 3,789, p = 0,049) (Figure 1). Multiple cardiovascular diseases during CT scan with intravenous contrast media and analyze
regression model for testing risk factors SAPS II score, Oxiris membrane, UF, lactate, the efficacy and safety of various statin dosing regimens for prevention of CI-AKI.
hemoglobin concentration, platelet count, Activated Partial Thromboplastin Time and METHOD: A randomized controlled open prospective study is planned. Statin naive
Prothrombin Time on hemofilter survival has shown a significant linear relationship patients with cardiovascular diseases will be divided into 3 groups. Patients in the first
without statistical significance in both RCA groups (R=0.544 ; F=1.575) and NA group will receive atorvastatin 80mg 24 hours and 40mg 2 hours before CT scans and
(R=0.757; F=1.171) (Table 3). 40 mg after. The second group – 40 mg 2 hours before CT scans and 40 mg after. A
third group is a control group. Exclusion criteria were current or previous statin
treatment, contraindications to statins, severe renal failure, acute coronary syndrome,
administration of nephrotoxic drugs. The primary endpoint will the development of
CI-AKI, defined as an increase in serum Cr concentration 0.5 mg/dl (44.2 mmol/l) or
25% above baseline at 72 h after exposure to the contrast media.
RESULTS: We assume a higher incidence of contrast-induced acute kidney injury in
the group of patients not receiving statin therapy (about 5-10%). At the same time, it is
unlikely to get a significant difference between statin dosing regimens. Risk factors such
as age over 75 years, the presence of chronic kidney disease, diabetes mellitus, and
chronic heart failure increase the risk of contrast-induced acute kidney injury.
CONCLUSION: Despite the significantly lower incidence of CI-AKI with intravenous
contrast compared to intra-arterial, patients with CVD have a greater risk of this
complication even with intravenous contrast. Therefore, the development of
prevention methods and scales for assessing the likelihood of CI-AKI is an important
problem. As a result of the study, we expect to conclude the benefits of statins in CI-
AKI prevention and the optimal dosage regimen. This information will help us to
reduce the burden of CI-AKI after CT scanning in statin naive patients with
cardiovascular diseases in everyday clinical practice.
ClinicalTrials.gov ID: NCT04666389

MO420 ROLE OF IL-6 ON ACUTE KIDNEY INJURY (AKI)


DEVELOPMENT AFTER LIVER TRANSPLANTATION

Francesca Tinti1, Martina Colicchio1, Stefano Ginanni Corradini2,


Gianluca Mennini3, Massimo Rossi3, Sandro Mazzaferro1, Annalisa Noce4, Anna
Paola Mitterhofer4
1
Sapienza University of Rome, Department of Translational and Precision Medicine -
Nephrology Unit, Rome, Italy, 2Sapienza University of Rome, Department of
Translational and Precision Medicine - Gastroenterology Unit, Rome, Italy, 3Sapienza
University of Rome, Department of General Surgery and Organ Transplantation -
Hepato-Bilio-Pancreatic and Liver Transplant Unit, Rome, Italy and 4University of
Rome Tor Vergata, Department of Systems Medicine - UOC of Internal Medicine-Center
oh Hypertension and Nephrology Unit, Rome, Italy

BACKGROUND AND AIMS: Acute kidney injury (AKI) post-liver transplantation is


a frequent complication with an incidence up to 70%, requiring renal replacement
therapy in about 25% of transplant patients. AKI in patients with normal renal
function is a recognized risk factor (FR) of chronic renal failure (CKD) de novo,
associated with a 4.5 times greater mortality at 5 years post-transplant.
Pathogenesis of AKI is multifactorial. Beyond the classical pre-transplant risk factors,
the hypoxia of the graft and the ischemia-reperfusion injury (IRI) have recently been
recognized to exert a pathogenetic role with specific mechanisms.
It has been recently demonstrated in experimental setting that ischemic tissues put in
place protective mechanisms in response to hypoxia aimed at increasing the release of
oxygen with the activation of angiogenesis mediated by the expression of factors
induced by hypoxia (HIF)-1-alpha.
HIF1-alfa has been shown to promote cell survival under hypoxic conditions by
MO418 Figure 1: The Kaplan-Meier survival analysis using the log-rank test switching metabolism from oxidative to glycolytic, by affecting the production of ATP
(Mantel-Cox test) for comparing the hemofilter lifespan between regional citrate to prevent excessive mitochondrial generation of reactive oxygen species, by promoting
anticoagulation (RCA) and no anticoagulation (NA) regime. secondary release of vascular endothelial growth factor (VEGF) and transforming
CONCLUSION: RCA-CRRT did not show a significant difference in the prevalence of growth factor-beta 1 (TGF-ß1), with following activation of inflammatory cytokines
bleeding compared to NA-CRRT in the patients with a high risk of bleeding, but the responsible for systemic inflammatory response syndrome (SIRS).
survival rate of hemofilters was significantly longer in RCA-CRRT, which suggested the Tumor necrosis factor-a, IL-1 and IL-6 are the most important cytokines released in
need for further research. IRI and seem to play a pivotal role in the onset of AKI in SIRS and sepsis.
The development of AKI after hypoxia/ischemia of the graft, as observed more
frequently in the population of recipients from donors after cardiocirculatory death
(DCD) compared to donation after brain death (DBD), confirms this pathogenetic
mechanism.
Aim of the study is to evaluate AKI occurrence among liver transplanted patients and
its relationship with IRI and cytokines systemic release.

i274 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: Data of 78 patients (62 males, 79.5%) undergone liver transplantation of less than 200ml/ hour at six-hours post-transplant.
(2007-2011) were retrieved. CONCLUSION: The findings of our study suggest that longer duration of graft
RESULTS: The following clinical investigations were performed: ischemic time, history of previous cardiac operation and transfusion of more than four
blood units can independently predict the chance of developing AKI following heart
transplant. Therapies, which target these modifiable risk factors, may offer protection
• AKI developed in 40 patients (51.3%), of these 30 patients developed AKI stage 1, against this complication.
5 patients AKI stage 2 and 5 AKI stage 3. Patients with AKI stages 2&3 presented
more deteriorated pre-tx liver function as suggested by higher MELD score
(AKI2&3 20 [16-25] vs no AKI-AKI1 15 [11-18]; p=0.008), higher bilirubin
(AKI2&3 5.7 mg/dl [3.5-10.8] vs no AKI-AKI1 2.8 mg/dl [1.2-4.9]; p=0.009) and
INR (AKI2&3 1.9 [1.6-2.5] vs no AKI-AKI1 1.4 [1.3-1.6]; p<0.0001) at transplant,
despite superior renal function (serum creatinine in AKI2&3 0.7 mg/dl [0.5-0.8]
vs no AKI-AKI1 0.9 mg/dl [0.7-1.1].
MO422 Table 1: Comparison of baseline demographic and clinical data and
transplant characteristics in patients with and without post-transplant AKI
• Patients with AKI2&3 experienced greater ischemia-reperfusion injury based on
functional recovery of the transplanted liver (higher peak AST in the first 7 days
post-LT p=0.029, and higher peak ALT level p=0.062).
• The evaluation of IL-6 levels at transplant, 1- and 12-days post- LT were per-
formed in 21 patients, 8 with AKI and 13 with no AKI.
AKI patients demonstrated a progressive increasing of IL-6 after liver transplantation
Abbreviations: IABP: intraaortic balloon pump; BMI: body mass index
(AKI 34.4-37.8-88.2 ng/ml vs no AKI 30.5-21.6-23.3 ng/ml).
CONCLUSION: Patients who experienced greater ischaemia-reperfusion injury of the
liver graft developed more frequently AKI. Patients with AKI experienced an increased
release and circulation of IL-6, that probably is involved in AKI development with
interesting implications in future therapy. MO422 Table 2: Table 2. Comparison of perioperative treatments and
complications in patients with and without post-transplant AKI

MO421 THE EFFECT OF RENIN-ANGIOTENSIN-ALDOSTERONE


SYSTEM BLOCKADE MEDICATIONS ON CONTRAST-
INDUCED NEPHROPATHY IN PATIENTS UNDERGOING Continuous data are presented as median (Q1-Q3) and categorical vari-
CORONARY ANGIOGRAPHY
ables are presented as frequency (percentage)
Emna Chaabouni1, Hela Jbali1, Najjar Mariem2, Mzoughi Khadija3, Abbreviations: DM: Diabetes mellitus; ECMO: Extracorporeal
Zouaghi Mohamed karim1 Membrane Oxygenation; ATG: Anti-thymocyte globulin.
1
La Rabta, Nephrology, Tunis, Tunisia, 2Charles Nicolle Hospital, Nephrology, Tunis,
Tunisia and 3Habib Thameur Hospital, cardiology, Tunis, Tunisia

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN) is the main


complication of contrast media administration in patients undergoing coronary MO423 PROENKEPHALIN AS A BIOMARKER OF KIDNEY
angiography (CAG). This complication may be accelerated by concurrent renin- FILTRATION IN ACUTE KIDNEY INJURY
angiotensin-aldosterone system (RAAS) blockers . Current literature is inconclusive.
We investigated the impact of RAAS blockade on the occurrence of CIN in patients Camila Lima1, Etienne Macedo2
undergoing CAG. 1
University S~ ao Paulo, Brazil and 2
ao Paulo, Department of Internal Medicine, S~
METHOD: We prospectively enrolled 158 patients who underwent CAG with or
University of California San Diego, Department of Medicine, Nephrology Division, CA,
without percutaneous coronary intervention from December 2017 to February 2018 at
United States of America
a cardiology department .
CIN was defined as an increase in serum creatinine level >25% or 0.5 mg/dL after 48
hours postcardiac catheterization. BACKGROUND AND AIMS: In the last decades, clinical research biomarker (BM) to
RESULTS: Of 158 patients (females=36.1%, mean age 60.0 6 11 years) who improve assessment of kidney function have been intensive, and proenkephalin
underwent CAG , 15 (9,5%) developed CIN . Eighty one patients (51,2%) were chronic (PENK) has been identified as a new BM of filtration. We hypothesized whether PENK
RAAS blockade users. would have a better accuracy for the diagnosis of severe AKI than serum cystatin (CYS)
There was no significant difference between the two groups, RAAS blockade ’used’ and the serum creatinine (Scr). We evaluate patient in the peri op of liver transplant
versus ’not-used’, in the incidence of postprocedural CIN (7,5% vs 11,5%, p=0,38). (LT).
However , the pre-contrast use of RASS blockers decrease the risk of CIN in patients METHOD: Blood samples were collected during the pre and post (until 48 hours)
with chronic renal failure (12,5% vs 66,6% , p=0,042) . operative (op.) period of LT in 57 eligible patients. Where was analyzed PENK
CONCLUSION: RAAS blockade isn’t associated with a significantly higher incidence (SphingotestV R ), CYS (Milipex) and Scr (Quimioluminence). AKI diagnosis was based

of CIN, whereas it has the potential to mitigate the incidence of CIN in patients with on the Kidney Disease International Global Outcomes (KDIGO) criteria using Scr.
chronic renal failure. This low cost intervention could be considered when referring a KDIGO 1 was subclassified according to the International Club of Ascites (ICA).
patient for cardiac catheterization. RESULTS: Of the 57 patients undergoing LT, 50 (88%) developed AKI according to
the KDIGO criteria in the first week after LT. Twenty-one patients without AKI and
with KDIGO 1-A (37%) were summarized as the no AKI/mild AKI group, whereas 36
patients with KDIGO 1-B, 2 and 3 (63%) were summarized as the severe AKI group.
MO422 ACUTE KIDNEY INJURY AFTER HEART TRANSPLANTATION , Before the intra - operative insult only PENK was significantly higher in patients that
INCIDENCE AND PREDICTIVE FACTORS developed severe AKI, median 55 [P25-75(44,25 – 94,55)] in no AKI/mild AKI versus
90,16 [P25-75(64,70 – 135,76)] pmol/l in severe AKI p 0,021, an AUC 0,685 (CI 0,536
Nooshin Dalili1 – 0,833), with a cutoff 55 pmol/l, sensibility of 0,86 and specificity 0,52, accuracy 0,75
1
Shahid Beheshti University of Medical Sciences, Labbafinejad Medical Center ,CKDRC , to severe AKI. Scr levels in pre-op. were non- significantly higher in severe AKI;
Tehran, Iran p=0,088. The CYS in the pre-op was similar within the groups. Pos-operative 48 hours
after LT, PENK was significantly higher in severe AKI, median 81 [P25-75(61,25 –
BACKGROUND AND AIMS: Abruptly decreased kidney function is one of the 101,50)] versus 161,45 [P25-75(122,85 – 294,03)] in severe AKI - p <0,0001 an AUC
common scenarios after heart transplantation and the risk factors for renal dysfunction 0,83 (CI 0,72 - 0,94) with a cutoff 119,05 pmol/l, sensibility of 0,80 and specificity 0,90,
in this population can be various. The purpose of the present study was to determine accuracy 0,84 to severe AKI. Scr levels in post-op achieve an AUC 0,77 (CI 0,63 - 0,92)
the incidence and predictors for renal dysfunction among 126 patients in early with a cutoff 1,49mg/dl, sensibility of 0,94, specificity 0,67 and accuracy 0,82. In a
postoperative heart transplantation period between January 2015 and November 2019. multivariate linear regression analysis adjusted for age, anestesia time, urine output
METHOD: The study was conducted at the department of cardio-thoracic intensive and fluid balance, the PENK only was independently associated of severe AKI in pre-
care unit of an affiliated teaching hospital. 126 patients had cardiac transplantation op. with OR 4,40 (CI 1,40 – 13,88) – p0,001 and the post-op. with OR 44,64 (CI 5,40 –
surgery during four years. Information from these patients collected on a daily basis 368,5) – p<0,0001.
using standardized forms. CONCLUSION: PENK is a promisor filtration biomarker and showed a better acuracy
RESULTS: Out of 126 heart transplant recipients 58.7 % (n=74) developed AKI and to severe AKI in pre-operative than standard AKI diagnostic by Scr. Prediction of
10% (n=13) required renal replacement therapy after transplant. After performing severe AKI in pre-operative period by PENK can help the management of these
univariate analysis, predictors of AKI were: age, duration of anesthesia, cold ischemia patients in the future.
time, Voluven (Starch) dose, pre-operative BUN, creatinine and serum albumin, level
of liver function tests, and Hemoglubin at three-days post-transplant and urine output

10.1093/ndt/gfab083 | i275
Abstracts Nephrology Dialysis Transplantation

 USING CLINICAL RISK FACTORS AND CHANGES


IN BOGOTA
MO423 Figure 1: Curve ROC AUC for Scr and PENK in pre and post- operative.
IN SERUM CREATININE

Alejandra Molano-Trivin ~o1,2,3, José Garcia-Habeych2,4, Juan Camilo Castellanos


De la Hoz2,4, Noelia Nin ~o Caro3, Juan Pablo Montoya2, Laura Gutiérrez Rueda2,
Manuel Antonio Pérez Hettinga5, Ana Milena Mejia Sanjuanelo6, Carlos
Mauricio Martinez Montalvo6, Luis Alejandro Castro Durango2, Yilmar Meza
Gonz alez6, Claudio Ronco1, Eduardo Zu ~iga2,3, Santiago Baro
n n7,
Sandra Saumett2
1
Ospedale San Bortolo di Vicenza, International Renal Research Institute Vicenza,
Vicenza, Italy, 2Universidad Del Rosario, Universidad del Rosario escuela de medicina y
ciencias de la salud, Bogota, Colombia, 3Fundaci on Cardioinfantil, Nephrology, Bogot
a,
Colombia, 4Fundaci on Cardioinfantil, 1.Internal medicine and Nephrology Fundaci on
5
Cardioinfantil, Bogota, Colombia, Universidad del Rosario, 3.Internal medicine,
Universidad del Rosario, escuela de medicina y ciencias de la salud, Bogot a, Colombia,
6
Universidad del Norte, Colombia, Internal medicine, Universidad del Norte.,
7
Barranquilla, Colombia and Universidad de La Sabana, Universidad de la Sabana,
medicine school, Chıa, Colombia

BACKGROUND AND AIMS: Acute Kidney Injury (AKI) has remarkable


cardiovascular and mortality outcomes, both short and long term potentially
preventable with adequate ICU support, thus, early diagnosis is mandatory. Full AKI
diagnosis according to KDIGO criteria can result in delayed interventions at admission
in ICU, giving potential benefits to alternatives in early diagnosis.
Cruz and NEFROINT research group described a scale for prediction of severe AKI,
based on risk factors and establishing creatinine cuts as markers of kidney distress.1
Our aim is to describe the predictive capacity of small changes in serum creatinine
correlating with clinical risk factors in adult critical care patients.
1
. Clin J Am Soc Nephrol (2014) 9, 663-672.
METHOD: We retrospectively selected from our Critical Care Nephrology database
adult patients admitted in any of our hospitals ICU between February to August 2020,
excluding those at admission with diagnosis of AKI, serum creatinine > 2.5 mg/dl, or
those receiving dialysis (acute or chronic) or kidney transplantation. We defined AKI
according to KDIGO criteria.
We calculated Cruz et al scale of prediction of severe AKI. The minimally acceptable
criteria for this test was a sensitivity of 95%. A point estimate and confidence intervals
of sensitivity and specificity were derived from a contingency table.
RESULTS: From 1204 new ICU patients, according to selection criteria we found 372
patients (women 40.3%), with mean age of 60.9 years (range 18-98), mainly
hospitalized for medical conditions.
Mean values of APACHE II was 22.9. Hemodynamic support was required in 41.1% of
patients and mechanical ventilation in 58.6% of patients. (Table 1).
AKI KDIGO 2-3 was diagnosed in 65 (26.8%) of patients.
Creatinine at admission was statistically different in patients that developed AKI (CI
0.95 -0.51 - 0.15 mg/dl, p=0.0004). Requirement of hemodynamic (p = 0.003) and
ventilatory support (p = 0.009), sepsis (p = 0.003), and diagnosis of COVID-19 (p =
0.03) were more frequent in patients who developed AKI.
Clinical risk for severe AKI was present in 356 patients (95.7%): 66,5% at very high
risk, 9,8% at high risk and 19,2% at moderate risk. Patients without risk criteria were
classified as low risk (4,3%).
In patients with risk factors for AKI, and a significative increase in creatinine adjusted
to risks, diagnostic performance for predicting diagnosis of KDIGO 2-3 AKI had a
sensitivity, specificity, positive and negative predictive value of 89% (CI95% 79 – 95%),
58% (CI95% 52 – 64%), 0.31 (CI95% 0.25 – 0.39) and 0.96 (CI95% 0.92 – 0.98)
respectively (Figure).
Renal replacement therapy was required in 39 (60%) of patients with severe AKI
(incidence 10.5%). (Table 2)
CONCLUSION: Regardless of the risk stratification for AKI, the absence of significant
early changes in serum creatinine rules out the possibility of progression to KDIGO 2-3
AKI in the first seven days after ICU admission.

MO423 Figure 2: Bar chart severe AKI and the diagnostic by cutoff by Scr and
PENK in pre-operative.

MO424 RENAL ANGINA: RISK OF ACUTE KIDNEY INJURY IN


 CARDIOINFANTIL
CRITICALLY ILL ADULTS IN FUNDACION

i276 | Abstracts
Nephrology Dialysis Transplantation Abstracts

MO425 RENAL SURGERY APPROACHES AND POST-OPERATIVE AKI


DEVELOPMENT IN NORMAL RENAL FUNCTION PATIENTS;
AN HIDDEN TREATH

Francesco Trevisani1, Federico Di Marco1, Giuseppe Rosiello1, Francesco Florio1, MO425 Figure 1: Kruskal-Wallis rank sum test
Alessandra Cinque1, Arianna Bettiga1, Umberto Capitanio1, Andrea Salonia1, Pearson’s Chi-squared test
Francesco Montorsi1 CONCLUSION: Our study highlights that both radical (55%) than partial (21%)
1
San Raffaele Scientific Institute, Urological Department, Milano, Italy nephrectomies harbor a non-negligible risk of post-operative AKI even in normal renal
function patients without renal abnormalities. In addition, the impact of RN in normal
renal function patients shows a dramatic incidence of AKI in the 50% of cases,
BACKGROUND AND AIMS: Acute kidney injury (AKI) is a major postoperative
suggesting that nephron sparing surgeries techniques should be always indicated to
complication in renal surgery for cancer, both in radical than in partial nephrectomy.
preserve renal function also in patients with an eGFR> 80 ml/min/1,73. A prospective
One of the most intriguing arguments is to understand if normal renal function
comparison multicentric study with kidney living donor is on going.
patients without renal urinary abnormalities can develop post-operative AKI after
renal surgery. Aim of our study was to compare the AKI incidence in the two major
renal surgeries approaches (radical and partial nephrectomies) in a selected cohort of
patients with normal renal function. MO426 HANTA HEMORRHAGIC FEVER WITH RENAL SYNDROME
METHOD: We performed a retrospective study of 216 patients who underwent radical CAUSED BY HANTAAN SEROTIPE IN BALKAN PENINSULA -
(RN) or partial nephrectomy (PN) due to the presence of a kidney mass from 2000- AN UNESPECTED FINDING
2020 in a tertiary care Institution. Inclusion criteria: 1) Age> 18; 2) eGFR >;80 ml/
min/1,73 using CKD-EPI formula 2012 3) absence of urinary abnormalities 4) presence Gabriela Elena Lupusoru1,2, Ioana-Georgiana Ailincai2, Andreea
of two kidneys at time operation. The following data were considered: age, gender, Gabriella Andronesi1,2, Mircea Lupusoru3, Lavinia Maria Bernea2, Andreea
body mass index (BMI), TNM staging, hypertension, diabetes. Serum creatinine values Ioana Berechet2, Mihaela Banu4, Danut Andronesi5, Gener Ismail1,2
were collected before surgery (t 0), at 48 hours after surgery and at dismissal. GFR was 1
“Carol Davila” University of Medicine and Pharmacy, Bucharest, Nephrology
estimated at each time point using creatinine-based estimated glomerular filtration rate Department, Bucharest, Romania, 2Fundeni Clinical Institute, Nephrology Department,
(eGFR) formula: CKD-EPI. We evaluated eGFR variation from the pre-surgical value Bucharest, Romania, 3“Carol Davila” University of Medicine and Pharmacy, Bucharest ,
to 48 h post and at dismissal. eGFR categories were created according to the KDIGO Physiology Department, Buharest, Romania, 4“Carol Davila” University of Medicine and
guidelines for G categories. Comparisons between groups were performed using Pharmacy, Bucharest , Morphological Sciences Department, Bucharest, Romania and
Kruskal-Wallis ranks sum test for numerical variables and Pearson’s Chi square test for 5
Fundeni Clinical Institute, General Surgery and Liver Transplant Department,
categorical variables. Logistic regression was used to identify variables ODDS Ratio for Bucharest, Romania
AKI onset after surgery.
RESULTS: Clinical and pathological characteristics are reported in table 1. The cohort
BACKGROUND AND AIMS: Hantavirus infection is a zoonosis rare in the Balkan
was composed by 216 patients with median Age 55 (IQR: 47, 64), M/F ratio 2.4,
Peninsula but with increasing frequency and geographic spread, causing two major
median BMI 25.8 (IQR: 23.3, 28.4), median eGFR 94.3 (IQR: 89.1, 101.6). According to
syndromes, depending on the viral serotype: hemorrhagic fever with renal syndrome
CKD G classes, 79% were stage 1 and 2 1 were stage 2. The cohort was divided in two
(HFRS) and cardiopulmonary syndrome (CPS). Because there is no specific treatment
groups according to the type of surgery: 51% as RN and 49% as PN. Differences
or vaccine for this condition, the key for minimizing the progression to chronic kidney
between the two groups were detected for Gender (Radical M/F ratio: 3.3; Partial M/F
disease, secondary hypertension or death is early diagnosis and prompt therapy. This
ratio: 1.8; p=0.4), basal eGFR (Radical Median:92.9 (88.1, 101.0); Partial Median:95.3
paper presents a case of HFSR in which needle kidney biopsy played a major role in
(90.7, 102.4); p=0.03) and CKD G class (Radical I:64%, II:36%; Partial I:78%, II:22%;
diagnosis and draws attention on this zoonosis that might be highly underdiagnosed in
p=0.02). Logistic regression for AKI onset showed as significant parameter (p<0.001)
Balkan Peninsula.
only the type of surgery observing for Radical Nephrectomy and ODDS Ratio of 4.6
METHOD: A 26-year-old female with no medical history was admitted in our
(Confidence Interval: 2.6,8.5). The proportions of patients who developed AKI were
department with acute kidney injury (AKI), nephritic syndrome with nephrotic range
21% for PN and 55% for RN (Figure 1).
proteinuria, high blood pressure, hepatic cytolysis, severe thrombocytopenia, anemia
and leukocytosis, elevated LDH, normal haptoglobin, positive Coombs test (Table 1).
Immunological testing (C3, C4, ANA, ANCA, antiGBM), viral infection markers
(hepatitis B/C, HIV, Epstein-Barr, Cytomegalovirus), IgA/M/G were all negative and
ADAMTS13 activity was normal.
Abdominal sonography showed both kidneys of normal size and shape.
A kidney biopsy was performed. The biopsy specimen showed macroscopic features of
hemorrhage in the renal medulla. In immunofluorescence the staining was negative for
IgA, IgG, IgM, C1q, C3c, k and k chains, albumin and fibrinogen. Light microscopy

10.1093/ndt/gfab083 | i277
Abstracts Nephrology Dialysis Transplantation

(LM) revealed normal glomeruli and arterioles, dilated proximal tubules with collecting ducts. We present a young woman, with a history of hyperuricaemia, who
resorption droplets at the apical pole and erythrocytes in the lumen, important was treated with allopurinol for acute UAN during her first pregnancy. She also
interstitial hemorrhage in the medulla, with no inflammation or interstitial fibrosis. continued allopurinol treatment during her second pregnancy for prevention of further
The electron microscopy (EM) showed segmental foot process effacement, acute UAN. To the author’s knowledge, this is the first case report of biopsy-confirmed
endotheliosis of the peritubular capillaries, rare plasmocytes and macrophages in the acute UAN during pregnancy.
interstitium (Figure 1). The aspect of hemorrhagic interstitial nephritis suggested CASE REPORT: A 20 year old woman, who was 13 weeks pregnant, was admitted
Hantavirus infection. Serological testing revealed both IgM and IgG antibodies for the with AKI.
Hantaan serotype (HTNV). The final diagnosis was HTNV hemorrhagic interstitial Past medical history included chronic kidney disease (CKD) and gout since the age of
nephritis with intrinsic AKI and secondary hypertension. 17. She had an extensive family history of CKD and gout (without diagnosis, despite
genetic testing). She had been on daily allopurinol 300mg, but this was stopped 8 weeks
prior by her rheumatology team due to concerns about teratogenicity. At that time
serum creatinine was at her baseline of 100 lmol/L (normal range 50-120 lmol/L) and
MO426 Figure 1: A, B: LM, Toluidine Blue staining. Normal glomerulus. Resorption serum uric acid had been 740 lmol/L (normal range 140-360 lmol/L).
droplets in the proximal tubular cells. C, D: LM, Toluidine Blue staining. Extensive On admission, she felt well and was euvolemic. Serum creatinine was now 352 lmol/L
interstitial hemorrhage in medulla, tubulitis. E: EM. Interstitial extravasation of and her serum uric acid level was 1720 lmol/L, with an elevated urine uric acid to
erythrocytes. F: EM. Endothelial swelling, foot process effacement. creatinine ratio of 1.1. She underwent renal biopsy, which showed significant
RESULTS: The patient was treated with oral methylprednisolone 16mg/d for 2 weeks, deposition of uric acid crystals in the renal tubules, confirming a diagnosis of acute
with progressive tampering of the dose and removal after 2 months. She received UAN. She was given intravenous fluids. The uncertainties of allopurinol use in
antihypertensive and antiproteinuric treatment with ramipril. The evolution was good, pregnancy were discussed with her, and she was restarted on allopurinol 200 mg daily.
with creatinine and liver enzymes returning to normal. Over the next 3 weeks, serum uric acid decreased to 470 lmol/L and serum creatinine
CONCLUSION: HFRS belongs to a group of rare zoonoses in Balkan Peninsula, the to 116 lmol/L. She was maintained on allopurinol during her pregnancy and delivered
most involved serotypes being Dobrava and Puumala. This case had positive serology a healthy baby girl.
for HTNV usually being found in China and Russia, but our patient didn’t travel She was advised against further pregnancies due to increased risk of maternal and fetal
abroad before she got ill, so we can’t consider the case as being an imported infection. complications. However, three years later she presented at 15 weeks’ gestation. After a
That highlights a possible underdiagnosis of the disease in this region and also the need discussion regarding the potential teratogenic effects of allopurinol versus the risk of
to re-evaluate geographic distribution of different strains and changes in ecological recurrent severe AKI due to acute UAN if it was again discontinued, she chose to
aspects given that they may pose a major risk to public health. The disease begins with continue allopurinol. The pregnancy proceeded without complication.
flu-like symptoms and progresses to AKI with severe thrombocytopenia, anemia and Her daughters are now 8 and 5 years old. They do not have any congenital
coagulation disorders, being easily mistaken for haemolytic uremic syndrome. In a malformations, though both have mild to moderate learning difficulties.
region with sporadic cases, we face diagnosis difficulties related especially to the DISCUSSION: Allopurinol is approved for the treatment of hyperuricaemia outside of
absence of initial diagnosis suspicion, so we emphasize the need to include this pregnancy, but given it interrupts purine synthesis there is a biologically plausible
pathology in the differential diagnosis algorithm of diseases evolving with concern regarding teratogenicity. However, in our patient with long-standing
thrombocytopenia, anemia, hepatic cytolysis and renal injury. hyperuricaemia it was the discontinuation of allopurinol that precipitated AKI due to
the resultant crystal formation when serum uric acid reached very high levels.
Biopsy confirmation of acute UAN was vital in this case, given the possibility of
missing an alternative diagnosis and the risks of giving empirical allopurinol therapy.
MO427 SAFE USE OF ALLOPURINOL TO TREAT ACUTE URIC ACID Once the diagnosis for her severe AKI was confirmed, it was clear our patient would
NEPHROPATHY IN PREGNANCY: A CASE REPORT benefit from uric acid lowering therapy.
Our patient had two healthy girls despite using allopurinol from week 16 in her first
Fahd Khan1, Aizaz Ali2, Jamie Willows1, Didem Tez1 pregnancy and throughout her second pregnancy. Unfortunately, both girls have mild
1 to moderate learning needs, though it is unprovable whether allopurinol was causative
James Cook University Hospital, Renal Directorate, United Kingdom and 2Shifa as no study has followed up long term outcomes after foetal exposure during
International Hospital pregnancy.

INTRODUCTION: Acute uric acid nephropathy (UAN) is characterized by acute


kidney injury (AKI) due to uric acid crystal precipitation within the distal tubules and

i278 | Abstracts
Nephrology Dialysis Transplantation 35 (Supplement 3): i279–i282, 2021
10.1093/ndt/gfab088

CKD. LAB METHODS, GFR MEASUREMENT, URINE Munich Wistar Frömter rats (MWF) and to test the feasibility of the innovative
linescan approach. In order to validate this method in conditions known for reduced
PROTEOMICS and increased SNGFR, it was applied to ischemia reperfusion injury (IRI) and low-dose
dopamine treated conditions, respectively.
RESULTS: The glomeruli connected to S1 proximal tubules extending at least 100 lm
from the exit of the Bowman’s space were chosen for the measurement. A linescan path
MO428 25-HYDROXYVITAMIN D AND TUBULAR DYSTROPHY IN starting from the urinary pole and crossing many times the tubular lumen orthogonally
PATIENTS WITH CKD STAGES 1-3* to the cellular wall was hand drawn. The linescan was acquired soon after a i.v. bolus of
low-molecular weight fluorescent marker was injected. The tubular length, the mean
Olga Galkina1, Evdokia Bogdanova1, Irina Zubina1, Elena Levykina1, diameter and the transit time of the fluorescent marker within two lines of interest
Anastasiia Anpilova1, Vassili Sipovski1, Iraida Panina2, Yurii Kovalchuk3, (called cross1 and cross2) were measured to obtain the SNGFR. SNGFR measured in
Alexei Smirnov1 control rats was comparable with previous reported data both at MPM and
1
Pavlov University, Nephrology Research Institute, Saint Petersburg, Russia, 2Pavlov micropuncture. Significantly higher values compared to control were obtained in 3 lg/
University, Department of Propaedeutics of Internal Diseases, Saint Petersburg, Russia kg/min dopamine-treated rats. In IRI-treated rats the SNGFR was reduced about 35%
and 3Pavlov University, Saint Petersburg, Russia compared to the controls.
CONCLUSION: The results achieved with our linescan method were quite similar to
those obtained with conventional micropuncture, suggesting that the two methods
BACKGROUND AND AIMS: According to a recent data the 25-hydroxyvitamin D
overlap for the normal, dopamine and IRI treatment. Our results show that linescan
(25OHD) level is known to be reduced in advanced stages of CKD presumably due to i)
approach is a promising and cheap alternative to the fast full frame acquisition for the
catabolic activity of CYP24 in damaged tubules and ii) increase in renal excretion of
investigation of SNGFR in health and disease, offering results comparable to
25OHD/Vitamin D binding protein complex. The association of the 25OHD level with
conventional micropuncture with unprecedent temporal resolution.
different types of tubular damage in early stages (1-3) of CKD is not well investigated.
METHOD: The cross-sectional study included 100 patients (37 male; age 38 (30-50)
yrs.) with biopsy proven primary glomerulopathy (membranoproliferative
glomerulonephritis (n=9); minimal change disease (n=10); membranous nephropathy MO430 MASS-SPECTROMETRIC IDENTIFICATION OF POST-
(n=11); focal segmental glomerulosclerosis (n=20); IgA nephropathy (n=50)) and CKD TRANSLATIONAL GUANIDINYLATED PROTEINS IN THE
stages 1-3 (median eGFR was 64 (33-90) ml/min/1.73 m2). Patients with AKI, CONTEXT OF SYSTEMIC LUPUS ERYTHEMATOSUS
infectious diseases, heart failure, respiratory failure and cancer pathology were
excluded. The levels of proteinuria, intact parathyroid hormone (PTH) (Beckman Juliane Hermann1, Ute Raffetseder2, Michaela Lellig1, Joachim Jankowski1,
Coulter), 25OHD (Abbott) were estimated in all patients. In all cases the following Vera Jankowski1
types of tubular damage were analyzed by light microscopy of kidney tissue 1
Institute for Molecular Cardiovascular Research (IMCAR), RWTH-Aachen University,
(hematoxylin and eosin, periodic acid Schiff, Masson’s trichrome, Congo red, and Aachen, Germany and 2Dep. of Nephrology and Clinical Immunology, RWTH-Aachen
Jones’ silver) and calculated semi-quantitatively (0 – <10%; 1 – 10-25%; 2 – 26-50% University, Aachen, Germany
and 3 – >50% of tissue sample): granular dystrophy, hyaline-drop dystrophy, hydropic
dystrophy, foamy degeneration and atrophy. The association between clinical and
BACKGROUND AND AIMS: With continuous identification of post-translational
morphological variables was estimated by Spearman’s coefficient and multiple linear
modified isoforms of proteins, it is becoming increasingly clear that post-translational
regression analysis.
modifications limit or modify the biological functions of native proteins are majorly
RESULTS: The patients had a lack or deficiency of 25OHD [Me (Q1-Q3): 13.1 (7.6-
involved in development of various chronic disease. This is mostly due to technically
19.3) ng/ml]. There was no correlation between serum 25OHD and PTH (r = -0.03, p =
advanced molecular identification and quantification methods, mainly based on mass
0.86). Proteinuria was negatively associated with level of 25OHD (r = -0.56, p = 0.012).
spectrometry. Mass spectrometry has become one of the most powerful tools for the
The level of 25OHD was associated with granular (r = -0.39, p <0.05) and hyaline-drop
identification of lipids.
(r = -0.39, p <0.05) tubular dystrophy. In multiple regression analysis the 25OHD level
METHOD: In this study, we used sophisticated high-resolution mass-spectrometric
was the independent predictor of the severe hyaline-drop tubular dystrophy (b = -0.33
methods to analyze the soluble ligand of receptor Notch-3, namely the Y-box protein
6 0.11, p = 0.046) when adjusted for proteinuria (b=0.2260.11, p=0.062).
(YB)-1, in serum from systemic lupus erythematosus (SLE) patients. In addition,
CONCLUSION: In patients with CKD stages 1-3 decline in serum 25OHD is
kidneys of lupus-prone (MRL.lpr) mice were analyzed by mass-spectrometric imaging
associated with the severity of tubular dystrophy. 25OHD level may be useful in
techniques to identify the underlying pathomechanisms. Serum YB-1 was isolated by
laboratory diagnosis as a risk factor of tubular damage in early stages of CKD.
chromatographic methods, afterwards digested by trypsin and analyzed by matrix
assisted laser desorption/ionization mass spectrometry (MALDI-MS). The kidneys
were fixed in paraffin, then kidney sections were deparaffinized, tryptic digested and
MO429 A NOVEL METHOD LINESCAN-DRIVEN FOR SNGFR analyzed by mass-spectrometric imaging techniques. Mass-spectrometry of
MEASUREMENTS AS ALTERNATIVE TO HIGH FULL FRAME extracellular YB-1 in SLE patient serum revealed post-translational guanidinylation of
MULTIPHOTON MICROSCOPY ACQUISITION two lysine’s within the highly conserved cold shock domain (CSD) of the YB-1 protein
(YB-1-2G). Patients with increased disease activity and those with active renal
Vincenzo Costanzo1,2, Luciano D’Apolito1,3, Donato Sardella4, Anna Iervolino1, involvement (lupus nephritis, LN) had a higher degree of dual-guanidinylation within
Sebastian Frische4, Gaetano La Manna2, Giovambattista Capasso1,3, the CSD. Of note, at least one of these modifications was present in all analyzed LN
Francesco Trepiccione1,3 patients, whereas single-guanidinylated YB-1 was present in only one and double
1
Biogem A. C. S. R. L., Ariano Irpino (AV), Italy, 2Alma Mater Studiorum - University of modification in none of the control individuals. Mass-spectrometric imaging analyses
Bologna, Department of Specialistic, Diagnostic and Experimental Medicine, Bologna, specifically localized YB-1-2G and increases Notch-3 expression in kidney sections
Italy, 3University of Campania Luigi Vanvitelli, Department of Translational Medical from MRL.lpr mice.
Sciences, Naples, Italy and 4Aarhus University, Department of Biomedicine, Aarhus, RESULTS: The data from this study clearly demonstrate the high potential of high-
Denmark resolution mass spectrometric methods as well as mass spectrometric imaging
techniques to identify pathomechanisms of diseases like SLE/LN.
BACKGROUND AND AIMS: Renal micropuncture, which requires the direct access
to the renal tubules, has been for long time the technique of choice to measure the
single nephron glomerular filtration rate (SNGFR) in animal models, but this approach
is challenging by virtue of complex animal preparation and numerous careful steps.
The introduction of intravital multiphoton microscopy (MPM) permitted to improve
the study of renal functions exploiting the high laser penetration and the optical
sectioning capacity. Previous MPM studies measuring in vivo the SNGFR relied on fast
full frame acquisition during the filtration process obtainable with microscope
resonant scanners, which represent optional expensive equipment able to reach very
high acquisition speed. In this work we propose an innovative linescan-based MPM
method to calculate SNGFR in rodents doable without using the fast acquisition rate
offered by resonant scanners.
METHOD: An in vivo MPM approach was used to measure the SNGFR in control

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

MO431 LIPIDOMIC ANALYSIS IN A NON-DIABETIC RAT MODEL measured one time and in 10 PMN patients treated IST – in dynamic, from 2 to 5
WITH HYPERFILTRATION AND ALBUMINURIA REVEALS times. Statistical comparisons among groups were performed using Mann–Whitney U-
DYNAMIC CHANGES IN THE PROSTAGLANDIN E2 PATHWAY test and Kruskal-Wallis H tests. The association between variables was estimated using
DURING ONSET OF ALBUMINURIA AS A POTENTIAL Spearman’s coefficient. Sensitivity and specificity of the methods were calculated.
CAUSATIVE MECHANISM RESULTS: The correlation coefficient between IIF and ELISA was 0.82 (p <0.005).
There were more PLA2R-Ab-positive cases detected by ELISA, both before treatment
Eva Mangelsen1, Michael Rothe2, Juliane Bolbrinker1, Aikaterini Kourpa3, (ELISA - 80%, IIF - 67%) and among patients treated with IST (ELISA - 63%, IIF -
Daniela Pana kova 3,4, Reinhold Kreutz1,4, Angela Martina Schulz1
50%). In control group, ELISA showed no positive results for PLA2R-Ab (specificity
1
Charité – Universit€
atsmedizin Berlin, Institute of Clinical Pharmacology and was 100%). The levels of proteinuria and eGFR were associated with autoantibodies
Toxicology, Berlin, Germany, 2LIPIDOMIX GmbH, Berlin, Germany, 3Max Delbrück Center determined by ELISA, both quantitative and semi-quantitative (proteinuria: r = 0.69, p
for Molecular Medicine, Electrochemical Signaling in Development and Disease, Berlin, = 0.001; eGFR: r = -0.38, p = 0.035) but not by IIF (proteinuria: r=0.33, p=0.061; eGFR:
Germany and 4German Centre for Cardiovascular Research, Berlin, Germany r=-0.26, p=0.082). The levels of PLA2R-Ab measured by ELISA correlated with the
course of disease in patients treated with IST, while IIF did not show any dynamics is
BACKGROUND AND AIMS: We recently identified prostaglandin reductase 2 some cases.
(Ptgr2) and the prostaglandin E2 (PGE2) pathway as potential causative mechanism in CONCLUSION: Both quantitative and semi-quantitative ELISA were considered to be
the Munich Wistar Frömter (MWF) non-diabetic rat model of chronic kidney disease. more preferable methods since the obtained results correlate with renal dysfunction
MWF is characterized by early onset of spontaneous albuminuria during a critical time and allow to assess the concentration of PLA2R-Ab in the course of disease more
window between 4 and 8 weeks of age, that associates with hyperfiltration, due to low accurately, that may contribute to timely correction of treatment and improvement of
nephron number, and podocyte injury. Ptgr2 plays an important role in the outcome.
prostaglandin metabolism, in which PGE2 is metabolized by 15-prostaglandin
dehydrogenase (15-PGDH) to 15-keto-PGE2. The latter is terminally degraded by
prostaglandin reductases (PTGRs) 1, 2, and 3 to 13,14-dihydro-15-keto-PGE2. MO433 IDENTIFICATION AND VALIDATION OF PEPTIDIC FEATURES
Recently, we detected elevated glomerular levels of PGE2 and 15-keto-PGE2 in MWF IN CKD PATIENTS AND UNRAVELLING OF A POTENTIAL
compared to spontaneously hypertensive rats (SHR) with no albuminuria. The aim of INFLAMMATION INDUCER
the present study was to characterize in detail the renal PGE2 metabolic pathway in
MWF by lipidomic analysis during the time window of albuminuria onset. Giulia Ilaria Bagarolo1, Laura Stricker,2, Christian Hemmers,2, Sonja Vondenhoff,2,
METHOD: Male MWF and SHR rats were studied at week 4 and 8, respectively; 24 h- Vera Jankowski,2, Heike Bruck3, Joachim Jankowski,2,4
urine was collected in metabolic cages. In addition, plasma and kidney tissues 1
including kidney cortex and isolated glomeruli were obtained from anesthetized rats. RWTH Aachen University Hospital, IMCAR, Aachen, Germany, 3Helios Klinikum Krefeld,
Lipidomic analysis was done by liquid chromatography electrospray ionization tandem Department of Internal Medicine, Nephrology, Rheumatology, Diabetology and
mass spectrometry. Statistical analysis was performed by unpaired, two-tailed Student’s Endocrinology, Krefeld, Germany and 4Maastricht University, CARIM, Maastricht, The
t-test, or otherwise the Mann-Whitney test. Netherlands
RESULTS: Urinary PGE2 was significantly lower (p<0.01), while urinary 15-keto-
PGE2 and 13,14-dihydro-15-keto PGE2 levels were significantly increased in MWF BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is causing serious
compared to SHR at week 4 (p<0.01, respectively). All three analytes were significantly cardiovascular diseases. Creatinine quantification and eGFR estimation are suboptimal
decreased in urine of MWF with increased albuminuria at week 8 (p<0.05 vs. SHR). approaches for the diagnosis of CKD, especially at early stages. Therefore, there is a
The urinary metabolic ratio of 15-keto-PGE2/13,14-dihydro-15-keto-PGE2 as a strong need for identification of mediators for CKD diagnosis and prediction of disease
surrogate for PTGRs activities was significantly increased at week 4 (p<0.01), whereas progression. In this study we follow a cohort of renal healthy patients (controls) and
it was significantly decreased in MWF vs. SHR at week 8 (p<0.05). Plasma levels of CKD patients (cases) for two years, defining three time points (baseline, after 12
PGE2 and 13,14-dihydro-15-keto-PGE2 did not differ between strains at both time months and after 24 months), with the aim of identifying and characterizing mediators
points, while 15-keto-PGE2 was below the detection limit. Glomerular levels of PGE2 of disease which could be an indication for the development and progression of CKD
and 15-keto-PGE2 were increased in MWF at week 4 and 8 (p<0.01, respectively). In and its outcome.
contrast, 13,14-dihydro-15-keto-PGE2 was only significantly higher at week 4 METHOD: By the employment of liquid chromatography-mass spectrometry (LC-
compared to SHR (p<0.01). In isolated glomeruli, the metabolic ratios of PTGRs were MS) we analyzed the plasma samples from the patients and identified the mediators1 :
similar between the strains at week 4, but significantly increased in MWF compared to lysine (K), an angio-associated migratory cell protein (AAMP) peptide and an
SHR at week 8 (p<0.01, respectively). In kidney cortex, 15-keto-PGE2 and 13,14- amiloride-sensitive oxidase (AOC1) peptide, which were consistently and differentially
dihydro-15-keto-PGE2 were increased in MWF at week 4 (p<0.05 and p<0.01, expressed in cases and controls at all time points.
respectively), whereas PGE2 levels were comparable to SHR. No difference for cortical Correlation analyses between the mediators and clinical markers were performed using
levels of PGE2 and its metabolites was observed at week 8. the software R-Studio (RStudio Team (2020). RStudio: Integrated Development for R.
CONCLUSION: This study provides the first insights into age-dependent dynamic RStudio, PBC, Boston, MA URL http://www.rstudio.com/).
changes in the PGE2 pathway that support potential causality for the onset of The AAMP peptide was subsequently tested in a fibroblasts cells culture to investigate
albuminuria in the setting of non-diabetic hyperfiltration due to low nephron number. whether it was an inflammation inducer, its action was investigated at four different
Notably, the increased glomerular levels of PGE2 and its downstream metabolites in 4- concentrations (0.1nM, 1nM, 100nM, 1000nM). Cells were stimulated for 48h and
week-old MWF point towards an early activation of this pathway, i.e. before relative expression of two inflammation markers (CCL2 and IL6) was measured
albuminuria occurs. This finding corroborates the hypothesis that glomerular PGE2 through PCR.
signaling is relevant in the early stages of hyperfiltration and suggests this pathway as a RESULTS: Correlation analyses revealed that the AAMP peptide showed from modest
target for future therapeutics to modify the manifestation and progression of renal to strong relations with clinical markers such as creatinine, hemoglobin, blood urea
disease. nitrogen, homocysteine, fibrinogen and parathyroid hormone.
Results showed that the peptide after 48h of stimulation did not cause an increase in
the expression of gene CCL2 at any concentration, but caused a strong increase of gene
IL6 (interleukin-6), a cytokine promoting inflammation and B cells maturation.
MO432 COMPARATIVE ANALYSIS OF INDIRECT CONCLUSION: In conclusion, angio-associated migratory cell peptide, might be
IMMUNOFLUORESCENCE AND ENZYME-LINKED involved in CKD by inducing inflammation and driving the development of
IMMUNOSORBENT ASSAYS FOR ANTI-PLA2R ASSESMENT cardiovascular consequences such as atherosclerosis.
IN PATIENTS WITH PRIMARY MEMBRANOUS ACKNOWLEDGMENTS: This project has received funding from the European
NEPHROPATHY Union’s Horizon 2020 research and innovation programme under the Marie
Skłodowska-Curie grant agreement No 764474.
Olga Galkina1, Evdokia Bogdanova1, Irina Zubina1, Elena Levykina1,
Alexei Smirnov1
1
Pavlov University, Nephrology Research Institute, Saint Petersburg, Russia References
1. Gajjala Prathibha R., Bruck Heike, Noels Heidi, Heinze Georg, Ceccarelli Francesco,
BACKGROUND AND AIMS: Antibodies to M-type phospholipase A2 receptor (PLA2R- Kribben Andreas, Saez-Rodriguez Julio, Marx Nikolaus, Zidek Walter, Jankowski
Ab) are considered to be a promising biomarker for laboratory diagnosis of primary Joachim, Jankowski Vera, Novel plasma peptide markers involved in the pathology
membranous nephropathy (PMN) and may be useful in the evaluation of the response to of CKD identified using mass spectrometric approach. J Mol Med (Berl), 2019.
therapy and CKD prognosis. The aim of the study was to compare two immunoassay 97(10): p. 1451–1463
methods – indirect immunofluorescence (IIF) and enzyme immunoassay (ELISA) for the
determination of circulating PLA2R-Ab in patients with PMN.
METHOD: The study included 54 patients aged 55 (40-63) yrs. (M: F [33:21]) with
PMN before treatment (n=16) and treated with immunosuppressive therapy (IST)
(n=38), and apparently healthy individuals of the corresponding gender and age
(n=10). Proteinuria and estimated glomerular filtration rate (eGFR) were determined
in all participants. The levels of PLA2R-Ab were determined by IIF and quantitative/
semi-quantitative ELISA (EURUIMMUN AG test, Germany). In 16 PMN patients
without treatment and 28 PMN patients treated with IST the level of PLA2R-Ab was

i280 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO434 CHRONIC KIDNEY DISEASE AND ITS RELATIONSHIP WITH CONCLUSION: A successful fusion of MALDI MSI data and different histological and
THE STATE OF THE INTESTINAL MICROBIOTA AND immunohistochemical staining datasets of a whole organ is performed.
INDICATORS OF SYSTEMIC INFLAMMATION

Komilakhon Olimkhonova1
1
Tashkent Medical Pediatric Institute, Internal disease, Tashkent , Uzbekistan MO436 PLASMA OXALATE VALUES IN PATIENTS WITH END-STAGE
KIDNEY DISEASE
BACKGROUND AND AIMS: In view of the fact that the human microbiota varies Ella Metry1, Sander Garrelfs1, Michiel Oosterveld1, Aegida Neradova2,
depending on many factors, including comorbid pathology, it seems reasonable to Joost Bijlsma2, Fred Vaz3, Jaap Groothoff1
investigate the gut microbiota in patients with chronic kidney disease and its likely 1
relationship with markers of systemic inflammation. Amsterdam University Medical Centers, Pediatric Nephrology, Amsterdam, The
To reveal the relationship between some biomarkers of inflammation with changes in Netherlands, 2Amsterdam University Medical Centers, Nephrology, Amsterdam, The
the composition of the intestinal microbiota in patients with chronic kidney disease. Netherlands and 3Amsterdam University Medical Centers, Department of Clinical
METHOD: The study included 85 patients with CKD C 2-4. The average age of the Chemistry, Amsterdam, The Netherlands
patients was 52 6 4 years (48 men and 37 women). The control group consisted of 30
healthy volunteers aged 50 6 3 years, 15 men and 15 women, comparable to the main BACKGROUND AND AIMS: Patients with end-stage kidney disease (ESKD) are
group in terms of sex and age. Blood samples were taken using standard methods. GFR known to have higher plasma concentrations of metabolic waste products than healthy
was assessed using the CKD-EPI formula (2011). In addition, biomarkers such as individuals. Patients with Primary Hyperoxaluria (PH), a rare congenital cause of
interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a) were evaluated. ESKD, suffer from hepatic overproduction of the metabolic end product oxalate.
Bacteriological examination of feces was carried out in the bacteriological Plasma oxalate (POx) levels are determined in the diagnostic and therapeutic work-up
laboratory.Markers of systemic inflammation were assessed based on an increase in the for PH. Remarkably, correct interpretation of these values is hampered by the absence
level of leukocytes (> 11  109 / L), C - reactive protein (> 5.0 mg / L) by of knowledge concerning POx levels in patients with ESKD due to common causes.
immunoturbodimetric method, fibrinogen (> 4.0 g / L), as well as interleukin 6 by METHOD: In this observational study, we obtained POx values in patients with ESKD
enzyme immunoassay. Differences between groups were considered statistically due to another cause than PH, to establish reference values in this patient group. We
significant at p0.05; correlation analysis was performed using Spearman’s collected blood samples from 120 adults with eGFR < 15 mL/min/1.73 m2 who
nonparametric rank correlation method. required maintenance hemodialysis or peritoneal dialysis at the Amsterdam UMC.
RESULTS: Analysis of fecal matter showed a deficiency of Bifidobacterium bacteria RESULTS: While there was a wide variation in POx levels in patients with ESKD, the
(<108 CFU) in the examined patients. In addition, the examined patients showed an median was 50 umol/L and lowest values were twice the upper reference limit that
increase in the number of Echerichia (> 108 CFU). According to the results of the applies to healthy individuals (6.7 umol/L).
study, in the group of CKD patients, the level of inflammatory markers was higher CONCLUSION: This study shows that POx levels of 50 umol/L are not necessarily
(CRP-55%, IL-6-60%, leukocytes 62%) than in the control group (CRP-45%, IL-6-40%, suggestive for PH which contradicts the current literature. This study could lead to a
leukocytes 38% ). paradigm shift in the diagnostic and therapeutic work-up for patients with ESKD.
In men, the IL-6 index was higher than in women. The results of the study
demonstrated that in patients with CKD, an imbalance of the intestinal microbiota is
combined with an increased level of CRP, IL-6, and leukocytes. MO437 RENAL RESISTIVE INDEX IS INDEPENDENTLY ASSOCIATED
CONCLUSION: The study of markers responsible for pro-inflammatory effects in the WITH THE RENAL BLOOD FLOW IN HYPERTENSIVE
body showed that indicators such as IL-6, CRP, fibrinogen showed a significant PATIENTS
correlation with the composition of the microbiota in patients with CKD.
Arkadiusz Lubas1, Arkadiusz Zegadło2, Anna Grzywacz1, Stanisław Niemczyk1
1
Military Institute of Medicine, Internal Diseases, Nephrology and Dialysis, Warsaw,
MO435 MULTIMODAL IMAGING FOR MOLECULAR TISSUE Poland and 2Military Institute of Medicine, Radiology, Warsaw, Poland
ANALYSIS
BACKGROUND AND AIMS: The Renal Resistive Index (RRI) measured in
Michaela Lellig1, Kai Brehmer2, Mathias Hohl3, Thimoteus Speer4, intrarenal arteries is considered a marker of cardiovascular damage, and its value can
Stefan Schunk4, Herbert Thiele2, Joachim Jankowski1,5,6, Vera Jankowski1,6, express the amount of renal perfusion. However, some experimental investigations
Juliane Hermann1 don’t confirm this association. Moreover, in recent works, End Diastolic Velocity
1
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, (EDV) was used as a better than RRI marker of kidney damage. The study aimed to
Aachen, Germany, 2Institute of Mathematics and Image Computing, University of investigate relations between different ultrasound Renal Doppler parameters (RRI,
Lübeck, Lübeck, Germany, 3Clinic for Internal Medicine-Cardiology, Angiology and acceleration (ACC), acceleration time (ACT), and EDV) with the Renal Blood Flow
Internal Intensive Care Medicine, Saarland University, Homburg, Germany, (RBF) estimated in contrast-enhanced computed tomography (CE-MDCT).
4
Department of Internal Medicine IV, Nephrology and Hypertension, Saarland METHOD: In 25 patients (14F, 11M; age 58.9 619.0; eGFR 56,9 627.4 mL/min/
University Hospital, Homburg, Germany, 5School for Cardiovascular Diseases (CARIM), 1.73m2) with hypertension and suspected renal artery stenosis, ultrasound Color
Maastricht University, Maastricht, The Netherlands and 6European Uremic Toxin Work Doppler examination of intrarenal segmental arteries (GE Logiq P6) was performed.
Group (EUTox) Then CE-MDCT (GE Discovery 750 HD) of renal arteries with RBF assessment was
completed. Renal Doppler parameters (RRI, ACC, ACT, and EDV) and RBF were
BACKGROUND AND AIMS: MALDI mass spectrometric imaging (MALDI MSI) is evaluated for each kidney separately. Finally, 31 kidneys without a narrowing of
a powerful histologic tool for the analysis of biomolecules in tissue samples. MALDI supplying arteries were considered for statistics.
MSI measurements result in a high sensitivity and accuracy of spatial distribution of RESULTS: Mean values of intrarenal Doppler parameters were calculated: RRI = 0.699
biomolecules in tissue samples. For more detailed analysis of MALDI MSI data and 60.113; ACC = 7.41 62.75 [m/s2]; ACT = 35.8 68.4 [ms]; EDV = 13.68 68.41 [cm/s].
correlation between the molecular and microscopic levels, a combination of MALDI CE-MDCT RBF = 218.04 671.92 [ml/s/100g]. Only RRI and EDV correlated
MSI data and histological staining is essential. By combining MALDI MSI data and significantly with RBF (r = -0.544; p=0.002 and r=0.428; p=0.018, respectively). The
histological data, much more information are obtained than by analyzing both retrograde multivariable regression analysis included all investigated ultrasound renal
methods individually. Therefore, MALDI MSI datasets and histological staining were Doppler parameters showed an independent association only between RRI and RBF (b
fused to a 3D model presenting a biomolecule distribution of the whole organ and = -0.544; R2 = 0.27, p < 0.002).
provides more information than a single tissue section. We have developed, established CONCLUSION: Only Renal Resistive Index measured in intrarenal segmental arteries
and validated an algorithm for an automatic registration of MALDI data with different is independently related to the Renal Blood Flow from investigated ultrasound renal
histological image data for cross-process evaluation of multimodal datasets to create Doppler parameters. Although End Diastolic Velocity is positively correlated with RBF,
3D models. This multimodal imaging approach simplifies and improves molecular this association is not superior to Renal Resistive Index.
analyses of tissue samples in clinical research and diagnosis.
METHOD: The datasets for fusion and creation of a 3D model consist of mass
spectrometric data, histological and immunohistochemical staining methods. MO438 STUDY OF IMMUNOLOGICAL STATUS IN PATIENT OF CKD
Histological tissue sections of a whole mouse kidney were prepared. For MALDI MSI IN PREDIALYSIS STAGES
data, organ sections were analyzed by using a Rapiflex mass-spectrometer.
RESULTS: A mathematical registration was used to achieve a perfect superposition of the Komilakhon Olimkhonova1
individual histological sections of mass spectrometric data. It is feasible to combine mass 1
spectrometric data, histological and immunohistochemical datasets in high numbers and Tashkent Medical Pediatric Institute, Internal disease, Tashkent, Uzbekistan
reconstruct the measured mouse kidney. By using different imaging methods, a variety of
information about tissue structure as well as tissue changes and protein distributions can be BACKGROUND AND AIMS: It is known that inflammation is an important factor
obtained. The fusion of the data also offers a virtual incision of the organ from arbitrary associated with the variability of the clinical picture in patients with chronic diseases.
angle and level. The algorithms are adapted to take the data fusion automatically offering a However, the question remains not completely clear: are immunological changes
high-throughput approach for clinical diagnostics and the possibility to involved artificial predictors of less stable control of the course of CKD.
intelligence in its interpretation in research. The aim of this study was a comprehensive assessment of the immunological status in
patients with pre-dialysis stages of CKD.

10.1093/ndt/gfab088 | i281
Abstracts Nephrology Dialysis Transplantation

METHOD: 80 patients (46 men and 36 women) with CKD in the outcome of RESULTS: In patients with CKD, violations were observed in almost all links of
nephropathies of diabetic and nondiabetic etiology, admitted to the Republican immunological reactivity, first of all, a significant decrease in indicators of natural
Medical Scientific and Practical Center for Therapy and Medical Rehabilitation, were resistance (CD16 þ, PS, PI) (p <0.05). The results of immunological monitoring
examined. Chronic pyelonephritis without exacerbation was diagnosed in 31 patients, showed a predominant violation of cellular defense mechanisms (CD3 þ, CD4 þ, CD8
chronic glomerulonephritis - in 29, diabetic nephropathy - in 25 polycystic kidney þ) (p <0.05), a multiple increase in inflammatory cytokines Il-4, TNF-a, IL-6 (p
disease - in 6 patients. Glomerular filtration was calculated based on serum creatinine <0.05), in the absence of activation of humoral link and inadequacy of elimination
concentration using the CKD-EPI formula (2011). A complex of immunological mechanisms (CEC, p <0.05).
studies was performed. Immunotyping of lymphocytes was performed by flow CONCLUSION: Our study showed that the immunological parameters were
cytofluorometry with the characterization of the main markers of immunocompetent characterized by insufficient activation of the first line of defense of natural resistance,
cells. as well as specific mechanisms - an imbalance of the cellular and humoral links of
immunity, hyperactivation of cytokine regulation in the absence of effector functions.

i282 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i283–i299, 2021
10.1093/ndt/gfab090

CKD. PATHOPHYSIOLOGY, PROGRESSION AND RISK


FACTORS

MO439 NATURAL IMMUNISATION AGAINST ATHEROSCLEROSIS IN


BEARS DURING HIBERNATION*

Peter Stenvinkel1, Shailesh Shamal2, Ole Fröbert3, Johan Frostegård4


1
Karolinska Institutet, Dept of Renal medicine, Stockholm, Sweden, 2Division of
Immunology and Chronic Disease, Institute of Environmental Medicine, Stockholm,

Sweden, 3Department of Cardiology, Faculty of Health, Orebro €
University, Orebro,
Sweden and 4Division of Immunology and Chronic Disease, Institute of Environmental
Medicine, Stockholm, Sweden

BACKGROUND AND AIMS: Brown bears (Ursus arctos) hibernate for 5-6 months
during winter, but in spite of kidney insufficiency, dyslipidemia, insulin resistance and
inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD).
Antibodies against phosphorylcholine (anti-PC) are associated with protection in MO440 Figure: ROC curves for serum and mRNA PBCs expression levels of Klotho
atherosclerosis, CVD and uremia. Potential underlying protective mechanisms include predicting sCVD.
anti-inflammatory effects, inhibition of cell death, promotion of T regulatory cells,
clearance of dead cells and inhibition of oxidized Low density lipoprotein (OxLDL)-
uptake in macrophages in atherosclerotic plaques. PC is an important antigen on
nematodes, parasites, some bacteria, dead and dying cells and OxLDL.
METHOD: Paired serum from 12 brown bears sampled during winter and summer MO440 KLOTHO AS A BIOMARKER OF SUBCLINICAL
were analyzed for metabolic parameters and for IgM, IgG, IgG1/2 and IgA anti-PC by CARDIOVASCULAR DISEASE IN CHRONIC KIDNEY DISEASE:
enzyme linked immunosorbent assay (ELISA). Differences in antibody levels between A PROOF-OF-CONCEPT STUDY*
winter and summer were determined by paired Students t test or Wilcoxons signed
rank test (when not normally distributed). Carla Ferri1, Javier Donate-Correa1, Ernesto Martın-Nu ~ez1, Nayra Pérez-
n
RESULTS: As expected, marked differences in metabolic parameters were found Delgado1, Ainhoa Gonza lez-Luis1, Carmen Mora-Ferna ndez1, Juan F. Navarro-
comparing median summer vs winter values; Cholesterol 5.9 vs 11.3 mmol/L; p<0.001, Gonzalez1
triglycerides 1.9 vs 3.7 mmol/L; p<0.001, glucose 5.4 vs 7.7 mmol/L; p<0.05, S- 1
Hospital Universitario Nuestra Se~
nora de Candelaria, Unidad de Investigaci
on, SANTA
creatinine 76 vs 203 mmol/L; p<0.001, urea 12.1 vs 2.9 mmol/L; p<0.002. When CRUZ DE TENERIFE, Spain
determined as arbitrary units (AU; median set at 100 at summer), marked and
significant differences were observed between summer and winter.
CONCLUSION: Anti-PC (strikingly so for IgA and IgG1) are significantly raised BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the major cause of
during hibernation as compared to levels during summer. We hypothesize that these mortality among chronic kidney disease (CKD) patients. Reductions in serum Klotho
changes contribute to the protection of arteries, but also kidneys and other organs, levels are related to the prevalence of CVD in CKD patients. However, it is unclear
during the metabolic vulnerable hibernation period. Our observation may represent a whether circulating Klotho, and its expression in peripheral blood cells (PBCs), are
natural immunization with microorganisms, preventing atherosclerosis during a associated with subclinical atherosclerotic cardiovascular disease (sCVD) in these
period of severe kidney insufficiency and could have therapeutic implications for subjects. In this proof-of-concept study, we analyzed in a group of CKD patients the
patients with chronic kidney disease. relationship between Klotho and two markers of sCVD: ankle-brachial index (ABI)
and carotid intima-media thickness (CIMT).
METHOD: Gene expression in PBCs and serum levels of Klotho and inflammatory
cytokines (TNF, IL6 and IL10) were measured in 103 CKD patients (stages 3-4), older
than 18 years of age, and without known atherosclerotic cardiovascular disease.
Biochemical data were obtained following standardized clinical methods. The presence
of sCVD was defined as ABI < 0.9 and/or CIMT  0.9 mm. Patients with ABI values 
1.3 were excluded.
RESULTS: Patients with sCVD presented lower serum and PBCs expression levels of
Klotho (P<0.001 for both). Stratified analysis showed that upper tertiles of both serum
and PBCs expression levels of Klotho presented significantly higher ABI (P<0.001 for
both Klotho determinations) and lower CIMT (P<0.001 for serum levels and P<0.01
for KL expression in PBCs), which resulted in a lower prevalence of sCVD (P<0.001
for both determinations of Klotho).
Correlation analysis showed that both serum and PBCs mRNA Klotho levels were
positively correlated with ABI (r=0.556, P<0.0001; and r=0.373, P<0.0001,
respectively) and inversely correlated with CIMT (r=-0.541, P<0.0001; and r=-0.437,
P<0.0001, respectively). Among inflammatory markers, only serum IL6 levels
presented significant associations with sCVD, being inversely related with ABI (r=-
0.568, P<0.0001) and positively associated with CIMT (r=0.558, P<0.0001).
Multiple regression analysis with ABI and CIMT as dependent variables demonstrated
that both Klotho variables, together with serum IL6, were positively and significantly
associated with ABI (adjusted R2=0.511, P<0,0001) and CIMT (adjusted R2=0.445,
P<0,0001) values, independently of traditional and emergent cardiovascular risk
factors.
Multivariate logistic regression, using the presence/absence of sCVD as the dependent
variable, showed that circulating Klotho, and its expression in PBCs constituted

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

independent protective factors for sCVD [OR (95% CI): 0.993 (P=0.002) and 0.231 complications and increased mortality in CKD stage 3-4 patients (Figure A). Moreover,
(P=0.025), respectively]. Receiver operating curve (ROC) analysis pointed to the we showed that higher serum calprotectin was associated with increased vascular
prognostic ability for sCVD of serum Klotho (area under the curve [AUC]: 0.817, 95% calcification levels in CKD stage 5 patients (Figure B). In vitro, calprotectin promoted
CI: 0.736–0.898, P<0.001) and its gene expression in PBCs (AUC: 0.742, 95% CI: calcification of human VSMCs (p<0.0001) (Figures C-D) and in mouse aortic rings
0.647–0.836, P<0.001). (p<0.0001) (Figure E-F). Interestingly, these effects were significantly attenuated by
CONCLUSION: The reductions in serum soluble and PBCs expression levels of paquinimod, a calprotectin inhibitor (Figures C-F).
Klotho in CKD patients are independently associated with the presence of sCVD. CONCLUSION: Circulating calprotectin is a novel predictor of CV outcome and
Further research exploring whether therapeutic approaches to maintain or elevate the mortality in CKD patients. Calprotectin also shows calcification-inducing properties
Klotho level could reduce the impact of CVD in CKD patients is warranted. and its blockade by paquinimod alleviates its effects. Future experiments will consist in
deciphering the signalling pathways involved in the regulation of calcification by
calprotectin and evaluating in vivo the therapeutic potential of paquinimod on the
development of medial vascular calcification lesions associated with CKD.

MO441 Figure:(A) Serum calprotectin levels and cardiovascular (CV) outcome.

Kaplan–Meier plot of cumulative probability of a first major fatal or non-fatal CV


event in 112 CKD3-4 patients grouped according to calprotectin tertiles (T). (B) Serum
calprotectin levels and calcification degree. Calprotectin measurement using ELISA
in the serum of 222 CKD5 patients with various degree of vascular calcification. (C-F)
Effect of calprotectin and paquinimod on calcification. Primary human VSMCs (C-
D) and mouse aortic rings (E-F) were treated with calprotectin (Calp) with or without
paquinimod (Paq) in control (Ctrl) or high phosphate medium (Pi) for 5-7 days.
MO440 Figure: ROC curves for serum and mRNA PBCs expression levels of Klotho Calcification was assessed by calcium content measurement (C, E), Alizarin red
predicting sCVD. staining (D) or Von Kossa (black) staining (F).

MO442 ACUTE ADVERSE EFFECTS OF LOW POTASSIUM ON HEART


AND KIDNEY*
MO441 CALPROTECTIN IS A NOVEL CONTRIBUTING FACTOR IN
VASCULAR CALCIFICATION AND A PREDICTOR OF Turgay Saritas1, Lu Chen1, Anne Babler1, Anne Rix2, Katharina C. Reimer1,
CARDIOVASCULAR OUTCOME IN CKD PATIENTS* Jitske Jansen1, Xiao-Tong Su3, Andrew S. Kerker4, Catherina A. Cuevas5,
Sylvie Menzel1, Christoph Kuppe1, Peter Boor1, Lucas Falke6,
Ana Amaya Garrido1, José M. Valdivielso2, Stanislas Faguer1, Arnaud Del Bello3, Christian Bleilevens1, James McCormick3, Jürgen Floege1, David H. Ellison3,
Benedicte Buffin-Meyer1, Alexis Piedrafita1, Mylene Camus4, Odile Schiltz4, Jean- Rafael Kramann3
Loup Bascands5, SAM HOBSON6, Karolina Kublickiene6, Peter Stenvinkel6, 1
University Hospital RWTH Aachen, Med. Klinik 2, Nephrology, Aachen, Germany, 2Institute of
Joost Schanstra1, Julie Klein1 Experimental Molecular Imaging, Aachen, Germany, 3Oregon Health & Science
1
INSERM, I2MC, U1297, Toulouse, France, 2Institute of Research of Lleida, Lleida, Spain, University, Nephrology, Portland, United States of America, 4Vanderbilt University
3
CHU Rangueil, Toulouse,, 4CNRS, PBS 6270, Toulouse, France, 5Inserm, U1188, Saint- Medical Center, Nashville, United States of America, 5Erasmus University Rotterdam,
Denis, France and 6Karolinska Institute, Stockholm, Rotterdam, The Netherlands and 6UMC Utrecht, Utrecht, The Netherlands

BACKGROUND AND AIMS: Vascular calcification, leading to aortic stiffening and BACKGROUND AND AIMS: Chronic hypokalemia causes kidney fibrosis with cystic
heart failure, is decisive risk factor for cardiovascular (CV) mortality in patients with lesions and arterial hypertension. In contrast, potassium-rich diet lowers blood
chronic kidney disease (CKD). Promoted by bone mineral disorder and systemic pressure. The acute effects of hypo- and hyperkalemia on heart and kidney are not well
inflammation in CKD patients, vascular calcification is a complex mechanism understood.
involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) METHOD: Wild-type mice were fed with low (LK), normal (NK) and high (HK)
and abnormal deposition of minerals in the vascular wall. Despite intensive research potassium diet for 4 and 20 days. Kidneys were examined for site of acute injury,
efforts in recent years, available treatments have limited effect and none of them inflammation and fibrosis. Blood analysis of electrolytes and kidney parameters were
prevent or reverse vascular calcification. The aim of this study was to analyse the serum analyzed. Echocardiography and ECG were used to assess heart function. Further,
proteome of CKD stage 3-4 patients in order to unravel new molecular changes KCNJ10 knockout mice were used to investigate kidney damage in a genetically
associated to CV morbid-mortality and to decipher the role of novel candidates on induced hypokalemia model.
vascular calcification to provide potential new therapeutic agents. RESULTS: Proximal tubule injury as detected by KIM-1þ staining and yH2AXþ DNA-
METHOD: In this study we used serum samples from two independent cohorts: 112 damage was observed after 4 and 20 days of LK diet. Injury was associated with strong Ki-67þ
CKD stage 3-4 patients with a 4 years follow-up for CV events and 222 CKD stage 5 proliferation of proximal tubule cells. No injury was detected in mice on NK and HK diet. After
patients exhibiting a broad range of calcification degree determined by histological 20 days of LK diet, F4/80þ inflammation and aSMAþ extracellular matrix accumulation, typical
quantification in the epigastric and/or iliac artery. Serum proteome analysis was for fibrosis, were observed. LK mice developed polyurie, volume depletion, loss of body weight
performed using tandem mass-spectrometry in a subcohort of 66 CKD3-4 patients and and high BUN. Lower cardiac output and signs of myocardial stress was seen in
validation of protein candidates was performed using ELISA in the two full cohorts. echocardiography and ECG. Consistent with WT mice on LK diet, KCNJ10 knockout mice
Human primary vascular smooth muscle cells and mouse aortic rings were used for developed same pattern of kidney injury. Nine months after deletion of KCNJ10, cysts were
calcification assays. Calcium content was quantified using QuantiChrom calcium assay observed in the proximal tubule in outer medzulla.
kit and calcium deposition was visualized by Alizarin Red and Von Kossa staining. CONCLUSION: Acute hypokalemia causes kidney injury and myocardial stress.
RESULTS: Among 443 proteins detected in the serum of CKD3-4 patients, 134 Cystic lesions originate from late proximal tubule. Hypokalemia should be corrected
displayed significant modified abundance in patients with CV events (n=32) compared rapidly to stop progression into kidney fibrosis.
to patients without (n=34). One of the most prominent changes was increased level of
calprotectin (up to 8.6 fold, P<.0001). Using ELISA, we validated that higher serum
calprotectin levels were strongly associated with higher probability of developing CV

i284 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO443 EFFECTS OF SHORT-TERM POTASSIUM CHLORIDE MO444 MACROPHAGE DENSITIES CORRELATE WITH LONG-TERM
SUPPLEMENTATION IN PATIENTS WITH CHRONIC KIDNEY FUNCTION IN PAUCI-IMMUNE AND MEMBRANOUS
DISEASE* GLOMERULONEPHRITIS AS WELL AS IN HYPERTENSIVE
NEPHROPATHY
Martin Gritter1, Rosa Wouda2, Stanley Ming Hol Yeung3, Liffert Vogt2, Martin De
Borst3, Joris Rotmans4, Ewout Hoorn1 Maren Bettina Pfenning1, Jessica Schmitz1, Kevin Schulte2, Carsten Hafer3,
1
Erasmus Medical Center, Internal Medicine, Rotterdam, The Netherlands, 2Amsterdam Abedalrazag Ahmad Khalifa1, Anke Kulschewski4, Thorsten Feldkamp5, Jan
UMC, locatie AMC, Internal Medicine, The Netherlands, 3University Medical Center T Kielstein3, Wilfried Gwinner6, Ulrich Kunzendorf2, Sebastian Dietrich2, Jan
Hinrich Bra €sen1
Groningen, Internal Medicine, Groningen, The Netherlands and 4Leiden University
1
Medical Center, Internal Medicine, The Netherlands Hannover Medical School (MHH), Nephropathology Unit, Institute of Pathology,
Hannover, Germany, 2University Hospital Schleswig-Holstein, Christian-Albrechts-
BACKGROUND AND AIMS: A high potassium (Kþ) diet is part of a healthy lifestyle University, Department of Nephrology and Hypertension, Kiel, Germany, 3Academic
and reduces blood pressure. Indeed, salt substitution (replacing NaCl by KCl) reduces Teaching Hospital Braunschweig, Medical Clinic V, Nephrology, Rheumatology and
the incidence of hypertension. Furthermore, emerging data show that high urinary Kþ Blood Purification, Braunschweig, Germany, 4University Hospital Oldenburg, Clinic for
excretion in patients with chronic kidney disease (CKD) is associated with better Nephrology and Hypertension, Oldenburg, Germany, 5Nephological Center of Lower
kidney outcomes. This suggests that higher dietary Kþ intake is also beneficial for Saxony, Klinikum Hann. Münden, Department of Internal Medicine and Nephrology,
patients with CKD, but a potential concern is hyperkalemia. Thus, there is a need for Kidney Transplant Center, Hann. Münden, and 6Hannover Medical School (MHH),
data on the effects of KCl supplementation in patients with CKD. Department of Nephrology, Hannover, Germany
METHODS: The effect of KCl supplementation (40 mEq/day) was studied by
analyzing the 2-week open-label run-in phase of an ongoing randomized clinical trial BACKGROUND AND AIMS: Macrophages and monocytes are main players in
studying the renoprotective effects of 2-year Kþ supplementation in patients with innate immunity. In renal diseases, their role is poorly understood. Our multicentric
progressive CKD and hypertension. The aims were to (1) analyze the effects of KCl cross-sectional study aimed to study the prevalence of macrophages and monocytes in
supplementation on whole-blood Kþ (WBKþ) and acid-base balance, (2) identify various human native kidney diseases. For this, we used precise pixel-based digital
factors associated with a rise in WBKþ, and (3) identify risk factors for hyperkalemia quantification of their densities in renal biopsies and correlated our findings with
(WBKþ > 5.5 mEq/L) . clinical data.
RESULTS: In 200 patients (68 6 11 years, 74% males, eGFR 32 6 9 mL/min/1.73 m2, 84% METHOD: We included 324 patients, who underwent a diagnostic renal biopsy.
on renin-angiotensin inhibitors, 39% with diabetes mellitus), KCl supplementation increased Additional normal kidney samples from 16 tumour nephrectomies were used as
urinary Kþ excretion from 73 6 24 to 106 6 29 mEq/day, urinary chloride excretion from 144 controls. According to the diagnosed diseases, we established 17 patient groups.
6 63 to 174 6 60 mEq/day, WBKþ from 4.3 6 0.5 to 4.7 6 0.6 mEq/L, and plasma Biopsies were stained for CD68þ-macrophages using automated
aldosterone from 294 to 366 ng/L (P < 0.01 for all). Plasma chloride increased from 104 6 4 to immunohistochemistry (Ventana Ultra) and selected groups were further subtyped for
106 6 4 mEq/L, while plasma bicarbonate decreased from 24.4 6 3.4 to 23.6 6 3.5 mEq/L and CD14þ-monocytes and CD163þ-M2-macrophages (67 cases, pauci-immune
venous pH from 7.36 6 0.03 to 7.34 6 0.04 (P < 0.001 for all); urinary ammonium excretion glomerulonephritis (PIGN), IgA-nephropathy (IgAN) and control samples). Digitized
did not increase (stable at 17.2 mEq/day). KCl supplementation had no significant effect on sections (Leica) were analysed using the open-source software QuPath to quantify cell
plasma renin (33 to 39 pg/mL), urinary sodium excretion (156 6 63 to 155 6 65 mEq/day), densities (positively stained areas displayed as percentages of ROI) in renal cortex,
systolic blood pressure (134 6 16 to 133 6 17 mm Hg), eGFR (32 6 9 to 31 6 8 mL/min/1.73 medulla and extrarenal tissue, respectively. Detailed clinical and laboratory data at
m2) or albuminuria (stable at 0.2 g/day). Multivariable linear regression identified that age, timepoint of biopsy were available for all patients. Additional data for follow-up were
female sex, and renin-angiotensin inhibitor use were associated with an increase in WBKþ, achievable in 158 cases.
while diuretic use, baseline WBKþ, and baseline bicarbonate were inversely associated with a RESULTS: Renal disease samples presented higher mean macrophage densities
change in WBKþ after KCl supplementation (Table 1). The majority of patients (n = 181, 91%) compared to control cases (CD68: cortex 1.2 vs. 0.2%, p<0.001, medulla 0.8 vs. 0.04%,
remained normokalemic (WBKþ 4.6 6 0.4 mEq/L). The 19 patients who did develop p<0.001; CD163: cortex 3.2 vs. 0.5%, p<0.001, medulla 2.3 vs. 0.6%, p<0.05), but
hyperkalemia (WBKþ 5.9 6 0.4 mEq/L) were older (75 6 8 vs. 67 6 11 years), had lower CD14þ-density did not differ between patients and control samples. The highest
eGFR (24 6 8 vs. 32 6 8 mL/min/1.73 m2), lower baseline bicarbonate (22.3 6 3.6 vs. 24.6 6 cortical CD68þ-density occurred in PIGN (1.98%) and in medulla in ascending
3.3 mEq/L), higher baseline WBKþ (4.8 6 0.4 vs. 4.2 6 0.4 mEq/L), and lower baseline urinary infections (1.86%). The lowest cortical CD68þ-densities were measured in thin basal
Kþ excretion (64 6 16 vs. 73 6 25 mEq/day, P < 0.05 for all). membrane syndrome / Alport-syndrome (0.56%) and in medulla in immunotactoid
and fibrillary glomerulopathy (0.26%). Chronic kidney disease displayed lower
percentages of CD68þ-densities (cortex: 1.15%; medulla: 0.49%) compared to acute
MO443 Table 1: Factors associated with change in whole-blood Kþ kidney injury (cortex: 1.84%, p<0.001; medulla: 1.08%, p<0.001) and acute on chronic
kidney injury (cortex: 1.81%, p<0.001; medulla: 1.43%, p<0.001). We detected a
correlation of CD68þ- and CD163þ-infiltration with kidney function (eGFR) in cortex
and medulla at the time of biopsy (CD68: r=-0.51 for cortex, r=-0.60 for medulla;
Variable Unstandar- 95% CI Standar- CD163: r=-0.71 for cortex, r=-0.73 for medulla; p<0.001) and follow up (CD68: r=-
dized b dized b 0.41 for cortex, r=-0.34 for medulla, p<0.001; CD163: r=-0.46 for cortex, r=-0.50 for
Female sex 0.1 0.01, 0.3 0.1 medulla, p<0.05). Older patients (>64 years) showed a higher medullary M2-
infiltration (1.81% vs. 4.34%, p<0.005). The eGFR at the time of biopsy inversely
Age, years 0.01 0.002, 0.01 0.2 correlated (p<0.05) with cortical CD68þ-density in IgAN (r=-0.39), PIGN (r=-0.53),
Diabetes mellitus 0.08 -0.03, 0.2 0.1 membranous glomerulonephritis (MGN; r=-0.70), focal segmental glomerulonephritis
(r=-0.63), and hypertensive nephropathy (HNP; r=-0.44). At follow-up, this
Renin-angiotensin 0.2 0.008, 0.3 0.1
correlation (p<0.05) was still present in PIGN (r=-0.43), MGN (r=-0.58), and HNP
system inhibitor use (r=-0.77). In PIGN, cortical CD163þ-density and eGFR were associated (p<0.001) at
b-blocker use 0.08 -0.03, 0.2 0.1 timepoint of biopsy (r=-0.51) and follow-up (r=-0.51). Particularly, cANCA-vasculitis
showed a strong correlation between eGFR and cortical CD68þ- as well as CD163þ-
Diuretic use -0.1 -0.2, -0.01 -0.2 densities at time of biopsy (CD68: r=-0.78; CD163: r=-0.75, p<0.001) and also for
eGFR, mL/min/1.73 m2 -0.005 -0.01, 0.002 -0.1 follow-up (CD68: r=-0.48; CD163: r=-0.68, p<0.05).
Whole-blood bicarbonate, -0.03 -0.05, -0.01 -0.2 CONCLUSION: Macrophages may promote progression of human renal diseases,
whereas monocytes do not correlate with eGFR-decline. Especially, in cANCA-
mEq/L vasculitis CD163þ- infiltration is associated with renal outcome. Additional studies are
Whole-blood Kþ, mEq/L -0.3 -0.4, -0.1 -0.3 needed to investigate, whether macrophages can serve as predictive markers or
therapeutical targets in native renal diseases.
24-hour urinary Kþ -0.002 -0.004, 0.001 -0.1
excretion, mEq/24h
CONCLUSIONS: The majority of patients with advanced CKD remains
normokalemic upon KCl supplementation, despite low eGFR, diabetes mellitus, or the
use of renin-angiotensin inhibitors. This short-term study illustrates the feasibility of
investigating the renoprotective potential of increased Kþ intake or KCl-enriched salt
in patients with CKD and provides the characteristics of patients in whom this is safe.
Our study also shows that KCl supplementation causes a tendency towards metabolic
acidosis, possibly by preventing an increase in ammoniagenesis. Longer-term studies
are required to study the anti-hypertensive and renoprotective potential of Kþ
supplementation.

10.1093/ndt/gfab090 | i285
Abstracts Nephrology Dialysis Transplantation

MO445 BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: association between renal function, in terms of estimated glomerular filtration rate
FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION (eGFR) categories, and diagnosis of HFpEF and LVDD was assessed with multivariable
PROTEINS logistic regression analyses, adjusted for cardiovascular and lifestyle risk factors. The
association between renal function, in terms of creatinine and cystatin C levels, and
Leah Hernandez1, Liam Ward1, Thomas Ebert1, Samsul Arefin1, echocardiographic parameters, including E/e’ ratio, LAVI (Left atrial volume index),
Olof Heimbürger1, Franz Peter Barany1, Lars Wennberg2, Peter Stenvinkel1, LVMI (left ventricular mass index), and E/A (early (E) to late (A) ventricular filling
Karolina Kublickiene1 ratio, was assessed with multivariable linear regression analyses, adjusted for age, sex,
1
Karolinska Institutet, Department of Clinical Science, Intervention and Technology cardiovascular and lifestyle risk factors. Adjusted odds ratios (OR) were reported and
(CLINTEC), Division of Renal Medicine, Huddinge, Sweden and 2Karolinska Institutet, the corresponding 95% confidence interval (95%CI).
Department of Clinical Science, Intervention and Technology (CLINTEC), Division of RESULTS: 777 participants were included, mean age 62.9 (SD: 9.3) years, 67.3% were
Transplantation Surgery, Huddinge, Sweden female. Hundred and fifty-six (20.1%) participants had mild renal dysfunction (eGFR:
60-89 ml/min/1.73 m2), and 24 (3.1%) moderate renal dysfunction (eGFR: 30-59 ml/
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a progressive min/1.73 m2). HFpEF and LVDD was more common in participants with moderate
systemic disease that affect the microvascular permeability of the blood-brain barrier renal dysfunction (13% and 33%, respectively) than in those with normal renal
(BBB) and intestinal barrier leading to increased morbidity, mortality and central function (6% and 16%, respectively). In the multivariable regression model.
nervous system symptoms. In this study we examined the relationship of blood brain participants with both mild and moderate renal dysfunction had a higher likelihood of
and intestinal barrier dysfunction in relation to uraemic environment and increased being diagnosed with HFpEF (OR: 2.82, 95%CI: 1.32 to 5.91; and OR: 5.37, 95%CI: 1.11
risk of developing neurologic complications and mortality. In addition, potential to 19.88, respectively), LVDD (OR: 2.08, 95%CI: 1.28 to 3.36; and OR: 2.92, 95%CI:
proteins conferring the junctional communications were assessed. 1.04 to 7.55, respectively), compared with participants with a normal renal function.
METHOD: The study included serum samples from 216 prevalent haemodialysis However, no significant association between creatinine or cystatin C with E/e’, LAVI,
(HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was LVMI, and E/A ratio was found after adjustment for age, sex, and cardiovascular risk
evaluated by measuring serum concentrations for brain-specific biomarkers S100B, and lifestyle factors.
NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial CONCLUSION: Mild renal dysfunction is related to both LVDD and HFpEF,
fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate however, this might be partly explained by a higher age in patients with renal
of gut generated uraemic toxins was analysed by mass spectrophotometry. dysfunction. Further studies are warranted to determine if preventive cardiac treatment
Subcutaneous fat tissues with identified microvessels from 10 kidney transplant in patients with early renal dysfunction will benefit clinical outcomes.
recipients and 11 donors were examined for expression of tight junction proteins
claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by
immunohistochemical staining.
RESULTS: HD and PD groups showed elevated cholesterol, triglyceride, creatinine, MO447 PROTEIN ARGININE METHYLTRANSFERASE 3 INHIBITS
hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum RENAL INTERSTITIAL FIBROSIS THROUGH ENHANCING
concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/ RENAL ASYMMETRIC DIMETHYLARGININE LEVELS
mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum
concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, Feng Yang1, Ming Wu1, Chaoyang Ye1
IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum 1
Department of nephrology, Shanghai Shuguang Hospital affiliated to Shanghai
concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, University of Traditonal Chinese Medicine, Department of nephrology, Shanghai, P.R.
IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration China
were also higher in both HD (6.4 ng/lL, IQR 4.0-11.2) and PD (3.8 ng/lL, IQR 2.2-6.3)
vs controls (0.4 ng/lL, IQR 0.3-0.6). No significant sex differences in biomarker
concentration were found, except for TMAO in healthy controls. BACKGROUND AND AIMS: Mammalian Protein Arginine Methyltransferase 3
Immunohistochemistry studies of endothelial tight junction proteins in microvessels, (PRMT3) catalyzes the monomethylation and dimethylation of the Arginine residues
within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), of proteins. The role of PRMT3 in renal fibrosis is currently unknown. We aimed to
occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and study the role of PRMT3 in renal fibrosis and explored its underlining mechanisms.
8%, respectively), and ongoing studies are indicating a trend for altered expression of METHOD: Sham or Unilateral Ureter Obstruction (UUO) operation was performed
tight junction proteins after ex vivo stimulation with TMAO. in Prmt3 wild-type (WT), heterozygous (Het) and homozygous (Homo) mutant mice,
CONCLUSION: We report that CKD5 patients showed disruption of BBB and which were sacrificed at day 14. A single dose of aristolochic acid (5mg/kg) was
intestinal barrier resulting in altered circulating serum levels of brain-specific injected in WT or HE mice, which was sacrificed at day 42.
biomarkers, secondary to a disruption in the tight junction protein markers in RESULTS: A strong interstitial fibrosis was observed in WT UUO mice as shown by
microvasculature of adipose tissue. These findings imply that it is important to Masson staining, and heterozygous or homozygous deletion of Prmt3 gene further
continuously monitor cognitive function(s) in CKD. Further studies are needed to enhanced interstitial fibrosis in mouse kidneys. The expression of collagen-I in mouse
assess direct effect of TMAO on tight junction proteins which confer vascular kidneys were analyzed by Western blotting. UUO operation increased the expression
permeability. of collagen-I in WT mouse kidneys, which were further increased by genetic deletion of
Prmt3 gene in a dose-dependent manner. A mild renal interstitial fibrosis was observed
in AAN mice, which was enhanced by heterozygous deletion of Prmt3 gene. Western
blot analysis showed that aristolochic acid increased the expression of collagen-I in WT
mice, which was further increased in Prmt3 Het mutant mice. Mechanismly,
MO446 THE ASSOCIATION BETWEEN RENAL FUNCTION AND LEFT asymmetric dimethylarginine levels were elevated in UUO or AAN mouse kidneys as
VENTRICULAR DIASTOLIC DYSFUNCTION AND HEART compared with its controls as shown by immnohistochemistry staining or ELISA.
FAILURE WITH PRESERVED EJECTION FRACTION Renal ADMA levels were not elevated in Prmt3 mutant UUO or AAN mice. Moreover,
renal injection of ADMA in UUO kidneys blocked the enhanced renal interstitial
Robin Vernooij1,2, Anne-Mar Van Ommen3, Frans Rutten2, Marianne Verhaar1, fibrosis in Prmt3 Het mutant mice as shown by Masson staining and Western blot
Michiel Bots2, Hester Den Ruijter3 analysis of collagen-I.
1
University Medical Center Utrecht, Department of Nephrology and Hypertension, CONCLUSION: Prmt3 inhibits renal interstitial fibrosis through enhancing renal
Utrecht, The Netherlands, 2University Medical Center Utrecht, Utrecht University, Julius ADMA levels.
Center for Health Sciences and Primary Care, Utrecht, The Netherlands and 3University
Medical Center Utrecht, Laboratory of Experimental Cardiology, Utrecht, The
Netherlands
MO448 MICRORNAS IMPLICATED IN CHRONIC KIDNEY DISEASE
BACKGROUND AND AIMS: Impaired kidney function increase the risk of
cardiovascular disease. However, it remains unclear whether this crosstalk between
organs already exists at early stages in the disease trajectory and whether this risk varies Laurent Metzinger1
with age and other factors. We aim to investigate the association between renal 1
Amiens, UR-UPJV 4666 HEMATIM, Amiens, France
dysfunction and early structural and functional cardiac abnormalities in a cohort of
participants referred to a cardiology outpatient department. BACKGROUND AND AIMS: The gene program is controlled at the post-
METHOD: We included participants from HELPFul (i.e. HEart failure with Preserved transcriptional level by the action of small non-coding RNAs known as microRNAs
ejection Fraction in patients at risk for cardiovascular disease), a case-cohort study at (miRNAs), short, single-stranded molecules that control mRNA stability or
Dutch cardiology outpatient clinics, who were aged 45 years and older without history translational repression via base pairing with regions in the 3’ untranslated region of
of cardiovascular disease. A random sample of participants enriched with cases their target mRNAs. Recently, considerable progress has been made to elucidate the
(defined as an early filling (E) to early diastolic mitral annular velocity (e’) (E/e’) ratio roles of miRNAs in vascular pathogenesis and develop the use of miRNAs as
of 8 measured with echocardiography) was included in our study. Routine care biomarkers, and innovative drugs. We demonstrated during the last decade that
measurements, including echocardiography and laboratory testing at the outpatient miRNAs miR-126 and miR-223 are implicated in the course of chronic kidney disease
clinic were collected for all participants. An expert panel decided on presence or (CKD) and cardiovascular damage. miR-223 expression is enhanced in vascular
absence of heart failure with preserved ejection fraction (HFpEF), and left ventricular smooth muscle cells (VSMCs) subjected to an uremic toxin and also in aortas of a
diastolic dysfunction (LVDD), guided by available international guidelines. The murine model of CKD.

i286 | Abstracts
Nephrology Dialysis Transplantation Abstracts
As restenosis is a common complication of angioplasty, in which neointimal in a Spanish population of patients with ADPKD. The prediction of future GFR with
hyperplasia results from migration of VSMCs into the vessel lumen we measured the the Irazabal equation is acceptable as a group, although it shows a loss of precision at
effect of miR-223 modulation on restenosis in a rat model of carotid artery after the individual level, especially in patients with higher GFR at baseline.
balloon injury. We over-expressed and inhibited miR-223 expression using adenoviral
vectors, coding a pre-miR-223 sequence or a sponge sequence, used to trap endogenous
microRNA, respectively. We demonstrated that inhibiting miR-223 function
significantly reduced neointimal hyperplasia by almost half in carotids. Thus down- MO450 ANEMIC PATIENTS WITH ELEVATED RED CELL
regulating miR-223 could be a potential therapeutic approach to prevent restenosis DISTRIBUTION WIDTH (RDW) ARE LIKELY TO HAVE FASTER
after angioplasty. FUTURE CKD PROGRESSION
We also correlated miR-126 and miR-223 expression with clinical outcomes in a large
cohort of CKD patients, in collaboration with the University Hospital of Ghent Hiroshi Tanaka1
(Belgium) and Ambroise Paré Hospital, France. We evaluated both miRNA’s link with 1
Mihara Red Cross Hospital, Department of Medicine/Division of Nephrology, Mihara,
all-cause mortality and cardiovascular and renal events over a 6-year follow-up period.
Hiroshima, Japan
The serum levels of miR-126 and miR-223 were decreased as CKD stage advanced, and
patients with higher levels of miR-126 and miR-223 had a higher survival rate. Similar
results were observed for cardiovascular and renal events. In conclusion, CKD is BACKGROUND AND AIMS: Elevation in red cell distribution width (RDW), a
associated with a decrease in circulating miR-126 and miR-223 levels in CKD patients. marker of size variance in red blood cells, recently has been reported to predict future
We will also present links between several uremic toxin concentrations and miRNA cardiovascular event. RDW elevation has also been reported to be associated with faster
concentration in the patients of this cohort. CKD progression. It is not known whether the elevation of RDW is merely a sequela of,
Finally, anemia is a common feature of CKD that is associated with cardiovascular or truly a predictor of, the decline in kidney function.
disease and poor clinical outcomes. A mixture of uremic toxins accumulates in the METHOD: A hospital-wide study with all the laboratory data for a period of 4 years
blood of CKD patients during the course of the disease, and there is good evidence that and 2 months was conducted. All the adult patients in whom an eGFR slope was
they modulate erythropoiesis, explaining at least partly anemia. The exact molecular obtained over 731 days or more with haemoglobin (Hb) measurements of at least twice
mechanisms implicated are however poorly understood, although recent progresses over 731 days or more were included. Hb and RDW values were classified according to
have been made to identify key components in the CKD process. We will present the timing of measurement: first-year measurements during the period vs last-year
results on the effect of uremic toxins on erythropoiesis, having an impact on cell values. The effects of Hb and RDW on the annual decline in eGFR (mL/min/1.73m2/
metabolism during this process. year) were analyzed. Statistical analysis was performed with R 3.6.0 on Ubuntu.
Taken together, our findings could be of interest to both researchers and clinicians RESULTS: A total of 4,611 patients (M:F = 2124:2487, age 18-105 (median 68) years)
working in the field since they might shed new light on the molecular mechanisms were included. The first-month Hb and RDW were 7.5  20.2 (median 13.6) g/dL and
involved in the CKD process. 10.5  34.6 (median 12.6). eGFR was 3.4  195 (median 69.3) mL/min/1.73m2.
MicroRNAs implicated in Chronic Kidney Disease Patients with the highest tertile in the first-year RDW had significantly faster decline in
Pr. Laurent Metzinger, UR-UPJV 4666 HEMATIM, CURS, Université de Picardie Jules eGFR than the rest (-1.74 vs -1.51, P=0.04), while patients with the highest tertile in the
Verne, CHU Amiens Sud, Avenue René La€ennec, Salouel, F-80054, Amiens, France. last-year RDW had virtually identical eGFR decline compared with the rest. Patients
Tel: (þ33) 22 82 53 56, Email: laurent.metzinger@u-picardie.fr with higher RDW (>=median) and lower Hb (< median) had significantly faster
decline in eGFR than the rest (-1.8464.11 vs -1.4762.95, P =0.002).
CONCLUSION: Anemic patients with elevated RDW are likely to have faster CKD
progression in the future.
MO449 VALIDATION OF MAYO CLINIC CLASSIFICATION AS A
PREDICTOR OF FUTURE RENAL FUNCTION IMPAIRMENT IN
PATIENTS WITH AUTOSOMAL POLYCYSTIC KIDNEY
DISEASE (ADPKD) IN A POPULATION IN THE SOUTH OF MO451 GUANIDINYLATED APOLIPOPROTEIN C3 (APOC3) A NOVEL
SPAIN PLAYER IN CKD AND CKD-ASSOCIATED CARDIOVASCULAR
DISEASES
Francisco-Jose Borrego-Utiel1, Rafael Jose Esteban de la Rosa2, Enoc Merino
Garcia1, Aurora Polo Moyano2, Clara Moriana Dominguez1, Ana Isabel Morales Stefan Schunk1, Juliane Hermann2, Triem Sarah1, Michaela Lellig2, Eunsil Hahm3,
Garcıa2, Juan Antonio Bravo Soto2 Peter Boor2, Jochen Reiser3, Joachim Jankowski2, Danilo Fliser1,
1 Vera Jankowski2, Thimoteus Speer1
Hospital Universitario de Jaén, UGC Nefrologıa, Jaén, Spain and 2Hospital “Virgen de 1
las Nieves”. Granada, UGC Nefrologıa, Spain Saarland University, Department of Internal Medicine IV, Homburg/Saar, , 2RWTH
Aachen University Hospital, Aachen, Germany and 3Rush University Medical Center,
Chicago, United States of America
BACKGROUND AND AIMS: The Mayo Clinic classification (MCC) is used in
patients with ADPKD to identify those who may experience a more rapid deterioration
of glomerular filtration rate (GFR). It has been developed in the American population BACKGROUND AND AIMS: Cardiovascular diseases (CVD) and chronic kidney
but has not been validated in other populations. Our objective was to analyze whether diseases (CKD) are highly prevalent in Western populations and account for a
the CCM predictive model is valid in an ADPKD population from southern Spain and substantial proportion of mortality. We found that apolipoprotein C-3 (ApoC3), a
whether it can identify populations with different renal survival. constituent of triglyceride-rich lipoproteins, induces alternative NLRP3 inflammasome
METHOD: We selected patients with ADPKD with measurements of height-adjusted activation in human monocytes and thus causes sterile inflammation. The aim of the
total renal volume (HtTKV) performed with CT or MR and with GFR CKD-EPI> 15 present study was to screen ApoC3 for the presence of posttranslational protein
mL / min / 1.73 m2. We estimated the GFR at the end of the follow-up using the modifications and to assess its relevance in vitro, in vivo, as well as in a prospective
Irazabal equation and the rate of GFR deterioration, bias and precision were calculated. cohort of CKD patients.
We analyzed the predictive power of BC using survival analysis using the Kaplan- METHOD: ApoC3 was subjected to proteomic analysis. The proinflammatory
Meier technique and using Cox regression models. properties of ApoC3 were assessed in human monocytes and in humanized mice.
RESULTS: We included 128 patients, aged 44 6 13 years and a follow-up time of 79 6 Moreover, posttranslationally modified ApoC3 was quantified in prospective cohort of
45 months (median 88), at the end of which 22 (17.2%) patients had a GFR <10 mL / 543 patients with various etiologies of CKD and linked to kidney and cardiovascular
min / 1.73 m2 or were included in renal replacement therapy. The distribution of outcomes.
patients according to the CM classification was: 1A 4.7%, 1B 28.1%, 1C 33.6%, 1D RESULTS: We identified posttranslational guanidinylation of lysine residues of ApoC3
22.7%, 1E 10.9%. Age decreased progressively: 1A 58 6 11, 1B 48 6 14, 1C 46 6 13, (gApoC3) in patients after acute myocardial infarction and in patients with CKD.
1D 40 6 8, 1E 30 6 7 (p <0.001). In contrast, HtTKV increased significantly: 1A 275 gApoC3 accumulates in kidneys and hearts after injury as determined by 2D-
6 52, 1B 486 6 191, 1C 887 6 410, 1D 1222 6 510, 1E 1324 6 800 mL / m (p proteomic analyses. In human monocytes, guanidinylation enhanced the binding of
<0.001). While the initial GFR was not different between classes, the GFR at the end of ApoC3 to the cell surface and exerted substantially stronger pro-inflammatory effects
the follow-up decreased significantly: 1A 59 6 36, 1B 63 6 29, 1C54 6 35, 1D 48 6 26, as compared native ApoC3. In humanized mice, gApoC3 strongly induced kidney
1E 44 6 33 mL / min / 1.73 m2 (p <0.001). The GFR variation rate was significantly fibrosis and abolished the regeneration after vascular injury. In a prospective clinical
different according to the MCC classes: 1A 1.31 6 6.80, 1B -2.48 6 3.12, 1C -4.13 6 trial of 543 patients, higher gApoC3 blood levels as determined by mass spectrometry
4.33, 1D -4.70 6 2.66, 1E -6.18 6 3.03 mL / min / 1.73 m2 / year (p = 0.008). The final were associated with increased mortality as well as cardiovascular and renal events
GFR predicted with the Irazabal equation was not significantly different from the real during a long-term follow-up.
one. The absolute bias of the final GFR estimated with the MC equation was 2.6 6 16.0 CONCLUSION: The present study provides evidence from preclinical models and a
mL / min / 1.73 m2 and the relative bias was 38.7 6 110, and it was not significantly prospective clinical trial that gApoC3 plays an important role in the development of
different in the MCC classes. The P10 precision was low, with values of 65.1%, 51.7% organ injury in patients with CKD, myocardial infarction and other clinical conditions.
and 50% for classes 1C, 1C and 1E respectively. The rate of deterioration of the GFR The clinical study represents one of the largest trials, in which the association of a
was underestimated in classes 1C, 1D and 1E. In the renal survival analysis with the specific PTM and clinically relevant outcomes was assessed. These findings highlight
Cox regression analysis, we found that the MCC classification is a predictor of survival, gApoC3 as a pathophysiologically relevant factor in development of organ dysfunction.
with classes 1D and 1E having the worst prognosis.
CONCLUSION: The MCC classification is capable of identifying populations that will
suffer a more rapid deterioration of the GFR and constitutes a marker of renal survival

10.1093/ndt/gfab090 | i287
Abstracts Nephrology Dialysis Transplantation

MO452 CHRONIC KIDNEY DISEASE TEN YEARS AFTER PEDIATRIC MO453 SERUM AND VASCULAR FIBROBLAST GROWTH FACTOR 23
ALLOGENEIC HEMATOPOIETIC STEM CELL (FGF23) ARE ASSOCIATED WITH VASCULAR
TRANSPLANTATION CALCIFICATION

Dorine Bresters2, Els Jol-van der Zijde1, Eiske Dorresteijn4, Marloes Louwerens3, Javier Donate-Correa1, Ernesto Martın-Nu ~ez1, Carolina Herna
n ndez-Carballo1,
Carlijn Jordans1, Arjan Lankester1, Gertjan Lugthart1, Anne De Pagter1, Roos Van Carla Ferri1, Miguel Arévalo-Go mez2, Ainhoa Gonza lez-Luis1, Sergio Rodrıguez-
Rooij-Kouwenhoven1, Ram Sukhai1 Lopez1, Purificacion Cerro-Lo pez1, Angel Lo
pez-Castillo1, Carmen Mora-
1
Leiden University Medical Center (LUMC), Willem-Alexander Children’s Hospital, depart- ndez1, Juan F. Navarro-Gonza
Ferna lez1
ment of pediatrics, Leiden, The Netherlands, 2Princess M
axima Center for Pediatric 1
Hospital Universitario Nuestra Se~
nora de Candelaria, Unidad de Investigaci
on, SANTA
Oncology, Utrecht, The Netherlands, 3Leiden University Medical Center (LUMC), depart- CRUZ DE TENERIFE, Spain and 2Universidad de Salamanca, Spain
ment of internal medicine, Leiden, The Netherlands and 4Erasmus University Medical
Center, Sophia Children’s Hospital, Rotterdam, The Netherlands BACKGROUND AND AIMS: Mineral metabolism imbalances and inflammation are
related to the development of vascular calcification (VC). Fibroblast growth factor-23
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is an important sequela (FGF23) is the main regulator of phosphate homeostasis and various studies have
of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after shown the existence of an association between elevated levels of FGF23 and the
pediatric HSCT are limited. appearance of cardiovascular disease (CVD). We conducted a case-control study to test
METHOD: In this single center cohort study, we evaluated eGFR dynamics, the hypothesis that serum and vascular levels of FGF23 are associated with the
proteinuria and hypertension in the first decade after HSCT and assessed risk factors presence of VC. In addition, we determined the influence of inflammation in these
for chronic kidney disease in 216 pediatric long term HSCT survivors, transplanted levels.
between 2002 and 2012. METHOD: One hundred and thirty-three patients diagnosed with clinical
RESULTS: The eGFR decreased from median 148 to 116 ml/min/1.73m2 between pre- atherosclerotic disease undergoing elective vascular surgery, and 20 cadaveric organ
HSCT and ten years after HSCT. CKD, defined as an eGFR <90 ml/min/1.73m2 and/ donors with no medical history of CVD, were included in this study. Serum levels of
or proteinuria (KDIGO stage G2 or A2) occurred in 21% of patients. In intact FGF23 (iFGF23), together with tumor necrosis factor-alpha (TNFa), interleukin
multivariate analysis, hematological malignancy as HSCT indication (HR 5.5, 95% CI (IL)10, were determined by ELISA. Vascular fragments of aorta, carotid and femoral
1.2-25) and cytomegalovirus reactivation (HR 2.4, 95% CI 1.1-5.4) were independent arteries were obtained for assaying the gene expression of FGF23, TNF, IL10 and
risk factors for CKD. One third of patients with CKD had both an eGFR <90 ml/min/ RUNX2 by qPCR. Immunohistochemical procedures were employed to determine
1.73m2 as well as proteinuria, one third had isolated eGFR reduction and one third vascular protein levels of FGF23, TNFa and IL10. VC was diagnosed by imaging
only had proteinuria. Hypertension was observed in 27% of patients with CKD techniques and confirmed by histological procedures including von Kossa staining.
compared to 4.4% of patients without CKD. Tubular proteinuria was present in 7% of RESULTS: Case group presented a higher prevalence of hypertension,
the subgroup of patients (n=71) in which b2-microglobulinuria was measured. hypercholesterolemia and reduced estimated glomerular filtration rate, with no
CONCLUSION: In conclusion, a significant proportion of pediatric HSCT recipients differences regarding other parameters. Serum iFGF23 and TNFa/IL10 ratio were
developed chronic kidney disease within ten years after HSCT. Our data stress the higher in the case group (P<0.01 and P<0.001, respectively). Vascular expression of
importance of structural long term monitoring of eGFR, urine and blood pressure after FGF23 was detected in 58.6% of CVD patients vs 35% of donors, with mean expression
HSCT to identify patients with beginning CKD who could benefit most from levels significantly higher in the first group (P<0.01). Vascular expression of TNF/IL10
nephroprotective interventions. was also increased (P<0.001) in CVD patients. FGF23 immunoreactivity was detected
in 84% of CVD patients and only in 35% of controls. Immunoreactivity for FGF23 and
TNFa/IL10 ratio were significantly higher in CVD patients (P<0.001 and P<0.0001,
respectively).
Stratified analysis according to serum iFGF23 levels showed a higher prevalence of VC
in the upper tertiles. Patients with VC presented increased levels of all the FGF23
variables including serum [1.5 (1.2-1.6) vs. 1.4 (0.9-1.5) pg/mL, P<0.01], vascular
mRNA [26.1 (14.3-67.4) vs. 18.8 (8.8-312.9) log AU, P<0.01] and vascular
immunoreactivity [4.6 (3.8-4.9) vs. 3.7 (3.1-4.1) log mm2, P<0.05]. Moreover, FGF23
immunoreactivity was detected in 92.3% of fragments with VC and only in 53.6% of
those without VC. Serum TNFa/IL10 and RUNX2 mRNA levels were also higher in
this group (P<0.01 for both).
Correlation analysis showed associations of serum iFGF23 with serum TNFa (r=0.375,
P<0.001), neutrophil/lymphocyte (r=0.142, P<0.05), vascular RUNX2 mRNA (r=0.55,
P<0.05), and vascular FGF23 immunoreactivity (r=0.281, P<0.05) in the CVD group.
Vascular FGF23 expression correlated with RUNX2 mRNA (r=0.315, P<0.05) and
FGF23 immunoreactivity (r=0.254, P<0.05). Multiple regression analysis showed that
iFGF23 levels were determined by UAE, HDL, FGe, calcium and TNFa levels (adjusted
R2= 0.473, P<0.0001) and that vascular FGF23 mRNA expression was determined by
TNFa, PCR, glucose and age (adjusted R2= 0.795, P<0.0001). Multivariate logistic
regression, with VC as dependent variable, showed that both iFGF23 and vascular
mRNA constitute independent risk factors for the existence of VC [OR (95% CI): 1.05
and 1.12, P<0.05 for both].
CONCLUSION: Patients with atherosclerosis and VC present significantly higher
serum concentrations of FGF23, as well as higher immunoreactivity and gene
expression levels in the vascular wall compared to patients without VC. Moreover, both
serum and vascular mRNA levels of FGF23 are associated with the inflammatory
status. Whether the increase in systemic and vascular FGF23 can directly promote or
favor the calcifying process in the vascular bed is currently an issue under discussion.

MO454 A NEW AKI TO CKD PROGRESSION IN VIVO EXPERIMENTAL


MODEL

Giampiero A. Massaro1, Joana Mercado-Hernandez2, Isabel Fuentes-Calvo2,


Sandra M. Sancho Martinez2, Yaremi Quiros1, Carlos Martinez Salgado1,
Francisco J. Lopez-Hernandez1
1
Institute of Biomedical Research of Salamanca (IBSAL), Spain and 2University of
Salamanca, Spain, Physiology and Pharmacology

BACKGROUND AND AIMS: Chronic kidney disease (CKD) represents an enormous


problem for healthcare systems. It is estimated that in USA more than 37 million
people suffer from this disease. Risk factors include hypertension, diabetes mellitus,
older age, proteinuria and previous episodes of acute kidney injury (AKI). Indeed,
several studies have shown that AKI increases the risk of CKD, independently of other
risk factors, especially when the episode is severe or recurrent. Under these
circumstances, maladaptive responses may occur leading to structural and functional
abnormalities. Renal fibrosis is the hallmark for maladaptive repair and is considered

i288 | Abstracts
Nephrology Dialysis Transplantation Abstracts
the final common outcome of progressive kidney disease. We hypothesized that after CONCLUSION: Significant inverse associations between lipid profile and small water-
multiple renal insults, the mechanisms of adaptive repair could be less effective soluble or protein-bound uremic toxins in advanced CKD highlight the complexity of
generating a progressive accumulation of extracellular matrix and a progressive the uremic environment. Our data suggest that not all URS interactions with
deterioration of kidney function. conventional CV risk markers may be pathogenic.
METHOD: We used 8 weeks old male Wistar rats and we analyse their evolution
during 9 months. Animals were subdivided into 4 experimental groups: Control group:
SHAM operated rats, saline solution, i.p.; “CDDP5-I/R60-I/R60” group: 5 mg/kg
cisplatin i.p., after renal function normalization, 60-minute ischemia-reperfusion (I/ MO456 DOES PHOSPHORUS EXCRETION PER NEPHRON AFFECT
R60) on left kidney, and 2 weeks later 60-minute ischemia-reperfusion (I/R60) on right THE PROGNOSIS OF CHRONIC KIDNEY DISEASE?
kidney; “5/6 RMR” group: 5/6 renal mass reduction; “UNX” group: nephrectomy.
Blood and urine were collected at: day 0 (basal); day 4 (AKI development); day 8 Takayuki Fujii1, Junya Koshizaka1, Nobuaki Yamauchi1, Takahiro Matsunaga1,
(normalized renal function after AKI and induction of renal ischemia); day 9 (1 day Mayu Morimoto1, Noriko Terasaki1, Hiroaki Tanaka1, Satoshi Suzuki1
after ischemia); day 13, day 20 and monthly thereafter. Renal function was analyzed by 1
Seirei Sakura Citizen Hospital, Kidney center, Sakura, Japan
sCr, creatinine clearance, blood urea nitrogen and proteinuria determination using
colorimetric methods. Tissue samples were stained with Massons trichrome and Sirius
Red at days 13, 20, 56, 165 and 270 and renal fibrosis was quantified using Image J BACKGROUND AND AIMS: Serum phosphorus is an important factor associated
program. with mortality and cardiovascular disease in dialysis patients as well as in non-dialysis
RESULTS: The addition of several AKI episodes induces a progressive accumulation of patients with chronic kidney disease (CKD) and healthy individuals. One observational
extracellular matrix. In addition, the “CDDP5-I/R60-I/R60” group presented an initial study reported that elevated phosphorus is a risk factor for end-stage renal disease and
reduction in renal function that remained stable in the last 6 months of the study. On is linked to reduced renal function, even within the normal range. Although the
the contrary, we observed a spontaneous and progressive decline of kidney function in mechanism is unknown, an excessive load of phosphorus to the kidney is presumed to
the “5/6 RMR” group, which nevertheless presented a significant lower degree of cause renal damage via phosphorus-containing nanoparticles. In this study, we
interstitial fibrosis than the “CDDP5-I/R60-I/R60” group. examined the association between phosphorus excretion per nephron and the
CONCLUSION: We have generated a new in vivo experimental model of AKI to CKD prognosis of CKD.
transition combining nephrotoxic and ischemic AKI. We demonstrate that after METHOD: A single-center, retrospective cohort study was conducted in 276 patients
recurrent episodes of AKI, kidneys show progressive interstitial fibrosis which however with CKD category G3 to G5 who were admitted to our hospital and received an
does not correlate with a progressive decline of renal function. inpatient educational program on CKD between June 2016 and November 2019 and
who could be followed up for at least 1 year or started on dialysis within 1 year after
hospitalization. Phosphorus excretion per nephron was defined as daily phosphorus
excretion divided by creatinine clearance (Ccr), and its association with the annual rate
of decline in estimated glomerular filtration rate (eGFR) was investigated for each CKD
MO455 LIPID PROFILE AND UREMIC RETENTION SOLUTES IN
category. For statistical analysis, multiple regression analysis was performed using the
PATIENTS WITH END-STAGE KIDNEY DISEASE
following covariates: age, sex, presence/absence of diabetes mellitus, mean arterial
blood pressure, amount of daily urine protein, serum phosphorus level, and use of a
Sam Hobson1, Jetty De Loor2, Karolina Kublickiene1, Pieter Evenepoel2,
renin-angiotensin system inhibitor.
Peter Stenvinkel1, Thomas Ebert1
1
RESULTS: There were 108 patients with CKD G3, 106 patients with CKD G4, and 62
Karolinska Institutet, Department of Clinical Science, Intervention and Technology, patients with CKD G5. Daily phosphorus excretion was 442 mg in G3, 350 mg in G4,
Stockholm, Sweden and 2Katholieke Universiteit Leuven, Department of Immunology and 350 mg in G5 patients. Phosphorus excretion per nephron was 8.4 mg/Ccr in G3,
and Microbiology, Laboratory of Nephrology, Leuven, Belgium 14.0 mg/Ccr in G4, and 24.2 mg/Ccr in G5 patients. It increased with the progression
of renal damage. In G4 patients, phosphorus excretion per nephron was significantly
BACKGROUND AND AIMS: Patients with end-stage kidney disease (ESKD) have an negatively correlated with the rate of decline in eGFR (p = 0.004); however, no
extremely high incidence of cardiovascular (CV) diseases, partly driven by insufficient correlation was found between the two in G3 and G5 patients (p = 0.09 and p = 0.16,
clearance of uremic toxins. ESKD patients have a characteristically adverse lipid profile, respectively). Multiple regression analysis showed that phosphorus excretion per
however data investigating the relationship between uremic toxins and lipid profile, nephron was not a significant worsening factor for renal function in G3, G4, and G5
potentially contributing to increased CV risk, is scarce. To determine if uremic patients (p = 0.09, p = 0.36, and p = 0.41, respectively). On the other hand, serum
retention solutes (URS) associate with an adverse lipid profile in ESKD, we studied a phosphorus level was a significant worsening factor for renal function in G3 and G5
large, trinational cohort with a detailed lipid profile, as well as a comprehensive panel patients (p = 0.03 and p = 0.01, respectively).
of uremic toxins. CONCLUSION: No association was found between phosphorus excretion per
METHOD: Total, high density lipoprotein (HDL), non-HDL, low density lipoprotein nephron and the rate of the subsequent decline in renal function.
(LDL), and remnant cholesterol, as well as triglyceride, levels were associated with a
panel of 15 uremic retention solutes in a combined cohort of 591 European, adult
patients with advanced chronic kidney disease (CKD) from UZ Leuven, Belgium
(n=150), Karolinska Hospital, Stockholm, Sweden (n=235) or University of Leipzig MO457 PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE
Medical Center, Leipzig, Germany (n=226). Total and HDL cholesterol, as well as IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A CASE-
triglycerides, were quantified at each study center, whereas non-HDL cholesterol, LDL CONTROL STUDY
cholesterol, and remnant cholesterol were calculated. In all subjects of this trinational
study, a selected panel of solutes, including CMPF, TMAO, aromatic amino acids and Therese Adrian1, Mads Hornum1, Ida Maria Hjelm Soerensen1, Ellen
corresponding end-products of endogenous and microbial metabolism, was centrally Linnea Freese Ballegaard1, Susanne Bro1, Joergen Tobias Kühl2, Per
quantified in a single lab by liquid chromatography - tandem mass spectrometry. Ejlstrup Sigvardsen2, Andreas Fuchs2, Klaus F. Kofoed2, Filip K. Knop3, Bo Feldt-
Univariate correlations were assessed using non-parametric Spearman’s rank Rasmussen1
correlation method. To identify independent associations between solutes and lipid 1
Rigshospitalet, University of Copenhagen, Nephrology, Copenhagen OE, Denmark,
profile, multivariate linear regression models were used with adjustment for age, sex, as 2
Rigshospitalet, University of Copenhagen, Cardiology and 3Herlev and Gentofte
well as markers of inflammation, protein energy wasting, renal function, diabetes and
Hospital, Center for Clinical Metabolic Research
dialysis.
RESULTS: In total, 189 patients in CKD stage 3-5 not on renal replacement therapy
(RRT), as well as 402 subjects on RRT, were included. All URS except phenylalanine BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most
significantly differed between patients on RRT vs. not on RTT. In univariate analyses, common liver disease and is characterised by hepatic accumulation of lipids. NAFLD
URS negatively correlated with most lipid markers, including LDL and HDL represents a wide spectrum ranging from mild steatosis over non-alcoholic
cholesterol. In contrast, the amino acids tryptophan, phenylalanine, and tyrosine were steatohepatitis with and without fibrosis to overt cirrhosis. Patients with NAFLD have
positively correlated with a large majority of lipid markers. After combining URS a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So
concentrations based on molecule size, similar associations were observed for the far, there is scarce evidence of the prevalence of NAFLD among patients with CKD.
respective groups, i.e. small water-soluble molecules, protein-bound molecules, and The aim of this study was to investigate the prevalence of moderate to severe steatosis
amino acids. After adjustment for age, sex, presence of diabetes, dialysis treatment, in a cohort with patients with different stages of CKD not on dialysis.
inflammation, protein energy wasting, and renal function, significant associations were METHOD: A total of 291 patients from the Copenhagen Chronic Kidney Disease
lost for URS and total cholesterol or HDL cholesterol, excluding total cholesterol and Study were included. For comparison, 866 participants with normal kidney function
phenylacetyl glutamine. However, high triglyceride levels were independently from the Copenhagen General Population Study were identified as controls. Blood
predicted by p-cresyl sulphate, tryptophan, indole-3 acetic acid, phenylalanine, TMAO, samples, clinical demographics, information about smoking and alcohol were collected.
small water-soluble molecules combined, and protein-bound molecules combined. Hepatic liver fat fraction was evaluated in all participants by computed tomography
Non-HDL cholesterol was independently predicted by phenyl glucuronide, TMAO, (CT). Liver attenuation density <48 Hounsfield Units was used as cut-off value for
phenylacetyl glutamine and small water-soluble molecules combined, while remnant moderate to severe steatosis corresponding to 10% liver fat after transformation of the
cholesterol was independently associated with 10 out of the 15 URS, as well as small CT attenuation.
water-soluble molecules combined and amino acids combined. Furthermore, LDL RESULTS: The prevalence of moderate to severe steatosis was 7.9% and 10.7% among
cholesterol independently associated with tryptophan, TMAO, phenylacetyl glutamine patients with CKD and controls, respectively. Data of the continuous Hounsfield Units
and protein-bound molecules combined.

10.1093/ndt/gfab090 | i289
Abstracts Nephrology Dialysis Transplantation

showed lower values among patients with CKD compared with the control group. No MO459 RENAL FUNCTION AMONG PATIENTS WITH NEW
significant association between liver fat fraction and CKD stage was found. Pooled data DIAGNOSIS OF ATRIAL FIBRILLATION - RESULTS FROM THE
from both cohorts showed that adjusted odds ratios (OR) for steatosis were strongly NATIONWIDE FINACAF- STUDY
significant among persons with diabetes (OR 3.1, 95% confidence interval (CI) 1.6-5.9),
overweight (OR 14.8, 95% CI 4.6-47.9) and obesity (OR 42.0, 95% CI 12.9-136.6), Heini Jyrkila€1,2,3, Kati Kaartinen1,4, Leena Martola1,4, Olli Halminen5, Jari Haukka3,
respectively. Miika Linna5, Pirjo Mustonen6, Jukka Putaala4,7, Saga Ita €inen-Strömberg4,8,
CONCLUSION: In the present cohort of 291 patients with CKD, kidney function was Janne Kinnunen4,7, Elis Kouki4,8, Alex Luojus4,9, Paula Tiili2,4,7,
not associated with the prevalence of hepatic steatosis as assessed by CT scan. Juha Hartikainen10,11, KE Juhani Airaksinen12,13, Mika Lehto4,8
1
Helsinki University Hospital, Abdominal Center, Department of Nephrology, Helsinki,
Finland, 2Helsinki University Hospital, Heart and Lung Center, Helsinki, Finland,
3
University of Helsinki, Faculty of Medicine, Helsinki, Finland, 4University of Helsinki,
Helsinki, Finland, 5Aalto University, Department of Industrial Engineering and
Management, Espoo, Finland, 6Central Finland Health Care District, Department of
Internal Medicine, Jyv€ a, Finland, 7Helsinki University Hospital, Department of
askyl€
Neurology, Helsinki, Finland, 9Helsinki University Hospital, Helsinki, Finland, 10Kuopio
University Hospital, Heart Center, Department of Cardiology, Kuopio, Finland,
11
University of Eastern Finland, Kuopio, Finland, 12Turku University Hospital,
Department of Cardiology, Turku, Finland and 13University of Turku, Turku, Finland

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a global public health
problem with increasing number of patients due to obesity, hypertension, diabetes, and
aging. CKD is an independent risk factor for atrial fibrillation (AF) and the incidence
of AF in patients with CKD is two- to threefold higher compared to the general
population. Relationship between CKD and AF is bidirectional, and the incidence of
impaired renal function is higher in patients with AF. Both AF and CKD are associated
with increased risk of stroke and systemic thromboembolism, and also bleeding. The
Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study among
AF patients conducted as a retrospective register-based linkage study combining data
from several Finnish health care registers. We aimed to characterize demographics and
comorbities of AF patients included in FinACAF according to stages of renal function.

MO457 Figure:The liver fat content determined by CT attenuation density


measured in Hounsfield units. Since CT attenuation correlates inversely with liver fat
content, an increase in fatty infiltration of the liver is depicted as a decrease in
attenuation.
A=patients with chronic kidney disease, B=controls without chronic kidney disease

MO458 URINARY GROWTH DIFFERENTIATION FACTOR-15 (GDF15)


LEVELS AS BIOMARKER OF ADVERSE OUTCOMES AND
BIOPSY FINDINGS IN CHRONIC KIDNEY DISEASE

Maria Vanessa Perez Gomez1, Elena Goma -Garcés1, Maria Soledad Pizarro
Sanchez1, Carolina Gracia-Iguacel1, Santiago Cano1, Pablo Cannata-Ortiz1,
Jinny Sanchez-Rodrıguez1, Ana Sanz1, Maria Dolores Sanchez-Nino1,
Alberto Ortiz1
1 MO459 Figure 1:Mean age by cohort entry year.
Hospital Universitario Fundaci
on Jiménez Dıaz, Madrid, Spain
eGFR= estimated glomerular filtration rate
BACKGROUND AND AIMS: Growth differentiation factor-15 (GDF15) is a member
of the TGF-b superfamily. Increased serum GDF15 has been associated with increased
risk of CKD progression. However, no prior study had addressed the significance of
urinary GDF15 in adult CKD.
METHOD: We have now assessed serum and urinary GDF15 in a prospective cohort
of 84 patients who underwent kidney biopsy and then were followed for 29617
months.
RESULTS: There was a statistically significant correlation between serum and urine
GDF15 values. However, while serum GDF15 values increased with decreasing
glomerular filtration rate, urinary GDF15 did not. Immunohistochemistry located
kidney GDF15 expression mainly to tubular cells and kidney GDF15 staining
correlated with urinary GDF15 values. Urine GDF15 was significantly higher in
patients with a histological diagnosis of diabetic nephropathy than in diabetic patients
without diabetic nephropathy. This was not the case for serum GDF15. Both serum
and urine GDF15 were associated with patient survival in multivariate models.
However, when both urine and serum GDF15 were present in the model, lower urine
GDF15 predicted patient survival [B coefficient (SEM) -0.395 (0.182) p 0.03], and
higher urine GDF15 predicted a composite of mortality or renal replacement therapy
[0.191 (0.06) p 0.002] while serum GDF15 was not predictive. Decision tree analysis
yielded similar results. The AUC of the ROC for urine GDF15 as a predictor of
mortality was 0.95 (95% CI 0.89-1.00, p <0.001). MO459 Figure 2:Mean eGFR by cohort entry year.
CONCLUSION: In conclusion, urine GDF15 is associated with kidney histology eGFR= estimated glomerular filtration rate
patterns, mortality and need for renal replacement therapy in biopsied CKD patients.

METHOD: FinACAF- study collects data from 411 000 patients covering all Finnish
AF patients from 1 January 2004 to 31 December 2018. Using national unique personal
identification number, individual patients’ data from ten nationwide population
registries and six regional laboratory databases (282 000, 77% of the patients) are
linked together. Inclusion criteria of this substudy were all patients who had new ICD-
10 AF diagnosis (code I48) between January 2010 and December 2018 and measured
estimated glomerular filtration rate (eGFR) within the proximity of AF the diagnosis.
RESULTS: Of the whole study cohort, 128 538 were included in this substudy. The

i290 | Abstracts
Nephrology Dialysis Transplantation Abstracts
mean age at the time of AF diagnosis was 73 years (range 18 to 107 years) and 48.9 % of carbamylation. It will be further explored whether fecal levels of SCFAs are affected in
the patients were female. The age of AF patients increased (Figure 1) and eGFR parallel and could be potential targets to restore gut dysbiosis and uremia.
decreased (Figure 2) in various stages of glomerular filtration at the cohort entry during
2010-2018 are shown in Figures 1 and 2. Prevalence of various comorbidities and the
mean age at the baseline are shown in the Table. Most of the comorbidities were more
common in patients with lower eGFR levels. MO461 FGF19 IMPROVES GLUCOSE METABOLISM IN CKD MICE

MO459 Table. Prevalence of various comorbidities and mean age at entry to the Emilie Bres1,2, Bérengère Benoit2, Claudie Pinteur2, Denis Fouque1,2,
cohort.
Hubert Vidal2, Laetitia Koppe1,2
1
eGFR eGFR eGFR eGFR eGFR Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Department of Nephrology,
Variable Total PIERRE BENITE, France and 2Univ. Lyon, CarMeN lab, INSERM U1060, INRAE, Université
90 60-89 30-59 15-29 <15
Claude Bernard Lyon 1, PIERRE BENITE, France
Age, years (mean) 60.1 74.2 80.6 81.9 74.4 73.0
Hypertension (%) 70.4 80.9 87.6 91.5 93.0 80.7 BACKGROUND AND AIMS: Chronic kidney disease (CKD) is associated with high
Diabetes (%) 15.8 16.6 23.6 34.5 44.1 18.9 cardiovascular mortality rate, especially because of altered glucose metabolism and
insulin resistance. Fibroblast growth factor 19 (FGF19), an intestinal postprandial
Hyperlipidemia (%) 13.4 19.0 21.7 20.8 21.4 18.5
hormone, has been shown to improve metabolic disturbances and insulin resistance. In
Heart failure (%) 10.1 15.8 30.2 49.0 41.6 19.2 CKD, postprandial secretion of FGF19 seems blunted in hemodialyzed patients but the
Coronary artery disease (%) 16.3 25.7 36.5 42.7 39.8 26.8 role and regulation of FGF19 in this population is unknown. The aim of our study is to
ascertain if FGF19 can improve glucose homeostasis in a mouse model of CKD
TIA (%) 4.6 7.4 9.1 8.3 6.4 7.2 induced by 5/6 subtotal nephrectomy.
Stroke (%) 8.0 11.5 14.6 16.3 14.7 11.7 METHOD: Four weeks post-surgery, CKD mice or sham mice were treated during 18
Other vascular disease (%) 3.3 5.0 9.1 14.9 20.7 6.0 days with subcutaneous injections of placebo or human recombinant FGF19 (0.01mg/
kg of body weight). The effect on metabolic disturbances was estimated in vivo by
Pulmonary embolism (%) 1.5 1.9 3.0 4.1 2.9 2.1 glucose tolerance test (GTT, 1g/kg/body weight).
Other venous thrombosis (%) 5.3 6.6 8.5 9.2 10.3 6.9 RESULTS: Fasted hyperglycemia was observed in CKD groups compared to sham
mice (151.3 þ/- 10.6mg/l and 170.7 þ/- 10.9mg/L, p < 0.001 in sham and CKD mice,
Cancer (%) 11.8 18.2 22.6 25.7 24.6 18.1
respectively) and FGF19 tended to improve fasting glycemia in CKD mice (158.9 þ/-
Dementia (%) 1.0 3.6 6.5 8.2 4.0 3.9 18mg/L, p<0.09). The GTT area under the curve (AUC) was significantly decreased in
Psychiatric disease (%) 21.2 15.4 17.9 21.8 19.9 17.5 CKD-FGF19 group compared to CKD placebo (P < 0.0001) and control groups (P =
0.0063). Urea blood level was significantly higher in CKD groups (9.6 þ/- 1.4 mmol/L
eGFR= estimated glomerular filtration rate (mL/min/1.73m2), TIA= tran- and 25.5 þ/- 5.6 mmol/L in sham and CKD, respectively) and was not affected by
FGF19 treatment (24.8 þ/- 5.8 mmol/L, p = 0.91).
sient ischemic attack CONCLUSION: Our results show that FGF19 could contribute to improve glucose
intolerance observed in CKD and suggest that this hormone could be a novel
CONCLUSION: During 2010-2018 the mean age of new AF patients increased in therapeutic target for reducing mortality associated with CKD. The comprehension of
Finland, and simultaneously the renal function decreased. Also, patients with impaired the molecular and cellular events through which FGF19 exerted its benefits needs
glomerular filtration rate had more often comorbidities increasing the risk of however further studies.
thromboembolism and bleeding. The findings emphasize appropriate control of these
risks in AF patients, especially with reduced renal function.

MO462 TIME-TRAJECTORIES OF RENAL FUNCTION AND


OUTCOMES IN ELDERLY INDIVIDUALS WITH CKD OF
MO460 ASSOCIATION BETWEEN CARBAMYLATED ALBUMIN, GUT VARIOUS ETIOLOGY
MICROBIOTA AND THEIR DERIVED METABOLITES IN
CHRONIC KIDNEY DISEASE Mariateresa Zicarelli1, Alessandro Comi1, Gemma Patella1, Paola Cianfrone1,
Giuseppe Coppolino1, Nicolino Comi1, Giorgio Fuiano1, Davide Bolignano1,
Mieke Steenbeke1, Sophie Valkenburg1, Wim Van Biesen1, Joris Delanghe2, Michele Andreucci1
1
Marijn Speeckaert1,3, Griet Glorieux1 Magna Græcia University, Nephrology and Dialysis Unit, Catanzaro, Italy
1
Ghent University Hospital, Department of Internal Medicine and Pediatrics,
Nephrology Unit, Gent, Belgium, 2Ghent University, Department of Diagnostic Sciences, BACKGROUND AND AIMS: Despite hypertension ranks among the leading causes
Gent, Belgium and 3Research Foundation Flanders (FWO), Brussel, Belgium of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the
so-called “nephrosclerosis” (NS), on CKD progression towards end-stage kidney
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is characterized by gut disease (ESKD) is often unpredictable, particularly in older populations. We run a
dysbiosis. We recently demonstrated a decrease of short-chain fatty acid (SCFA) prospective, observational study to define renal function patterns and outcomes in
producing bacterial species with the progression of CKD. Besides, levels of protein- elderly individuals with or without NS-related CKD.
bound uremic toxins (PBUTs) and post-translational modifications of protein are METHOD: 304 elderly patients with already established CKD (mean age 6964 y;
increased in CKD, both are risk factors for accelerated cardiovascular morbidity and mean eGFR 44.2619.6 mL/min/1.73 m2; male= 64.1%), followed in our outpatients’
mortality. The link between the gut-kidney axis and protein carbamylation is unclear. clinic were categorized according to the etiology of CKD. NS was defined as the
The aim of the study was to explore the relation between carbamylated albumin, presence of CKD associated with long-term essential hypertension, hypertensive
estimated by the albumin symmetry factor, and plasma levels of PBUTs, fecal levels of retinopathy, left ventricular hypertrophy and minimal proteinuria. Time-trajectories in
SCFAs (ongoing), and the abundance of related gut microbiota in different stages of eGFR (CKD-Epi) were computed over a 4-year follow-up. In addition, we analysed the
CKD (1-5). occurrence of a composite outcome of doubling of serum creatinine, eGFR reduction
METHOD: The study cohort includes 103 non-dialyzed CKD patients (stages 1-5). 25% and/or ESKD needing dialysis or kidney transplantation.
Serum proteins were detected by capillary electrophoresis and UV absorbance at 214 RESULTS: CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%) patients.
nm with the symmetry factor as a marker of albumin carbamylation [the lower the Among the remaining 84 (27.7%), glomerular/diabetic diseases were the most frequent
symmetry factor, the more carbamylated albumin]. cause of CKD (47.6%). In the whole cohort, the average estimated annual GFR slope
The quantification of PBUTs and SCFAs in plasma and fecal samples, respectively, was of 1.8 mL/min/1.73 m2. eGFR decline was slower in CKD-NS as compared with
using validated UPLC methods. the one of others (1.4 vs. 3.4 mL/min/1.73 m2; p<0.001. Figure 1). The composite
RESULTS: The Pearson correlation coefficient (r) shows a positive correlation between renal outcome during follow-up (median 36 mo.; range 6-48) occurred less frequently
the albumin symmetry factor and the estimated glomerular filtration rate (eGFR) among elderly with CKD-NS (16/204 vs 14/70; p=0.01 Crude HR 0.43, 95%CI 0.22-
(r=0.3025; p=0.0019). 0.85) and was associated at logistic analyses with etiology of CKD, serum total
The albumin symmetry factor correlates positively with the abundance of cholesterol, serum LDL cholesterol levels and glycemia (p ranging from 0.01 to 0.04).
Butyricicoccus spp. (r= 0.3211; p=0.0009), Faecalibacterium prausnitzii (r=0.2765;
p=0.0047) and Roseburia spp. (r=0.2527; p=0.0100) and negatively with the PBUTs, p-
cresyl sulfate (pCS) (r=-0.2819; p=0.0039), p-cresyl glucuronide (pCG) (r=-0.2819;
p=0.0039) and indoxyl sulfate (IxS) (r=-0.2650; p=0.0068).
CONCLUSION: The decreased abundance of SCFA producing gut bacteria with the
progression of CKD can evoke unfavorable conditions in the gut. This can contribute
to increased plasma levels of PBUTs potentially (indirectly) playing a role in albumin

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MO464 TWO-YEARS CHANGES IN ABPM, CARDIAC AND RENAL


PARAMETERS PREDICT CARDIOVASCULAR OUTCOME OF
PATIENTS WITH CKD AND HYPERTENSION

Elisabetta Bussalino1, Maura Ravera1, Laura Mallia1, Roberto Minutolo2,


Simone Vettoretti3, Ernesto Paoletti1
1
Ospedale Policlinico San Martino, Nephrology, Dialysis, and Transplantation, Genoa,
Italy, 2University of Campania Luigi Vanvitelli, Division of Nephrology, Naples, Italy and
3
Fondazione IRCCS Ca’ Grande Ospedale Maggiore Policlinico, Unit of Nephrology-
Dialysis, Urology and Renal Transplantation, Milan, Italy

BACKGROUND AND AIMS: Changes over time in eGFR and albuminuria provide
better accuracy than baseline values for end-stage risk prediction in CKD patients,
whereas no studies have evaluated the impact of changes in renal, cardiac, and BP
parameters on cardiovascular (CV) outcome.
METHODS: We prospectively evaluated 249 hypertensive CKD patients with available
baseline and 2-year echocardiography and ambulatory blood pressure monitoring
(ABPM). Outcome was a composite of death or any non fatal CV event. Predictors of
outcome were tested by multivariable regression analysis. The accuracy of prediction
models that included baseline and 2-year changes (D) in cardiac, renal and BP
parameters was assessed by ROC analysis.
RESULTS: During a follow-up period of 71 months, 69 CKD patients (28%)
experienced a major CV event or died. By multivariable Cox regression analysis
baseline nighttime pulse pressure (PP) (HR 1.01, 95% CI 1.00 to 1.04), left ventricular
mass (LVMi) (HR 1.03, 95% CI 1.02 to 1.04), ejection fraction (EF) (HR 0.96, 95% CI
0.90 to 0.97), D nighttime PP (HR 1.04, 95% CI 1.01 to 1.07), D LVMi (HR 1.02, 95%
CI 1.00 to 1.04), and DEF (0.93, 95% CI 0.89-0.97) were associated with outcome. A
model that includes 2-year changes in LVMi, EF, proteinuria, and nighttime PP was
more accurate than a model that only evaluated baseline values (Dc-statistic 0.08, 95%
CONCLUSION: Despite being highly prevalent in the elderly, NS is associated with a CI 0.02 to 0.13, P=0.006; net reclassification improvement -NRI- 0.24, P= < 0.0001).
more favorable renal disease course as compared with other conditions. Therapeutic CONCLUSION: Estimation of 2-year changes in renal, cardiac, and BP parameters
efforts to delay CKD progression in older populations should go beyond just improve the predictive accuracy of adverse CV outcome in CKD patients followed in
optimizing blood pressure control and focus more on concomitant diseases. tertiary care.

MO463 EVIDENCE OF MICROALBUMINURIA AND ESTIMATED


GLOMERULAR FILTRATION RATE DECLINE AS CHRONIC
KIDNEY DISEASE RISKS IN NON-ALCOHOLIC FATTY LIVER
DISEASE PATIENTS: META-ANALYSIS OF COHORT STUDIES

Boby Pratama Putra1, Felix Nugraha Putra2


1
Medical doctor, Blitar, Indonesia and 2Universitas Airlangga, Faculty of Medicine,
Surabaya, Indonesia

BACKGROUND AND AIMS: Recent evidences showed an association between


NAFLD and extrahepatic manifestations such as chronic kidney disease (CKD)
although the result is still inconclusive. This study aims to measure the association of
microalbuminuria and estimated glomerular filtration rate (eGFR) decline as CKD
risks in NAFLD patients.
METHOD: Comprehensive searching using predefined queries was done through
online databases Pubmed, EMBASE, ScienceDirect, and The Cochrane Library to
include all relevant literature until November 2020. We included all cohort studies of
NAFLD patients diagnosed by ultrasonography (USG), commutated tomography
(CT), or scoring system fatty liver index (FLI) that reports microalbuminuria and
eGFR decline below 60 ml/min/1.73m2. Bias risk was assessed by The Newcastle-
Ottawa Scale for cohort studies. Analysis of this study was performed to provide pooled
hazard ratio (HR) with 95% confidence interval (CI) using random-effect
heterogeneity test.
RESULTS: We included 10 cohort studies met our criteria. Analysis of 6 NAFLD
cohort studies diagnosed by USG is significantly associated with eGFR decline (pooled
HR = 1.54, 95% CI 1.13 to 2.11, p=0.006, I2=88%), while NAFLD patients diagnosed by
MO465 PROGNOSTIC IMPLICATION OF URINARY POTASSIUM
FLI also showed significant association with eGFR decline (pooled HR = 1.58, 95% CI
EXCRETION IN PATIENTS WITH CHRONIC KIDNEY DISEASE
1.52 to 1.64, p<0.0001, I2=0%), thus overall analysis combined with CT diagnostic
modalities showed significant association between NAFLD and eGFR decline (pooled
Daisuke Mori1, Shinjiro Tamai1, Maho Tokuchi1, Natsumi Inoue1, Hideaki Kawai1,
HR=1.53 95%CI 1.29-1.80 p<0.00001 I2=82%). Microalbuminuria risk is significantly
Naoyuki Shimada1, Hiroki Nomi1, Ryota Haga1, Katsuyuki Nagatoya1,
increased in NAFLD patients (pooled HR = 1.93, 95% CI 1.39 to 2.67, p<0.0001,
Atsushi Yamauchi1
I2=0%). Surprisingly, NAFLD patients whose increased gamma-glutamyltransferase 1
(GGT) has higher eGFR decline risk (pooled HR = 1.73, 95% CI 1.02 to 2.92, p=0.04, Osaka Rosai Hospital, nephrology, Sakai, Japan
I2=78%).
CONCLUSION: Microalbuminuria and eGFR decline are associated as CKD risks in BACKGROUND AND AIMS: Plasma potassium levels are impacted by decreased
NAFLD patients. However, further studies are still needed to establish the causality. kidney function and are known to be associated with increased mortality, adverse
cardiovascular events and adverse kidney events. However, the prognostic implication
of urinary potassium is unclear.
METHOD: We conducted an observational study of 1102 patients with chronic kidney
disease (CKD) who were hospitalized between 2010 and 2018. The expected primary
outcomes were all-cause mortality, adverse cardiovascular events and CKD
progression. CKD progression was defined as a 30% increase in serum creatinine, the
initiation of maintenance dialysis or the need for kidney transplantation. The Cox
proportional hazards model was used to analyse the association between urinary
potassium excretion and adverse clinical outcomes after adjustment for potential
confounders.

i292 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: At baseline, 66% of the patients were men, with a median age of 72 years RESULTS: In the entire cohort of patients, MHR appeared to be positively correlated
(interquartile range or IQR, 64–79 years); 61% of the patients were diabetic, and 54% of with ten-year risk (q=0.469; P <0.0001) (Figure 1) and lifetime risk of myocardial
them were hypertensive. The median values for estimated glomerular filtration rate infarction, stroke, or CV death (q=0.428; P <0.0001) (Figure 2). Furthermore, patients
(eGFR) was 12 mL/min/1.73m2 (IQR, 8–18), serum potassium 4.5 mmol/L (IQR, 4.1– with higher MHR levels had a significantly smaller number of years of CVD-free life
5.1) and urinary potassium/creatinine ratio (UK/Cr) 27 mmol/gCr (IQR, 20–38). Over expectancy (q=-0.364; P <0.0001) (Figure 3).
a median follow-up period of 2.6 years (IQR 0.2–4.5), the number of all-cause deaths
was 87. There were 171 cases of cardiovascular events and 860 cases of CKD
progression. After adjusting for the eGFR, serum potassium level, proteinuria, renin–
angiotensin system inhibitors, diuretics and other potential confounders, UK/Cr was
found to be neither significantly associated with all-cause mortality nor with adverse
cardiovascular events. However, a low UK/Cr was associated with an increased risk of
CKD progression (adjusted hazard ratio [95% confidence interval] for the first, second
and third quartiles, compared with the fourth quartile, were as follows: 2.09 [1.43-
3.06], 1.33 [0.96-1.86] and 1.05 [0.75-1.46])
CONCLUSION: A low UK/Cr might be an independent risk factor for poor renal
outcome.

MO466 A NOVEL PREDICTION MARKER OF 10-YEAR RISK AND


LIFETIME RISK OF RECURRENT CARDIOVASCULAR EVENTS
IN PATIENTS WITH CKD AND DIABETES MELLITUS

Guido Gembillo1,2, Valeria Cernaro2, Rossella Siligato2, Alfio Edoardo Giuffrida2,


Vincenzo Labbozzetta2, Ersilia Satta3, Domenico Santoro2
1
University of Messina, Department of Biomedical, Dental, Morphological and
Functional Imaging Sciences., Messina, Italy, 2University of Messina, Unit of Nephrology
and Dialysis, Department of Clinical and Experimental Medicine., Messina, Italy and
3
Nefrocenter Research Network, Dialysis Unit, Naples, Italy

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is one of the most
prevalent complication of Diabetes Mellitus and patients with both diseases are more
exposed to atherosclerosis injury and premature death from cardiovascular disease
(CVD).
CVD is worsened by inflammation, oxidative stress, lipid accumulation and high-
density lipoprotein cholesterol (HDL) reduction: patients with altered lipid metabolism
more often present monocyte profile changes, with an altered pro-inflammatory
phenotype leading to a significant risk of plaque formation and atherosclerosis. The
alteration of the balance between monocyte and HDL, represented by the Monocyte/
HDL ratio (MHR), is an easy way to evaluate the inflammatory status and to study
appropriate strategies to treat high-risk patients.
METHOD: We evaluated 150 consecutive diabetic patients with CKD hospitalized in
the Unit of Nephrology and Dialysis of the Policlinic G. Martino of Messina, Italy, with
a history of CVD. We used the SMART-REACH SCORE, a model created to estimate
life expectancy without recurrent cardiovascular events for individuals with a history of
CVD. We performed a retrospective analysis of the MHR status of our patients to
study its correlations with the 10-year risk and lifetime risk for myocardial infarction,
stroke or vascular death, recurrent CVD events and free life-expectancy if standard
care is provided.

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MO468 NEW URINARY BIOMARKERS DETECT SUBCLINICAL RENAL


CONCLUSION: MHR can represent a valid tool to predict the recurrence of CVD in DAMAGE AFTER SEVERAL ACUTE KIDNEY INJURY
CKD patients with diabetes. This easy-to-perform marker of oxidative stress and CVD EPISODES
risk can be used alone or in a multiple biomarker panel, improving the stratification
and management of patients with comorbidities and risk of life- threatening Giampiero A. Massaro1, Joana Mercado-Hernandez2, Ana Carbajo-Un ~a2,
conditions. Isabel Fuentes-Calvo2, Sandra M. Sancho Martinez2, Laura Ramudo2, Francisco
J. Lopez-Hernandez1, Carlos Martinez Salgado1
1
Institute of Biomedical Research of Salamanca (IBSAL) and 2University of Salamanca,
Spain, Physiology and Pharnmacology
MO467 SINGLE NEPHRON GFR AND GLOMERULAR HYDROSTATIC
PRESSURE IN JAPANESE HEALTHY SUBJECTS BACKGROUND AND AIMS: Acute kidney injury (AKI) represents a clinical
problem due to its increasing prevalence and association with further morbidities.
Hiroki Nobayashi1, Go Kanzaki1, Takaya Sasaki1, Rina Oba1, Observational studies have shown that AKI increases the risk of a new AKI episode,
Yusuke Okabayashi1, Kotaro Haruhara1, Kentaro Koike1, Akimitsu Kobayashi1, chronic kidney disease (CKD), CKD progression, end-stage renal disease (ESRD), and
Izumi Yamamoto1, Tsuboi Nobuo1, Takashi Yokoo1 mortality. Serum creatinine (sCr) is the parameter most used by clinicians for
1
The Jikei University School of Medicine, Division of Nephrology and Hypertension, determining AKI and the subsequent recovery, however its use presents several
Department of Internal Medicine, Tokyo, Japan limitations. sCr lacks sensitivity for AKI and provides minimal insight into the renal
structure. Indeed, increases in sCr are observed only when glomerular filtration rate
decreases more than 50%. Therefore, new markers need to be identified to predict
BACKGROUND AND AIMS: Hemodynamic abnormalities such as intraglomerular recovery after AKI and to detect residual structural alterations that can cause
hypertension and glomerular hyperfiltration associated with the nephron loss are progression to CKD. We hypothesised that after AKI, there are renal structural
deeply involved in renal damage progression. Recent studies in humans have described abnormalities that cannot be detected by common clinical parameters but may be
a new method to calculate single nephron GFR (SNGFR), which is defined as GFR detected by urinary biomarkers.
divided by the estimated total number of non-sclerosed glomeruli. We have previously METHOD: We used 4 weeks old male Wistar rats. Animals were divided into 5
shown that a higher SNGFR, which indicates glomerular hyperfiltration, is associated experimental groups: Control group: SHAM operated rats, saline solution i.p.;
with CKD risk factors. However, it is still unknown that the hemodynamic changes in “CDDP5-SHAM” group: 5 mg/kg cisplatin i.p.; “Ctrl-I/R60” group: 60-minute renal
humans within the glomerulus in response to SNGFR. In the present study, we ischemia reperfusion in the left kidney; “CDDP5-I/R60” group: 5 mg/kg cisplatin i.p.
analysed the renal microcirculatory dynamics with SNGFR in healthy individuals and after renal function normalization, 60-minute ischemia-reperfusion (I/R60); “5/6
without CKD. NEF” group: 5/6 nephrectomy. Blood and urine were collected at: day 0 (basal); day 4
METHOD: We retrospectively identified 51 living kidney donors who underwent (AKI development); day 8 (normalized renal function after AKI and induction of renal
enhanced computed tomography and kidney biopsy at the time of donation from ischemia); day 9 (1 day after ischemia); day 13, day 20 and every week thereafter. Renal
January 2007 till December 2020. Nglom was calculated as the cortical volume of both function was analyzed by sCr, creatinine clearance, blood urea nitrogen and
kidneys assessed on computed tomography times the 1-hour posttransplant renal proteinuria determination using colorimetric methods. Urinary biomarkers were
biopsy-determined glomerular density. SNGFR was calculated by dividing GFR analyzed at day 20 (12 days after the second damage and 20 after the first one) by
(calculated from the corrected creatinine clearance) by the non-sclerosed Nglom. western blot and ELISA. Animals were sacrificed at the same time point in which
Glomerular hydrostatic pressure (Pglom) and afferent / efferent arteriolar pressure urinary biomarkers were determined, and renal tissue samples were stained with
were calculated from the Gomez / Ohm’s formula. Massons trichrome, Sirius Red and Periodic Acid-Schiff for histological analysis.
RESULTS: Age was 57.0 6 10.4 years, mean blood pressure was 88.7 6 13.2 mmHg, RESULTS: Frequency of AKI episodes is related to the amount and degree of
GFR was 73.3 6 16.7 mL/min, and Nglom was 807,774 6 401,0352 / kidney. SNGFR subclinical alterations detected in the kidneys, even though renal filtration is apparently
was significantly associated with renal blood flow and Pglom (p for trend = 0.02, and normal. We characterized a novel panel of urinary biomarkers (bk1-bk4) several days
0.02, respectively), but not with age, mean blood pressure, renal plasma flow, filtration after the last insult (day 20) when renal function appeared normal; these biomarkers
fraction, afferent / efferent arteriolar pressure (Table1). were present in highest concentrations in the CDDP5-I/R60 experimental group.
CONCLUSION: Our results showed that the increase in SNGFR is associated with CONCLUSION: These results demonstrate the importance of the clinical
elevated Pglom, indicating that glomerular hyperfiltration may lead to intraglomerular implementation of biomarkers as useful tools for medical support and underline the
hypertension. limitations of the clinical parameters (e.g. sCr, estimated GFR) currently used for renal
function assessment. The frequency of AKI episodes is related to a poor prognosis, so a
MO467 Table1. Clinicopathological characteristics of the 51 subjects follow up is necessary after AKI episodes in order to prevent mortality and progression
of the disease.

Low Intermediate High P for


SNGFR SNGFR SNGFR trend
N 17 17 17
Age (years) 56.4611.9 56.869.2 57.8610.4 0.76 MO469 POSSIBLE MECHANISMS OF THE SARS-COV-2-INDUCED
BMI (kg/m2) 23.263.8 22.862.7 24.662.8 0.07 AKI PROGRESSION TO CKD: A FORWARD-LOOKING
mean blood pressure 89.4613.1 85.1612.6 91.7613.7 0.62 PERSPECTIVE

(mmHg) Fatemeh Masjedi1, Jamshid Roozbeh1, Zeinab Karimi1


Nglom (/kidney) 1,119,5236 708,4436 595,3546 <0.001 1
Shiraz University of Medical Sciences, Shiraz Nephro-Urology Research Center, Shiraz,
530,777 157,331 187,671 Iran
Renal plasma flow 381694 413687 4656123 0.051
BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID 19) was identified
(mL/min) in December 2020 and is still growing in most parts of the world. The wide range of
Renal blood flow 6366170 7016152 8046214 0.02 affected organs is likely based on the shared expression of the main severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) entry-receptor angiotensin-
(mL/min) converting enzyme 2 (ACE2). Therefore, broad distribution of ACE2 receptors in
Filtration fraction (%) 0.1860.06 0.1760.04 0.1960.04 0.46 various tissues play a key role in the multi-organ dysfunction and death due to
Pglo (mmHg) 52.764.8 52.363.9 56.663.9 0.02 COVID-19.
METHOD: International databases including PubMed, Embase, Web of Science,
Afferent arteriolar 4,8666 3,9696 3,7746 0.21 Scopus, and Cochrane Library Databases were used for search of articles by 30
pressure (dyne  s  cm-5) 2,344 2,150 1,905 December 2020. Keywords were nephropathy, COVID-19, coronavirus, renal injury,
Efferent arteriolar pressure 2,0856973 1,8726471 1,9896499 0.45 acute kidney injury, chronic kidney injury, and SARS-CoV-2 or a combination of them
in the titles/abstracts.
(dyne  s  cm-5) After the collection of related studies, Mendeley software was used to categorize and
eliminate the duplicate titles. Then, studies with inappropriate purposes were removed.
The selected studies were done on humans and published in English.
RESULTS: Due to high prevalence of acute kidney injury (AKI) in patients with
COVID-19, we summarize the molecular insights into viral infection mechanisms and
implications for AKI. Moreover, mechanisms of the AKI to chronic kidney disease
(CKD) transition such as relative contribution of immune cell response, fibroblasts
activation, endothelial dysfunction and subsequent hypoxia may contribute to
association of AKI with worse outcomes during this virus pandemic.

i294 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: We highlight the state of the knowledge on SARS-CoV-2-dependent
mechanisms for AKI and list the potential management options for prevention of AKI
worsening and the imminent possibility of CKD. Finally, we aim to provide a better
understanding of why Coronavirus induce AKI and, subsequently, progression to CKD
in the coming years and further discuss the acute as well as long-term renal
consequences.

MO469 Figure:Potential interrelationship between endothelial dysfunction, tubular


epithelial injury, interstitial inflammation, and fibrosis are likely to create a vicious
cycle that can lead to the progression of acute kidney injury to chronic kidney disease
(AKI to CKD) during COVID-19.

MO470 PATIROMER PHARMACOUTILIZATION IN REAL-WORLD


GERMAN CKD PATIENTS WITH MODERATELY TO SEVERELY
REDUCED EGFR

Roberto Pecoits-Filho1, Daniel Muenz1, KP McCullough1, Johannes Duttlinger2,


Viviane Calice-Siva3, Ziad Massy4,5, Brian Bieber1, John Golden6,
Bruce Robinson1, Danilo Fliser7, Liliana-Georgiana Wegmann6, Helmut Reichel2
1
Arbor Research Collaborative for Health, Ann Arbor, United States of America,
2
Wissenschaftliches Institut für Nephrologie, Düsseldorf, Germany, 3Pro-rim Foundation,
Joinville, Brazil, 4Div of Nephrol, Ambroise Paré Univ Hospital, APHP, Boulogne
Billancourt, France, 5INSERM U1018, CESP, UVSQ, and UPS, Vilejuif, France, 6Vifor
Pharma Group, Glattbrugg, Switzerland and 7Universit€ at des Saarlandes, Saarbrücken, MO471 USE OF SACUBITRIL/VALSARTAN IN PATIENTS WITH
Germany CHRONIC KIDNEY DISEASE: A NEW APPROACH

BACKGROUND AND AIMS: Hyperkalemia (HK) (serum K>5.0 mEq/L) is a chronic Rafael Del Pozo Alvarez1, Teresa V azquez1, Dolores Martınez Esteban1,
condition in patients with chronic kidney disease (CKD) associated with high Daniel Gaitan Roman2, Alicia Moreno Ortiz2, Domingo Hern andez1
1
morbidity and mortality, and it is a frequent reasons for renin angiotensin aldosterone Hospital Regional Universitario de M
alaga (Carlos de Haya), Nephrology Department,
inhibition (RAASi) discontinuation. Patiromer is a non-absorbed, sodium-free, Kþ Malaga, Spain and 2Hospital Regional Universitario de M
alaga (Carlos de Haya),
binder that has been shown to reduce serum Kþ in patients with HK, and thereby Cardiology Department, M alaga, Spain
enable RAASi therapy, which is supported by randomized trial evidence. The
description of patiromer utilization in patients with moderate to advanced CKD in the BACKGROUND AND AIMS: Neprilysin inhibition (NEPi) combined with a renin-
real-world setting in Europe is lacking. The objective of this analysis was to describe angiotensin system (RAS) blocker has been shown to play an important role among
predictors of patiromer initiation and time to discontinuation among CKD patients patients with heart failure (HF), whose main cause of inpatient admission is
using contemporary (April 2018-October 2020) data from German participants in congestion, reducing effectively HF hospitalization and cardiovascular death. These
CKD Outcomes and Practice Patterns Study (CKDopps). benefits stem from NEPi being a natriuresis and diuresis factor while RAS, which
METHOD: We identified 136 patiromer users (116 with matching K measurement) activates subsequently, staying blocked. Thanks to this, sacubitril/valsartan is a
during the observation period. Patients with eGFR <60ml/min/1.73m2 and a serum promising tool targeting patients with chronic kidney disease (CKD) and HF, which
potassium 4mEq/L who never initiated patiromer during the follow up were used as a frequently coexist and lead one to the other, challenging their management. There is
comparison. We used the most recent lab and drug use information available within evidence NEPi-RASb may be beneficial in this population but long-term outcome still
the 6-month period prior to baseline, which was defined as either first use of patiromer, lacks. The primary aim is to analyse potential improvement in HF and advanced CKD.
April 1, 2018, or entry into the PDOPPS study. The median time between the most Secondary, to evaluate the tolerability and safety profile in this population.
recent Kþ measurement and baseline was 45 days for non-patiromer users and 4 days METHOD: A prospective observational study, conducted from October 2016 to
for patiromer users. Logistic regression models were used to test associations between December 2020. Twenty-five patients were included meeting the following criteria:
patient factors and whether the patient was in the patiromer initiation group or the diagnosis of HF plus reduced left ventricular ejection fraction (LVEF) and New York
comparison group. Time on patiromer was estimated using a Kaplan-Meier curve, Heart Association (NYHA) functional class of II-IV with indication of sacubitril/
censoring for death, dialysis, transplantation, or loss of follow-up. valsartan, and CKD stages 3-4. All of them were followed periodically by a
RESULTS: Patiromer was prescribed to 2 patients in 11 clinics, one patient in 19 Nephrologist at our Department.
clinics, and zero patients in 57 clinics. Patients prescribed patiromer had lower eGFR RESULTS: The male:women ratio was 4:21, with a mean age of 73.2 6 5.9 years. All
(23.2 [15.8, 28.6] vs 36.9 [27.7, 46.3]ml/min) and higher serum K levels (5.6 [5.4, 6.1] patients had diagnosed hypertension, 32% type 2 diabetes, and 92% dyslipidemia. By
vs 4.6 [4.3, 5.0]ml/min). There were no major differences according to patiromer use in December 2020, seven patients had completed three-year follow-up, whereas 17 were
other demographic, clinical, and biochemical characteristics. Despite the differences in followed successfully through one year of treatment. Six patients died during the study
serum K, use of RAAS inhibitors was similar in patiromer users (83%) versus non- (50% due to cardiovascular event, none due to renal malfunction), another
users (80%). Thirty three percent of patiromer users were prescribed polystyrene discontinued treatment due to hypotension, and no patient started renal replacement
sulfonate (SPS) before patiromer initiation. In a multiple logistic regression models therapy. The median of the studied time of treatment was 31 months (IQR 23.5 - 35).
(including serum K, CKD stage, gender, age, prescription of RAASi, diabetes, coronary Cardiac and renal characteristics are listed in Table 1. At first year a significant
artery disease, heart failure), patiromer use was strongly associated more advanced improvement in LVEF was found (p=0.018). Although it is observed a tendency to this
CKD stage (independently of high serum K), with odds ratios of initiation >3 for CKD enhancement at second and third years, statistical analysis was not significative,
stage 4 or 5 versus CKD stage 3. Among new users, 90% of patients had active arguably because a limited sample. Nonetheless, the number of visits to the Emergency
prescription at 30 days and about one-half had active prescription at one year (Figure). Department (ED) regarding congestion symptoms were significantly reduced at these
CONCLUSION: The main predictors of Patiromer initiation were advanced CKD periods. More interesting, kidney function improved at first year when comparing
stage and hyperkalemia. Treatment decisions did not appear to be based on other serum creatinine (p=0.043) and eGFR (p=0.008), and this improvement stays in the
patient or clinical characteristics. Patiromer was often prescribed to patients already long term at second and third years (p=0.019, p=0.046 respectively).
receiving alternative HK treatment (SPS), suggesting use for chronic hyperkalemia There were no significant changes in potassium nor in blood pressure, still urine
rather than response to acute event. Further analysis with a larger population and protein excretion was significantly higher at third year (p=0.043), understandable
measurements of Kþ before and after patiromer initiation may improve the possibly due to hyperfiltration mechanisms and diabetic nephropathy progression.
understanding of its pharmacoutilization in moderate to advanced CKD. CONCLUSION: Sacubitril/valsartan showed a long-term improvement in cardiac and
kidney function, explaining a reduction in the number of visits to ED due to congestion
and eventually a better quality of life. Besides, the improvement in kidney function
cannot be totally understood in the context of enhanced LVEF at first year as this effect
fades with time. Future research should explore this line.

10.1093/ndt/gfab090 | i295
Abstracts Nephrology Dialysis Transplantation

RESULTS: Compared to controls, we found significantly higher values of all studied


markers in CKD patients (stage 1 and stage 2): BTP, TIMP-1, IL-6, pro-BNP, and
cfDNA.
mean (SD) In CKD patients, GFR was negatively correlated with circulating levels of pro-BNP (r =
-0.610, P = 0.004, n = 20) and cfDNA (r = -0.408, P = 0.028, n = 29); and,
Baseline,
First Second Third microalbuminuria was positively correlated with circulating levels of BTP (r = 0.465, P
n=22 year, year, year, = 0.013, n = 28). The biomarker cfDNA was positively correlated with TIMP-1 (r =
0.445, P = 0.16, n = 29) , a marker of tubulointerstitial injury, and with IL-6 (r = 0.670,
n=17 n=13 n=7 P < 0.001, n = 29), a marker of inflammation.
Serum creatinine, 2.20 (0.56) 1.85 (0.46)* 1.68 (0.44) 1.87 (0.31) All patients presented at least two of the studied biomarkers with higher values than
mg/dL the median value presented by controls. Of all studied biomarkers, BTP was the one
that was most altered in patients (86.2% presented higher values than the highest value
eGFR, mL/min/ 28.9 (8.1) 35.8 (9.4)* 39.8 (12.0)* 36.1 (7.3)* presented by controls).
1.73m2 CONCLUSION: Our results suggest that the studied biomarkers are sensitive to the
Potassium, mEq/L 4.61 (0.59) 4.90 (0.64) 4.87 (0.64) 4.94 (0.43) primary response to renal injury, being significantly elevated in the earlier stages of
CKD, particularly BTP. Pro-BNP and cfDNA correlate well with disease severity
Urine protein: 312 (530) 237 (219) 591 (805) 1009 (983)* assessed by GFR.
creatinine, mg/g The use of a panel comprising several biomarkers, related with different
pathophysiological mechanisms underlying CKD initiation and progression, may
Systolic blood 129.1 (20.2) 124.2 (17.3) 123.0 (18.1) 128.0 (13.0) increase the potential to detect patients at risk, when compared with the evaluation of
pressure, mmHg each biomarker alone.
Diastolic blood 70.2 (14.9) 72.4 (11.0) 70.4 (11.6) 76.0 (6.5) Further validation for the use of these new potential biomarkers requires larger studies
with standardized analytical methodologies.
pressure, mmHg Acknowledgments: This work was supported by Applied Molecular Biosciences Unit
LVEF, % 36.40 (8.87) 39.64 (10.20)* 38.84 (8.78) 45.33 (14.98) (UCIBIO) and financed by FEDER COMPETE2020 funds UIDB/04378/2020 and
Visits to ED 1.48 (1.97) 0.50 (1.42) 0.28 (1.06)* 0.16 (0.40)* UIDP/04539/2020 (CIBB); by POCI-01-0145-FEDER-007440; by FCT doctoral grant
SFRH/BD/145939/2019; by funds from Portugal Regional Coordination and
Development Commissions (Norte-01-0145-FEDER-000024).
*marks p-values under 0.05, comparing characteristic’s value to the
baseline. Non-parametric tests were used (missing cases excluded by
test). MO473 INTERACTION OF SCLEROSTIN AND OSTEOPROTHERIN IN
THE DEVELOPMENT OF VASCULAR CALCIFICATIONS AT
STAGE 3-5 OF CHRONIC KIDNEY DISEASE

Fatima Dzgoeva1
1
MO472 A PRELIMINARY STUDY OF POTENTIAL BIOMARKERS FOR North Ossetian State Medical Academy of the Ministry of Health of the Russian
EARLY DIAGNOSIS IN CHRONIC KIDNEY DISEASE Federation, Department of Internal Medicine @5, fflºalbradraÅ, Russia

Irina Lousa1, Maria Jo~ ao Valente1, Susana Rocha2, Sofia D. Viana3,4, BACKGROUND AND AIMS: BACKGROUND AND AIMS: .: Vascular calcification
Ine^s Preguiça3, Filipe Mira5, Rui Nogueira5, Susana Coimbra1,6, (VC) due to bone-mineral metabolism disorders is a predictor of high cardiovascular
Cristina Catarino1, Petronila Rocha-Pereira7, Elsa Bronze-da-Rocha1, Maria do mortality in patients with late-stage chronic kidney disease (CKD) . The established
Sameiro Faria1,8, Rui Alves5, Idalina Beira ~o9, Flavio Reis3, Luıs Belo1, bone-vascular axis in CKD, which relates to interactions between changes in the bone
Alice Santos-Silva1 and vascular systems that have similar mechanisms, allows bone metabolism inhibitors
1
UCIBIO, REQUIMTE, Laborat orio de Bioquımica, Departamento de Ci^encias Biol ogicas, to act as potential risk factors for VC. Morphogenetic protein osteoprotegerin (OPG)
Faculdade de Farm acia da Universidade do Porto, Porto, Portugal, 2LAQV, REQUIMTE, and glycoprotein sclerostin are opposite inhibitors of bone metabolism: OPG inhibits
Laboratorio de Quımica Aplicada, Departamento de Ci^encias Quımicas, Faculdade de osteoclastogenesis, sclerostin has an inhibitory effect on osteoblastogenesis. Although
Farmacia da Universidade do Porto, Porto, Portugal, 3iCBR, CIBB, Faculdade de both proteins are recognized as high-risk factors for remodeling the heart and large
Medicina da Universidade de Coimbra, Coimbra, Portugal, 4ESTESC-Coimbra Health arteries in patients with CKD, the mechanisms and possibilities for correcting these
School, Pharmacy, Polytechnic Institute of Coimbra, Coimbra, Portugal, 5Centro changes are not fully clear.
Hospitalar e Universitario de Coimbra, Coimbra, Portugal, 6Instituto de Investigaç~ao e of the study was to investigate the mechanisms of the relationship between OPG and
Formaç~ao Avançada em Ci^encias e Tecnologias da Sa ude (IINFACTS), Cooperativa de sclerostin in the development of cardiovascular complications due to calcification of
Ensino Superior Politécnico e Universitario (CESPU), Gandra, Paredes, Portugal, 7Centro the aorta and large arteries in the late stages of CKD.
de Investigaç~ao em Ci^encias da Sa ude, Universidade da Beira Interior, Covilh~
a, METHOD: METHOD: The cross-sectional study included 105 patients with stage 3-5
Portugal, 8Clınica de Hemodi alise de Felgueiras, Felgueiras, Portugal and 9Centro CKD [49 men; 64.0 (23.0-76.0)years]. The glomerular filtration rate determined using
Hospitalar Universitario do Porto, Porto, Portugal the CKD-EPI equation was 38.4 (8.6–92.3) ml / min / 1.73 m2. The general clinical
examination included assessment of hematopoiesis (hemoglobin, hematocrit, ferritin
and transferrin), determination of total protein and albumin levels, cholesterol,
BACKGROUND AND AIMS: The conventionally used biomarkers for chronic
electrolytes (sodium, potassium) in the blood, and indicators of nitrogen metabolism
kidney disease (CKD) diagnosis are not very sensitive for early diagnosis. Their values
(creatinine, urea). Parameters of bone-mineral metabolism – parathyroid hormone
become clinically significant only when kidney damage is advanced, and a substantial
(PTH), calcium, phosphorus, alkaline phosphatase of blood serum-were evaluated. The
filtration capacity has been lost. The reliance on these biomarkers may result in a long-
level of morphogenetic protein OPG and glycoprotein sclerostin was determined using
time lapse in diagnosis, compromising the earlier use of successful therapeutic
commercial ELISA kit from Biomedica (Austria) by enzyme immunoassay. The
interventions to prevent CKD progression and reduce the risk of other common
morphofunctional features of the aorta and large arteries were studied by duplex
comorbidities.
scanning using the Doppler effect. We determined the peak systolic velocity of blood
The study of earlier and more sensitive biomarkers for CKD diagnosis is an important
flow in the aortic arch (Vps-peak systolic velocity) , which indirectly indicates the state
medical need. Potentially new biomarkers reflecting different pathophysiological
of the aortic wall and its lumen. Echocardiography with Doppler imaging was
processes underlying CKD, such as changes in renal function, tubulointerstitial injury,
performed on the "ALOKA 4000" device. The LV myocardial mass index (LVMI), LV
inflammation and fibrosis, have been proposed. The use of a panel of biomarkers is
hypertrophy variants, LV systolic and diastolic function were determined.
likely to be synergetic in detecting CKD, since there are several different mechanisms
RESULTS: Cardiovascular damage, which manifests itself in the form of various
by which CKD can initiate.
variants of left ventricular hypertrophy, aortic rigidity, arteriosclerosis and vascular
Our aim was to identify markers of renal damage/dysfunction and evaluate their
calcification, and directly correlated with the severity of renal failure, was detected in
sensitivity for CKD detection, in patients at the earlier stages of the disease, stages 1
86% of the examined patients with stage 3-5 CKD. The level of OPG and sclerostin in
and 2.
the blood serum increased with the progression of renal failure from the 3rd to the 5th.
METHOD: This study included 32 healthy controls and 29 CKD patients at stages 1
The main associations with Vps changes were high OPG levels [OR = 2.39 95%
and 2, categorized according to the KDIGO guidelines, using the CKD-EPI equation
confidence interval (95% CI) (1.34–4.86) for levels ranging from 5.98 to 9.26 pmol / L
based on serum creatinine to estimate the glomerular filtration rate (GFR). Causes of
and OR = 5.54 95% CI (2.64–13.5) for levels 9.26 pmol / L; P <0.0001] and high
CKD in the studied patients were diabetes mellitus (n = 19), polycystic kidney disease
sclerostin levels [OR = 2.64 95% CI (1.42–5.16) for levels ranging from 0.744 to 1.211
(n = 1) and of unknown cause (n = 7) or other (n = 2).
ng / ml and OR = 3.69 95% CI (1.76–7.31) for a level 1.211 ng / ml; P = 0.0001].
Circulating levels of creatinine and b-trace protein (BTP), as markers of renal function;
Thus, the logistic regression model showed that the risk of aortic calcification was
interleukin 6 (IL-6), as a marker of inflammation; tissue inhibitor metalloproteinase 1
significantly increased when both OPG (5.98 pmol / L) and sclerostin (0.744 ng /
(TIMP 1), as a marker of tubulointerstitial injury; pro B-type natriuretic peptide
ml) levels were high [ uncorrected model: OR = 11.93 (4.54–25.2); P <0.0001; on the
(proBNP), as a marker of cardio-renal dysfunction; and cell-free DNA (cfDNA), as a
marker of cellular damage, were evaluated.

i296 | Abstracts
Nephrology Dialysis Transplantation Abstracts
model adjusted for generally recognized cardiovascular disease risk factors: OR= 5.55 higher values in the clinical group than in the control group: BNP (p<0.001), cystatin
(1.43–1914); P = 0.02]. C (p<0.001). Figures 1 and 2 shows flowcharts of the used inputs and outputs and how
CONCLUSION: The results suggest that bone metabolism inhibitors, OPG and they are implemented in the ANFIS networks. There are two ANFIS networks since
sclerostin, are independently associated with aortic calcification with potential additive there are two outputs. ANFIS networks shold determine which input has the strongest
effects in patients with stage 3-5 CKD. The risk of vascular calcification was influence on the given outputs nased on root mean squre errors or prediciton
significantly increased when OPG and sclerostin levels were high accuracy.Based on the training error (trn) one can determine the inputs influence on
the given output. Checking error (chk) is used to track the results validity. In other
words the checking errors could track training error. It was found that BNP (pg/mL)
has the most influence on the - EPI creatinine-cystatin C formula. Serum sodium (Na)
MO474 PCSK9 LEVELS AND MARKERS OF INFLAMMATION,
has the most influence on the ejection fraction (EF).
OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION IN A
POPULATION OF NON-DIALYSIS CHRONIC KIDNEY DISEASE
PATIENTS: IS THERE AN ASSOCIATION?

Evangelia Ntounousi1, Konstantinos Tellis2, Paraskevi Pavlakou3, Anila Duni1,


Vassilios Liakopoulos4, Aikaterini Papagianni5, Alexandros Tselepis2
1
University of Ioannina, Department of Nephrology, Ioannina, Greece, 2University of
Ioannina, Atherothrombosis Research Centre/Laboratory of Biochemistry, Department
of Chemistry, IOANNINA,, 3University of Patras, Department of Nephrology, Patras,
Greece, 4School of Medicine, Aristotle University of Thessaloniki, Division of Nephrology
and Hypertension, Thessaloniki, Greece and 5Aristotle University of Thessaloniki,
Department of Nephrology, Thessaloniki, Greece

BACKGROUND AND AIMS: Proprotein convertase subtilisin / kexin 9 (PCSK9)


plays an important role in lipid metabolism while available literature regarding its
involvement in the pathogenesis of atherosclerosis and in the expression of genes MO475 Figure 1: ANFIS prediction of ejection fraction (EF) (%)
associated with apoptosis and inflammation is constantly increasing. Patients with
chronic kidney disease (CKD) experience disproportionately increased cardiovascular
morbidity and mortality due to dyslipidemia, accelerated atherosclerosis,
inflammation, oxidative stress and other risk factors. In the present cross-sectional
study, we investigated the possible association of serum PCSK9 levels with markers of
inflammation, oxidative stress and endothelial damage in patients with CKD.
METHOD: Ninety-two patients with CKD stage II-IV (eGRF CKD-EPI 47.3 625.7ml/
min/1,73m2, mean age 66 years, 51 men) were included. Plasma PCSK9 levels were
correlated with comorbidities (arterial hypertension; diabetes mellitus, history of
cardiovascular disease), renal function indices (eGFR, proteinuria – UPR/24h), lipid
parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp (a), APO-A1, APO-
B), as well as soluble biomarkers of inflammation, oxidative stress and endothelial
damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-a, sICAM-1,
sVCAM-1).
RESULTS: The mean plasma value of PCSK9 was 278.1ng/ml. PCSK9 levels showed
direct correlation with serum triglycerides (p = 0.03), Lp(a) (p = 0.01), and sICAM-1
levels (p = 0.03). There was no significant correlation between PCSK9 levels and MO475 Figure 2: ANFIS prediction of EPI cistatin C (ml/min/1.73 m2)
indices of renal function, other lipid profile parameters, inflammatory markers or co-
morbidities. Multiple regression analysis showed a significant effect of the Lp(a) on
PCSK9 levels, for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: CONCLUSION: Serum sodium-potassium disturbances are associated with advanced
0.935 - 5.228, p=0.006). At the same time, patients receiving statins are expected to heart failure and reduced prognosis. ANFIS is suitable for nonlinear systems with
have on average 63.8ng/ml higher PCSK9 values compared to patients not receiving highly redundant data. Although there are encouraging advances around this unsolved
statins (95% CI: 14.6 - 113.5 p=0.012). clinical problem, further investigation should consider the progressive inclusion of
CONCLUSION: Plasma levels of PCSK9 in non-dialysis CKD patients are correlated patients with advanced renal impairment to allow a better understanding of
with endothelial dysfunction and lipid metabolism parameters. Statin intake increases cardiorenal syndrome. The result of our research shows that if the values of BNP and
PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated Na significantly deviate from normal values, it is expected that EPI creatinine-cystatin
with the severity of kidney disease. Major prospective studies are necessary to C formula and EF indicate impaired organ function and that such patients are
investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD candidates for hospital treatment.

MO475 PREDICTION OF CARDIORENAL SYNDROME BY ARTIFITIAL MO476 EFFECT OF ESTROGEN DEFICIENCY ON THE STATE OF
INTELLIGENCE BONE AND MINERAL METABOLISM IN WOMEN WITH STAGE
III-V CHRONIC KIDNEY DISEASE
Danijela Tasic1, Katarina Djordjevic2, Slobodanka Galovic3, Milos Milovancevic4,
Gordana Kocic5, Sonja Radenkovic5, Zorica Dimitrijevic1, Nina Jancic1, Bff ffKfffflff1, Fatima Dzgoeva2
Tamara Vrecic1, Andriana Jovanovic1 1
North Ossetian State Medical Academy of the Ministry of Health of the Russian
1
University of Nis Faculty of medicine, CC Clinic of nephrology, Nis, Serbia, 2Belgrade, Federation, Raaelha arełehcnda b ubyerjºjubb @1, fflºalbradraÅ, Russia and
2

University of Belgrade, Faculty of Physics Belgrade, Belgrade, Serbia, 3Belgrade, ,,VINCA" North Ossetian State Medical Academy of the Ministry of Health of the Russian
Institute of Nuclear Sciences - National Institute of the Republic of Serbia, Belgrade, Federation, Department of Internal Medicine @5, fflºalbradraÅ, Russia
Serbia, 4Nis, University of Nis, Faculty of Mechanical Engineering, Nis, Serbia and
5
University of Nis, Faculty of medicine, Nis, Serbia BACKGROUND AND AIMS: Clinical studies in recent years have revealed a close
relationship between hormonal disorders in women with CKD and the duration and
BACKGROUND AND AIMS: Potassium excretion is a secretory phenomenon and quality of life, bone mineral and related disorders of the cardiovascular system. In
levels are often abnormal in patients with heart failure. An abnormal sodium serum individual studies, there is a tendency to improve the indicators of mineral and bone
level is the most common electrolyte disorder and independent predictor of metabolism and the state of the cardiovascular system in hormonal or other drug-
readmission for heart failure and post discharge death. Since different factors could induced correction of hormonal dysfunctions in women.
affect balance of Potassium in Cardiorenal syndrome, in this study soft computing was - Aims to study the effect of estrogen deficiency on bone and mineral metabolism in a
used to predict most important factors for the detection of the severity of systolic heart population of women suffering from CKD stages III-V
failure by ejection fraction (EF), and a subclinical phase of the cardiorenal disease by METHOD: The study included 52 women who met the clinical criteria for the possible
EPI creatinine-cystatin C formula (Chronic Kidney Disease Epidemiology appointment of hormone therapy (both replacement and combined oral
Collaboration). contraceptives) for the purpose of a detailed examination of the state of their
METHOD: The balance of potassium in Cardiorenal syndrome is analyzed by soft cardiovascular system and bone-mineral metabolism in dynamics (with an interval of
computing approach namely adaptive neuro fuzzy inference system or ANFIS. 10-12 months) in order to assess the degree of influence of estrogen-deficient
RESULTS: The clinical group consisted of 79 patients, 40 of whom were men (50.63%) conditions on the course of such common complications of CKD as cardiovascular
and 39 of whom were women (49.37%), in the average age of 70.72 6 9.26 years. After diseases and pathology of the bone system. The age of the patients ranged from 26 to
comparing serum electrolytes (Naþ, Kþ) did not differ significantly in the clinical 61 years (mean age-50.6569.17 years). The duration of CPN averaged 77.02 months..
group from those of the control group. The tested biomarkers showed significantly The stages of CKD were determined according to the K/DOQI (2012) criteria, and the

10.1093/ndt/gfab090 | i297
Abstracts Nephrology Dialysis Transplantation

glomerular filtration rate was calculated using the CKD-EPI formula. The following MO478 FACTORS ASSOCIATED IN RAPID PROGRESSION OF
parameters were evaluated: the concentration of sclerostin, osteoprotegerin, fibroblast CHRONIC KIDNEY DISEASE: A MULTICENTRE,
growth factor 23 (FGF-23), parathyroid hormone, total calcium, phosphorus, alkaline RETROSPECTIVE COHORT STUDY
phosphatase, creatinine, and urea. Follicle-stimulating hormone( FSH), luteinizing
hormone(LH) and estradiol were determined by solid-phase chemiluminescent Fei Yee Lee1,2, Farida Islahudin1, Hin-Seng Wong2,3, Sunita Bavanandan4, Nurul
enzyme immunoassay (commercial sets of Alkor-Bio, St. Petersburg). Serum Ain Mohd Tahir1, Mohd Makmor-Bakry1
1
concentrations of sclerostin, sRANKL (soluble RANKL), and osteoprotegerin were Universiti Kebangsaan Malaysia, Faculty of Pharmacy, Malaysia, 2Ministry of Health
determined by the enzyme-linked immunoassay using Biomedica gruppe test systems. Malaysia, Clinical Research Centre, Malaysia, 3Selayang Hospital, Ministry of Health
RESULTS: The examined patients showed hormonal dysfunctions (82%), Malaysia, Department of Nephrology, Malaysia and 4Kuala Lumpur Hospital, Ministry
accompanied by changes in the content of sex hormones: the concentration of estradiol of Health Malaysia, Department of Nephrology, Malaysia
was below normal: 123.4672.5 pmol/l and 150.0-450.0 pmol/l, respectively, in patients
and in normal (p<0.01), which confirms the presence of estrogen deficiency in the BACKGROUND AND AIMS: Identification of risk factors linked with rapid chronic
examined patients . Concentrations of FSH and LH exceeded the norm in the group of kidney disease (CKD) progression is beneficial in shaping preventative and
patients as a whole: 91.6646.1 IU/l and 3.0-8.0 IU/l FSH content in patients and management strategies for maximal benefits out of the existing resources and capacity
normal; 51.8632.1 IU/l and 3.0-10.0 IU/l LH in patients and normal. In the group of of care. To this end, the study aims to investigate the factors associated with rapid
patients as a whole, an increase in the level of sclerostin to 28.5 6 9.2 pmol/l was progression of CKD in the Asian population.
detected ( norm 12633.45 pmol/l), an increase in the level of osteoprotegerin to METHOD: This multi-centre, retrospective cohort study recruited adult CKD patients
6.960.4 pmol/l (norm 2.7 pmol/l). Positive and negative correlations were found of 18 years in two tertiary hospitals with a history of at least two years of Nephrology
between the levels of morphogenetic proteins, sex hormones, and characteristic CKD clinic follow-up and with index eGFR, defined by the first identified estimated
parameters of hormonal dysfunctions glomerular filtration rate (eGFR) during the study period, of 30 ml/min/1.73 m2.
CONCLUSION: Pre-and postmenopausal women with CKD have hormonal eGFR was calculated via CKD-EPI equation. Patients with less than three nephrology
dysfunctions, including disorders of sexual and reproductive function, menstrual cycle, CKD clinic visits and outpatient eGFR values during the study period were excluded.
decreased fertility, increased risks of miscarriage at its onset, the basis of hormonal Demographic data, clinical information, laboratory data and medication history were
dysfunctions is the absence of LH peaks and changes in the concentration of estradiol collected from the electronic medical records from January 2018 to March 2020.
depending on the phase of the cycle, hypoestrogenemia. It is assumed that there is a Annual slopes of eGFR change were quantified using linear regression of outpatient,
pathogenetic link between hormonal dysfunctions and disorders in the system of bone non-emergency eGFR values, with a decline of >5ml/min/1.73m2/year defined as rapid
metabolism regulatory proteins in patients with CKD. CKD progression. Multiple logistic regression was used to identify factors associated
with rapid CKD progression, in which variables with p  0.05 were considered as
factors associated with rapid progression of CKD, followed by the examination of
MO477 SERUM C-REACTIVE PROTEIN AND PROCALCITONIN multicollinearity and correlation between the factors, and the use of the Hosmer-
LEVELS IN HEMODIALYSIS AND INTRADIALYTIC Lemeshow goodness-of-fit test, classification tables and area under the receiving
ALTERATIONS operator characteristic (ROC) curve. Statistical analysis was performed using SPSS
Version 23.
Makrouhi Sonikian1, Aggeliki Barbatsi1, Eugenia Karakou3, Theodoros Chiras1, RESULTS: Among the 357 patients, 199 (55.7%) were men, median age was 61 years,
Jacob Skarakis5, Pagona Sklapani6, Nikolaos Trakas3 while 105 (29.4%) patients had rapid CKD progression. The factors associated with
1 rapid CKD progression after adjusting for possible confounding factors were Category
Sismanoglio General Hospital, Athens, Nephrology Department, Marousi, Greece,
3 A3 albuminuria (adjusted Odds Ratio [aOR] 2.217, 95% confidence interval [CI]:
Sismanoglio General Hospital, Athens, Biochemistry Department, Marousi, Greece,
5 1.241, 3.961), and adjustments to antihypertensives (aOR 1.158, 95% CI: 1.034, 1.296).
DEMO S.A,Pharmaceutical Industry, Research and Development Department, Kryoneri,
Multicollinearity and interaction terms were not found, while the Hosmer-Lemeshow
Greece and 6Mitera-Ygeia Hospital, Department of Cytology, Marousi, Greece
test (p=0.675), classification table (overall correctly classified percentage =69.8%) and
area under the ROC curve (62.9%) were supportive of the model’s fitness.
INTRODUCTION: C-reactive protein (CRP) and procalcitonin (PCT) are widely CONCLUSION: Rapid CKD progression was observed among one-third of CKD
used as markers of inflammation and infection in general population and in chronic patients in our practice setting. Category A3 albuminuria and adjustment to
hemodialysis (HD) as well. However, in dialysis (D) patients, serum CRP and PCT antihypertensives were factors of rapid CKD progression. Maladaptation from
levels may be elevated even in the absence of inflammatory or infectious disease and adjustments to antihypertensives might cause medication-related problems that might
diagnostic process is a challenge in such cases. We studied HD patients’ laboratory accelerate the progression of CKD. An alternative explanation is that adjustments were
profile concerning CRP and PCT. necessary because of poorly controlled hypertension which is a well-known risk factor
SUBJECTS AND METHODS: We studied 25 stable HD patients, M/F=22/3, aged for progressive CKD. Furthermore, with worsening kidney failure, hypertension
68(44-89) years, dialyzed thrice weekly for 55(6-274) months with a dialysate flow rate becomes more difficult to control hence also necessitating medication adjustments.
of 700 ml/min, with a residual daily diuresis less than 200 ml, Kt/V values of 1,4460,3 The findings could guide identification of CKD patients for enhanced pharmaceutical
and no signs of infection. Patients were classified in two groups. Group A included 10 care and monitoring, especially when antihypertensives are adjusted, and during
patients on pre-dilution online hemodiafiltration (HDF). Group B consisted of 15 transition from hospitalisation to outpatient care.
patients on conventional HD with low-flux polysulfone membrane. Twenty healthy
subjects formed a control group C. Serum CRP and PCT levels were measured in
duplicate in A and B groups before and at the end of mid-week dialysis sessions and
also in C group. MO479 BLOOD PRESSURE CONTROL AND OUTCOMES IN DIABETIC
RESULTS: Pre-D serum CRP values in the total of patients were higher than those in RENAL DISEASE : EVIDENCE FROM A TUNISIAN COHORT
healthy controls (10,89619,29 vs 2,5461,28 mg/L-p=0,004). Compared with group C,
pre-D CRP values were higher only in B group (15,98624,54 mg/L-p=0,001) but not in Boukhtioua Mariem1, Mami Ikram1, Tlili Syrine2, Ghabi Hiba2, Hela Jbali2,
A group (4,0963,33 mg/L-p=NS). There was a significant difference in pre-D serum Lilia Ben Fatma2, Karim Zouaghi2, Fethi Ben Hmida3
1
CRP values between A and B groups (p=0,028). At the end of D session serum CRP Rabta Hospital, Nephrology, dialysis and transplantation department, Tunis, Tunisia,
2
values showed a tendency to increase in both groups A (5,1664,81 mg/L) and B Rabta Hospital, Nephrology, dialysis and transplantation department, Tunisia and
3
(17,00627,00 mg/L) but differences were not significant. Charles Nicolle Hospital, Internal Medicine M8 department, Tunisia
Pre-D serum PCT values in the total of patients were higher than those in healthy
controls (0,8260,9 vs 0,2960,55 ng/ml-p<0,001). Compared with group C, pre-D BACKGROUND AND AIMS: Diabetic nephropathy (DN) is associated with a high
PCT values were higher in both A group (0,5260,15 ng/ml-p<0,001) and B group incidence of cardiovascular morbidity and mortality. The relationship between
(1,0161,13 ng/ml-p=0,006). There was no significant difference in pre-D serum PCT hypertension and diabetic nephropathy is complex and blood pressure (BP) control is
values between A and B groups (p=0,261). At the end of D session serum PCT values an important management strategy in the prevention of its onset and progression .The
decreased in A group (0,3260,11 ng/ml-p<0,001) and increased in B group aim of this study was to determine whether blood pressure control delays the
(1,1261,21 ng/ml-p=0,014). progression of DN and prevents macrovascular complications in patients with diabetes
CONCLUSIONS: In patients on both conventional low-flux HD and online HDF pre- mellitus.
D serum CRP and PCT levels were higher than those in healthy subjects. Dialysis METHOD: Hypertension guidelines advocate treating systolic blood pressure to less
modality and membrane flux did not affect post-D serum CRP values, but post-PCT than 130 mm Hg and diastolic blood pressure to less than 80 mmHg for patients with
values decreased in online HDF. PCT usefulness might be limited in dialysis with high- diabetes mellitus and overt nephropathy.The relationship between blood pressure and
flux membranes. Cut-off values have to be established for both markers to eliminate progression of nephropathy was studied in 120 diabetic and hypertensive patients with
confusion in diagnosis of inflammatory and infectious diseases in hemodialyzed established diabetic nephropathy. We divided hypertensive patients with stage 1 to 3
patients. CKD already treated with antihypertensive therapy into 2 groups: those with BP <
130/80 mmHg were designated as Group A (n=66) and those with BP> 130/80 as
Group B (n=54). Serum creatinine level as well as urinary albumin excretion were
measured at 3 months,6 months, one year,2 years and at last visit during follow-up.The
GFR was calculated using the Modification of diet in renal disease formula.The kidney
disease outcome was defined as time to end-stage renal disease. The cardiovascular
outcome was defined as time to myocardial infarction, stroke,ischemic stroke,
hospitalization for heart failure, or revascularization.

i298 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: During the mean follow up period of 33,8 6 11,7 months, the primary end patients with normal birth weight was 65.23 (31.23-84.73) ml/min/1.73m2, among
point of end-stage renal disease occured in 9 patients (7 patients in Group B versus 2 LBW – 68.93 (24.59-98.9) ml/min/1.73m2, so there were no differences in kidney
patients in groupe A) while 11 hypertensive patient experienced a cardiovascular function between the two groups (p=0.64). The median (IQR) level of serum FGF-23 in
event. The decline rate in GFR was significantly more important in groupe B patients with normal birth weight was 1.75 (0.68- 2.5) pmol/l, in LBW children was
(p<0,05). However, little difference existed between the two groups in urinary albumin 1.85 (0.78 -3.1) pmol/l. Analysis of serum level of FGF-23 in relation to weight at birth
excretion. Blood pressure control was not associated with improved cardiovascular revealed no statistical differences in patients with LBW and those with normal birth
outcomes when comparing the two groups. weight (p=0.719), and the Spearman rank correlation was insignificant as well (r=-0.08,
CONCLUSION: The results of our study indicate that an uncontrolled hypertension is p=0.560).
associated with a rapid progression of kidney impairment in diabetic patients with CONCLUSION: FGF-23 is an important biomarker of CKD-MBD. FGF-23 does not
overt nephropathy but no relationship with the incidence of cradiovascular events was depend on the birth weight although LBW is considered as a risk factor for CKD.
seen in our population. However, further investigations and studies in this area are needed to make the right
conclusions regarding the association between this bone biomarker and birth weight.

MO480 FGF-23 AND LOW BIRTH WEIGHT: IS THERE ANY


ASSOCIATION?

Altynay Balmukhanova1, Kairat Kabulbayev2 , Dinara Batyrbayeva3,


Abay Shepetov 2
1
Asfendiyarov Kazakh National Medical University, Nephrology, Almaty, Kazakhstan
and 3Asfendiyarov Kazakh National Medical University, Scientific clinical and diagnostic
laboratory, Almaty, Kazakhstan

BACKGROUND AND AIMS: According to Barker’s theory and Brenner’s hypothesis,


persons were born with low birth weight (LBW) have a higher risk of CKD due to low
nephron number. Also, it is well known that mineral-bone disorder (MBD) is one of
the most serious complications of CKD. Views on the pathogenesis of CKD-MBD have
changed considerably since Fibroblast growth factor 23 (FGF-23) was discovered. It is
thought that FGF-23 increases as the nephron mass reduces. Therefore, we aimed to
determine if there is an association between LBW and FGF-23.
METHOD: We conducted a cross-sectional study on 56 children with CKD stages 1-4.
There were approximately equal numbers of participants in each stage. The mean age
was 8.9 64.9 years old. We measured the concentration of FGF-23 (C-terminal) in
serum by a sandwich enzyme-linked immunosorbent assay (ELISA) kit (Biomedica
Medizinprodukte GmbH, Austria). The exclusion criteria: tubulopathy, active
inflammatory, infectious, oncological and bone diseases, renal transplant, as well as
taking steroids, calcium, and vitamin D. The informed consent was obtained from the
parents. The study was conducted in accordance with the Declaration of Helsinki and
approved by the Local Ethical Committee. FGF-23 concentration more than 1.5 pmol/l
was considered as abnormal. Statistical analysis was performed using GraphPad Prism
9.0.0 (San Diego, USA)
RESULTS: Mineral-bone disorder was diagnosed as CKD complication in 20 (35.7%)
children. LBW was revealed in 14 (25%) patients. The median (IQR) eGFR among

10.1093/ndt/gfab090 | i299
Nephrology Dialysis Transplantation 36 (Supplement 1): i300–i324, 2021
10.1093/ndt/gfab087

MO482 URINE METABOLITE LEVELS OF CKD PATIENTS ARE


CKD. CLINICAL EPIDEMIOLOGY ASSOCIATED WITH ADVERSE KIDNEY OUTCOMES AND
MORTALITY*

Inga Steinbrenner1, Ulla T. Schultheiß1,2, Fruzsina Kinga Kotsis1,2,


MO481 KIDNEY FUNCTION MEASURES AND THE RISK OF CANCER
Pascal Schlosser1, Helena Stockmann3, Robert P. Mohney4, Matthias Schmid5,
INCIDENCE, CANCER DEATH AND ALL-CAUSE MORTALITY*
Peter Oefner6, Kai-Uwe Eckardt3,7, Anna Köttgen1, Peggy Sekula1
1
Jennifer Lees1, Frederick Ho1, Solange Parra-Soto1,2, Carlos Celis-Morales1,2, Faculty of Medicine and Medical Center – University of Freiburg, Institute of Genetic
Paul Welsh1, Michael Sullivan1, Bhautesh Jani1, Naveed Sattar1, Jill Pell2, Epidemiology, Freiburg, Germany, 2Faculty of Medicine and Medical Center – University
Angela Webster3, Patrick Mark1 of Freiburg, Department of Medicine IV – Nephrology and Primary Care, Freiburg,
1 Germany, 3Charité - Universit€atsmedizin Berlin, Department of Nephrology and Medical
University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow,
Intensive Care, Berlin, Germany, 4Metabolon Inc., Durham, NC, United States of
United Kingdom, 2University of Glasgow, Institute of Health and Wellbeing, Glasgow, 5
America, University Hospital Bonn, Department of Medical Biometry, Informatics and
United Kingdom and 3The University of Sydney, Sydney School of Public Health,
Epidemiology, Bonn, Germany, 6University of Regensburg, Institute of Functional
Camperdown, Australia
Genomics, Regensburg, Germany and 7University Hospital Erlangen, Friedrich-
Alexander-Universit€ at Erlangen-Nürnberg, Department of Nephrology and
BACKGROUND AND AIMS: Cancer is more common in end-stage kidney disease Hypertension, Erlangen, Germany
and in patients on dialysis. We hypothesise that chronic kidney disease (CKD) across
the spectrum of disease is associated with increased risk of cancer incidence and cancer
BACKGROUND AND AIMS: Chronic kidney disease (CKD) affects >10% of the
death and that this risk is independent of known risk factors for cancer. Furthermore,
adult population worldwide and is associated with increased risk of kidney failure (KF)
we assess if risk of cancer incidence (overall and cancer subtypes), cancer death and all-
and mortality. Mechanisms underlying the variable course of disease progression are
cause mortality is more strongly associated with kidney function-estimating equations
incompletely understood. This study aimed at identifying novel metabolite biomarkers
incorporating cystatin C.
of adverse kidney outcomes and overall mortality, which may offer insights into
METHOD: Participants from UK Biobank with baseline measurements of serum
pathophysiological mechanisms.
creatinine and cystatin C were included, excluding patients with pre-existing cancer.
METHOD: Using measurements of 1,487 metabolites in urine of 5,087 CKD patients
Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI formulae
enrolled in the German Chronic Kidney Disease study, we evaluated the association of
for creatinine (eGFRcr), cystatin C (eGFRcys) and a combination of creatinine and
urine metabolite levels with adverse events. Main endpoints include KF, a combined
cystatin C (eGFRcr-cys). Associations of each eGFR with incidence and mortality from
endpoint of KF and acute kidney injury (KFþAKI), and overall mortality. Statistical
overall and specific cancer sites as well as all-cause mortality were tested using Cox
analysis was based on a discovery-replication design (ratio 2:1) and multivariable
proportional hazards models, adjusted for established risk factors for cancer (age, sex,
adjusted Cox regression models. We performed cause-specific hazard regression as well
smoking status, alcohol intake, body mass index, ethnicity and deprivation index).
as subdistribution hazard analyses with death of other causes as a competing event for
RESULTS: .In 443,441 eligible participants in UK Biobank over median follow-up of 11.3 (IQR
the endpoints KF and KFþAKI. Statistical significance was defined using a Bonferroni
10.6-12.0) years, there were 41,991 incident cancers, 11,854 cancer deaths and 23,708 total
correction for the number of tested metabolites per stage. An association was
deaths. After adjustment for established cancer risk factors and compared to those without
considered replicated if effect estimates from both stages were significant and
significant CKD (eGFR >60 ml/min/1.73m2), CKD G3-5 (eGFR <60 ml/min/1.73m2) was
direction-consistent.
associated with an increased risk of cancer incidence (eGFRcr-cys HR 1.16 (95% CI 1.10 – 1.22);
p<0.001), cancer death (eGFRcr-cys HR 1.36 (95% CI 1.25 – 1.48); p<0.001) and all-cause
mortality (eGFRcr-cys HR 2.29 (95% CI 2.18-2.41); p<0.001). CKD G3-5 was more strongly
associated with risk of cancer incidence, cancer death and all-cause mortality in younger men
and women (age <65 years). In particular, younger men and women with CKD G3-5 were
more than twice as likely to die from cancer than younger men and women without CKD
(eGFRcr-cys HR 2.39 (95% CI 1.99-2.87); p<0.001 and HR 2.12 (95% CI 1.72-2.62); p<0.001
respectively). CKD G3-5 was associated with increased risk of cancer of the abdominal solid
organs (eGFRcr-cys HR 1.31 (95% CI 1.07-1.60); p=0.009), respiratory (eGFRcr-cys HR 1.36
(95% CI 1.18-1.56); p<0.001) and renal tracts (eGFRcr-cys HR 1.38 (95% CI 1.18-1.61);
p<0.001) and haematological cancers (eGFRcr-cys HR 1.77 (95% CI 1.54-2.03); p<0.001), but
was not associated with increased risk of female (breast and reproductive system) or male
(prostate, penile and testicular) cancers, cancers of the digestive tract or melanoma (Figure
below). For all outcomes, the strongest associations were found using measures that
incorporated cystatin C and were similar for eGFRcys and eGFRcr-cys.
CONCLUSION: These data support routine implementation of cystatin C testing to
identify individuals at increased risk of cancer. Younger men and women in particular
are increased risk of cancer incidence and cancer death in the context of CKD G3-5.
Further exploration is warranted to identify the reasons for worse cancer outcome,
particularly in younger patients with CKD.

RESULTS: Median follow-up time was 4 years. At time of analysis, 362 patients died, 241
experienced KF, and 382 KFþAKI. Overall, we identified 55 urine metabolites whose levels
were significantly and reproducibly associated with adverse kidney outcomes and/or mortality.
Cause-specific and subdistribution hazard analyses showed almost identical results. Higher
levels of the amino acid C-glycosyltryptophan in urine were associated with higher risk for all
three endpoints (KF: hazard ratio 1.43, 95% confidence interval [1.27;1.61], KFþAKI: 1.40
[1.27;1.55], mortality: 1.47 [1.33;1.63]). The cumulative incidence function of KF was higher for
each quartile of urine C-glycosyltryptophan levels and the effect were most pronounced in the
highest quartile (see Figure). The replicated metabolites belong to different biochemical classes,
and those belonging to the phosphatidylcholines pathway showed enrichment. Members of this
pathway contributed to the improvement of the prediction performance for KF observed when
multiple metabolites were added to the well-established kidney failure risk equation by Tangri.
CONCLUSION: This comprehensive screen of the association between urine
metabolite levels and adverse kidney outcomes and mortality identified and replicated
55 urine metabolites associated with adverse kidney events, potentially providing new

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
insights into the mechanisms of kidney disease progression. The study represents a MO484 ADVERSE OUTCOMES ASSOCIATED WITH ORAL
valuable resource for future experimental studies of biomarkers of CKD progression. ANTITHROMBOTIC USE IN PATIENTS WITH MODERATE-TO-
ADVANCED CHRONIC KIDNEY DISEASE*

Solene Laville1, Oriane Lambert1, Aghiles Hamroun1,2, Marie Metzger3,


MO483 CHA2DS2-VASC SCORE IN PATIENTS WITH EGFR<30 ML/ Christian Jacquelinet4, Maurice Laville5, Luc Frimat6,7, Denis Fouque8,
MIN/1.73 M2 AND ATRIAL FIBRILLATION* Christian Combe9,10, Carole Ayav6, Roberto Pecoits-Filho11, Benedicte Stengel1,
Ziad Massy1,12, Sophie Liabeuf13,14
Ellen Linnea Freese Ballegaard1, Jonas Bjerring Olesen2, Anne Lise Kamper1, 1
INSERM U1018 - CESP, Paris-Saclay University, Versailles Saint-Quentin University,
Bo Feldt-Rasmussen1, Gunnar Gislason2,3, Christian Torp-Pedersen4, Clinical epidemiology, Villejuif Cedex, France, 2CHRU Lille, University of Lille, Nephrology
Nicholas Carlson3,5 Department, Lille, France, 3INSERM U1018 - CESP, Clinical epidemiology, Villejuif Cedex,
1
Copenhagen University Hospital Rigshospitalet, Nephrology, Copenhagen, Denmark, France, 4Biomedecine Agency, France, 5Lyon University, CarMeN INSERM 1060, AURAL,
2
Copenhagen University Hospital Herlev and Gentofte, Cardiology, Hellerup, Denmark, France, 6Lorraine University, APEMAC, France, 7CHRU Nancy, Nephrology Department,
3
The Danish Heart Foundation, Copenhagen, Denmark, 4North Zealand Hospital, France, 8CH Lyon, Lyon University, Nephrology Department, France, 9CHU Bordeaux,
Cardiology, Hillerod, Denmark and 5Copenhagen University Hospital Rigshospitalet, Néphrologie, Transplantation, Dialyse et Aphérèse, France, 10INSERM U1026, Bordeaux
Cardiology, Copenhagen, Denmark Segalen University, France, 11Arbor Research Collaborative for Health, Ann Arbor,
United States of America, 12Ambroise Paré University Hospital, Nephrology Department,
BACKGROUND AND AIMS: CHA2DS2-VASc score (congestive heart failure, France, 13Amiens University Hospital, Department of Clinical Pharmacology, France
hypertension, age 75 years, diabetes mellitus, stroke or transient ischemic attack, and 14University of Picardie Jules Verne, MP3CV Laboratory, EA7517, France
vascular disease, age 65-74 years, female sex) is a validated tool for evaluation of risk of
stroke and systemic emboli in patients with atrial fibrillation without nephropathy. The BACKGROUND AND AIMS: The use of oral antithrombotics in patients with
validity of risk determination based on the CHA2DS2-VASc score in patients with chronic kidney disease (CKD) is challenging because of altered pharmacodynamics/
severe nephropathy is untested. We investigate the validity of the CHA2DS2-VASc pharmacokinetics. Patients prescribed oral anticoagulant are at high risk of bleeding,
score in patients with eGFR<30 ml/min/1.73m2 (including dialysis treated patients) and possibly also acute kidney injury (AKI) and progression to kidney failure. We
and atrial fibrillation without anticoagulation treatment. assessed bleeding, AKI, and kidney failure risks associated with oral anticoagulant and/
METHOD: In a retrospective cohort study, all patients with atrial fibrillation and or antiplatelet agent prescription in patients with moderate-to-advanced CKD.
eGFR<30 ml/min/1.73 m2 were identified in nationwide Danish registers between METHOD: CKD-REIN is a prospective cohort of 3022 nephrology outpatients with
2008 and 2018 with subsequent exclusion of patients initiating anticoagulation CKD stages 2-5 at inclusion. Drug prescriptions and their duration were collected
treatment based on redeemed prescriptions. Cumulative incidences of stroke stratified prospectively. We used cause-specific Cox proportional hazard models to estimate
on CHA2DS2-VASc score were computed using the Aalen-Johansen estimator, and hazard ratios (HR) for bleeding (identified through hospitalizations), AKI (as defined
one-year risk of stroke was calculated with comparison of CHA2DS2-VASc score based according to KDIGO 2012), and kidney failure. Prescriptions of oral antithrombotics
on Cox regression models adjusted for age, sex and dialysis status with G-computation were treated as a time dependent variable and models were adjusted for baseline
of one-year risk standardized to the distribution of risk factors in the sample. comorbidities, laboratory data, and other medications.
RESULTS: From 2,452 patients with eGFR <30 ml/min/1.73 m2 and de novo atrial RESULTS: At baseline, 339 (11%) patients (65% men; median age 69 [interquartile
fibrillation, a total of 1,575 patients (64.2%) without anticoagulation treatment were range (IQR), 60-76] years; median eGFR 32 [IQR, 23-41] were prescribed oral
included. Mean age was 78.0 years (standard deviation 612.2), 53.3% were male, and anticoagulants only, 1095 (36%) antiplatelet only, and 101 (3%) both anticoagulant and
25.5% were on dialysis. The distribution of patients into CHA2DS2-VASc score antiplatelet.
categories of 0-1, 2, 3, 4 and 5 was 8.7%, 14.5%, 24.6%, 24.7% and 27.5%, respectively. Over a median follow-up of 3 years (IQR, 2.8-3.1), 152 patients experienced a bleeding
Cumulative incidence of stroke in non-dialysis dependent and dialysis-dependent event requiring hospital visit/stay (crude incidence rate (IR): 1.9% person-years
patients are shown in the figure. [95%CI,1.6-2.2]), 414 patients experienced AKI (crude IR: 5.4 % person-years [4.9-
Overall, standardized one-year risk of stroke was 3.3% (95%CI 1.3-6.4%), 2.5% (95%CI 5.9]), and 270 experienced kidney failure (crude IR: 3.4 % person-years [3.0-3.8]).
1.0-4.1%), 5.9% (95%CI 3.9-8.2%), 5.1% (95%CI 3.6-7.0%), and 7.3% (95%CI 5.2- A significant interaction was found between oral antithrombotics and eGFR
10.2%) for CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and 5, respectively. (interaction p=0.03). The adjusted HRs [95%CI] for bleeding associated with
Comparably, standardized one-year risk of stroke was 2.5% (95%CI 0.3-5.7%), 1.9% prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet þ oral
(95%CI 0.0-4.7%), 7.4% (95%CI 3.2-11.5%), 4.7% (95%CI 1.0-8.3%), and 16.5% anticoagulant were respectively 0.58 [0.30; 1.11], 2.62 [1.39; 4.93], and 5.76 [2.85;
(95%CI 7.9-27.2%) for CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and 5, 11.66] in patients with a baseline eGFR < 30 mL/min/1.73m2. In patients with baseline
respectively, in dialysis-treated patients, and 4.3% (95%CI 1.0-10.3%), 2.9% (95%CI eGFR  30 mL/min/1.73m2, the adjusted HRs [95%CI] for bleeding associated with
1.1-4.9%), 5.5% (95%CI 3.5-8.1%), 5.1% (95%CI 3.4-7.1%), and 5.9% (95%CI 3.8-8.5%) prescriptions of antiplatelets only, oral anticoagulants .......only, and antiplatelet þ oral
for CHA2DS2-VASc score categories of 0-1, 2, 3, 4 and 5, respectively, in non- anticoagulant were respectively 0.98 [0.48; 1.98], 1.91 [0.87; 4.20], and 1.54 [0.46; 5.12]
dialysis-dependent patients. (Figure 1A).
CONCLUSION: Overall, CHA2DS2-VASc score was associated with a progressive
increase in one-year risk of stroke. Although the association was most obvious in non-
dialysis dependent patients, discrepancy was evident with regard to risk in patients
with CHA2DS2-VASc score 1 in both subgroups, albeit less so in adjusted analyses.

MO483 Figure: Cumulative incidence of stroke stratified by CHA2DS2-VASc score

An increased risk of AKI risk was associated with the prescription of oral
anticoagulants (adjusted HR [95%CI]: 1.91[1.48; 2.46]) but not the prescription of
antiplatelets (1.24[0.98; 1.56], Figure 1B). No significant interactions were found
between oral anticoagulants and eGFR or antiplatelet agents.
Kidney failure was not associated with the prescription of oral antithrombotics of any
type (Figure 1C). No significant interactions were found with eGFR and antiplatelet
agents.

10.1093/ndt/gfab087 | i301
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: This study confirms the risk of AKI in CKD patients prescribed oral MO486 INSIDE CKD: MODELLING THE IMPACT OF IMPROVED
anticoagulants. It also highlights the potential aggravating effect of combining SCREENING FOR CHRONIC KIDNEY DISEASE IN THE
anticoagulants and antiplatelet on the risk of bleeding in this population. AMERICAS AND ASIA-PACIFIC REGION

Juan Jose Garcia Sanchez1, Alyshah Abdul Sultan1, Marcelo Costa Batista2,
Claudia Cabrera3, Joshua Card-Gowers4, Steven Chadban5, Glenn Chertow6,
MO485 PREVALENCE OF ANALGESICS USE AND ASSOCIATED Eiichiro Kanda7, Guisen Li8, Stephen Nolan1, Lise Retat4, Navdeep Tangri9,
ADVERSE OUTCOMES IN THE CHRONIC KIDNEY DISEASE Laura Webber4, Jay Wish10, Michael Xu4
POPULATION: A SYSTEMATIC REVIEW AND META- 1
AstraZeneca, BioPharmaceuticals Medical, Cambridge, United Kingdom, 2Universidade
ANALYSIS* Federal de S~ ao Paulo, Brazil, 3AstraZeneca,
ao Paulo, Nephrology Division, S~
BioPharmaceuticals Medical, Gothenburg, Sweden, 4HealthLumen, London, United
Emilie Lambourg1, Lesley Colvin1, Greg Guthrie2, Heather Walker1,2, Kingdom, 5Royal Prince Alfred Hospital, Renal Medicine, Camperdown, Australia,
Samira Bell1,2 6
Stanford University School of Medicine, Division of Nephrology, Palo Alto, United
1
University of Dundee, Division of Population Health and Genomics, Dundee, United States of America, 7Kawasaki Medical University, Medical Science, Okayama, Japan,
Kingdom and 2Ninewells hospital, Renal Unit, Dundee, United Kingdom 8
Sichuan Academy of Medical Science, Sichuan Provincial People’s Hospital, Chengdu,
P.R. China, 9University of Manitoba, Chronic Disease Innovation Center, Winnipeg,
BACKGROUND AND AIMS: Pain is one of the commonest symptoms in patients Canada and 10Indiana University School of Medecine, Division of Nephrology,
with chronic kidney disease (CKD), with a large proportion undertreated. Managing Indianapolis, United States of America
chronic pain in CKD patients is problematic due to the altered pharmacokinetic and
pharmacodynamic related to the reduced renal clearance making it challenging for BACKGROUND AND AIMS: With an estimated global prevalence of 10%, chronic
physicians to find appropriate pain management strategies. The aim of this systematic kidney disease (CKD) and its associated complications place a substantial strain on
review was to estimate the overall prevalence of different types of analgesia in patients healthcare systems worldwide, which is compounded by the burden of undiagnosed
with CKD and investigate their safety. CKD. Early CKD diagnosis followed by guideline-recommended interventions can
METHOD: The population comprised of all adult patients with CKD defined as an improve patient outcomes and reduce associated healthcare-related costs, particularly
estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73m2 which included by delaying or preventing the development of complications and progression to kidney
CKD-non dialysis (CKD-ND), kidney transplant recipients (KTR), patients undergoing failure. Urinary albumin-to-creatinine ratio (UACR) can be used to screen for CKD,
dialysis and those receiving palliative care. Analgesics investigated included opioids, but adherence to screening recommendations is suboptimal in routine care. Inside
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), gabapentinoids and acetaminophen. CKD aims to model the global clinical and economic burden of CKD using country-
All studies reporting a prevalence of analgesic use and/or exploring the association between specific, patient-level microsimulation models. We used the Inside CKD
analgesic consumption and adverse outcomes were included. Medline, Embase, microsimulation to model the potential clinical and economic impacts of routine
CENTRAL, CINAHL and the grey literature were searched up to December 2020. measurement of UACR followed by appropriate intervention in patients aged 45 years
Random-effect meta-analyses were conducted using a Generalised Linear Mixed Model and over in the US and Canada.
approach to estimate the overall prevalence of analgesics use in the CKD population, METHOD: The Inside CKD microsimulation model was used to model the clinical and
displayed in forest-plots. Evidence gathered from studies investigating the adverse economic impacts associated with measurement of UACR with subsequent appropriate
outcomes related to analgesics consumption was synthesised in ‘harvest plots’. intervention during routine primary care visits versus current practice in individuals
RESULTS: Sixty-three studies reporting a prevalence of analgesic use in patients with aged 45 years and over. The model covers the period 2020–2025. In preliminary
CKD were included. The overall prevalence of analgesic consumption was 42% (95% analyses, virtual populations representing the general populations of the US and
CI, 35-50%) in the general CKD population and 70% (95% CI, 62-68%) among those Canada were constructed using published country-specific data, including
experiencing chronic pain. Seventeen studies reported a prevalence of opioid use with demographics, prevalence of CKD and comorbidities (type 2 diabetes, uncontrolled
36% (95% CI, 23-51%) of patients with CKD receiving at least one opioid prescription hypertension and heart failure), incidence of complications (heart failure, myocardial
while 16% (95% CI, 11-22%) were on chronic opioid therapy. The chronic use of infarction, stroke and acute kidney injury) and costs associated with CKD. The model
oxycodone, tramadol, propoxyphene, fentanyl and hydromorphone were 3.6%, 2.0%, also included parameters relating to the proportion of patients who visit a primary care
1.3%, 1.1% and 0.05% respectively. NSAIDs usage was estimated to 20% (95% CI, 15- physician at least once a year, the proportion of patients who agreed to UACR
25%) among patients with CKD (ibuprofen 4.6%, diclofenac 1.7%) and 8% (95% CI, 5- measurements, and the diagnostic sensitivity and specificity of UACR measurements.
12%) took NSAIDs chronically, with a higher prevalence among dialysis patients (17%) The modelling is being expanded to additional countries in the Americas and the Asia-
compared with CKD-ND (7%) and KTR (5%) (p<0.01). Prevalence of gabapentin and Pacific region.
pregabalin use was estimated at 10% and 3.5% respectively, on pooling of 3 studies. RESULTS: Preliminary results from the US and Canada show that over the 2020–2025
Finally, five studies yielded an overall prevalence of 24% for acetaminophen use. period routine measurement of UACR during primary care visits followed by
Twenty studies assessing the association between analgesic use and adverse outcomes appropriate intervention could prevent progression to CKD stages 3b–5 in
were included (Figure 1). Five of them demonstrated an association between opioid use approximately 1.3M patients in the US and 160 000 in Canada, compared with current
and increased mortality, in all CKD subgroups; and three out of four studies reported clinical practice, with linear increases in the cumulative numbers of prevented cases
more hospitalizations in opioid-users.Four studies highlighted an increased risk of (Figure). Associated savings in healthcare costs in 2025 are projected to be
gastro-intestinal bleeding associated with NSAIDs consumption and three studies approximately US$16B in the US and C$2.5B in Canada, corresponding to a reduction
found a significant association between gabapentin use and neurologic adverse events. in cost for that year of 4.4% and 7.4%, respectively, compared with current clinical
practice.
CONCLUSION: Preliminary results from the Inside CKD microsimulation model in
the US and Canada show that routine measurement of UACR with subsequent
intervention in primary care would prevent progression to CKD stages 3b–5 in a
substantial number of patients compared with current screening practices, and could
therefore decrease associated healthcare costs considerably. This analysis is being
extended to further countries in the Americas and the Asia-Pacific region.

MO485 Figure: Harvest plot summarizing current evidence on adverse outcomes related
to analgesic consumption in the CKD population. Number above bar: 1= CKD-ND, 2=
dialysis, 3=KTR. Height of bar is proportional to the log of the study’s sample size.
CONCLUSION: Only 70% of CKD patients experiencing chronic pain received an
analgesic, suggesting that pain remains a significant public health burden. Despite
limited evidence, opioids, NSAIDs and gabapentinoids seem to be associated with
major adverse events. Their use requires cautious prescription, consideration of
optimal dosage, and the development of therapeutic patient education to promote risk
awareness. More evidence is warranted to better understand the adverse outcomes
associated with long-term analgesic consumption and provide safe pain management
strategies for patient with CKD.

i302 | Abstracts
Nephrology Dialysis Transplantation Abstracts
range for greatest survival was between 139-146 mmol/L [HR 1.02 (1.00-1.03) and HR
1.19 (1.02-1.38) respectively, while for CV mortality, the optimal range was much
narrower at 134-143mmol/L [HR 1.16 (1.02-1.23) and HR 1.09 (1.01-1.89)
respectively] (Figure 1). The impact of serum Naþ on mortality was modified by
baseline kidney function (p value < 0.001 for interaction). In stratified analysis, the
impact of serum Naþ on all-cause mortality was greatly attenuated among patients
with GFR< 60 ml/min/m2, than above. This pattern was replicated in analyses of CV
mortality.
CONCLUSION: This study supports the view that hypernatraemia and
hyponatraemia are better tolerated with poorer kidney function. The risk thresholds
for mortality were much narrower for CV death than all-cause death suggesting that
these thresholds be taken into account to inform decision making and therapeutic
interventions.
FUNDING SOURCE: Health Research Board (HRB-SDAP-2019-036), Midwest
Research and Education Foundation (MKid)

MO487 Figure 1: The relationship between serum sodium levels (mmol/L) and all-
cause and cardiovascular mortality in patients both with and without CKD

MO488 HOSPITALISATION EVENTS IN PEOPLE WITH CHRONIC


KIDNEY DISEASE AND MULTIPLE LONG-TERM CONDITIONS

Michael Sullivan1, Bhautesh Jani2, Alex McConnachie3, Frances Mair2,


Patrick Mark1
1
University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow,
United Kingdom, 2University of Glasgow, General Practice and Primary Care, Glasgow,
United Kingdom and 3University of Glasgow, Robertson Centre for Biostatistics,
MO486 Figure: Cumulative numbers of CKD cases prevented from progressing to Glasgow, United Kingdom
CKD stages 3b-5 over the 2020-2025 period by routine measurement of UACR in
primary care with subsequent intervention in the US and Canada. BACKGROUND AND AIMS:Chronic Kidney Disease (CKD) typically co-exists with
multiple long-term conditions (LTCs). The impact of CKD combined with multiple
LTCs on hospitalisation rates is not known. We hypothesised that hospitalisation rates
MO487 DYSNATRAEMIA AND ASSOCIATED MORTALITY RISK would be high in people with multiple LTCs, particularly in those with CKD. We also
THRESHOLDS ARE MODIFIED BY KIDNEY FUNCTION IN THE hypothesised that the association between multiple LTCs and hospitalisation would be
IRISH HEALTH SYSTEM: THE NATIONAL KIDNEY DISEASE greatest in subgroups and with certain patterns of LTCs.Method:Two cohorts were
SURVEILLANCE SYSTEM (NKDSS) studied in parallel: UK Biobank (2006-2019) and Secure Anonymised Information
Linkage Databank (SAIL: 2011-2018, Wales, UK). UK Biobank is a prospective
Conor Walsh1, Leonard Browne1, Austin Stack1,2 research cohort. SAIL is a routine care database. Participants were included if their
1 kidney function was measured at baseline. LTCs were obtained from self-report (UK
University of Limerick, School of Medicine, Limerick, Ireland and 2University Hospital Biobank) and primary care read codes (SAIL). Participants were categorised into zero,
Limerick, Department of Nephrology, Limerick, Ireland one, two, three and four or more LTCs with and without CKD. CKD was defined as
estimated glomerular filtration rate less than 60 ml/min/1.73m2 (single blood test for
BACKGROUND AND AIMS: Dysnatraemia is associated with increased mortality UK Biobank, two blood tests three months apart for SAIL). Hospitalisation events were
risk in the general population, but it is unclear to what extent kidney function obtained from linked hospital records.Results:Among 469,344 of 502,503 UK Biobank
influences this relationship. We investigated the impact of dysnatraemia on total and participants, those without CKD had a median age of 58 and a median of 1 LTC. Those
cardiovascular (CV) mortality while exploring the concurrent impact of chronic kidney with CKD had a median age of 64 and a median of 2 LTCs. Among 1,620,490 of
disease. 2,768,862 SAIL participants, those without CKD had a median age of 50 and a median
METHOD: We utilised data from the Irish Kidney Disease Surveillance System of 1 LTC. Those with CKD had a median age of 79 and a median of 4 LTCs.
(NKSS) to explore the association of serum sodium (Naþ) (mmol/L) and mortality in a Participants with four or more LTCs had high event rates (Rate Ratios (RRs) 5.35 (95%
longitudinal cohort study. We identified all adult individuals (age > 18 years) who CI 5.20-5.51)/3.77 (95% CI 3.71-3.82)) with higher rates in CKD (RRs 8.99 (95% CI
accessed health care from January 1st, 2007 and December 31st, 2013 in a regional 8.47-9.54)/9.92 (95% CI 9.75-10.09)).
health system with complete data on serum Naþ, associated laboratory indicators and Amongst those with CKD, the association between each increase in LTC count and
vital status up to 31st December 2013 (n = 32, 686). Patients receiving dialysis were hospitalisation was greatest in those under the age of 50 (RRs 1.93 (95% CI 1.73-2.16)/
excluded. The primary exposure was serum Naþ first recorded during the study period 1.35(95% CI 1.29-1.41)). Event rates were highest in those with eGFR<30ml/min/
for each patient with a concurrent serum glucose measurement. Chronic kidney 1.73m2, but the impact of multiple LTCs was weaker in these participants compared to
disease was defined as eGFR <60ml/min/1.73m2 vs greater recorded at index date. The those with higher eGFRs.
association of serum Naþ with all-cause (ACM) and CV mortality was explored in Event rates were high in certain patterns of LTCs: cardiometabolic LTCs (RRs 4.45
categories and as a continuous variable using polynomial splines. Multivariable Cox (95% CI 4.02-4.92)/2.81 (95% CI 2.71-2.91)), complex patterns (RRs 3.60 (95% CI
regression with competing risks determined hazard ratios (HR) and 95% confidence 3.26-3.96)/2.91 (95% CI 2.81-3.01)) and physical/mental LTCs (RRs 3.30 (95% CI 2.86-
intervals with adjustment for baseline health indicators. 3.80)/3.18 (95% CI 3.06-3.30)).Conclusion:People with multiple LTCs have high rates
RESULTS: There were 5,118 deaths (15.7%) over a median follow up of 5.5 years. In of hospitalisation and the rates are augmented in those with CKD. The impact of
multivariable adjusted models, the association of serum Naþ with all-cause and CV multiple LTCs is greatest in younger patients and in those with certain patterns of
mortality followed a non-linear, u-shaped pattern. For all-cause mortality, the optimal

10.1093/ndt/gfab087 | i303
Abstracts Nephrology Dialysis Transplantation

LTCs. Strategies should be developed to prevent hospitalisations in these high-risk high symptom burden before and after adjusting for demographics and major
groups. comorbidities. Multiple linear regression accounting for clustering at the clinic level
Hospitalisation Events by Chronic Kidney Disease (CKD) status and number of Long- was used to examine associations between high symptom burden and physical and
term conditions (LTCs) in UK Biobank mental component summary (PCS and MCS, respectively) scores, with lower scores
Hospitalisation Events by Chronic Kidney Disease (CKD) status and number of Long- indicating poorer quality of life.
term conditions (LTCs) in SAIL RESULTS: Patients (mean age 68613 years, 40% women, mean eGFR at baseline
30.4612.2 mL/min/1.73m2) were very much to extremely bothered by a number of
symptoms, the prevalence of three of which - washed out or drained, nausea or upset
stomach, and lack of appetite – significantly increased in more advanced CKD stages
MO489 GESTATIONAL DIABETES AND THE LONG-TERM RISK OF
before and after adjusting for confounders (Figure). Nearly one in four patients
MATERNAL KIDNEY DISEASE: A SWEDISH NATIONAL
reported a high symptom burden, which was more prevalent in women, those with
COHORT STUDY.
obesity, anemia, or albumin<3.5 g/dL; it was also more common in France than in the
US and Brazil. In adjusted models, as compared to patients with low symptom burden,
Peter Barrett1,2, Fergus McCarthy2,3, Marie Evans4, Marius Kublickas5,
those with high symptom burden had a worse quality of life with PCS and MCS scores
Ivan Perry1, Peter Stenvinkel4, Karolina Kublickiene4, Ali Khashan1,2
1
14.6 (95% confidence interval [95% CI], 15.7 to 13.5) and 7.2 (95% CI, 8.3 to 6.1)
University College Cork, School of Public Health, Cork, Ireland, 2University College Cork, points lower, respectively.
INFANT, Cork, Ireland, 3University College Cork, Department of Obstetrics & CONCLUSION: Our findings demonstrate a high symptom burden even in
Gynaecology, Cork, Ireland, 4Karolinska Institute, CLINTEC, Stockholm, Sweden and nondialysis CKD stages 3-5 with a substantial impact on physical and mental health-
5
Karolinska University Hospital, Department of Obstetrics & Gynaecology, Stockholm, related quality of life. Several symptoms, particularly fatigue, and gastrointestinal
Sweden symptoms, appeared to worsen with increasing CKD stage, independent of patient
comorbidities.
BACKGROUND AND AIMS: Gestational diabetes (GDM) is increasingly common
worldwide. GDM is associated with increased risk of type 2 diabetes (T2DM) and
cardiovascular disease in women. It is uncertain whether GDM is independently
associated with long-term risk of maternal kidney disease. We aimed to examine the
association between GDM and maternal chronic kidney disease (CKD) and end-stage
kidney disease (ESKD) and to determine whether this depends on progression to overt
T2DM.
METHOD: A nationwide retrospective cohort study was designed using data from the
Swedish national registers. Women were included if their first delivery occurred
between 1 January 1987 and 31 December 2012. Previous GDM was the main exposure
variable, and this was stratified according to whether women developed T2DM after
pregnancy. We estimated the risk of CKD, ESKD and different CKD subtypes
(tubulointerstitial, glomerular, hypertensive, diabetic, other/non-specific). Cox-
proportional hazard regression models were used with time-dependent covariates. We
adjusted for a wide range of confounders including maternal age, country of origin,
maternal education, parity, antenatal BMI, gestational weight gain, smoking during
pregnancy and preeclampsia.
RESULTS: There were 1,121,633 women included, of whom 15,595 (1.4%) had a MO490 Figure: Prevalence of being very much to extremely bothered by any symptom
diagnosis of GDM. Overall, GDM-diagnosed women were at increased risk of CKD in moderate to advanced by CKD stage
(aHR 1.81, 95% CI 1.54-2.14) and ESKD (aHR 4.52, 95% CI 2.75-7.44). Associations
were strongest for diabetic CKD (aHR 8.81, 95% CI 6.36-12.19), hypertensive CKD
(aHR 2.46, 95% CI 1.06-5.69), and glomerular CKD (aHR 1.86, 95% CI 1.37-2.51). MO491 ASSOCIATION BETWEEN SERUM URIC ACID LEVEL AND
However, these associations were largely explained by progression to post-pregnancy CHRONIC KIDNEY DISEASE INCIDENCE STRATIFIED BY SEX
T2DM. Among women who had GDM þ subsequent T2DM, strong associations were IN MIDDLE-AGED ADULTS
observed with CKD (aHR 21.70, 95% CI 17.17-27.42) and ESKD (aHR 112.37, 95% CI
61.22-206.38). By contrast, women who only experienced GDM (and no future T2DM) Shingo Nakayama1,2,3, Michihiro Satoh2, Takahisa Murakami2,4,
were not at significantly higher risk of CKD (aHR 1.11, 95% CI 0.89-1.38) or ESKD Yukako Tatsumi5, Tomoko Muroya2,3,6, Takuo Hirose1,7, Takayoshi Ohkubo5,8,
(aHR 1.58, 95% CI 0.70-3.60). Takefumi Mori1, Atsushi Hozawa3, Hirohito Metoki2,8
CONCLUSION: Women who experience GDM are at increased risk of CKD and 1
ESKD if they develop T2DM. However, GDM-diagnosed women who do not develop Tohoku Medical and Pharmaceutical University, Division of Nephrology and
overt T2DM in later life have a similar risk of CKD/ESKD to those with uncomplicated Endocrinology, Faculty of Medicine, Sendai, Japan, 2Tohoku Medical and
pregnancies. Pharmaceutical University, Division of Public Health, Hygiene and Epidemiology,
Faculty of Medicine, Sendai, Japan, 3Tohoku University, Department of Preventive
Medicine and Epidemiology, Tohoku Medical Megabank Organization, Sendai, Japan,
4
Tohoku University Graduate School of Dentistry, Division of Aging and Geriatric
MO490 SYMPTOM BURDEN AND ITS IMPACT ON QUALITY OF LIFE Dentistry, Department of Oral Function and Morphology, Sendai, Japan, 5Teikyo
IN PATIENTS WITH MODERATE TO ADVANCED CKD University School of Medicine, Department of Hygiene and Public Health, Tokyo, Japan,
6
Izumi Hospital, Department of Internal Medicine, Sendai, Japan, 7Tohoku University
Elodie Speyer1, Charlotte Tu2, Jarcy Zee2, Ricardo Sesso3, Antonio Lopes4, Graduate School of Medicine, Department of Endocrinology and Applied Medical
Junichi Hoshino5, Carole Ayav6, Ronald Pisoni2, Roberto Pecoits-Filho2,7, Science, Sendai, Japan and 8Tohoku Institute for Management of Blood Pressure,
Benedicte Stengel1 Sendai, Japan
1
Université Paris-Saclay, Université Versailles Saint-Quentin-en-Yvelines, Université Paris-
Sud, Inserm, Equipe Epidémiologie Clinique, Villejuif, France, 2Arbor Research BACKGROUND AND AIMS: While previous studies have reported the association
Collaborative for Health, Ann Arbor, United States of America, 3Universidade Federal de between serum uric acid (SUA) and chronic kidney disease (CKD) incidence, the sex
S~ao Paulo, S~ao Paulo, Brazil, 4Department of Internal Medicine, Federal University of differences in this association remain controversial. Therefore, we examined the
Bahia, Bahia, Brazil, 5Nephrology Center, Toranomon Hospital, Tokyo, Japan, association between SUA levels and CKD incidence in middle-aged adults stratified by
6
Epidémiologie Clinique, Inserm CIC-EC, CHU de Nancy, Vandoeuvre-lès-Nancy, France sex using data from a large-scale health check-up.
and 7School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, Brazil METHOD: We analyzed information from the JMDC database, which included the
annual health check-up data of Japanese employees and their dependents aged <75
BACKGROUND AND AIMS: It is generally considered that the early stages of CKD years. Among those individuals, we analyzed data from 138,511 individuals without
are asymptomatic, and that CKD becomes apparent once kidney function is CKD, kidney disease, or a history of cardiovascular disease at baseline. CKD was
significantly impaired, but large-scale studies in real-world non-dialysis CKD patients defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or
under nephrology care are still scarce. We evaluated symptom burden and its impact proteinuria. We divided the participants into 9 and 7 groups according to SUA levels
on quality of life in patients with moderate to advanced CKD. for men and women, respectively. A Cox model was applied to assess the adjusted
METHOD: 4423 patients with CKD Stage 3 to 5 from Brazil (N=548), France hazard ratios (HRs) for CKD incidence in each SUA level group using an SUA
(N=2691), and the US (N=1184) enrolled in the Chronic Kidney Disease Outcomes concentration of 4.0–4.9 mg/dL as the reference after adjusting for age, body mass
and Practice Patterns Study (CKDopps) from 2013-2019 completed the Kidney Disease index, current or ex-smoker, current or ex-drinker, diabetes mellitus, dyslipidemia,
Quality of Life (KDQOL) questionnaire at baseline to assess how much they were systolic blood pressure, use of anti-hyperuricemic drugs, and baseline eGFR.
bothered by 13 symptoms. Response options ranged from “not at all” to “extremely” RESULTS: The mean participant age was 44.1 years, and 29.6% were women. The
bothered. From these Symptoms/Problems of Kidney Disease items, a score was mean SUA levels were 5.9 mg/dL and 4.1 mg/dL in men and women, respectively.
calculated, ranged from 0 to 100, and analyzed in 3 categories: low (90), intermediate During the mean follow-up period of 4.68 years, 12,589 participants developed CKD.
(66-90), or high symptom burden (<66). Poisson regressions were used to estimate The age-standardized incidence rates for CKD were 17.88/17.80 per 1000 person-years
prevalence ratios for each symptom and to study associations between CKD stage and a in men/women with SUA concentrations of 4.0–4.9 mg/dL, 209.76 per 1000 person-

i304 | Abstracts
Nephrology Dialysis Transplantation Abstracts
years in men with SUA 11.0 mg/dL, and 73.38 per 1000 person-years in women with measurement-based sensitivity was 72.1% (range 1.1%-100%, Fig. 1). Sensitivity and
SUA  9.0 mg/dL. The fully adjusted HRs (95% confidence interval [CI], P value) for specificity were especially high for angiotensin-II receptor blockers (92%-96%; 99-
CKD incidence in the groups with SUA concentrations of <4.0, 10.0–10.9, and 11.0 100%), calcium channel blockers (85-100%; 91-100%), and metoprolol (90%; 98%
mg/dL compared with those with SUA of 4.0–4.9 mg/dL among men were 1.13 (1.01– respectively) commonly prescribed and important medications for blood pressure
1.26, P=0.030), 1.98 (1.32–2.97, P=0.0010), and 3.74 (1.68–8.35, P=0.0013), control and cardiovascular risk reduction in CKD patients. MMPs showing sensitivity
respectively. In women, the fully adjusted HRs for CKD incidence in the groups with <80% included several substances found in over-the-counter (OTC) analgesic
SUA concentrations of <4.0, 8.0–8.9, and 9.0 mg/dL were 1.08 (1.01–1.16, P=0.032), medications, suggesting that their use is not always reported. While self-reported use of
2.39 (1.07–5.35, P=0.034), and 3.20 (0.80–12.8, P=0.10), respectively. Similar results the OTC analgesics acetaminophen and ibuprofen was <3% each, their corresponding
were observed when we performed the sensitivity analysis excluding 8,411 individuals drug metabolites indicated higher usage (acetaminophen: 10-26%; ibuprofen: 10-18%,
with hypertensive treatment from the main analysis. The HRs for the outcomes caused depending on the number of evaluated drug metabolites). Typical examples of
by the onset of eGFR <60 mL/min/1.73 m2 or proteinuria separately were similar to medication co-prescriptions (e.g., trimethoprim and sulfamethoxazole) were detected
those for the main results. as the combined presence of their drug metabolites in urine. This result validates the
CONCLUSION: The results of the present study demonstrated an increased risk of abstraction of single substances from combination medications and this urine-based
CKD in men with SUA concentrations of <4.0 and 10.0 mg/dL and <4.0 and 8.0 metabolomic approach.
mg/dL in women compared to those with SUA concentrations of 4.0–4.9 mg/dL after
adjusting for various covariates. Both high and low SUA levels were risk factors for
CKD in middle-aged men and women. Hyperuricemia was demonstrated to cause
renal injury due to the intraluminal deposition of uric acid crystals in the renal
collecting duct. Hyperuricemia may also induce endothelial dysfunction, activation of
the renin-angiotensin system, and induction of inflammation and stimulation of
vascular smooth muscle cell proliferation by the induction of cyclooxygenase-2.
However, as uric acid is one of the most important antioxidants in human plasma, low
SUA levels may increase the risk of CKD incidence through decreased antioxidant
activity. These mechanisms are implicated in the pathogenesis of CKD caused by high
and low SUA levels. In addition, the SUA levels and ranges associated with increased
risks of CKD incidence differed by sex.

MO492 Figure 1: Specificity (y-axis) and sensitivity (x-axis) of evaluated MMPs


MO492 SELF-REPORTED MEDICATION USE AND URINARY DRUG involving single substances using measured drug metabolites as the reference. MMPs
METABOLITES IN THE GERMAN CHRONIC KIDNEY DISEASE with <80% sensitivity or specificity are annotated and listed (values in %). Numbers
(GCKD) STUDY: A PHARMACOMETABOLOMIC APPROACH refer to the reported medication of the MMP. (Acetylsalicylic acid listed by indication:
2a - antithrombotic use, 2b - analgesic use).
Fruzsina Kinga Kotsis1,2, Ulla T. Schultheiß1,2, Matthias Wuttke1,2, CONCLUSION: This study provides a comprehensive screen of the associations
Pascal Schlosser1, Peter Oefner3, Robert P. Mohney4, Kai-Uwe Eckardt5,6, between urine drug metabolite levels and self-reported medication use. It supports the
Johanna Mielke7, Michael Becker8, Peggy Sekula1, Anna Köttgen1 usefulness of pharmacometabolomics to assess medication use, frequency of OTC
1
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center – University analgesics use, and prescription patterns in persons with CKD.
of Freiburg., Freiburg , Germany, 2Faculty of Medicine and Medical Center – University
of Freiburg., Department of Medicine IV – Nephrology and Primary Care, Freiburg,
Germany, 3Institute of Functional Genomics Image, University of Regensburg,
MO493 PATTERNS OF HYPERKALEMIA AND ASSOCIATED
Regensburg, Germany, 4Metabolon Inc., Durham, United States of America, 5Charité -
ADVERSE HEALTH OUTCOMES IN PERSONS WITH CHRONIC
Universit€atsmedizin Berlin, Department of Nephrology and Medical Intensive Care,
KIDNEY DISEASE
Berlin, Germany, 6University Hospital Erlangen, Friedrich-Alexander-Universit€
at
Erlangen-Nürnberg, Department of Nephrology and Hypertension, Erlangen, Germany,
7 Marco Trevisan1, Catherine M. Clase2, Marie Evans3, Jonas Ludvigsson1,
Bayer AG, Division Pharmaceuticals, Open Innovation & Digital Technologies,
Arvid Sjolander1, Juan Jesus Carrero1
Wuppertal, Germany and 8Bayer AG, Division Pharmaceuticals, Cardiovascular 1
Research, Wuppertal, Germany Karolinska Institutet, Medical Epidemiology and Biostatistics, Stockholm, Sweden,
2
McMaster University, Medicine and Health Research Methods, Evidence and Impact,
Ontario, Canada and 3Karolinska Institutet, Clinical Science, Intervention and
BACKGROUND AND AIMS: Chronic kidney disease (CKD) patients are prone to
Technology, Stockholm, Sweden
prescription of multiple medications. Medication adherence is a well-recognized
problem in the management of patients with chronic diseases requiring polypharmacy.
This study aimed to evaluate the connection between self-reported medication use and BACKGROUND AND AIMS: Patients with CKD are often described as having
urine drug metabolite levels in a large cohort of CKD patients, the GCKD study, as a chronic hyperkalemia, but earlier studies have relied on a single potassium
basis for future pharmacometabolomics studies. measurement. Whether the hyperkalemia in CKD is chronic or transient, and whether
METHOD: Self-reported medication use of 160 substances and 41 medication groups temporal patterns have different outcome implications, is unknown.
was ascertained at study baseline and coded according to the Anatomical Therapeutic METHOD: Observational study from the Stockholm Creatinine Measurements
Chemical classification system. A non-targeted mass spectrometry-based approach (SCREAM) project of patients with confirmed CKD G3-5. We extracted all data on
(Metabolon HD4TM) was used for concomitant metabolite quantification in urine. potassium measured during routine outpatient care and estimated its longitudinal
Specificity, sensitivity and accuracy of medication use and the corresponding urine trajectories. At each month, we created a rolling assessment of the proportion of time
metabolite measurements were calculated. Multivariable regression models (adjusted in which potassium was abnormal during the previous year, defining patterns of
to age, sex, eGFR, log(UACR), systolic blood pressure, LDL, log(triglycerides), normokalemia (100% of time with potassium 3.5-5.0 mmol/L), transient (<50% of
log(HBA1c) were used to establish associations in prescription patterns. time with potassium >5.0 mmol/L) and chronic hyperkalemia (50% of time with
RESULTS: Among 4,885 participants, 78 drug metabolites were detected in urine potassium >5.0 mmol/L). We described the presence of chronic and transient
(frequency range: 0.4-58%) and assigned into 110 medication – drug metabolite pairs hyperkalemia throughout the spectrum of CKD G3-5 and identified clinical predictors
(MMPs) based on reported individual substances and medication groups. For all 68 by logistic regression. Through time-dependent Cox models we examined whether
MMPs of individual substances, accuracy of medication use and the corresponding previous hyperkalemia patterns offer prognostic gain beyond that of the current
drug metabolite measurement was excellent (median 97.0%, range 43%-100%), as was potassium value.
measurement-based specificity (median 99.3%, range 73.3%-100%; Fig. 1). Median

10.1093/ndt/gfab087 | i305
Abstracts Nephrology Dialysis Transplantation

RESULTS: We included 36,511 participants (56% women) with confirmed CKD G3-5,
median age 81 years, and eGFR 46 ml/min/1.73 m2. During 3-year-median follow-up,
patterns of transient and chronic hyperkalemia were observed in 15% and 4% of
patients with CKD G3a, increasing to 50% and 17% of patients with CKD G5. Factors
associated with chronic hyperkalemia were younger age, male sex, more severe CKD
category, presence of diabetes or heart failure, use of renin-angiotensin system
inhibitors, and use of potassium binders. Major cardiovascular events (MACE)
occurred in 13,104 (36%) patients and 13,570 (37%) died. In time-dependent models,
independent of identified confounders and of time-updated potassium values,
compared with the normokalemic pattern, patients with transient (HR 1.37, 95% CI
1.29-1.46) or chronic (HR 1.17, 95% CI 1.04-1.32) hyperkalemia patterns were at
higher risk of MACE. Transient hyperkalemia pattern (HR 1.43, 95% CI 1.35-1.52) and
time-updated elevated potassium, but not a state of chronic hyperkalemia (HR 1.07,
95% CI 0.95-1.20), predicted the risk of death.
CONCLUSION: Chronic hyperkalemia occurs in 4-17% of patients with CKD G3-5.
We did not observe a clear dose-response for the association between hyperkalemia
pattern (normal, transient, chronic) with either MACE or death. There was modest
incremental information in the previous potassium pattern, beyond potassium
measured at a single time point.
MO494 Figure: Modelled annual healthcare costs associated with CKD in the UKa

MO494 INSIDE CKD: MODELLING THE ECONOMIC BURDEN OF


CHRONIC KIDNEY DISEASE IN EUROPE USING PATIENT-
LEVEL MICROSIMULATION MO495 UNDERSTANDING INTERNATIONAL VARIATION IN KIDNEY
€ FAILURE INCIDENCE: IMPACT OF DISPARITIES IN RAAS
Alyshah Abdul Sultan1, Johan Arnlöv 2
, Claudia Cabrera3, Joshua Card-Gowers4, INHIBITOR PRESCRIPTION AND BLOOD PRESSURE
Luca De Nicola5, Juan Jose Garcia Sanchez1, Jean-Michel Halimi6, Francesco CONTROL
Saverio Mennini7, Juan F. Navarro-Gonza lez8, Stephen Nolan1, Albert
John Power9, Lise Retat4, Laura Webber4, Michael Xu4 Natalia Alencar de Pinho1, Roberto Pecoits-Filho2, Brian Bieber2, Daniel Muenz2,
1
AstraZeneca, BioPharmaceuticals Medical, Cambridge, United Kingdom, 2Karolinska Antonio Lopes3, Helmut Reichel4, Christian Combe5, Bruce Robinson2,
Institutet, Stockholm, Sweden, 3AstraZeneca, BioPharmaceuticals Medical, Gothenburg, Benedicte Stengel1
Sweden, 4HealthLumen, London, United Kingdom, 5University Luigi Vanvitelli, Naples, 1
Inserm-CESP, Villejuif, France, 2Arbor Research Collaborative for Health, Ann Arbor,
Italy, 6University Hospital of Tours, Tours, France, 7University of Rome “Tor Vergata”, United States of America, 3Federal University of Bahia, Brazil, 4Nephrological Center,,
Rome, Italy, 8University Hospital Nuestra Se~ nora de Candelaria, Santa Cruz de Tenerife, Villingen-Schwenningen, Germany and 5Hospital Center University De Bordeaux,
Spain and 9North Bristol NHS Trust, Bristol, United Kingdom Bordeaux, France

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a debilitating and BACKGROUND AND AIMS: Blood pressure (BP) control and renin-angiotensin-
costly condition, affecting approximately 10% of people globally. Progression of CKD aldosterone system (RAAS) blockade are key measures to slow CKD progression, and
is associated with an increased incidence of adverse renal and cardiovascular outcomes, the achievement of targets for these measures vary greatly across countries. We sought
and premature mortality, as well as increased requirement for renal replacement to evaluate to what extend this might explain international variations in kidney failure
therapies (RRTs), which are associated with significant healthcare costs and resource incidence.
use. The trajectories of CKD prevalence, progression, outcomes and the related costs METHOD: We used data from the CKD Outcomes and Practice Patterns Study
are therefore critical considerations for public health and policy planning. Using (CKDopps), a cohort study of adult patients recruited from national samples of
country-specific, patient-level microsimulation, Inside CKD aims to model the global nephrology clinics. Patients with CKD G3 or G4, from Brazil (n=498), France
clinical and economic burden of CKD from 2020 to 2025. (n=2702), Germany (n=2314), and the US (n=905) were included. Those neither with
METHOD: We used the Inside CKD microsimulation to model the economic burden hypertension nor with albuminuria were excluded (n=103). We assessed systolic BP
of CKD in Europe. A virtual general population was developed for each country using and RAAS inhibitor prescription at baseline, and their association with time to kidney
national survey data and relevant data from published literature. Data inputs included failure, defined as an estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73m2
country demographics, the prevalence of CKD and RRT, comorbidities and or kidney replacement therapy initiation. Death was treated as a competing event. Cox
complication rates, as well as associated healthcare costs. CKD stages were defined proportional-hazards model was used to estimate cause-specific hazard ratios (cs-HR)
according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 and 95% confidence intervals (CI) for kidney failure according to country, before and
recommendations and patients were categorized according to estimated glomerular after adjusting for systolic BP and RAAS inhibitor prescription, as well as
filtration rate and albuminuria status. RRT modelling was calibrated against historical demographics, and known risk factors for CKD progression.
trends from country-specific renal registries. Model validation and calibration were RESULTS: Median age (years) ranged from 67 in Brazil to 75 in Germany; and mean
conducted following established methods for health economic modelling. Here, we baseline eGFR (ml/min/1.73m2), from 27 in Germany to 33 in France. Prevalence of
report the initial results from the UK analysis, with further analyses currently diabetes ranged from 20% in France to 36% in Brazil, and that of stage A3 albuminuria
underway for additional European countries. (>300 mg/g), from 31% in Brazil to 44% in the US. Mean systolic BP (mm Hg) ranged
RESULTS: The UK analysis revealed that annual healthcare costs associated with CKD from 132 in Brazil to 143 in France, and the percentage of patients prescribed RAAS
will increase linearly from £12.51B to £13.99B between 2020 and 2025. The largest inhibitor, from 58% in the US to 81% in Germany. After median follow-up of 4.0 (2.6-
absolute increase in cost was observed in CKD stage 3b (£0.75B); however, CKD stage 5.0) years, 1897 participants progressed to kidney failure and 522 died before meeting
5 had the largest relative increase in cost with an approximately three-fold increase this outcome. Two-year crude cumulative incidence of kidney failure was the lowest in
(£0.14B to £0.41B). By 2025, costs associated with CKD will increase across all age France (14%), where patients were recruited at an earlier CKD stage, and similar across
categories (18–34, 35–64 and 65þ years); the 35–64 age group had the largest absolute Germany (25%), the US (26%), and Brazil (27%); that for all-cause death, the lowest in
increase in costs with an increase of £1.14B (£2.02B to £3.16B). The largest relative Brazil (2.5%), followed by France (3.4%), the US (4.4%), and Germany (4.6%).
increase in cost was observed in the 18–34 age category, with a three-fold increase in Sequential adjustment for demographics and progression risk factors, in particular
costs (£0.09B to £0.27B). baseline eGFR and albuminuria, significantly reduced the gap between France and the
CONCLUSION: Initial results from Inside CKD demonstrate that CKD poses a other countries (Figure). Despite the associations of systolic BP (cs-HR 1.14, 95%CI
significant economic burden over the next 5 years. CKD stages 3b and 5 were 0.95-1.38 for 120-129; 1.18, 95%CI 0.95-1.46 for 130-139; and 1.46, 95%CI 1.23-1.74
associated with the most pronounced cost increases, likely due to increased prevalence for 140 versus <120 mm Hg) and RAAS inhibitor prescription (cs-HR 0.81, 95%CI
for stage 3b and greater treatment cost for stage 5. Notably, the largest increase in CKD 0.70-0.95 at 6 months of follow-up) with kidney failure, adjustment for these two
costs was observed in the 35–64-year-old ‘working’ population. Further policy treatment targets only marginally changed comparisons across studied countries.
interventions aimed at early diagnosis and proactive management should be CONCLUSION: In CKD patients under nephrology care, BP control and RAAS
considered to slow disease progression, improve patient outcomes and reduce the inhibitor prescription were associated with lower risk of kidney failure and
economic burden associated with CKD. substantially varied across countries. Despite this variation in practice, BP control and
RAAS inhibitor prescription appear to explain little of the differences in risk of kidney
failure by country.

i306 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO497 COVID-19 INCIDENCE AND MORTALITY IN PRE-DIALYSIS
CHRONIC KIDNEY PATIENTS DURING THE FIRST WAVE OF
THE PANDEMIC IN ITALY

Dino Gibertoni1, Chiara Reno1, Paola Rucci1, Maria Pia Fantini1,


Andrea Buscaroli2, Giovanni Mosconi3, Angelo Rigotti4, Antonio Santoro5,
Francesca Bravi6, Mattia Altini6
1
University of Bologna, Department of Biomedical and Neuromotor Sciences, Bologna,
Italy, 2Ospedale Santa Maria delle Croci, Unit of Nephrology and Dialysis, Ravenna,
Italy, 3Ospedale Morgagni-Pierantoni, Unit of Nephrology and Dialysis, Forlı, Italy,
4
Ospedale degli Infermi, Unit of Nephrology and Dialysis, Rimini, Italy, 5University of
Bologna, Specialty School in Nephrology, Bologna, Italy and 6Local Health Authority of
Romagna, Ravenna, Italy

MO495 Figure: Sequentially adjusted cause-specific hazard ratios (cs-HR) of kidney BACKGROUND AND AIMS: Many studies are available that reported a higher risk
failure associated with country. of COVID-19 disease among patients on dialysis or with kidney transplantation, and
the poor outcome of COVID-19 in these patients. Patients in conservative therapy for
Abbreviations : BMI, body mass index ; BP, blood pressure ; BR, Brazil ; DE, Germany; chronic kidney disease (CKD) have received lower attention, therefore little is known
eGFR, estimated glomerular filtration rate ; FR, France; RAAS, renin-angiotensin- about how COVID-19 may affect this population. The aim of this study was to analyse
aldosterone ; Ref, reference; US, United States. the COVID-19 incidence and mortality in CKD patients followed up in an integrated
healthcare program, living in a small area of Northern Italy.
METHOD: The study population included CKD patients from the Emilia-Romagna
Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4
MO496 PRESCRIPTION OF DIRECT ORAL ANTICOAGULANTS TO nephrology units (Ravenna, Forlı, Cesena and Rimini) of AUSL Romagna (Italy) and
PATIENTS WITH MODERATE TO ADVANCED CKD : TOO alive at 1.01.2020. All patients were in conservative therapy and none of them had
LITTLE OR JUST RIGHT? initiated dialysis or received kidney transplantation. The hospital discharge database
was used to identify patients hospitalized with COVID-19 up to 31.07.2020, and the
Sophie Liabeuf1, Solène M. Laville2, Brian Bieber3, Charlotte Tu3, mortality database was used to assess mortality among patients with COVID-19 at the
Benedicte Stengel2, Michelle Wong3, Viviane Calice-Siva4, Danilo Fliser5, same date. Multivariable logistic regression was used to identify predictors of COVID-
Bruce Robinson3, Roberto Pecoits-Filho3, Ziad Massy2 19 disease, and Kaplan-Meier survival analysis to identify predictors of COVID-19
1
Amiens University Hospital, Pharmacology Department, Amiens, France, 2Université mortality. Excess mortality of 2020 compared to mortality in 2015-19 in the PIRP
Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en cohort was also estimated.
Epidémiologie et Santé des Populations), Villejuif, France, 3Arbor Research Collaborative RESULTS: COVID-19 incidence among CKD patients was 4.09% (193/4716 patients),
for Health, Ann Arbor, United States of America, 4Pro-rim Foundation, Joinville, Brazil while in the general population it was 0.46% (5,195/1,125,574). COVID-19 was more
and 5Saarland University Medical Center, Department of Internal Medicine IV, likely in CKD patients with older age (Odds Ratio=1.038), cardiovascular
Homburg, France comorbidities (OR=2.217), COPD (OR=1.559) and less likely in patients living in the
province of Ravenna (OR=0.468), that was hit later by the first wave of pandemic
BACKGROUND AND AIMS: Prescription of anticoagulants in patients with chronic compared to the other areas of AUSL Romagna. Baseline eGFR was lower in CKD
kidney disease (CKD) is challenging, since these patients are at high risk of patients with COVID-19 (31.7 vs. 35.8 ml/min/1.73 m2), but this difference did not
thromboembolic episodes, but are also prone to bleeding events. Based on a number of reach statistical significance (p=0.066). As of 31.07.2020, the crude mortality rate
pivotal trials, four direct oral anticoagulants (DOACs) have been approved for use in among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/
non-valvular atrial fibrillation (AF) since 2010. These DOACs have now supplanted 4523) in CKD patients without COVID-19 and to 14.5% (4289/29670) in the general
vitamin K antagonists (VKAs) as first-line treatment in non-CKD patients. Following population with COVID-19 of the Emilia-Romagna region. Factors associated with
post-hoc analyses of randomized clinical trials of DOACs in CKD patients performed mortality of CKD patients with COVID-19 were older age (p=0.034) and the period of
between 2011 and 2016, a 2018 Kidney Disease Improving Global Outcomes COVID-19 onset (p=0.003). The highest crude mortality rate (71.4%) was found in
Controversies Conference stated that although there is not enough evidence to CKD patients for whom COVID-19 onset occurred between 8 and 21 March. The
recommend DOACs in patients with advanced CKD, these medications are safer than excess mortality of January-July 2020 with respect to the average mortality of January-
VKAs and not inferior for stroke preventing in patients with AF and an estimated July 2015-19 in the PIRP cohort was þ17.7%, corresponding to 77 excess deaths.
glomerular filtration rate (eGFR) between 30 and 50 ml/min/1.73 m2. Here, in a study March-April was the period with the highest excess mortality (þ69.8%), while in
of stage 3 to 5 CKD patients, we sought to describe multinational prescription patterns January-February a 15.9% lower mortality was observed with respect to the
for oral anticoagulants in general and for VKAs vs. DOACs in particular. corresponding months of the five previous years.
METHOD: We analyzed data from the international CKD Outcomes and Practice CONCLUSION: In our study, including a cohort of regularly followed up CKD
Patterns Study (CKDopps) of non-dialysis CKD patients  18 years of age with an patients, the risk of COVID-19 disease and of COVID-19 related mortality was
eGFR <60 mL/min/1.73 m2 at study enrollment. Participants were selected from comparable, or even somewhat higher, to that observed in patients on dialysis and
national samples of nephrologist-run CKD clinics in Brazil, France, Germany, and the those who received kidney transplantation. The incidence of COVID-19 in CKD
USA between January 2013 and April 2019. The CKDopps is ongoing, and at least 3 patients was higher in the areas of AUSL Romagna earlier affected by the pandemic
years (for the USA, Germany, and Brazil) or 5 years (for France) of prospective follow- wave, whereas mortality rates were similar across all areas. CKD patients represent a
up are planned. We assessed prescription patterns for oral anticoagulants regardless of population very vulnerable to COVID-19 disease, and their protection should be highly
indication at baseline and during follow-up. prioritized in the models of care and prevention measures.
RESULTS: Of the 8154 patients enrolled, 7092 had drug prescriptions data available at
baseline, and 1080 (15%) of these had at least one prescription of an oral anticoagulant.
At baseline, VKAs were the most frequently prescribed oral anticoagulants (n=984, MO498 INSIDE CKD: MODELLING THE CLINICAL AND ECONOMIC
91%), and only 97 of the 1080 patients (9%) were on DOACs (91 on a direct factor Xa IMPACTS OF TARGETED URINARY ALBUMIN-TO-
inhibitor and 6 on a direct thrombin inhibitor). This low DOAC prescription rate was CREATININE RATIO SCREENING IN EUROPEAN COUNTRIES
observed in France, the USA, Brazil and Germany. There was an upward trend in
DOAC prescription (relative to VKAs) over the course of the study. Over a median Juan Jose Garcia Sanchez1, Alyshah Abdul Sultan1, Johan Arnlöv € 2
,
[interquartile range] follow-up period of 3 years [1.5-4.5], 287 incident oral Claudia Cabrera3, Joshua Card-Gowers4, Luca De Nicola5, Jean-Michel Halimi6,
anticoagulant prescriptions were reported, 177 started on VKAs and 110 started on 7
Francesco Saverio Mennini , Juan F. Navarro-Gonza lez , Stephen Nolan1, Albert
8

DOACs. Among the patients receiving a VKA at baseline, only 44 switched to a John Power10, Lise Retat4, Laura Webber4, Michael Xu4
DOAC. 1
AstraZeneca, BioPharmaceuticals Medical, Cambridge, United Kingdom, 2Karolinska
CONCLUSION: In an international sample of non-dialysis CKD patients (eGFR
Insitutet, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden,
<60 mL/min/1.73 m2), we observed low prescription of direct oral anticoagulants (9%) 3
AstraZeneca, BioPharmaceuticals Medical, Gothenburg, Sweden, 4HealthLumen,
at baseline, relative to vitamin K antagonists (91%) across countries included in the
London, United Kingdom, 5University Luigi Vanvitelli, Department of Advanced Medical
analysis. However, there was an upward trend in DOAC prescriptions (relative to
and Surgical Sciences, Naples, Italy, 6University Hospital of Tours, Service de
VKAs) over the course of the study. In view of the risk of significant adverse events
Néphrologie-Hypertension, Dialyses, Transplantation rénale, Tours, France, 7University
associated with VKAs, the prescription of DOACs should be encouraged - particularly
of Rome “Tor Vergata”, Department of Economics and Finance, Rome, Italy, 8University
for CKD stage 3 patients and future studies of risk/benefit comparing VKAs and
Hospital Nuestra Se~
nora de Candelaria, Nephrology service, Santa Cruz de Tenerife,
DOACs are necessary in CKD patients.
Spain and 10North Bristol NHS Trust, Bristol, United Kingdom

BACKGROUND AND AIMS: With an estimated global prevalence of 10% or more,


chronic kidney disease (CKD) and its associated complications constitute a major
challenge for healthcare systems worldwide, which is worsened by the burden of
undiagnosed CKD. Early diagnosis of CKD followed by guideline-recommended

10.1093/ndt/gfab087 | i307
Abstracts Nephrology Dialysis Transplantation

interventions can improve patient outcomes, particularly by delaying or preventing MO499 CKD-MBD BIOMARKERS AND CKD PROGRESSION: AN
progression to kidney failure. This may result in a reduction in the costs associated ANALYSIS BY JOINT MODELS
with managing CKD. Elevated albuminuria is a strong predictor of risk of
complications and death in patients with CKD, and measurement of urinary albumin- Graziella D’Arrigo1, Francesca Mallamaci1,2, Patrizia Pizzini1, Maria
to-creatinine ratio (UACR) is an important diagnostic and prognostic tool. However, Carmela Versace1, Giovanni Luigi Tripepi1, Carmine Zoccali3, Of behalf of Mauro
adherence to screening recommendations is suboptimal in routine care. Inside CKD Working Group1
1
aims to model the global clinical and economic burden of CKD using country-specific, IFC-CNR, Section of Epidemiology and Physiopathology of Renal Disease and
patient-level microsimulation models. We used the Inside CKD microsimulation to Hypertension , Reggio Calabria, Italy, 2Grande Ospedale Metropolitano BMM,
model the potential clinical and economic impacts of routine UACR measurement Nephrology, Dialysis, and Transplantation Unit, Reggio Calabria, Italy and
3
with appropriate intervention in primary care settings in UK patients aged 45 years Associazione per le Ricerche su Ipertensione, Nefrologia e Trapianto Renale, IPNET,
and over. This analysis is being expanded to further European countries. Reggio Calabria, Italy
METHOD: We used the Inside CKD microsimulation to model the clinical and
economic impacts of measuring UACR with subsequent appropriate intervention BACKGROUND AND AIMS: Biomarkers of the Chronic Kidney Disease – Bone
during routine primary care visits in all individuals aged 45 years and over, versus Mineral Disorder (CKD-BMD)-including serum phosphate, calcium, PTH, 1,25
current practice (i.e. screening in patients with diabetes, hypertension or cardiovascular vitamin D, alkaline phosphatase and FGF23- have been implicated in CKD progression
disease). The model covers the period 2020–2025. First, a virtual population in follow up studies focusing on single measurements made at baseline only. The
representing the general population of the UK was constructed using data from the relationship between the time trend of these biomarkers over the course of CKD and
2016 Health Survey for England, covering demographics, prevalence of CKD and renal outcomes has never been tested.
comorbidities (type 2 diabetes, uncontrolled hypertension and heart failure) and METHOD: In this study we applied the joint model, an approach combining the
incidence of complications (heart failure, myocardial infarction, stroke and acute mixed linear model (MLM) and Cox’s regression analysis, to investigate the
kidney injury). The model also included parameters relating to the direct and indirect longitudinal relationship between repeated measurements (median 3, interquartile
costs associated with CKD (e.g. cost of renal replacement therapy), the proportion of range 2-5) of serum phosphate, calcium, PTH and alkaline phosphatase and a
patients who visit a primary care physician at least once a year, the proportion of composite renal outcome measure (eGFR reduction >30%, dialysis or transplantation)
patients who agree to UACR measurements, and the diagnostic sensitivity and cohort of 729 stage 2-5 CKD patients (average eGFR = 36613 ml/min/1.73 m2) over a
specificity of UACR measurements. 2.4 year follow up. Data were adjusted for traditional and CKD specific risk factors in
RESULTS: Preliminary results from the UK show that over the 2020–2025 period, models including also baseline serum 1,25 vitamin D and FGF23.
routinely measuring UACR in all patients aged 45 years and over during primary care RESULTS: On univariate MLM analyses, serum PTH was the sole CKD-BMD
visits could prevent progression to CKD stages 3b–5 in approximately 327 000 patients, biomarker which significantly changed over time [b=0.030 (95% CI from 0.018 to
compared with current clinical practice, with a linear increase in the cumulative 0.041), p<0.001]. In the multivariate mixed linear sub-model of the Joint Model,
number of prevented cases over the 5 years (Figure). Associated savings in costs related repeated measurements of PTH were related directly with male gender (P=0.033),
to the management of CKD and its complications are projected to be approximately alkaline phosphatase (P<0.01) and systolic BP (P=0.004) and inversely with calcium
£300M in 2025, corresponding to a 1.9% reduction from current clinical practice. (P<0.001), baseline eGFR (P<0.001), and CRP (P<0.045). In the survival analysis sub-
CONCLUSION: Preliminary results from this Inside CKD microsimulation model model of the joint model, the longitudinal series of PTH valuesover time were directly
show that implementation of routine measurement of UACR in primary care settings related to the incidence rate of renal events [HR (1 ln increase in PTH)=3.358 (95% CI
in the UK could prevent a substantial number of patients progressing to CKD stages from 2.628 to 4.293), p<0.001] and this was also true after data adjustment for a series
3b–5 and has the potential to reduce the associated healthcare-related costs of potential confounders [HR (1 ln increase in PTH)=2.25 (95% CI from 1.524 to
considerably. This analysis is being extended to other European countries. 3.321), p<0.001]. In this analysis, also serum phosphate, baseline FGF23, proteinuria,
baseline 1.25 vit D, calcium, and haemoglobin were significantly related to the
incidence rate of renal events and these relationships were all independent of the
baseline eGFR.
CONCLUSION: In this longitudinal study in stage 2-5 CKD patients investigating the
links of CKD-MBD biomarkers with a composite renal outcome, PTH was the sole
variable to show a linear increase overtime and to be directly related with the same
outcome. Even though stable over-time, also the longitudinal series of serum
phosphate (in a direct fashion) and calcium (in an inverse fashion) values were related
to the same outcome as it were baseline FGF23 and 1.25 vit D. Findings in this
longitudinal study further underscore the potential relevance of CKD-MBD
biomarkers as risk factors for CKD progression.

MO500 A NEW INDEX BASED ON THE DIFFERENCE BETWEEN


CREATININE-BASED EGFR AND CYSTATIN-C EGFR
ASSOCIATES WITH THE PHYSICAL COMPONENT OF THE
SF-36 AND PREDICTS CARDIOVASCULAR EVENTS AND
PROGRESION TO KIDNEY FAILURE IN CKD.

Francesca Mallamaci1,2, Graziella D’Arrigo2, Carmela Marino2, Patrizia Pizzini2,


Giovanni Luigi Tripepi2, Carmine Zoccali3, Of behalf of Mauro Working Group2
1
Grande Ospedale Metropolitano BMM, Nephrology, Dialysis, and Transplantation Unit,
Reggio Calabria, Italy, 2IFC-CNR, Section of Epidemiology and Physiopathology of Renal
Disease and Hypertension, Reggio Calabria, Italy and 3Associazione per le Ricerche su
Ipertensione, Nefrologia e Trapianto Renale, IPNET, Reggio Calabria, Italy

MO498 Figure: Figure. Cumulative numbers of CKD cases prevented from progressing BACKGROUND AND AIMS: Analyses in a large clinical trial in hypertensive patients
to CKD stages 3b-5 over the 2020-2025 period by routine measurement of UACR with (SPRINT) and in the Cardiovascular Health study cohort coherently showed that the
subsequent intervention in primary care in the UK. difference between the GFR as estimated by serum cystatin and creatine (eGFRDiff)
associates with frailty and predicts a lower risks for adverse outcomes including frailty,
falls, cardiovascular events and mortality. Whether eGFRdiff in CKD patients
associates with frailty metrics like the physical component summary (PCS) of the SF-
36 and cardiovascular (CV) and kidney outcomes has not been studied.
METHOD: In a cohort of 757 with stages 2-5 CKD we tested the relationship between
eGFRDiff with PCS (n=582) and in the whole cohort investigated the relationship
between the same indicator with the incidence rate of two combined endpoint: non
fatal CV events/death and renal events (dialysis/transplantation/eGFR reduction
>30%)/death over a median follow up of 35.6 months (inter-quartile range 21.3-
36.2months).
RESULTS: The eGFRDiff was strongly related to PCS (rho=0.25, P<0.001) and physical
functioning (rho=0.26, P<0.001) emerged as the strongest correlate of eGFRDiff among
PCS sub-domains. At baseline, eGFRDiff had a median value of 7.0 ml/min/1.73m2
(interquartile range: 2.2-13.0 ml/min/1.73m2) and h P=0.001), serum phosphate (b=-
0.11, P=0.003), and BMI (b=-0.08, P=0.043) had an independent relationship with the
eGFRDiff. During follow-up, 118 patients had fatal (n=29) and non fatal (n=89) CV

i308 | Abstracts
Nephrology Dialysis Transplantation Abstracts
events and 13 died of causes other than CV. Overall, 131 patients had the combined probabilities of cardiovascular and renal events with statistical significances (p<0.001
endpoint of non fatal CV event/death. Furthermore, 246 patients had renal outcomes and p<0.001, respectively). In the fully adjusted model, having lower eGFR slopes were
and 276 patients had the combined end-point renal events/death. On univariate Cox associated with HRs (95%CIs) for cardiovascular and renal events of 1.71 [1.08-2.70]
regression analyses, 1 unit increase in eGFRdiff associated with a 3% reduction of the and 1.79 [1.09-2.93], respectively.
HR of non fatal CV events/death (hazard ratio: 0.965, 95% CI: 0.951-0.978, P<0.001) CONCLUSION: These data suggest not only current eGFR but also eGFR trajectory is
and a 2% reduction of the HR of renal events/death ( 0.979, 95% CI: 0.969-0.990, an independent risk factor for cardiovascular and renal events in CKD patients.
P<0.001). Data adjustment for potential confounders (age, gender, smoking, diabetes,
cardiovascular comorbidities, antihypertensive therapy, BMI, systolic BP,
haemoglobin, albumin total cholesterol, 24h urinary protein, phosphate, and C-
MO503 SAFETY AND EFFICACY OF ANTICOAGULATION IN
reactive protein) did not materially modify the eGFRdiff- non fatal CV events-death
PATIENTS WITH EGFR<30 ML/MIN/1.73 M2 AND ATRIAL
(HR: 0.958, 95% CI: 0.939-0.977, P<0.001) as well as the eGFRdiff- renal events-death
FIBRILLATION
(HR: 0.984, 95% CI: 0.971-0.997, P=0.014).
CONCLUSION: The eGFRDiff, a new biomarker of frailty, associates with the Physical
Ellen Linnea Freese Ballegaard1, Jonas Bjerring Olesen2, Anne Lise Kamper1,
Component summary of SF36 and predicts cardiovascular events, progression to
Bo Feldt-Rasmussen1, Gunnar Gislason2,3, Christian Torp-Pedersen4,
kidney failure and death independently of other risk factors in CKD patients.
Nicholas Carlson1,3
Considering eGFRDiff as a marker of patients’ functional status may be helpful to 1
nephrologists as an indicator of poor prognosis. Copenhagen University Hospital Rigshospitalet, Nephrology, Copenhagen, Denmark,
2
Copenhagen University Hospital Herlev and Gentofte, Cardiology, Hellerup, Denmark,
3
The Danish Heart Foundation, Copenhagen, Denmark and 4North Zealand Hospital,
Cardiology, Hillerod, Denmark
MO501 INCREASED ALBUMINURIA RISK IN CHRONIC KIDNEY
DISEASE PATIENTS WHOSE WHITE COAT-, MASKED-, AND
BACKGROUND AND AIMS: Net benefit of anticoagulation in patients with eGFR
SUSTAINED HYPERTENSION: SYSTEMATIC REVIEW AND
<30 ml/min/1.73 m2 and atrial fibrillation remains uncertain. The aim of this study
META-ANALYSIS
was to evaluate the use, efficacy and safety of anticoagulation therapy in patients with
eGFR<30 ml/min/1.73m2 (including dialysis treated patients) and atrial fibrillation.
Boby Pratama Putra1, Felix Nugraha Putra2
1
METHOD: In a retrospective cohort study, all patients with atrial fibrillation and
Medical doctor, Blitar, Indonesia and 2Faculty of Medicine, Universitas Airlangga, eGFR<30 ml/min/1.73 m2 were identified in nationwide Danish registers between
Surabaya, Indonesia 2008 and 2018. Cumulative incidences of stroke and major bleeding stratified on
anticoagulation treatment were computed using the Aalen-Johansen estimator. One-
BACKGROUND AND AIMS: Latest classification of hypertension based on year risks of stroke and major bleeding were calculated with comparison of treatment
ambulatory blood pressure measurement was normotension (NT), white coat vs. no treatment based on Cox regression models adjusted for age, sex and dialysis
hypertension (WCHT), masked hypertension (MHT), and sustained hypertension status with G-computation of one-year risks standardized to the distribution of risk
(SHT). Recent studies suggest that WCHT, MHT, and SHT increase risk of target factors in the sample. Major bleeding was defined as any diagnosis of bleeding leading
organ damage, particularly albuminuria, although the results were still inconsistent. to hospitalization.
Albuminuria is not only the sign of early glomerular damage in CKD patients, but also RESULTS: A total of 2,452 patients with eGFR <30 ml/min/1.73 m2 and de novo atrial
the signs of hypertension progression and predictors for cardiovascular events fibrillation were identified. Mean age was 78.8 years, 51.3% were male and 20%
mortality. This study aims to compare the albuminuria risk among NT and WCHT, received dialysis therapy. Anticoagulation therapy was initiated in 877 patients
MHT, also SHT in CKD patients. (35.8%), with warfarin accounting for 58.6% of all prescriptions.
METHOD: We searched the literature comprehensively in online databases of Overall, one-year standardized risk of bleeding was 10.6% (95% confidence interval
Pubmed, EMBASE, ScienceDirect, and Cochrane Library to include all relevant studies (CI) 8.7%-12.7%) and 8.2% (95% CI 6.9%-9.5%) in patients with and without
using predefined terms until December 2020. We included studies that analyzed the anticoagulation, while the risks of stroke were 3.6% (95% CI 2.6%-4.5%) and 5.1%
albuminuria risk and compared the log2 urinary albumin-to-creatinine ratio (ACR) (95% CI 4.1%-6.1%), respectively.
among NT and WCHT, MHT, or SHT in CKD patients. We used the Newcastle- In subgroup analyses of patients dependent vs. non-dependent on dialysis, the
Ottawa Scale for Observational Study checklist for evaluating bias risks. Analysis of the standardized one-year risk of bleeding was 13.3% (95% CI 9.0%-19.8%) vs. 10.4% (95%
studies was conducted to provide pooled Odds Ratio (OR) for albuminuria risk and CI 8.6%-12.4%) in patients with anticoagulation and 9.0% (95% CI 6.5%-12.0%) vs.
standard mean difference (SMD) for log2 ACR comparison with 95% Confidence 7.8% (95% CI 6.5%-9.2%) in patients without anticoagulation. While the risk of stroke
Interval (CI) with random-effect heterogeneity test. was 3.5% (95% CI 0.8%-6.7%) vs. 3.5% (95% CI 2.5%-4.9%) in patients with
RESULTS: We included 7 observational studies met our inclusion criteria. WCHT anticoagulation and 5.7% (95% CI 3.5%-7.8%) vs. 4.9% (95% CI 3.7% vs. 6.3%) in
increases albuminuria risk although not statistically significant (pooled OR = 1.72, patients without anticoagulation. Cumulative incidences of major bleeding and stroke
95%CI 0.97 to 3.07, p = 0.06, I2 = 75%), while MHT and SHT significantly increase are shown in the figure.
albuminuria risk with pooled OR respectively 1.62 (95%CI 1.03 to 2.53, p = 0.04, I2 = CONCLUSION: Use of anticoagulation was associated with increased risk of bleeding
82%) and 3.17 (95%CI 1.66 to 6.05, p = 0.0005, I2 = 94%). Controlled hypertension and reduced risk of stroke in patients with eGFR<30 ml/min/1.73 m2 and atrial
significantly protects CKD patients against albuminuria risk based on log2 ACR fibrillation. Randomized controlled trials are needed to establish the benefit and harm
comparison with WCHT (SMD = 0.52, 95%CI 0.38 to 0.67, p<0.00001, I2 = 0%), MHT of anticoagulation in this population.
(SMD = 0.34, 95%CI 0.19 to 0.49, p<0.0001, I2 = 39%), and SHT (SMD = 0.63, 95%CI
0.31 to 0.95, p=0.0001, I2 = 76%).
CONCLUSION: White coat hypertension, masked hypertension, and sustained
MO504 LOW BIRTH WEIGHT ASSOCIATES WITH SMALLER KIDNEY
hypertension increase albuminuria risks in CKD patients. However, further studies are
SIZE IN MIDDLE-AGED WOMEN
needed to determine the causality.
Bjørn Steinar Lillås1,2, Tor Hatlestad Qvale1, Blazej Konrad Richter2,3,4, Bjørn
Egil Vikse1,2
MO502 EGFR TRAJECTORY AND RISKS OF CARDIOVASCULAR 1
Haugesund Hospital, Department of Medicine, Haugesund, Norway, 2University of
EVENTS AND ENDSTAGING KIDNEY DISEASE IN CKD Bergen, Clinical medicine, Bergen, Norway, 3Haugesund Hospital, Department of
PATIENTS Radiology, Haugesund, Norway and 4Stavanger University Hospital, Department of
Radiology, Stavanger, Norway
Maiko Kokubu1, Takayuki Uemura1, Masaru Matsui1
1
Nara Prefecture General Medical Center, Department of Nephrology, Nara, Japan BACKGROUND AND AIMS: Low birth weight is associated with increased risk of
kidney disease due to lower nephron endowment leading to hyperfiltration and
BACKGROUND AND AIMS: Growing evidence has shown the eGFR level is an subsequent nephron loss. Nephron number is thought to associate with kidney size.
established predictor of cardiovascular events, but the association of eGFR trajectory We compared kidney size measured by magnetic resonance imaging (MRI) with
with cardiovascular and renal events remained limited. ultrasonography and measured glomerular filtration rate (mGFR) in adults with
METHOD: We conducted a retrospective cohort study on 276 CKD patients in whom normal versus low birth weight.
at least two measurements of eGFR levels to calculate eGFR slope were confirmed. METHOD: Healthy individuals aged 42-52 years with Low birth weight (LBW – 1100-
Patients were divided into two groups according to the below and above cut-off values 2300g) and normal birth weight (NBW - 3500-4000g) were invited. GFR was measured
of eGFR slopes for outcomes using ROC curve. Outcomes are cardiovascular events using plasma clearance of iohexol. Kidney volume was measured on MRI images using
defined as heart failure requiring hospitalization, revascularization for IHD and PAD, axial T2 images and coronal T1 images with fat saturation without contrast
stroke or sudden death, and renal events defined as ESRD or baseline eGFR decline of enhancement, calculations were performed according to the ellipsoid formula - p/6 x
> 30%. Length x Width x Depth. Ultrasonographic imaging was done using a dorsal approach.
RESULTS: In total, the median (IQR) age of participants was 68 (5677) years and In the maximal longitudinal view the parenchymal area was calculated subtracting the
176 (64%) were male. The median (IQR) levels of baseline eGFR were 33 (2048) mL/ area of a manual tracing around the renal pelvis from the area of a manual tracing of
min/1.73m2 with the median eGFR slope of -5.2(-0.85-9.5) mL/min/1.73m2/yr. the whole kidney. Volume and area from the two kidneys were added and total value
During the study period, 92 cardiovascular events and 89 renal events occurred. Crude was used for analyses. Kidney size measurements were compared between the two
Kaplan-Meier analysis showed participants with lower eGFR slopes had higher groups of LBW vs NBW, and analysis using Pearson’s correlation coefficient R between

10.1093/ndt/gfab087 | i309
Abstracts Nephrology Dialysis Transplantation

kidney volume and measured GFR and parenchymal area was performed. reduced physical HRQOL during the COVID-19 pandemic. The impact of the
RESULTS: We included 102 individuals (54 LBW, 48 NBW). Total kidney volume was pandemic on this vulnerable patient group extends beyond increased mortality risk,
302 6 51 ml for female NBW vs 258 6 48 ml for female LBW (p=0.002). For men, and awareness of mental health problems during the pandemic is essential. More in-
total kidney volume was 347 6 51 ml vs 340 6 65 ml (p=0.7). Measured GFR was depth investigation on disease-related COVID-19 concerns and its implications for the
significantly associated with kidney volume with R=0.52 (p<0.001) for women and CKD population is needed.
R=0.39 (p=0.007) for men. Kidney parenchymal area measurements using
ultrasonography showed similar results with an R=0.77 between the MRI and the
ultrasonography measurement and similar differences for sex and birth weight were
MO506 RELATIONSHIP BETWEEN SODIUM CONSUMPTION, PRO-
seen.
INFLAMMATORY PARAMETERS AND KIDNEY DISEASE IN
CONCLUSION: Healthy middle-aged females born with LBW have smaller kidneys
THE JACKSON HEART STUDY
than healthy middle-aged females born with NBW, no difference were seen for males.
Kidney volume associate with measured GFR.
Eliane Wenstedt1, Liffert Vogt2
1
Amsterdam UMC, Internal Medicine, section of Nephrology, Amsterdam, The
Netherlands and 2Amsterdam UMC, location AMC, Internal Medicine, section of
MO505 IMPACT OF THE COVID-19 PANDEMIC ON SYMPTOMS OF Nephrology, Amsterdam, The Netherlands
ANXIETY AND DEPRESSION AND HEALTH-RELATED
QUALITY OF LIFE IN OLDER PATIENTS WITH CHRONIC
BACKGROUND AND AIMS: Kidney disease is thought to be linked to inflammation.
KIDNEY DISEASE.
Pro-inflammatory parameters like C-reactive protein (CRP), endothelin-1, and TNF-a
inversely associate with kidney function cross-sectionally and some have predictive
Carlijn Voorend1, Mathijs Van Oevelen1, Margot Nieberg1, Yvette Meuleman2,
value for longer-term kidney outcomes. Given the recently argued pro-inflammatory
Casper Franssen3, Hanneke Joosten4, Noeleen Berkhout-Byrne1, Alferso
effect of sodium, we questioned whether sodium consumption has a role in the
C. Abrahams5, Willem Jan W. Bos1,6, Marjolijn Van Buren1,7
1
relationship between pro-inflammatory parameters and renal outcomes.
Leiden University Medical Center (LUMC), Internal Medicine, Leiden, The Netherlands, METHOD: Our research question was investigated using the Jackson Heart Study,
2
Leiden University Medical Center (LUMC), Epidemiology, Leiden, The Netherlands, which is a large prospective cohort study involving n=5301 Afro-Americans residing in
3
University Medical Center Groningen, Nephrology, Groningen, The Netherlands, Jackson, Mississippi, US. Spot urine sodium was used to estimate 24-hour sodium
4
Maastricht University Medical Center+, Geriatric Medicine, Maastricht, The excretion with the Kawasaki formula, serving as a proxy for sodium consumption, and
Netherlands, 5UMC Utrecht, Nephrology, Utrecht, The Netherlands, 6St. Antonius was available for n=1831 participants (depicting a random sample of the total
Hospital, Internal Medicine, Nieuwegein, The Netherlands and 7Haga Hospital (Leyweg), population) that had a median follow-up of 8 years. Multiple linear regression was used
Internal Medicine, Den Haag, The Netherlands to assess the relationship between sodium consumption and pro-inflammatory
parameters. The parameters available for this cohort involved endothelin-1, high-
BACKGROUND AND AIMS: Older patients with advanced chronic kidney disease sensitivity CRP, and leukocyte subsets (monocytes, neutrophils, and lymphocytes).
(CKD) are at increased risk for a severe course of the coronavirus disease-2019 Models were adjusted for potential confounders, involving sex, age, body mass index,
(COVID-19) and vulnerable to mental health problems. We aimed to investigate estimated potassium intake, smoking status, and presence of diabetes. Subsequently,
prevalence and associated patient (demographic and clinical) characteristics of mental linear regression analyses between pro-inflammatory parameters and baseline
wellbeing (health-related quality of life [HRQoL] and symptoms of depression and estimated glomerular filtration rate (eGFR CKD-EPI) and change during follow-up
anxiety) before and during the COVID-19 pandemic in older patients with advanced were carried out with and without adjustment for sodium consumption as a
CKD. confounder, to explore the possibility of a causal mediating pathway.
METHOD: An ongoing Dutch multicentre prospective cohort study enrols patients of RESULTS: Increased sodium consumption significantly associates with increased
70 years with an eGFR <20 mL/min/1.73m2 from October 2018 onward. With serum endothelin-1 levels in both unadjusted and adjusted models (Table 1). There
additional questionnaires during the pandemic (May-June 2020), disease-related was no association between sodium consumption and leukocyte subsets. There was a
concerns about COVID-19 and general anxiety symptoms were assessed cross- negative association between sodium consumption and CRP (Table 2). CRP was not
sectionally, and depressive symptoms, HRQoL, and emotional symptoms associated with eGFR at baseline (p=0.20) or eGFR change from baseline (p=0.20).
longitudinally. Endothelin-1 was inversely associated with eGFR at baseline (beta -0.06, p<0.001) and
RESULTS: The 82 included patients had a median age of 77.5 years (inter-quartile with eGFR change from baseline (beta 2.3 p=0.03). However, when these models were
range 73.9-82.1), 77% was male and none had tested positive for COVID-19. Cross- corrected for sodium consumption, endothelin-1 was no longer a significant predictor
sectionally, 67% of the patients reported to be more anxious for COVID-19 because of (beta -0.01 p=0.4 for eGFR at baseline) or was inversed (beta -0.1; p=0.001 eGFR
their kidney disease, and 43% of the patients stated that their quality of life was reduced during follow-up).
due to the COVID-19 pandemic (Figure 1). Higher COVID-19-related stress was CONCLUSION: In this prospective cohort of Afro-Americans, increased sodium
associated with a lower education level (p=0.036), and patients who reported to feel consumption is associated with increased circulating endothelin-1 levels. If this
more down due to COVID-19 were more often female (p=0.020). Anxiety scores were relationship proves to be causal (as suggested by animal sodium loading studies), this
higher among females compared to males (median 4.0 [IQR 3.0-9.0] versus 2.0 [0.0- implies that sodium consumption may (at least partly) be underlying the relationship
6.0], p=0.020), and weakly associated to a decline in eGFR (correlation coefficient between endothelin-1 and worse renal outcomes.
0.197, p=0.023).

MO505 Figure 1: Respondents’ agreement to the COVID-19 related statements.


Questions were scored on a scale from 1 ‘totally disagree’ to 5 ‘totally agree’. Mean
score for question 1 was 3.6 (IQR 2.8-5.0) n=82, question 2 mean 2.7 (IQR 1.0-4.0)
n=82, question 3 mean 2.3 (IQR 1.0-4.0) n=82, question 4 mean 2.7 (IQR 1.0-4.0)
n=81.Compared to pre-COVID-19, presence of depressive symptoms had increased
(11% to 22%; p=0.022) and physical HRQoL declined (40.4610.1 to 36.1610.4,
p<0.001). Mental HRQoL (50.369.6 to 50.469.9; p=0.913) and emotional symptoms
remained similar. Males showed a greater decline in physical HRQoL (mean -5.3, SD
8.5) compared to females (mean -0.9, SD 5.7; p=0.039).
CONCLUSION: Our findings show that older patients with advanced CKD suffered
from disease-related anxiety for COVID-19, increased depressive symptoms, and

i310 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO507 ROCK STUDY: RESEARCH STUDY OF CANCER ASSOCIATED MO508 HEMATOCRIT, UREA AND GENDER (HUGE) EQUATION AND
KIDNEY DISEASES CARDIOVASCULAR EVENTS: A PROSPECTIVE STUDY IN
SPANISH POPULATION
Mariarosa Maiorana1,2, Francesco Iannuzzella2, Paolo Giorgi Rossi2,
Marta Ottone2, Mariacristina Gregorini2 Barbara Cancho Castellano1, Nicolas-Roberto Robles Perez-Monteoliva1,
1
University of Modena and Reggio Emilia, Modena, Italy and 2AUSL Reggio Emilia, Francisco Javier Felix Redondo2, Luis Lozano2, Daniel Fernandez-Berges2
1
Reggio Emilia, Italy Hospital Universitario de Badajoz, Nephrology, Badajoz, Spain and 2INUBE.
Universidad de Extremadura
BACKGROUND AND AIMS: The improvement in the survival rates of cancer
patients due to the new oncological and biological agents has led to an increase in those BACKGROUND AND AIMS: To evaluate the relationship between chronic kidney
who develop kidney diseases. disease (CKD) diagnosed by the hematocrit, urea and gender (HUGE) equation and
It is now well known that chronic kidney disease (CKD) and cancer are connected in the incidence of major adverse cardiovascular events and cardiovascular mortality in a
several ways. Nevertheless, although emerging evidence suggests that the risk of renal sample of Spanish general population.
impairment in cancer patients is high and increasing, the overall incidence and METHOD: The sample consisted of 2,668 subjects (mean age, 50.6614.5 years; 54.6%
prevalence of CKD in this population are still uncertain. The purpose of the study is to were female). Of them, 55 patients have a HUGE score > 0. The median follow-up was
provide data on the prevalence and incidence of CKD in patients included in the 81 (75-89) months. Serum creatinine, urea and haematocrit were analyzed after
Cancer Registry of the province of Reggio Emilia, Italy, since January, 1st to December, overnight fast. The HUGE formula score was calculated for all subjects.
31st 2016. RESULTS: Event-free survival was 98.4 % at three years and 97.1% at five years of
METHOD: single-center, observational and retrospective study. For all patients follow-up for patients with a HUGE score < 0. For patients with a estimated HUGE
included, data on sex, age, ethnicity, serum creatinine and related eGFR, type and score higher than 0 survival was 88.9% at three years and 87.0 at five years of follow-up.
number of tumors, diagnosis of diabetes mellitus were collected. The main cancer sites (p<0.0001). Cardiovascular death survival was 94.4 % at three and 88.0 at five years of
considered were breast, colorectal, lung, pancreas, stomach, prostate, lymphomas and follow-up for patients with a HUGE score higher than 0. For patients with a estimated
leukemias. An eGFR  60 ml/min1.73m2 was indicative of a normal kidney function, HUGE. score lower than 0 survival was 99.3% at three years, and 99.0% at five years of
while an eGFR <60 ml/min/1.73m2 as kidney impairment. All the eGFR data were follow-up. (p<0.001).
calculated not only with the CKD-EPI formula, now recognized as the reference CONCLUSION: A significantly increased cardiovascular risk was associated to the
formula for estimating eGFR in the general population, but also with the Wright diagnosis of CKD through HUGE formula. This effect on survival could be detected
formula which seems to provide the best estimate in cancer patients. despite of a very small sample of CKD patients. This relationship was close to those
RESULTS: 4254 patients with a cancer diagnosis were identified between January 1st obtained using MDRD estimated GFR in a bigger sample of patients. HUGE formula
and December 31st 2016; of these, 171 patients were excluded due to lack of data. Of may be a useful tool for diagnosing CKD and to evaluate the cardiovascular risk of
the remaining 4083 patients, 776 (19%) had at least an eGFR value <60 mL/min/ these patients.
1.73m2 prior to cancer diagnosis and 497 patients (11.7%) were identified as affected by
CKD. The incidence of new-onset CKD in the following 24 months since cancer
diagnosis was 4.4% (186 patients) [95% CI 3.9-5.3] using CKD-EPI formula; using
Wright formula, we identified 140 (3.4%) [95% CI 2.9-4.0] new cases of CKD in the MO509 DOSE-RESPONSE RELATIONSHIP BETWEEN ALCOHOL
same period. For both cohorts of patients (pre-existing CKD and CKD diagnosed after CONSUMPTION AND THE RISK OF DEVELOPING CKD:
cancer diagnosis), descriptive analyzes were conducted related to demographic and RETROSPECTIVE COHORT STUDY
clinical data. Referring to the CKD-EPI formula, in patients with pre-existing CKD
(497 patients, 11.7%), the mean age was 81 years (SD 6 8.4), 53.7% were men, 18.3% Yusaku Hashimoto1, Takahiro Imaizumi1,2, Akihiro Hori3, Sawako Kato1,
had a known diagnosis of type 2 diabetes mellitus, 3.6% of these patients had 2 or more Yoshinari Yasuda1, Shoichi Maruyama1
1
cancer diagnosis in the study period. 44.3% were alive at the end of the follow-up Nagoya University Graduate School of Medicine, Nephrology, Aichi, Japan, 2Nagoya
(December 31st, 2018). Using Wright formula, 504 (11.8%) patients with CKD already University Hospital, Center for Advanced Medicine and Clinical Research, Aichi, Japan
present at the time of cancer diagnosis were identified; these patients had an average and 3Kumiai Kosei Hospital, Takayama, Japan
age of 82 years (SD 6 8.4) and in 55.4% of cases were men; 18.8% had type 2 diabetes
mellitus and 3.8% had 2 or more cancer diagnosis. BACKGROUND AND AIMS: Drinking habits are one of the most important
CONCLUSION: The ROCK study is the first large cohort study that allows a clearer modifiable lifestyle factors to prevent the development of chronic kidney disease
estimation of the frequency of CKD in Italian cancer patients. Knowledge of the (CKD). Previous studies showed that it was inversely associated with the risk of
prevalence of CKD in cancer patients is essential for proper clinical and therapeutic developing CKD, but the dose-response relationship between alcohol consumption
management and implementation of preventive strategies. and the development of CKD is still controversial. In the present study, we aimed to
examine whether the amount of alcohol consumed at one time is associated with
new onset of CKD in general population.
METHOD: Study subjects were 11,162 Japanese aged 45 to 74 years, with an
estimated glomerular filtration rate 60 mL/min/1.73m2, no proteinuria, no past
history of cardiovascular disease, COPD or liver disease. The drinking status was
obtained by self-administered questionnaires. We categorized the study subjects
into four groups based on the amount of alcohol consumption: <20g/time of
ethanol equivalent (lowest); 20-40g/time (low intermediate); 40-60g/time (high
intermediate); >60g/time (highest). We set non-drinkers as a reference category.
The primary outcome was the incidence of CKD, defined as 25% reduction of eGFR
and to less than 60 mL/min/1.73 m2 and/or a dipstick urinalysis score of 11 or
greater (equivalent to 30 mg/dL) during the follow up period. We employed Cox
proportional hazards regression models to examine the dose-response relationship
between baseline alcohol consumption and the risk of CKD. Trend tests were
performed using Cox proportional hazards regression models that treated alcohol
consumption as a continuous linear term.
RESULTS: Lowest and low intermediate groups were significantly associated with a
decreased risk of CKD (hazard ratio [HR] 0.84; 95% confidence interval [CI], and
0.71–0.99; HR 0.79; 95% CI, 0.66–0.96, respectively) compared to non-drinkers.
MO507 Figure: Progression rate of CKD based on eGFR reduction in cancer site High intermediate group was associated with a decreased risk of CKD (HR 0.92;
evaluatedn CKD’s stage distribution at cancer diagnosis for every cancer site evaluated 95% CI, 0.70–1.21), and highest group was associated with an increased risk of
Breast cancer Colorectal cancer Lung cancer Pancreas cancer Stomach cancer Prostate CKD (HR 1.28; 95% CI, 0.84–1.95), but these associations did not reach statistical
cancer Lymphomas Leukemias CKD’s stage distribution for single cancer site evaluated significance. There was no dose-response relationship between baseline alcohol
consumption and risk of CKD (P-trend = 0.30).
CONCLUSION: A J-shape association was observed between self-reported alcohol
intake and the incidence of CKD. Moderate alcohol consumption at one time may
help reduce the risk of CKD.

10.1093/ndt/gfab087 | i311
Abstracts Nephrology Dialysis Transplantation

MO510 OLFACTORY AND GUSTATORY DYSFUNCTION AMONG estimated glomerular filtration rate (eGFR) 15–59 ml/min/1.73 m2 and/or by an
PATIENTS WITH KIDNEY IMPAIRMENT International Classification of Diseases (ICD) code, and confirmed by a second eGFR
value or ICD code 90–365 days apart (index date). Individuals had to be 18 years old
Api Chewcharat1, Elizabeth Phipps1, Khushboo Bhatai1, Sagar Nigwekar2 at index and have 365 days of continuous insurance coverage prior to the index event
1
Mount Auburn Hospital, Medicine, Cambridge, United States of America and (baseline period). Those with diabetes mellitus, CKD stage 5 or end-stage kidney
2
Massachusetts General Hospital, Nephrology, Medicine, Boston, United States of disease prior to the index date, or who experienced kidney failure (acute or
America unspecified), kidney transplant or dialysis at baseline, were excluded from the analysis.
Patient demographics, clinical characteristics, comorbidities and medications were
assessed at baseline.
RESULTS: Of the 64 million individuals in the Optum Clinformatics Data Mart during
the analysed time period, 504,924 satisfied the selection criteria. Median (interquartile
range) age was 75 (68–81) years, 60% were female, 63% were white and 10% were
black. The proportions of individuals with CKD stage 3 and 4 at index were 95% and
5%, respectively. At baseline, eGFR values were available for 62% of individuals;
median (interquartile range) eGFR was 53 (47–57) ml/min/1.73 m2. A urine albumin-
to-creatinine ratio was recorded in 6% of individuals, of whom 73%, 21% and 6% had
normal-to-mildly increased (<30 mg/g), moderately increased (30 to 300 mg/g)
and severely increased (>300 mg/g) albuminuria, respectively. The most common
baseline comorbidities were hypertension (85% of individuals), hyperlipidaemia (68%),
hypothyroidism (26%), anaemia (25%), pulmonary disease (24%) and coronary artery
disease (24%). Heart failure, atrial fibrillation and peripheral artery disease were
BACKGROUND AND AIMS: Poor appetite and food aversion are common in recorded in 16%, 15% and 14% of individuals, respectively. The most frequently used
chronic kidney disease patients. Olfactory and gustatory function changes might be medication classes at baseline were statins (47% of individuals), beta blockers (44%),
attributed to poor appetite among this population. Nevertheless, the associations nonsteroidal anti-inflammatory drugs (36%) and angiotensin-converting
between impaired kidney function and olfactory and gustatory dysfunction are less enzyme inhibitors (34%). Angiotensin receptor blockers and mineralocorticoid
clear. Moreover, the prevalences of olfactory and gustatory dysfunction among patients receptor antagonists were used by 21% and 4% of individuals, respectively. The
with impaired kidney function have not been reported. speciality of the diagnosing provider was reported on 26% of claims for the index event,
METHOD: We conducted a cross-sectional study among 3,529 US adults aged  40 the most common being family or internal medicine, followed by nephrology.
years old in the National Health and Nutrition Examination Survey (NHANES) 2013- CONCLUSION: This analysis contributes to the characterisation of a real-world
2014. We calculated the prevalences of olfactory and gustatory dysfunction among population with non-diabetic CKD treated in routine clinical practice in the US. A
patients with impaired kidney function aged  40 years old by using analytic survey large cohort of individuals with moderate-to-severe CKD was identified. The majority
weights and design factors. We also examined the association between impaired kidney were elderly with multiple serious cardiovascular and pulmonary comorbidities and
function and olfactory and gustatory dysfunction as well as the association between frequent use of nonsteroidal anti-inflammatory drugs. Overall, the analysis highlights
olfactory and gustatory dysfunction and nutritional markers among patients with the urgent need for improving early diagnosis, prevention and effective treatment of
impaired kidney function using weighted multivariable linear regression and logistic CKD.
regression.
RESULTS: The prevalences of olfactory impairment and gustatory dysfunction among
impaired kidney function participants were 25% and 14%, respectively. After adjusting MO512 THE RENAL CONSEQUENCES OF LUNG TRANSPLANTATION
for confounders, impaired kidney function was significantly associated with higher IN ADULT CYSTIC FIBROSIS PATIENTS.
odds of olfactory dysfunction (OR = 1.29, 95% CI [1.03, 1.60]; p=0.04) but not
gustatory dysfunction (OR = 1.41, 95%CI [0.96, 2.09]; p=0.08). Among impaired Etienne Novel1, Solenne Pelletier1, Laetitia Koppe1, Raphaele Nove Josserand1,
kidney function population, olfactory dysfunction was significantly associated with Quitterie Reynaud1, Denis Fouque1, Isabelle Durieu1
lower serum albumin and grip strength but not serum total cholesterol, LDL- 1
Lyon Sud Hospital Center, Pierre-Bénite, France
cholesterol or protein-energy malnutrition. However, gustatory dysfunction was not
significantly associated with any nutritional markers among the impaired kidney
function population. (Figure 1) BACKGROUND AND AIMS: Cystic fibrosis patients are at high risk for chronic
CONCLUSION: Impaired kidney function was associated with higher odds of kidney disease (CKD), because of chronic aminoglycoside exposure, high protein and
olfactory but not gustatory dysfunction. Among those with impaired kidney function, dietary salt intake, and Cystic Fibrosis Related Diabetes. Lung transplantation also
only olfactory but not gustatory dysfunction was associated with lower serum albumin entails a high renal burden in the long run because of calcineurin inhibitors exposure.
and grip strength. We aimed at studying kidney function by gold standard glomerular filtration rate
(mGFR) before and 1 year after lung transplantation, as well as identify risk factors for
kidney function impairment.
METHOD: Patients from the Cystic Fibrosis reference center in Lyon, France were
MO511 BASELINE CHARACTERISTICS OF A NON-DIABETIC CKD systematically referred to the nephrology department before lung transplantation.
COHORT IN A US CLAIMS DATABASE mGFR (iohexol or inulin clearance) was performed before and 12-18 months after lung
transplantation. Risk factors for a worse nephrological outcome (i.e. post
Christoph Wanner1, Johannes Schuchhardt2, Chris Bauer2, Stefanie Lindemann3, transplantation mGFR < 60mL/min/1.73m2) were searched for.
Meike Brinker4, Sheldon Kong5, Frank Kleinjung6, Andrea Horvat-Broecker4, RESULTS: 28 patients (10 males), mean age 32 yr, underwent pre transplantation
Tatsiana Vaitsiakhovich6 mGFR. Three died following lung transplantation and two progressed to end stage
1
Medizinische Klinik und Poliklinik 1, Schwerpunkt Nephrologie, Würzburg, Germany, renal disease rapidly thereafter. 23 patients benefited from both pre and post
2
MicroDiscovery GmbH, Berlin, Germany, 3Bayer AG, Medical Affairs & transplantation mGFR.
Pharmacovigilance, Berlin, Germany, 4Bayer AG, Wuppertal, Germany, 5Bayer Mean mGFR was 105621mL/min/1.73m2 and 67619 mL/min/1.73m2 before and
Pharmaceuticals, Whippany, United States of America and 6Bayer AG, Berlin, Germany after transplant respectively. Factors associated with a worse renal outcome in both
univariate and multivariate analysis were age at transplantation (p=0.03) and the
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a major global health occurrence of acute kidney injury in the post-operative period (p=0.005). Cumulated
problem, affecting an estimated 850 million people worldwide. Non-diabetic CKD aminoglycoside exposure and time spent under cardiopulmonary bypass were not
accounts for up to 70% of the CKD burden, which includes morbidity and mortality associated with renal outcome.
due to CKD progression to kidney failure and due to cardiovascular disease. This CONCLUSION: Lung transplantation is associated with a high renal burden in adult
analysis uses real-world evidence to provide insights into the baseline clinical Cystic Fibrosis patients. We advise a clinical referral to a nephrologist as part of the
characteristics of individuals with non-diabetic CKD treated in routine clinical systematic evaluation in lung transplantation candidates even if GFR is in the normal
practice. range.
METHOD: The Optum Clinformatics Data Mart was used to identify individuals with
non-diabetic CKD (enrolled in the database between January 1, 2008 and December
31, 2018), based on common diagnosis, procedure and laboratory codes. To be eligible
for inclusion, individuals were required to have CKD stage 3 or 4, as identified by

i312 | Abstracts
Nephrology Dialysis Transplantation Abstracts
glucocorticoids the most frequent medication. However, 26.8% of nephrotic range
patients were not prescribed any FSGS-related medications.

MO513 Figure 1: Annual all-cause medical costs per patient. A) FSGS and matched
MO513 CLINICAL AND ECONOMIC BURDEN OF FOCAL SEGMENTAL non-FSGS cohorts. B) Nephrotic range and non-nephrotic FSGS patients.
GLOMERULOSCLEROSIS (FSGS) IN THE UNITED STATES: A CONCLUSION: FSGS is associated with significant clinical and economic burdens
RETROSPECTIVE, OBSERVATIONAL COHORT STUDY with total annual medical costs > 7-fold higher than matched controls that were driven
by outpatient costs. The presence of nephrotic range proteinuria substantially and
Kam Kalantar-Zadeh1, Christine Baker2, J Brian Copley2, Daniel Levy2, significantly increased the economic burden. New treatment modalities leading to
Stephen Berasi2, Nihad Tamimi3, Jose Alvir2, Suneel Udani4 lower rates of proteinuria may help improve patient outcomes while reducing HCRU
1
University of California, Irvine, School of Medicine, Irvine, United States of America, and their associated costs.
2
Pfizer, New York, United States of America, 3Medicopharma Solutions Ltd., Canterbury,
Kent, United Kingdom and 4Chicago Glomerular Disease Institute, Chicago, United
States of America MO514 CARDIORENAL OUTCOMES AND MORTALITY IN PATIENTS
WITH TYPE 2 DIABETES MELLITUS: A MULTINATIONAL
BACKGROUND AND AIMS: The burden of disease associated with FSGS has not PROSPECTIVE COHORT STUDY (PROVALID)
been well characterized, especially with regard to health care resource utilization
(HCRU) and related costs. The aim of this study was to evaluate all-cause HCRU and Stefanie Thöni1, Felix Keller1, Sara Denicolo1, Susanne Eder1, Laszlo Rosivall2,
estimate associated costs in patients with FSGS compared with a matched non-FSGS Andrzej Jan Wiecek3, Patrick Mark4, Peter Rossing5, Hiddo Lambers Heerspink6,
cohort; a secondary aim was to evaluate the impact of nephrotic range proteinuria on Gert Mayer1
these outcomes. 1
Medical University of Innsbruck, Department of Internal Medicine IV (Nephrology and
METHOD: Data were from the Optum ClinformaticsV R Data Mart Database. Patients
Hypertension), Innsbruck, Austria, 2Institute of Translational Medicine, Semmelweis
with  1 claim (1st claim = index event) for FSGS between April 2016 and December University, International Nephrology Research and Training Center, Budapest, Hungary,
2018 were identified based on ICD-10-CM codes and matched 1:2 (FSGS:controls) on 3
Medical University of Silesia, Department of Nephrology, Transplantation and Internal
index date, age, sex, and race to non-FSGS controls; continuous enrollment 6 months Medicine, Katowice, Poland, 4University of Glasgow, Institute of Cardiovascular and
pre- and 12 months post-index was required. FSGS nephrotic range (either UPCR Medical Sciences, Glasgow, United Kingdom, 5University of Copenhagen, Steno
>3000 mg/g or ACR >2000 mg/g) and non-nephrotic subpopulations were also Diabetes Center Copenhagen, Gentofte, Denmark and 6University Medical Center
identified. Quan-Charlson Comorbidity Index (CCI) and individual comorbidities at Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The
baseline, and 12-month post-index all-cause HCRU and associated costs (per patient Netherlands
per year [PPPY]) as well as medication prescriptions related to FSGS treatment were
compared between the matched cohorts and between the FSGS subpopulations; t-tests
BACKGROUND AND AIMS: PROVALID is a prospective, observational,
were used for continuous variables and chi-square tests for categorical variables.
multinational cohort study in 4000 patients with type 2 diabetes mellitus. Our aim was
RESULTS: 844 patients with FSGS were matched with 1688 non-FSGS controls; 57.4%
to determine the incidence rate of renal and cardiovascular endpoints, as well as all-
male, 56.9% white, mean (SD) age 54.7 (18.4) years. Mean (SD) CCI was higher in the
cause-mortality in different European countries and to identify risk factors associated
FSGS cohort relative to matched controls (2.72 [2.12] vs 0.55 [1.29]; P < .0001), with
with the investigated outcomes.
prevalence of most individual comorbidities higher in the FSGS cohort. Only 308 FSGS
METHOD: Potential risk factors associated with the investigated outcomes were
patients (36.5%) had UPCR or ACR tests with available results during the review
identified by calculation of the incidence rate ratio. Crude and adjusted incidence rates
period; 112 (36.4%) were in the nephrotic range and 196 were non- nephrotic (63.6%).
for every country were estimated using generalized linear (poisson) regression models
The FSGS cohort was characterized by higher rates of all-cause HCRU across resource
and corresponding 95 % confidence intervals were computed. Incidence rates were
categories (all P < .0001) (Table 1); outpatient visits was the most frequently used
adjusted for different risk factors including age, sex, estimated GFR, albuminuria,
category (99.1% vs 69.0%), followed by prescription medications. Among patients who
HbA1c, LDL, HDL, total cholesterol, systolic blood pressure, BMI and cardiovascular
used these resources, units of use were significantly higher in FSGS vs matched controls
and renal comorbidities; among these several show significant impact on outcomes.
except for length of stay (Table 1). Readmission rates following 1st post-index
The renal outcome was a composite of a sustained decline in the estimated GFR of at
hospitalization were higher in the FSGS cohort vs matched controls at 30 days (16.1%
least 40%, a sustained increase in albuminuria of at least 30 % including the
vs 6.0%; P < .05) and 365 days (39.1% vs 22.9%; P < .05). Glucocorticoids were the
progression from normo- to micro- or macroalbuminuria, end-stage kidney disease, or
most frequently prescribed FSGS-related medication in both cohorts, with a higher rate
death from renal causes. The cardiovascular composite endpoint was death from
in FSGS vs matched controls (50.6% vs 23.3%; P < .0001); other FSGS-related
cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
medications were infrequently prescribed (< 14%). Inpatient, outpatient, and
RESULTS: 3461 participants of four European countries (Austria 18 %, Hungary 41 %,
prescription costs were higher in the FSGS cohort vs matched controls (all P < .0001)
Netherlands 26 % and Scotland 15 %) with a mean follow up time of 3.9 years were
resulting in mean total annual medical costs of $59,753 vs $8,431 PPPY (P < .0001)
included into this study. Participants from Poland were excluded due to missing
that were driven by outpatient costs (Fig. 1A). Nephrotic range proteinuria was
follow-up data. In total, 9.2 % and 6.4 % participants reached the renal and
associated with higher all-cause inpatient, outpatient, and prescription costs vs non-
cardiovascular composite endpoint, respectively. 7.0 % of the participants died within
nephrotic patients (all P < .0001; Fig. 1B), resulting in higher total costs ($70,481 vs
this timeframe.
$36,099 PPPY; P < .0001). A higher proportion of nephrotic range patients were
prescribed FSGS-modifying medications (73.2% vs 54.1%; P = 0.001), with

10.1093/ndt/gfab087 | i313
Abstracts Nephrology Dialysis Transplantation

The adjusted incidence rate for the renal endpoint ranged from 14.5 to 25.3 (per 1000
patient-years) with no significant differences between countries. On average, the MO515 Table 2: Clinical profile and its correlation with constipation in CKD
incidence rate was lower in Scotland (IR, 14.5; 95 % CI, 8.7 to 22.5) and in the Stage3-5
Netherlands (IR, 15.7; 95 % CI, 10.9 to 21.8) compared to Hungary (IR, 25.3; 95 % CI,
20.7 to 30.6) and Austria (IR 21.3; 95 % CI, 16.2 to 27.5). Clinical profile CKD CKD CKD p
The adjusted incidence rate for the cardiovascular endpoint ranged from 7.0 to 20.3
and was significantly lower in Hungary (IR, 7.0; 95 % CI, 5.1 to 9.3) and the Stage 3 Stage 4 Stage 5 value
Netherlands (IR, 7.6; 95 % CI, 4.4 to 12.2) compared to Austria (IR, 16.7; 95 % CI, 12.4 Diabetes 28 23 36 <0.001
to 22.1) and Scotland (IR, 20.3; 95 % CI, 13.8 to 28.9).
Hypertension 41 56 79 <0.001
The adjusted incidence rate for all-cause-mortality ranged from 4.2 to 15.9 and was
significantly lower in the Netherlands (IR, 4.2; 95 % CI, 2.2 to 7.6) compared to Cardiovascular disease 08 06 14 0.804
Scotland (IR, 15.9; 95 % CI, 10.9 to 22.6). No significant difference in the incidence Hypothyroidism 03 07 05 0.625
rates between Austria (IR, 9.8; 95 % CI, 7.0 to 13.4) and Hungary (IR, 9.3; 95 % CI, 6.8
to 12.4) was found. Non-ambulant 0 01 05 0.358
CONCLUSION: After adjustment for known risk factors, incidence rates of Medications:
cardiovascular endpoints, as well as all-cause-mortality still vary significantly between Opioid 05 22 18 0.003
four European countries. This may be due to manifold reasons. Further analysis of the
national therapeutic practice pattern within the PROVALID cohort may provide Iron supplements 23 58 45 0.083
additional information. Calcium supplements 18 27 19 0.779
Potassium binders 0 05 02 0.749
Phosphate binders 08 14 21 0.184
MO515 CONSTIPATION IN CHRONIC KIDNEY DISEASE:
PREVALENCE AND RISK FACTORS Tricyclic antidepressants 01 04 03 0.086

Sourabh Sharma1, Neha Sharma1, Kailash Sharma1 CONCLUSION: Constipation measured using Rome IV criteria affects around two-
1
Gaur Hospital, Nephrology, Sriganganagar, India third of CKD stage 3-5 patients. Diabetes, hypertension and opioid use has been found
to be significantly associated with constipation.
BACKGROUND AND AIMS: Among various gastrointestinal disorders, constipation
is one of the most common symptom in chronic kidney disease (CKD). However it is
often neglected by nephrologists as self-limiting condition. Constipation impacts MO516 A STRUCTURED EXPERT ELICITATION TO INFORM AND
quality of life in multiple ways and increases socio-psychological burden. Constipation VALIDATE MORTALITY EXTRAPOLATIONS FOR A COST-
and associated risk factors have been poorly studied and most studies are retrospective. EFFECTIVENESS ANALYSIS OF DAPAGLIFLOZIN
METHOD: We enrolled CKD stage 3 to 5 patients on regular follow-up with
nephrologist from June 2018 to June 2020, at a tertiary care centre in North India. Bartholomeus Willigers1, Mario Ouwens2, Andrew Briggs3, Oliver Darlington4,
Constipation was defined using Rome IV criteria (Functional constipation) which Purav Bhatt5, Eric Wittbrodt6, Marvin Sinsakul6, Hiddo Lambers Heerspink7,
is composed of six constipation related symptoms, and diagnosis of constipation is Carol Pollock8, Roberto Flavio Silva Pecoits Filho9, Navdeep Tangri10,
established by presence of two or more symptoms for at least 3 months. Patients were Csaba Kovesdy11, David Wheeler12, Juan Jose Garcia Sanchez1
also asked to maintain a 7 day prospective stool diary. It consisted of seven day written 1
AstraZeneca, BioPharmaceuticals Medical, Cambridge, United Kingdom, 2AstraZeneca,
prospective chart of stool form and frequency. Patients were instructed to record when BioPharmaceuticals Medical, Gothenburg, Sweden, 3London School of Hygiene &
each bowel movement happened and to mark stool form type for each movement as Tropical Medicine, Health Services Research and Policy, London, United Kingdom,
described in words and pictures on Bristol Stool Form Scale (BSFS). Opioid induced 4
HEOR Ltd, Cardiff, United Kingdom, 5AstraZeneca, BioPharmaceuticals Medical,
constipation was defined as per Rome IV criteria. The diagnostic criteria is similar to Wilmington, United States of America, 6AstraZeneca, BioPharmaceuticals Medical,
functional constipation, but with requisite that new or worsening symptoms occurred Gaithersburg, United States of America, 7University of Groningen, Faculty of Medical
when initiating, changing or increasing opioid therapy. Sciences, Groningen, The Netherlands, 8University of Sydney, Faculty of Medicine and
RESULTS: Two hundred twenty five patients were studied out of which 59 (26.2%) Health, Camperdown, Australia, 9Pontifical Catholic University of Paran a, School of
patients were in CKD stage3, eighty one (36%) patients were in CKD stage4 and 85 Medicine, Curitiba, Brazil, 10University of Manitoba, Max Rady College of Medicine,
(37.8%) patients were in stage5. Out of 85 CKD stage5 patients, 23 (27%) were on Winnipeg, Canada, 11University of Tennessee Health Science Center, Division of
dialysis. Mean age of patients was 49.1 years. Out of 225 patients, 135 (60%) were male. Nephrology, Memphis, United States of America and 12University College London,
Constipation symptoms and diagnosis reported in each stage has been depicted in Department of Renal Medicine, London, United Kingdom
Table 1. Clinical correlates of constipation has been depicted in Table 2.
BACKGROUND AND AIMS: Elevated albuminuria in patients with chronic kidney
disease (CKD) is associated with increased risks of CKD progression, cardiovascular
events and all-cause death. In the DAPA-CKD study, dapagliflozin significantly

MO515 Table 1: Constipation symptoms and diagnosis reported in each stage (Rome IV criteria)

Symptom or diagnosis CKD Stage 3 CKD Stage 4 CKD Stage5 Total


(n=59) (n=81) (n=85) (n=225)
Straining>25% of 19 35 55 109
defecations
Lumpy or hard stool 23 44 47 114
(BSFS type 1/2)
Incomplete evacuation 25 32 41 98
Anorectal obstruction/ 7 9 12 28
blockade
Manual maneuvers 3 8 6 17
Fewer than 3 bowel 28 46 59 133
movement per week
Functional constipation 32(54.2%) 52(81.3%) 64(75.3%) 148(65.8%)
diagnosis
Opioid induced consti- 01 09 06 16
pation diagnosis

i314 | Abstracts
Nephrology Dialysis Transplantation Abstracts
reduced the risk of all-cause death in patients with elevated albuminuria compared þthresholds for optimal survival were between 4.2-5.4 mmol/L. Similarly, mortality
with placebo (hazard ratio: 0.69; 95% confidence interval 0.53–0.88). To assess the cost- patterns were greatly attenuated for patients who were managed in the outpatient and
effectiveness of new treatments, decision makers require survival estimates over a general practice locations (p-value interaction <0.001) than the emergency room or
longer period than that of a typical clinical trial, usually over a lifetime time horizon. A inpatient settings (Figure 1).
formal elicitation process is currently underway to obtain estimates of long-term
survival of patients with albuminuric CKD from clinical experts. Their responses will
be used to validate extrapolations of all-cause mortality data from DAPA-CKD, which
could inform cost-effectiveness analyses for dapagliflozin.
METHOD: Targeted literature searches were conducted to collate data on all-cause
mortality in patients with CKD and elevated albuminuria. Clinical trials and
observational studies were included if they involved non-dialysis-dependent patients
with CKD aged 18 years and over, had more than 500 participants per study arm and
reported incidence of all-cause death and/or all-cause mortality/survival Kaplan–Meier
(KM) curves. To estimate long-term survival, KM curves were extrapolated to 20 years
by calculating standard mortality ratios (SMRs) using age- and sex-adjusted general-
population lifetable data. Study and patient characteristics and mortality data from
relevant studies were provided to clinical experts to inform their judgements in a
formal elicitation process. After receiving training on the elicitation process, six leading
disease area experts were invited to complete the elicitation survey using an Excel-
based tool, which consisted of 10 calibration questions, and three questions regarding
the survival of patients in the placebo arm of the DAPA-CKD study at 10 and 20 years.
The elicited estimates will be weighted and aggregated using Cooke’s method.
RESULTS: Literature searches identified 13 relevant articles (seven clinical trials and
six observational studies), with a range of 1094 to 5674 participants. Mean age varied
across studies (range: 55–70 years). Where reported, median follow-up was 9–144
months, and mean estimated glomerular filtration rate (eGFR) at baseline was 22.4–
56.3 mL/min/1.73 m2. Five studies exclusively included patients with type 2 diabetes
(T2D). The incidence of all-cause death was reported in nine studies and was 1.5–9.4
deaths per 100 patient-years, with the highest incidence observed in a study reporting
data for patients with CKD stage 4 and 5 (8.0 and 9.4 deaths per 100 patient-years,
respectively). Nine studies provided KM curves; from these, estimated survival at 2
years ranged from 86% (study population mean age 67 years, eGFR < 15 mL/min/
1.73 m2) to 98% (study population mean age 58 years, mean eGFR 46.2 mL/min/
1.73 m2). The SMR-extrapolated survival at 10 and 20 years was 36–80% and 2–69%,
respectively. The ranges defined by the expert judgements collected to date for survival
at 10 and 20 years are in line with the variability of the extrapolated KM survival
curves. The elicitation process is ongoing and therefore, to avoid biasing the
judgements that remain to be collected, preliminary results are not reported here.
Results of the expert elicitation will be presented in full at the congress.
CONCLUSION: Initial results from the survey calibration questions suggest that the
expert elicitation process provides expert judgements that are both informative and
precise. The elicitation of survival estimates for patients with CKD and elevated
albuminuria at 10 and 20 years will provide greater insight than extrapolated data
alone, and will increase the validity of long-term survival projections for dapagliflozin
cost-effectiveness analyses.

MO517 Figure 1: The relationship between serum potassium levels (mmol/L) and all-
MO517 EFFECT MODIFIERS OF SERUM POTASSIUM AND cause by location of medical supervision.
MORTALITY IN THE IRISH HEALTH SYSTEM: THE NATIONAL CONCLUSION: Risk thresholds for optimal survival for serum Kþ vary according to
KIDNEY DISEASE SURVEILLANCE SYSTEM (NKDSS) CKD and location of medical supervision in real-world clinical cohorts. Better
understanding of these thresholds and effect modifiers are essential for inform decision
Leonard Browne1, Austin Stack1,2 making and therapeutic interventions.
1
University of Limerick, School of Medicine, Limerick, Ireland and 2University Hospital FUNDING SOURCE: Health Research Board (HRB-SDAP-2019-036), Midwest
Limerick, Department of Nephrology, Limerick, Ireland Research and Education Foundation (MKid), Vifor Pharma.

BACKGROUND AND AIMS: Serum potassium (Kþ) exhibits a u-shaped association


with mortality but uncertainty exists regarding optimal thresholds for survival and MO518 INSIDE CKD: MODELLING THE ECONOMIC BURDEN OF
influencing factors. We examined the impact of serum K* on mortality in the Irish CHRONIC KIDNEY DISEASE IN THE AMERICAS AND THE
Health System with particular focus on kidney function and location of medical ASIA-PACIFIC REGION USING PATIENT-LEVEL
supervision. MICROSIMULATION
METHOD: We utilised data from the Irish Kidney Disease Surveillance System
(NKSS) to explore the association of serum Kþ and mortality in a longitudinal cohort Alyshah Abdul Sultan1, Marcelo Costa Batista2,3, Claudia Cabrera4, Joshua Card-
study. Gowers5, Steven Chadban6, Glenn Chertow7, Juan Jose Garcia Sanchez1,
We identified all adult individuals (age > 18 years) who accessed health care from 2007 Eiichiro Kanda8, Guisen Li9, Stephen Nolan1, Lise Retat5, Navdeep Tangri10,
and 2012 in a regional health system with complete data on serum Kþ, associated Laura Webber5, Jay Wish11, Michael Xu5
laboratory indicators and vital status up to 31st December 2013 (n = 32,643). We 1
AstraZeneca, BioPharmaceuticals Medical, Cambridge, United Kingdom, 2Hospital
randomly selected a single Kþ measurement per patient with date of measurement as ao Paulo, Brazil, 3Universidade Federal de S~
Israelita Albert Einstein, S~ ao Paulo,
index date. Chronic kidney disease was defined as eGFR <60ml/min/1.73m2 vs greater Nephrology Division, S~ ao Paulo, Brazil, 4AstraZeneca, BioPharmaceuticals Medical,
recorded at index date. Location of medical supervision was recorded as emergency Gothenburg, Sweden, 5HealthLumen, London, United Kingdom, 6Royal Prince Alfred
room, inpatient location; outpatient clinic, and general practice location. The Hospital, Camperdown, Australia, 7Stanford University School of Medicine, Palo Alto,
association of serum Kþ was explored in categories and as a continuous variable in United States of America, 8Kawasaki Medical University, Okayama, Japan, 9Sichuan
restricted cubic splines with mortality. Multivariable Cox regression determined Academy of Medical Science, Sichuan Provincial People’s Hospital, Chengdu, P.R. China,
hazard ratios and 95% confidence intervals with adjustment for baseline health 10
University of Manitoba, Winnipeg, Canada and 11Indiana University School of
indicators. Medicine, Indianapolis, United States of America
RESULTS: Mean age was 57.1 years, 5,056 died (15.4%) with a median follow-up of 5.1
years.
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a debilitating and
With adjustment, for age, sex, baseline health status, and location of medical
costly condition, with an estimated global prevalence of approximately 10%.
supervision, the pattern of mortality was non-linear and u-shaped with greatest risks
Progression of CKD is associated with end-stage renal disease, cardiovascular events
for patients with extreme values. Modelled as a continuous variable, the serum K
and premature mortality, as well as increased requirement for renal replacement
þthresholds for optimal survival were from 4.1 to 5.2 mmol/L. Compared to patients
therapies (RRTs), which are associated with significant healthcare costs and resource
without baseline CKD, the risks were attenuated for patients with CKD (p-value
use. Furthermore, patients with CKD often have additional comorbidities, which are
interaction 0.012). The associated risk thresholds were wider for CKD patients with
associated with CKD progression and increased costs. The trajectories of CKD
significant increased risk above 5.8 mmol/L whereas, for those without CKD, serum K

10.1093/ndt/gfab087 | i315
Abstracts Nephrology Dialysis Transplantation

prevalence, progression, outcomes and the related costs are therefore critical ANOVA or non-parametric tests, p < 0.05 is the level of statistical significance.
considerations for public health and policy planning. Using country-specific, patient- RESULTS: Eighty-eight patients were included (63.6% women, mean age: 61.8614.0
level microsimulation, Inside CKD aims to model the global clinical and economic years), 76.1% were on CKD stage 4 or 5. The estimated annual social cost of CKD was
burden of CKD from 2020 to 2025. 2231,12 US$ (95% CI, 1676,09-2793,93 US$). The direct cost accounted for 99,5% (direct
METHOD: We used the Inside CKD microsimulation to model the economic burden medical cost: 91,2%, direct non-medical cost: 8,3%), and the indirect cost accounted for 0,5
of CKD in the Americas and Asia-Pacific region. We developed a virtual general % of the social cost. Hospitalizations, diagnosis and treatments represented the main
population for each country using national survey data and relevant data from expenses of the direct medical cost (32,2%, 29,7%, 32,2% respectively). The social cost
published literature. Data inputs included country demographics, the prevalence of components were not significantly different between CKD stages.
CKD and RRT, comorbidities and complication rates as well as associated healthcare CONCLUSION: The cost of CKD in its early stages still lower than the cost of renal
costs. CKD stages were defined according to Kidney Disease Improving Global replacement therapy, which brings the light on the necessity of secondary prevention of
Outcomes (KDIGO) 2012 recommendations and patients were categorized according CKD to postpone or prevent the progression toward ESRD.
to estimated glomerular filtration rate and albuminuria status. We calibrated the RRT
modelling against historical trends from country-specific renal registries. We
conducted model validation and calibration using established methods for health
MO520 SARS-COVID19 INFECTION AT VARIOUS STAGES OF
economic modelling. Here, we report the results from the US and Canada analyses,
KIDNEY DISEASE: A SINGLE CENTRE EXPERIENCE
with further analyses currently underway for additional countries in the Americas and
Asia-Pacific region.
Marianna Napoli1, Gabriele Donati1, Lorenzo Gasperoni1, Fulvia Zappulo1,
RESULTS: Initial results for the US and Canada revealed that, between 2020 and 2025,
Valeria Aiello1, Anna Scrivo1, Marco Busutti1, Marco Ruggeri1, Federica Di
annual healthcare costs associated with CKD will increase linearly from US$232.3B to
Filippo1, Sarah Lerario1, Claudia Bini1, Francesco Tondolo1, Carlo Stefanini1,
US$376.2B in the US and from C$21.4B to C$34.1B in Canada (this figure does not
Giorgia Comai1, Gaetano La Manna1
include complication costs). In the US, the largest absolute increase in cost was 1
observed in CKD stage 3a ($98.4B); however, CKD stage 4 had the largest relative IRCCS S.Orsola University Hospital, Nephrology Dialysis and Renal Transplantation
increase in cost with an approximately three-fold increase (US$7.30B to US$23.3B). In Unit, Bologna, Italy
Canada, the largest absolute increase in cost was observed in CKD stage 3a (C$5.84B);
whereas CKD stage 5 had the largest relative increase in cost with an approximately BACKGROUND AND AIMS: Several chronic medical conditions appear to increase
five-fold increase (C$0.27B to C$1.41B). By 2025, costs associated with CKD will the risk of severe COVID-19. Chronic kidney disease (CKD) patients have a high risk
increase across all age categories (18–34, 35–64 and 65þ years) in both countries. In of symptomatic infection and severe respiratory symptoms because of chronic
the US, the 35–64 age group had the largest absolute increase in costs with an increase inflammation, uremic toxins accumulation, endothelial dysfunction and an impaired
of $74B (US$58.3B to US$132B). The largest relative increase in cost was observed in immune response. Even though the presence of one or more comorbidities increases
the 18–34 age category, with approximately a three-fold increase in costs (US$3.76B to the risk of mortality, information of the outcome of COVID-19 in CKD patients is not
US$10.2B). In Canada, the 65þ age group had the largest absolute increase in costs yet available. The aim of the study is to present the incidence and outcome of COVID-
with an increase of C$7.9B (C$16.4B to C$24.3B). Both the 18–34 and 35–64 age 19 in patients referring to our Nephrology Unit considering CKD patients, dialysis
categories had the largest relative increase in costs, with an approximately two-fold patients and kidney transplant recipients.
increase (C$0.25B to C$0.49B and C$4.77B to C$9.31B, respectively). METHOD: This study is prospective single centre carried out considering patients
CONCLUSION: Initial results from Inside CKD demonstrate that CKD poses a referring to the Nephrology Unit of St. Orsola University Hospital in Bologna with
significant economic burden over the next 5 years. CKD stage 3a was associated with COVID 19 diagnosis from 15THMarch to 30THMay 2020.
the most pronounced cost increases in both the US and Canada, likely due to the RESULTS: Our cohort included 52 patients admitted to our Nephrology Unit because
increased prevalence of this stage. In the US, the largest increase in CKD costs was of Sars Cov2 infection confirmed by positive reverse transcriptase polymerase chain
observed in the 35–64-year-old ‘working’ population, whereas the largest increase in reaction on nasopharyngeal swab. The mean age was 67.2 6 13.8 years (range, 33-88
Canada was observed in the 65 years old and over population. Further policy years). Demographic, clinical and radiological features in Table 1. Forty-eight patients
interventions aimed at early diagnosis and proactive management should be (92.3%) underwent chest TC. The main findings were: several bilateral interstitial
considered to slow disease progression, improve patient outcomes and reduce the pneumonia (39 patients, 81.2%), monolateral peripheral ground-glass opacities (6
economic burden associated with CKD. patients, 12.5%), no signs of pneumonia (3 patients, 6.2 %). Clinical course is highly
variable: 18 patients (34.6 %) were asymptomatic, 23 patients (44 %) had a mild course
requiring low flux oxygen therapy and 11 patients (21%) presented severe pneumonia
and respiratory distress that requires ventilatory support in intensive care unit. Forty
patients (70%) had hydroxychloroquine-azithromycin dual therapy, 3 patients (6%)
had antiviral therapy in addiction. Sixteen patients (31%) with P/F <150 mmHg were
treated with Tocilizumab. Heparin Therapy, to prevent the thromboembolic risk of
Sars-Cov2 infection, was administered according to the body weight in forty patients
(70%);, but not in patients in warfarin therapy (12 patients, 30%). Twenty-six patients
(50%) needed antibiotics for bacterial infections combined to the Sars-Cov2 infection.
Steroid therapy was added in 40% of cases. The average time of negativization for Sars
Cov2, tested with two nasopharyngeal swab specimens made seven days apart, was
31615 day. Fifty-one patients, 98% of diagnosed cases, required hospitalization with
an average stay of 35 6 26 days. Thirty patients (25%) died. Mean age of non-survivors
MO518 Figure: Modelled annual healthcare costs associated with CKDa was 72 6 11years while mean age of survivors was 646 11years. No differences in pre-
existing comorbidities were observed between survivors and non survivors; oxygen
saturation on presentation was statistically lower in non survivors.
CONCLUSION: CKD is an independent risk factor for COVID-19 associated in-
MO519 THE COST OF CHRONIC KIDNEY DISEASE BEFORE RENAL hospital mortality. The mortality rate (25%), much higher than in general population
REPLACEMENT THERAPY IN MOROCCO: A COST OF (1.8-8%) may be explained by the older age of patients and the presence of more
ILLNESS STUDY pathological conditions, especially cardiovascular disease.

Amina Chrifi Alaoui1, Mohammed Omari1, Noura Qarmiche1, Omar Kouiri2,


Basmat Amal Chouhani2,3, Tarik Sqalli Houssaini2,3, Samira El Fakir1,3,
Nabil Tachfouti1,3 MO521 OUTCOME OF CHRONIC KIDNEY DISEASE PATIENTS WITH
1 SARS COV-2 INFECTION- A SINGLE CENTRE EXPERIENCE
faculty of medicine and pharmacy of Fez, Department of epidemiology, clinical
research and biostatistics, FEZ, Morocco, 2Hassan II university hospital, Department of
Jelena Bjedov1,2, Ana Bulatovic1,2, Vesna Maslarevic Radovic1, Nada Dimkovic1,
nephrology and hemodialysis, FEZ, Morocco and 3faculty of medicine and pharmacy of
Radomir Naumovic1,2
Fez, Sidi Mohamed Ben Abdallah University of Fez, Laboratory of epidemiology and 1
health sciences’ researches (ERESS), FEZ, Morocco KBC“ZVEZDARA”, Nephrology, Beograd, Serbia and 2University of Belgrade - Faculty of
Medicine, Beograd, Serbia
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a leading public
health problem in Morocco, its consequences and costs have implications for public BACKGROUND AND AIMS: Since the outbreak of COVID 19 there have been 88.1
health policy. The present study aimed to estimate the social cost of CKD before the million confirmed cases and 1,9 million deaths in 218 countries, while in Serbia we
start of renal replacement therapy in a Moroccan region. have had 39.867 cases of COVID 19 and 3479 deaths with approximate death rate of
METHOD: A cross-sectional cost of illness study, using bottom-up approach was 1%. Fatality rate worldwide vary widely, from 0% in Singapore to 8,8% in Mexico with
performed at the department of nephrology in university hospital of Fez during 2020, the average value of 3%. Although there are many published studies about COVID 19,
among stages 3 to 5 CKD patients, followed up for at least one-year. The analyzed costs influence of chronic kidney disease and chronic dialysis on outcome of patients with
include the following annual expenditures: hospitalizations, outpatient visits, day care the coronavirus infection is still not clear. The aim of this study was to explore whether
hospital, drugs, laboratory tests, imaging, and medical specialized acts. Non-medical the presence of CKD including ESRD and chronic dialysis treatment increases COVID
costs such as transportation and indirect costs like loss of productivity were also 19 patients’ risk for adverse clinical outcome.
assessed. Determinants of CKD cost were identified by univariate analysis using t test,

i316 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO520 Table 1. Demographic, clinical and radiological features.

Variables Total (n=52) Survivors (n=39) Nonsurvivors(n=13)


Age, yr 67.26 13.8 656 14 726 12
Woman 21 (39%) 17 (44.7%) 5 (13%)
Comorbidity
CV disease 41 (78.8%) 30 (79%) 11(84.6%)
DM 22 (42%) 14 (36.8%) 8 (61.5%)
Cancer 18 (31%) 12 (31.6%) 6(46.1%)
BMI>30 7 (3%) 4(10.5%) 2(15.4%)
Dialysis 31(59.5%) 24 (63.1) 6 (46%)
Kidney transplantation 16 (30.7%) 11 (29%) 2 (15%)
CKD IV-V stage 4 (7%) 2 (5.2%) 1 (7.7%)
Onset of Symptoms
fever 29 (79%) 22(58%) 7 (13%)
cough 3(6%) 2 (5.2%) 1 (7.7%)
dyspnea 8 (15.4%) 4 (10.5%) 4 (30.8%)
Symptomless 8 (15.4%) 6 (15.8%) 2 (15.4%)
Admission HRCT
Bilateral peripheral ground-gass opacity 39(81.2%) 31 (79.5%) 8(88.8%)
Unilateral opacity 6 (12.5%) 5(12.8%) 1 (11.1)
No opacity 3 (6.2%) 3 (7.7%) 0
PaO2/FiO2 ratio 330 6 102. 376 693 286 686

METHOD: This retrospective study included 88 patients who were hospitalized at the METHOD: A total of 158 adults, with a history of type 2 diabetes for>10 years were
Nephrology department in Zvezdara University Clinical Center which was recruited. At baseline, urinary albumin to creatinine ratio (UACR), eGFR and cIMT
transformed into a COVID hospital at the time. These patients were treated from were evaluated. All patients were followed for a period of 7 years with fatal or nonfatal
01.04.2020. to 01.06.2020. and 37 (42%) of them had CKD, while 51 (58%) had no CV events as the primary endpoint. By adopting the Fine and Gray model, which takes
signs of kidney disease. We analysed data collection from the patients’ history, into account the competitive risk of death, we assessed the associations between CV
including age, sex, comorbidities, symptoms, blood and radiology findings, therapy and events and various candidate prognostic factors collected at baseline.
outcome. We compared outcome (fatal and need for mechanical ventilation) between In multiple Cox Fine and Gray models, we included all variables that were correlated
CKD and non CKD group and also analized dialysis as a risk factor for adverse with the study outcome in univariate analysis, (full model with 9 variables). The
outcome. Statistical analysis has been performed using SPSS software version 20 and prognostic performance of the full model was compared with that of a simpler (nested)
OR was calculated using Logistic Regression. model based only on three prognostic variables (simplified model).
RESULTS: We analysed 88 patients, a mean age of 62þ15 years, 59.1% males. Out of To compare the data fitting of the 2 models, we used 2 log likelihood (2 log L)
88 patients, 37 had CKD, while 27 of them were on hemodialysis and 2 on peritoneal statistics. The calibration and the discrimination abilities of both models were assessed
dialysis (CAPD). At the end of follow-up, 46 patients (52.3%) was discharged home, 27 by Hosmer-Lemeshow test and by receiver operating characteristic (ROC) curve,
(30.7%) was transferred to another hospital and 14 (15.9%) died. Regarding influence respectively.
of CKD on COVID-19 patients’ outcome it was shown that patients with CKD had 3- RESULTS: During the follow-up period (median 57.5 months, range 7–84 months), 75
fold higher chances for discharge than for the fatal outcome (p=0.05) and 4-fold less patients experienced CV events (33 fatal, 42 nonfatal), and 13 died of causes other than
risk for use of the mechanical ventilation (ns) as compared to non CKD patients. We CV. In univariate competitive risk analysis, hemoglobin (SHR 0.85, 95% CI 0.74–0.98,
also found that ESRD and chronic dialysis affect outcome with statistical significance P = 0.02), female sex (SHR 0.50, 95% CI 0.30–0.82, P = 0.006), eGFR (SHR 0.98, 95%
(p=0.01) in a way that it doubles the risk for the adverse outcome. CI 0.97–0.99, P <0.0001), serum albumin (SHR 0.43, 95% CI 0.26–0.74, P = 0.002),
CONCLUSION: Patients with CKD, especially those with ESRD had significantly and HDL cholesterol (SHR 0.97, 95% CI 0.95–0.99, P = 0.02) were inversely associated
higher risk for the lethal outcome and higher chances to require the mechanical with the incident rate of CV events, whereas the duration of type 2 diabetes (SHR 1.03,
ventilation. 95% CI 1.00–1.06, P = 0.04), background CVD (SHR 5.47, 95% CI 2.45–12.23, P
<0.0001), UACR (SHR 1.01, 95% CI 1.00–1.01, P <0.0001), and cIMT (SHR 7.45, 95%
CI 3.46–16.04, P <0.0001) were directly related to the same endpoint. In a multivariate
Fine and Gray model including all 9 univariate correlates of CV events (full model),
MO522 BIOMARKERS OF KIDNEY FUNCTION AS POTENTIAL
only history of CVD (SHR 5.86, 95% CI 2.15–13.36, P <0.0001), eGFR (SHR 0.99, 95%
PROGNOSTIC FACTORS FOR CARDIOVASCULAR DISEASE
CI 0.98–0.99, P = 0.009), UACR (SHR 1.01, 95% CI 1.00–1.01, P <0.0001), and cIMT
IN TYPE 2 DIABETIC PATIENTS
(SHR 3.92, 95% CI 1.24–12.35, P = 0.02) remained significantly associated to the study
outcome. In the simplified model only history of CVD (SHR 6.47, 95% CI 2.69–15.55,
Stefanos Roumeliotis1, Aikaterini Stamou2, Athanasios Roumeliotis1,
P <0.0001), UACR (SHR 1.01, 95% CI 1.00–1.01, P <0.0001), and eGFR (SHR 0.98,
Stylianos Panagoutsos3, Graziella D’Arrigo4, Giovanni Luigi Tripepi4,
95% CI 0.97–0.99, P <0.0001) maintained an independent relationship with CV
Vassilios Liakopoulos1
1
outcomes.
AHEPA Hospital, School of Medicine, Aristotle University of Greece, Division of The data fitting of the two models did not significantly differ (v2 = 9.48, 6 Df, P = 0.15)
Nephrology and Hypertension, 1st Department of Internal Medicine, Thessaloniki, and the assessment of the areas under the ROC curves (Figure 1) confirmed that the
Greece, 2AHEPA Hospital, School of Medicine, Aristotle University of Greece, Department two models had almost identical accuracy to predict the study outcome (full model
of Microbiology, Thessaloniki, Greece, 3Univeristy Hospital of Alexandroupolis, School of 87%, 95% CI 0.81–0.92, P <0.001, simplified model 84%, 95% CI 0.78–0.90, P <0.001).
Medicine, Democritus University of Greece, Department of Nephrology, Moreover, the Hosmer-Lemeshow test showed that the simplified model was better
Alexandroupolis, Greece and 4Institute of Clinical Physiology, Clinical Epidemiology and calibrated than the full model, because the P value of this test in the simplified model is
Physiopathology of Renal Diseases and Hypertension, CNR-IFC of Reggio Calabria, farther from statistical significance (v2 = 9.24, P = 0.32) than that of the full model (v2
Reggio Calabria, Italy = 11.09, P = 0.20).

BACKGROUND AND AIMS: Developing risk predictive models in high-risk


populations, such as patients with type 2 diabetes (T2DM), might provide an
individualized risk prediction. During the past decade, the studies assessing carotid
intima media thickness (cIMT) as a novel risk factor for cardiovascular (CV) disease,
produced controversial results. In this study, we assessed the prognostic value of
various risk factors, including cIMT and biomarkers of kidney function, to predict
incident CV events in T2DM patients.

10.1093/ndt/gfab087 | i317
Abstracts Nephrology Dialysis Transplantation

(p<0.0001). Estimating glomerular filtration rate (eGFR) was lower during the
hospitalization compared to the follow-up: 81 [62; 92] versus 87 [66; 98] mL/min/
1.73m2 (p=0.0222). At follow-up, a decreased renal function was observed in 10/72
(14%) of patients, with 50% of them presenting decreased renal function before
COVID-19 hospitalization and others developing severe AKI and/or proteinuria
during hospitalization.
CONCLUSION: In most hospitalized patients with COVID-19, proteinuria and eGFR
significantly improved after hospital discharge. Only patients who developed severe
AKI and/or heavy proteinuria will require a specific follow-up by nephrologists.

MO524 CALCIMIMETIC ADHERENCE AND PREFERENCE IN THE


MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM
IN EUROPE: A PILOT STUDY

Karly Louie1, Chidozie Nduka1, Jo Taylor3, Matthew Hall4, Filippo Aucella5,


Josep Artero6, Pablo Uren ~a7, Laura Labriola8, Per-Olof Andersson9,
Pieter Evenepoel10, Juan Carlos Gonzalez Oliva11, Ronald Pisoni12,
Bruno Fouqueray13, Robert Horne14
1
AMGEN Ltd, Centre for Observational Research, Uxbridge, United Kingdom, 3Dorset
County Hospital, Dorchester, United Kingdom, 4Nottingham University Hospital, United
Kingdom, 5Fondazione IRCCS - Casa Sollievo della Sofferenza, Nephrology and Dialysis
Unit, San Giovanni Rotondo, Italy, 6Hospital Universitari de Girona, Servicio de
MO522 Figure: ROC curves showing the performance of the full model and the Nefrologıa, Girona, Spain, 7Necker-Enfant Malades Hospital, Service de Néphrologie-
simplified model in predicting CV events in patients with type 2 diabetes. Dialyse, Paris, France, 8Cliniques Universitaires Saint-Luc, Université Catholique de
CONCLUSION: We propose a simple model for CV event prediction that includes Louvain, Department of Nephrology, Brussels, Belgium, 9Vrinnevisjukhuset,
only three easy-to-measure variables. eGFR, albuminuria, and history of CVD can be Medicinkliniken, Norrköping, Sweden, 10University Hospitals Leuven, Division of
used for prognosis of CVD, whereas cIMT adds little to the accuracy of this prediction. Nephrology, Leuven, Belgium, 11Fundaci on Privada Hospital de Mollet, Spain, 12Arbor
Research Collaborative for Health, Michigan, United States of America, 13Amgen
GmbH, Rotkreuz, Switzerland and 14University College London, School of Pharmacy,
London, United Kingdom
MO523 PATIENTS FROM COVID-19 MOSTLY RECOVER FROM
TUBULAR PROTEINURIA AND ACUTE KIDNEY INJURY
AFTER HOSPITAL DISCHARGE BACKGROUND AND AIMS: Oral cinacalcet (CIN) and IV-administered
etelcalcetide (ETEL) are calcimimetics available for the management of secondary
Antoine Bouquegneau1, Justine Huart2, Laurence Lutteri3, Pauline Erpicum1, hyperparathyroidism (SHPT) in hemodialysis (HD) patients. This pilot study assessed
Stéphanie Grosch1, Guillaume Résimont1, Patricia Wiesen4, Marie Thys3, Anne- patient adherence to calcimimetic therapy and calcimimetic preference of
Françoise Rousseau4, Christophe Bovy1, Jean-Marie Krzesinski1, nephrologists and nurses based on adapted questionnaires.
Bernard Lambermont4, Benoit Misset5, Hans Pottel6, Gilles Darcis5, METHOD: A cross-sectional survey was conducted with HD patients currently using a
Etienne Cavalier2, François Jouret1, Pierre Delanaye1 calcimimetic, and nephrologists and dialysis nurses who prescribed/administered
1 calcimimetic in 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden
CHU Sart Tilman, Nephrology Dialysis Transplantation, Liège, Belgium, 2CHU Sart
and the United Kingdom). Patient questionnaires were adapted from the Medication
Tilman, Clinical Chemistry, Liège, Belgium, 3CHU Sart Tilman, Medico-Economic
Adherence Report Scale (MARS), the Beliefs about Medicines Questionnaire (BMQ-
Information, Liège, Belgium, 4CHU Sart Tilman, ICU, Liège, Belgium, 5CHU Sart Tilman,
specific Necessity and Concern), and Treatment Intrusiveness Scale (TIS) to
Infectious Diseases, Liège, Belgium and 6KU Leuven Campus Kulak Kortrijk, Public
understand patterns of adherence and perceptions of medications; questions about
Health and Primary Care, Kortrijk, Belgium
gastrointestinal (GI) symptoms were included. Questionnaires for nephrologists and
nurses were adapted from the Treatment Rating Scale (TRS), Health Professional
BACKGROUND AND AIMS: Proteinuria, hematuria and acute kidney injury (AKI) Preference Scale (HPPS), and Prescribing Comparator Scale (PCS) to understand
are frequently observed in hospitalized patients with COVID-19. However, few data calcimimetic preference. Questionnaires were translated and administered in the local
are available on these parameters after hospital discharge. language.
METHOD: This retrospective, observational and monocentric study included 153 RESULTS: Sixty HD patients (33 CIN and 27 ETEL), 16 nephrologists and 18 dialysis
hospitalized patients, in whom urine total proteinuria and a1-microglobulin (a marker nurses participated in the survey. ETEL patients were younger than CIN patients
of tubular injury) were measured. Thirty patients died. Among the 123 survivors, (mean age: 57 vs. 59 yrs). ETEL patients also had a lower pill burden (mean no. of pills:
follow-up urine and creatinine analyses were available for 72 patients (after a median of 6 vs. 11) and had numerically fewer hospitalizations in the last 6 months (mean no. of
51 [19;93] days following hospital discharge). days: 1.5 vs 3.9) than CIN patients. Self-reported adherence to CIN was high (mean
RESULTS: The median proteinuria at hospitalization and follow-up (n=72) was 419 MARS: 4.760.7). ETEL and CIN patients did not perceive medications (excluding
[239; 748] and 79 [47; 129] mg/g, respectively (p<0.0001). The median concentrations dialysis, diet and dietary restrictions) as interfering with their life (mean TIS: 1.560.5
of urinary a1-microglobulin (n=66) were 50 [25; 81] and 8 [0; 19] mg/g, respectively vs. 1.661.6) and neither calcimimetic group had a specific belief in medicines in terms

Hospitalization (Hosp) Follow-up (F-U) Wilcoxon signed


rank/
McNemar test
Creatinine (mg/dL) (n=72) 0.92 [0.80;1.09] 0.87 [0.76;1.05] 0.0488
eGFR (mL/min/1.73m2) 81 [62;92] 87 [66;98] 0.0222
Decreased GFR (%) (age adapted definition) 20.8 14 ns
Decreased GFR (KDIGO) 23 18 ns
Proteinuria (mg/g) (n=72) 419 [239 ;748] 79 [47;129] <0.0001
ProteinuriaCategory 1 (%)Category 2 (%)Category 3 (%) 154342 83116
Urine a1-microglobulin (mg/g) (n=66) 50 [25;82] 8 [0;19] <0.0001
Urine a1-microglobulin>15 mg/g (%) 88 29
Urine b2-microglobulin (n=60) (mg/L) 0.92 [0.41;4.52] 0.00 [0.00;0.00] <0.0001
Urine b2-microglobulin >0.19 mg/L (%) 82 13
Hematuria (>10 per field) (%) (n=51) 19 12 ns

i318 | Abstracts
Nephrology Dialysis Transplantation Abstracts
of necessity (mean BMQ CIN: 2.460.6 and ETEL: 2.360.4) or concerns about MO526 REAL-WORLD EVIDENCE ON CLINICAL OUTCOMES IN NON-
potential side-effects (mean BMQ CIN: 3.160.6 and ETEL: 3.560.7). ETEL patients DIABETIC CKD
were less likely than CIN patients to experience GI symptoms in the prior month:
nausea (11% vs. 49%), vomiting (11% vs. 24%), and diarrhea (15% vs. 33%). Overall, Christoph Wanner1, Johannes Schuchhardt2, Chris Bauer2, Stefanie Lindemann3,
the adapted patient questionnaires showed good internal consistency for MARS Meike Brinker4, Sheldon Kong5, Frank Kleinjung3, Andrea Horvat-Broecker4,
(Cronbach’s a=0.99) and BMQ-Necessity and BMQ-Concerns scales (CIN: a=0.74 and Tatsiana Vaitsiakhovich3
1
ETEL: a=0.81) but lower consistency for TIS (a=0.3 for both CIN and ETEL). University Hospital Wuerzburg, Department of Medicine, Division of Nephrology,
Nephrologists and nurses had been practicing for a mean of 17 yrs. Nephrologists and Wuerzburg, Germany, 2MicroDiscovery GmbH, Berlin, Germany, 3Bayer AG, Berlin,
nurses viewed ETEL to have more efficacy, lower risk of side effects, lower risk of non- Germany, 4Bayer AG, Wuppertal, Germany and 5Bayer Corporation, Hanover, United
adherence, lower burden for patients compared to CIN according to the TRS. States of America
According to HPPS, the top 3 treatment attributes for ETEL preference vs. CIN among
nephrologists were encouraging patient adherence (93%; n=14/15), minimizing patient BACKGROUND AND AIMS: Chronic kidney disease (CKD) represents a global
burden (87%; n=13/15) and having fewer side effects (80%; 12/15). Similar for nurses, public health problem, with significant morbidity and mortality due to cardiovascular
encouraging patient adherence (88%; n=15/17) and minimizing patient burden (94%; disease during CKD progression and due to kidney failure. Although non-diabetic
n=16/17) were top attributes for ETEL preference as well as improving patient quality CKD accounts for up to 70% of the global CKD burden, its clinical consequences are
of life (82%; 14/17). Based on PCS, the majority of nephrologists agreed that compared poorly understood, and data are needed to help identify individuals at high risk of
to CIN, ETEL will ensure high adherence (100%), achieve better PTH control (93%; adverse outcomes. This analysis uses real-world evidence to provide insights into
14/15), reduce treatment burden for patients (87%; 13/15), improve patient’s quality of clinical characteristics, care and outcomes in individuals with non-diabetic CKD in
life (80%; 12/15), and improve effectiveness without increasing side-effects (80%; 12/ routine clinical practice.
15); they also agreed that ETEL created more work for nursing staff (80%; 12/15). Two METHOD: Individual-level data from the US administrative claims database, Optum
thirds of nephrologists (n=10/15) agreed that ETEL would be more efficacious than Clinformatics Data Mart, from January 1, 2008 to December 31, 2018 were analysed.
CIN. Adults with non-diabetic CKD stage 3 or 4 and 365 days continuous insurance
CONCLUSION: In this pilot study, CIN patients self-reported high adherence and coverage were included and followed until insurance disenrollment, end of data
both calcimimetic groups did not perceive medications to be concerning or intrusive. availability or death. Individuals with diabetes mellitus, CKD stage 5 or end-stage
Nephrologists and nurses showed preference for ETEL than CIN. The questionnaires kidney disease (ESKD) prior to the index date, or who experienced kidney failure
were validated and will be administered in a large study. (acute or unspecified), kidney transplant or dialysis in the baseline period, were
excluded from the analysis. Study outcomes, captured in the database, were defined
using common clinical coding systems. Primary outcomes were hospitalisation for
MO525 CHRONIC KIDNEY DISEASE IN NEOPLASIA PATIENTS, THE heart failure (HHF), a kidney composite of ESKD/kidney failure/need for dialysis, and
ANALYSIS OF A LARGE CANCER DATABASE worsening of CKD stage from baseline. Individual CKD stage was assigned based on
estimated glomerular filtration rate (eGFR) values (priority) or the respective
Mircea Ciorcan1, Lazar Chisavu2, Florica Gadalean 3 , Adelina Mihaescu 3 , International Classification of Diseases code at index and during follow-up. Further
Flaviu Bob 3 , Serban Negru4, Valeriu Boruga4, Oana-Marina Schiller5, prespecified kidney outcomes included individual components of the kidney
Iulia Dana Grosu 3 , Luciana Marc 3 , Flavia Chisavu6, Razvan Dragota Pascota7, composite, acute kidney injury, and absolute and relative change in eGFR from
Adalbert Schiller 3 baseline. Event-based outcomes were assessed by time-to-first-event analysis.
1 Summary statistics for time-course analysis of metric outcomes were generated on a
University of Medicine and Pharmacy “Victor Babes” Timisoara, Fundamental Clinical
quarterly basis.
Abilities, Timisoara, Romania, 2University of Medicine and Pharmacy “Victor Babes”
RESULTS: In total, 504,924 of 64 million individuals in the Optum Clinformatics Data
Timisoara, Nephrology, Timisoara, Romania, 4Oncohelp Medical Center Timisoara,
Mart satisfied the selection criteria. Over a median follow-up of 744 (interquartile
Oncology, Timisoara, Romania, 5Avitum BBraun Romania Timisoara, Nephrology,
range 328–1432) days, the incidence rates of primary outcomes of HHF, the kidney
Timisoara, Romania, 6Emergency Hospital for Children Louis T¸urcanu Timisoara,
composite and worsening of CKD stage from baseline were 3.95, 10.33 and 4.38 events/
Pediatric Nephrology, Timisoara, Romania and 7Timiş County Emergency Clinical
100 patient-years (PY), respectively.
Hospital, Nephrology, Timisoara, Romania
The incidence rates of the components of the kidney composite outcome, namely
ESKD/need for dialysis, kidney failure (acute and unspecified) and need for dialysis
BACKGROUND AND AIMS: Neoplasia is considered a risk factor for the were 1.78, 9.53 and 0.49 events/100 PY, respectively. Kidney failure events were driven
development of CKD, for many reasons: aggressive and repeated therapeutic mainly by acute kidney injury, with an incidence of 8.61 events/100 PY.
interventions, malnutrition, hyperuricemia and the disease per se. Taking into account In individuals with at least one available eGFR value at baseline and one value during
the improved cancer survival due to novel therapeutic interventions, the possibility of follow-up (n=295,174), the incidence rates of relative decreases in eGFR of 30%,
cancer patients with CKD to reach advanced CKD stages is increasing. The 40% and 57% from baseline were 1.98, 0.97 and 0.30 events/100 PY, respectively; in
information about cancer patients and CKD is still scarce. This paper tends to fill the this cohort, more rapid eGFR decline was associated with increased risk of HHF and
gap by analyzing the relation between cancer patients and CKD in a large cancer the kidney composite outcome. In individuals with a baseline eGFR value and at least
database from western Romania. one follow-up eGFR value and an available urine albumin-to-creatinine ratio
METHOD: 5831 patients (3365 female, average age 62.6 þ/- 10.4 years, median age 64 (n=25,824), time-course analysis of eGFR showed that eGFR decline mostly occurred
years) with neoplasia from a large cancer database in Western Romania have been randomly in individuals with moderately-to-severely increased albuminuria (30 mg/g).
assigned to this study. Serum creatinine at inclusion was used to estimate baseline GFR by CONCLUSION: This analysis generates real-world evidence on clinical outcomes in a
the CKD-Epi formula. During the 2-year follow-up, serum creatinine was repeatedly cohort of individuals with non-diabetic CKD treated in routine clinical practice in the
determined in order to estimate GFR (at least 2 determinations). CKD was defined as eGFR US. Despite known limitations of claims databases (e.g. low availability of some
< 60ml/min/1.73m2 persistent for more than 3 months. For our assessment, we used the laboratory data, limited individual follow-up time and tactical coding), individuals with
available personal and medical data from the analyzed database. For comparison, we used moderate-to-severe non-diabetic CKD are shown to be at high risk of serious clinical
the CKD epidemiology data in the general population of Romania. outcomes. This highlights the high unmet medical need, and urgency for new
RESULTS: GFR < 60ml/min/1.73m2 was identified at inclusion in 11.88% of the cases. treatments and targeted interventions for patients with non-diabetic CKD.
The prevalence of CKD according to GFR criteria was 14.49% after the first year of
follow-up, significantly higher if compared to the general population (8.8% - 2008)
(p<0.0001). In the second year, the prevalence increased to 14.98% (with 3%) and the
average decrease of eGFR was 4.7ml/min/year. MO527 REFERRAL CRITERIA TO NEPHROLOGY AND MATCHING
In the examined database, patients with breast cancers (1317 cases), lung (551), uterus DEGREE WITH THE CONSENSUS DOCUMENT FOR CHRONIC
(427), prostate (431) and colonic cancers (498) were dominant. The prevalence of CKD KIDNEY DISEASE DETECTION AND MANAGEMENT
was dependent of the type of cancer, being significantly higher in patients with renal
cancer (48,71%), urinary bladder cancers (34,1%), multiple myeloma (20%), liver Guillermo Ferrer Garcıa1, Lorena Herra ez Garcıa2, Maria Paz Castro Fern andez1,
carcinoma (20%) and pancreatic cancers (19.6%). The prevalence of CKD was Esperanza Moral Berrio1, Eliana Olazo Gutierrez1, Diego Sidel Tambo1,
significantly lower in patients with rectum cancers (9.9%), testicle cancers 8.8% and in Luis Guillermo Piccone Saponara1, Patricia Sanchez Escudero1,
patients with brain tumors (7.1%). Carmen Vozmediano Poyatos1, Agustın Carren ~o Parrilla1
1
The influence of CKD on the survival of cancer patients could not be estimated due to Hospital General Universitario Ciudad Real, Nephrology, Ciudad Real, Spain and
2
the short follow-up time. Hospital General Universitario Ciudad Real, Medicina Familiar y Comunitaria, Ciudad
CONCLUSION: The prevalence of CKD in patients with neoplasia is higher than in Real, Spain
the general population and increasing in time, but according to our results, the rate of
decrease of the kidney function is not high. The prevalence of CKD is dependent of the BACKGROUND AND AIMS: Consensus document of the Spanish Society of
type of cancer being higher in renal, urinary bladder, liver, pancreatic cancers and Nephrology and many Primary Care (PC) related societies for chronic kidney disease
multiple myeloma and lower in testicle cancers and in brain tumors. Taking in account (CKD) detection and management provides to the PC doctor referral criteria (RC) to
the increasing survival of cancer patients, the probability to reach ESKD is increasing nephrology clinic. The aim of the study is to describe the referrals to our center
also and that could influence the profile and needs of patients admitted to renal nephrology clinic and evaluate the influencing factors for RC adequacy.
replacement therapy. METHOD: Retrospective observational study. We included the referred patients to our
nephrology clinic from October 2019 to May 2020. We recollected demographic
variables, as well as comorbidity, renal function, RC adequacy and follow-up.

10.1093/ndt/gfab087 | i319
Abstracts Nephrology Dialysis Transplantation

Categorical variables are expressed as percentages and compared using Chi2 test.
Quantitative variables are expressed as mean 6 standard deviation and compared
using t-student test. Cox regression was performed to determine independent
predictors for RC adequacy. Statistical significance for a value of p< 0,05 or CI 95%.
Statistical analysis was performed with SPSS 25.0.
RESULTS: 238 patients, 55.5% male. Average age 63 6 17 years, being 34% older than
75 years. 67.6% had at least 3 cardiovascular risk factors. 85.3% were referred from PC
with 57.1% of them from a rural center. There was adequation to the RC on 55%. The
most frequent RC was CKD progression (37.4%). Mean serum creatinine at the time of
referring was 1.91 6 0.59 mg/dl with a glomerular filtration rate 34 6 11 ml/min/
1.73m2 and 329.43 6 992.01 mg/g or mg/24h of albuminuria. From the 45% of those
who did not had RC adequacy 51.4% had CKD III stage and 21.5% had false refractory
hypertension (controlled or under-treated). Mean time of follow-up was 5 6 1.7
months. RC adequacy was related with being referred from PC (59.6% vs 28.6%
p=0.001), smoking (65.9% vs 49% p=0.012), time of referring creatinine (1.54 6 0.86 vs
1.18 6 0.39 p=0.001) and albuminuria (43406 6 1009.7 vs 136.13 6 637.16 p=0.019)
and end of follow-up albuminuria (265.84 6 516.82 vs 81.67 6 250.7 p=0.007). RC
adequacy was associated with receiving follow-up on nephrology clinic (80.2% vs
19.8% p=0.001). Logistic regression showed that being referred from PC (OR 3.64 IC
95% 1.03-12.8 p=0.044) and a worse renal function at the referring (OR 2.49 IC 95%
1.19-5.24 p=0.015) were associated with RC adequacy.
CONCLUSION: The experience in our center shows that there is not an adequacy on
the current RC from the Spanish Society of Nephrology in almost half of the patients. MO529 PREVALENCE AND DETERMINANT FACTORS OF
That proportion decreases when patients are referred from PC close to 40%. CKD DEPRESSION AND ANXIETY IN PEOPLE WITH CHRONIC
progression is the main reason for referral with most of patients being elderly and with KIDNEY DISEASE : A MOROCCAN CROSS-SECTIONAL
a high cardiovascular risk. The need for greater dissemination of RC can be inferred STUDY
from the significant number of inappropriate referrals, encouraging us to propose their
review. Amina Chrifi Alaoui1, Mohammed Omari1, Noura Qarmiche1, Omar Kouiri2,
Basmat Amal Chouhani2,3, Tarik Sqalli Houssaini2,3, Nabil Tachfouti1,3,
Samira Ei Fakir1,3
1
faculty of medicine and pharmacy of Fez, Department of epidemiology, clinical
MO528 INFLUENCE OF CARDIOVASCULAR DISEASES ON SURVIVAL research and biostatistics, FEZ, Morocco, 2Hassan II university hospital, Department of
RATES IN DIALYSIS PATIENTS IN A COHORT OF THE UZBEK nephrology and hemodialysis, fez, Morocco and 3faculty of medicine and pharmacy,
POPULATION Sidi Mohamed Ben Abdallah University of Fez, Laboratory of epidemiology and health
sciences’ researches (ERESS), fez, Morocco
Olimkhon Sharapov1,2, Sherzod Abdullaev1
1
Tashkent Pediatric Medical Institute, Internal Disease, Tashkent, Uzbekistan and BACKGROUND AND AIMS: The Chronic kidney disease (CKD), like many chronic
2
Republican Specialized Scientific Practical Medical Center of Nephrology and Kidney illnesses, is invariably associated with various psychiatric conditions and poorer quality
transplantation, Nephrology, Tashkent, Uzbekistan of life. This study aims to assess the prevalence of depression and anxiety among CKD
patient and their determinant factors.
BACKGROUND AND AIMS: The mortality rate of patients on hemodialysis is 6.3- METHOD: this is a cross sectional single center study in a Moroccan university
8.2 times higher than in the general population. The presence of cardiovascular hospital. Patients aged  18 years old and followed for more than one year were
comorbidity worsens the prognosis and survival in this category of patients. According included. The data was collected using a questionnaire for sociodemographic and
to various sources, the mortality rate in patients with CVD is 3 times higher than in clinical information and the Hospital anxiety and depression scale (HADS) to assess
patients without CVD. The aim of our study was to study the effect of comorbidity of depression and anxiety prevalence. After the description of the population’s
the CVD on survival in patients with end-stage CKD receiving programmed characteristics, the statistical analysis aimed to assess the association between
hemodialysis among the population of Uzbekistan. depression and anxiety disorders and the estimated glomerular filtration rate before
METHOD: We conducted a multicenter prospective cohort study of 165 patients and after adjustment on several confounding factors.
among the Uzbek population. The study took place in 3 different dialysis centers in the RESULTS: 88 patients were included (63.6% of them were women, the mean age was
country for 30 months (from January 2018 to July 2020). All patients received 61.8614.0 years), 21 were on stage 3, 46 were on stage 4, and 21 were on stage 5 of the
programmed hemodialysis due to ESRD. All patients were of Uzbek nationality, there CKD. The median of depression sub-score was 5.00[2.00; 10.0], the median of anxiety
were 90 men, 75 women. The average age was 48.1 6 14.1 years. The duration of sub-score was 6.00[4.00; 9.00], and the median of the global score was 11.0[7.00; 20.0],
hemodialysis at the time of inclusion of patients in the study ranged from 6 to 165 22.0% of included patients had depression and 22.0% had anxiety. Both depression and
months. The main primary diseases were glomerulonephritis (46%), diabetes mellitus anxiety scores were associated to eGFR before and after adjustment (p= 0.001,
(27%) and urolithiasis (8%). 56% (n = 92) of patients (52 men and 40 women) had p<0.001and p=0.04, p=0.03 respectively).
CVD and 44% (n = 73) of patients (38 men and 35 women) had no CVD. The main CONCLUSION: This study showed that depression and anxiety are strongly related to
CVDs were hypertension, coronary heart disease, heart failure and various the CKD progression, which should motivate both doctors and nurses to improve their
arrhythmias. All patients were observed during the observation period, at the end of psychological care toward CKD patients.
which the outcome was noted: patients either died or continued to receive
hemodialysis. The survival rate was determined using the Kaplan-Meier method. The
95% confidence interval was determined using the Greenwood method.
RESULTS: After 30 months of follow-up, 43.6% (n = 72) of all observed patients died, MO530 IS THERE A ROLE FOR SCALES IN RENAL REPLACEMENT
56.4% (n = 93) patients survived (of which 11 underwent kidney transplantation). The THERAPY DECISION MAKING PROCESS?
average age of the deceased (53.6 6 1.6) was significantly higher than that of patients
continuing to receive HD (45.6 6 1.5). The average duration of hemodialysis in Marina De Cos Gomez1, Maria Rosa Palomar Fontanet1, Enrique Toledo
survivors (33.0 6 5.4) was higher than in the dead (28.6 6 3.9). The study of the Martinez2, Maria Kislikova1, Jaime Mazon Ruiz1, Mara Serrano Soto1, Vicente
Celestino Pin~era Haces1, Emilio Rodrigo1, Carlos Antonio Salas Venero3, Juan
further fate of patients, depending on the presence or absence of cardiovascular
Carlos Ruiz San Milla n 1
diseases, showed that among the deceased patients, 68.1% (n = 49) of patients were
1
patients who had CVD, while among those who survived, 53.7% ( n = 44) had no CVS University Hospital Marques de Valdecilla-IDIVAL, Nephrology, Santander, Spain,
2
pathologies. Among those continuing to receive programmed hemodialysis, there were University Hospital Marques de Valdecilla-IDIVAL, General Surgery, Santander, Spain
31.7% more patients without CVD than among patients with diagnosed CVD. In and 3University Hospital Marques de Valdecilla-IDIVAL, Microbiology, Santander, Spain
dialysis patients with CVD who died within the period of 30 months of prospective
observation was 39.6% higher than in patients without CVD. The survival rate of BACKGROUND AND AIMS: Optimal care of patients with advanced CKD is key for
patients with CVD was 0.44 [95% CI 0.34-0.55], while in patients without CVD it was reducing their morbidity and mortality. An accurate evaluation of these patients is
0.67 [95% CI 0.55-0.78]. necessary to improve their treatment and prepare them for renal replacement therapy
CONCLUSION: The concomitant pathology of the cardiovascular system affects the (RRT) when appropriate. Beyond laboratory values, an integral evaluation of this
survival rate of patients with end-stage CKD on hemodialysis. Dialysis patients of the group is essential, and it must cover a number of aspects, including physical, psychical,
population of Uzbekistan who do not have concomitant cardiovascular pathology have functional and social among others. The aim of this study is to evaluate the
a 33% higher survival rate than patients without CVD. performance of a group status scales regarding these areas in our advanced CKD Unit
and its potential utility in the eligibility decision making process.
METHOD: We performed a retrospective study including patients evaluated in our
clinic from 1st January 2019 to December 31th 2020. According to protocol, referrals to
our unit occurred when patients presented eGFR (CKD-EPI) < 25 ml/min (after
confirmation in two consecutive measurements). Scales and initiation of RRT election

i320 | Abstracts
Nephrology Dialysis Transplantation Abstracts
process were performed when eGFR (CKD-EPI) was below 20 ml/min. 8 scales were MO531 IMPACT OF INFLAMMATORY MARKERS IN COGNITIVE
performed to evaluate anxiety and depression, cognitive impairment, instrumental IMPAIRMENT IN CHRONIC KIDNEY DISEASE PATIENTS
activities decline, frailty, malnutrition, social status, comorbidity and self-report
situation. Scales were conducted separately (in an interview with one of the advanced Merita Rroji (Molla)1, Larisa Shehaj1, Myftar Barbullushi1
1
CKD nurses) and did not influence nephrologist eligibility decision. Information about UHC “Mother Tereza”, Department of Nephrology, Tirana, Albania
patients was extracted from the prospectively maintained database at our center.
RESULTS: During the period of study 699 patients were evaluated. Clinical BACKGROUND AND AIMS: Cognitive impairment is an increasingly identified
characteristics and RRT eligibility results are shown in Table 1. Scales results in RRT major cause of chronic disability and is commonly found in patients with chronic
candidates and conservative treatment candidates are shown in Table 2. 128 patients kidney disease (CKD). Knowledge of the link between kidney dysfunction and
had subsequent scales after 1 year follow up; paired comparison showed higher rates of impaired cognition may enhance our understanding of risk factors impacting cognitive
instrumental activities decline (18% vs. 25%, p 0.002), greater comorbidity (7.21 vs. dysfunction. Our study aimed to evaluate the relation between serum inflammatory
8.52, p < 0.001) and worse self-report subjective assessment (63.41 vs. 67.05, p < markers and the risk of cognitive decline among adults with CKD.
0.0019). There were not statistically significant differences in the other scale parameters METHOD: Forty-six patients predialysis patients CKD stage 5 (mean age 55.6611.5
analyzed. During the period of observation, 12.1% patients died. Multivariate cox years old) accepted to participate in the study. The Montreal Cognitive Assessment
regression analysis evaluating risk of death including scales (after adjustment by age) (MoCA) scale was administered to patients. Patients with a MoCA global score of 24/
showed a significant relation between and malnutrition (HR 7.98 CI95% (2.24-18.47), 30 were considered cognitively impaired. Descriptive analysis was done for the socio-
p = 0.001) and comorbidity (HR 1.29 CI95% (1.05-1.60) p = 0.017). demographic and clinical variables. We measured high-sensitivity C-reactive protein
(hs-CRP), ferritin level, albuminemia, and fibrinogen in baseline plasma samples.
RESULTS: The mean total MoCA score for all the patients was 22.9 63.8 points.
Thirty-seven patients, 57.7%, were evaluated with CI, where 74.6 % with Mild CI
(MCI) and 25.4% with severe CI (SCI) under 20 points). MoCA subscale analysis
revealed that the mean score for visuospatial/executive domain and attention were the
lowest with 5.4161.1 /8max and 2.9361.75/6 max, and scores for orientation were the
highest 5.9260.57/6 max. At baseline, higher levels of each inflammatory marker were
associated with poorer age-adjusted performance. In analyses adjusted for baseline
cognition, demographics, comorbid conditions, and kidney function, participants in
the highest tertile of hs-CRP, the highest tertile of fibrinogen, and the highest tertile of
ferritin had an increased risk of impairment in attention compared to participants in
the lowest tertile of each marker (p=0.043, p=0.047, p=0.029, respectively. The high
level of ferritin was evaluated as a risk of impairment visuospatial/executive ability, and
no relationship of inflammatory markers was observed with impairment of orientation
p=0.01. hs-CRP and ferritin and low albumin level were independently associated with
longitudinal global cognitive function (p=0.04, p=0.02, p=0.49 respectively).
CONCLUSION: In CKD patients, we have a relatively high risk for cognitive
impairment. Our results extend the findings from prior studies by showing that
inflammatory markers used in routine practice contribute and are independently
associated with longitudinal changes in some domains of cognitive function in patients
with CKD going in parallel with the inflammatory mechanisms that have been
implicated in the pathogenesis of vascular and Alzheimer’s dementia.

MO532 WHICH UNHEALTHY LIFE-BEHAVIOR IS THE MOST IMPACT


FOR THE PRESENCE OF PROTEINURIA?

Jun Muratsu1, Masahiko Hara2, Atsuyuki Morishima1, Katsuhiko Sakaguchi1,


Takashi Fujimoto3
1
Sumitomo Hospital, Department of Nephrology and Hypertension, 2Shimane
University, Center for Community-based Healthcare Research and Education and
3
Sumitomo Hospital, Physical Check up Center

BACKGROUND AND AIMS: Unhealthy life-behaviors such as dietary habits, lack of


exercise, drinking large amount of alcohol and smoking cause obesity, hypertension,
diabetes, dyslipidemia, cardiovascular disease (CVD). These are also closely associated
with chronic kidney disease (CKD). CKD is characterized by proteinuria and low
glomerular filtration rate (GFR). Independent of GFR, proteinuria is an important
predictor of ESKD. Few studies have assessed which is the most clinical impact among
the unhealthy life-behaviors: skipping breakfast, snacking, late-night dinner, smoking,
heavy alcohol intake and lack of exercise habits for proteinuria in normal renal
function patients.
METHOD: This cross-sectional study included 29,780 normal renal function patients:
CONCLUSION: Advanced CKD is rising worldwide and represents an important eGFR60 mL/min/1.73 m2 and no history of kidney diseases who underwent health
burden for patients and nephrology services. Evaluation of this group remains checkup at the Physical Checkup Center of Sumitomo Hospital. The endpoint of this
particularly challenging, and in order to guarantee its adequate management, an investigation is defined as dipstick proteinuria of 1þ. To assess the association of life-
integral and reproducible evaluation of these patients has to be ensured. This is behaviors and the presence of proteinuria, their odds ratios were calculated in adjusted
especially important with regard to patients’ eligibility and RRT decision making univariable and multivariable logistic regression model. Multivariable logistic
process. According to our study, clinical scales are useful for this purpose and eligibility regression model was performed by not selected items, the same with univariable
results (after conventional nephrologist follow-up) were associated with scale results. model. We would like to investigate the most impact unhealthy life-behavior for the
The parameters that particularly correlated with eligibility and specifically, renal proteinuria.
replacement therapy contraindication, were mostly instrumental (cognitive RESULTS: Among 29,780 total study subjects (male: 60.3%; mean age: 49611 years),
impairment, functional activities decline, frailty and social deterioration). Additionally, 1,118 (3.75%) subjects were shown as urinary protein above 1þ. The presence of
repeated assessment could be helpful to highlight which aspects are deteriorating faster unhealthy dietary life-behaviors: skipping breakfast, snacking and late-night dinner
and find strategies to minimize them. In accordance to literature, mortality in our was 5,293 (17.3%), 3,899 (13.1%) and 11,231 (37.7%), respectively. About sleeping
cohort was higher in patients with malnutrition and comorbidity, showing the duration, the population of <6 hours, 6-8 hours and >8 hours were 12,027 (40.4%),
importance of a systematic evaluation of these items in the management of advanced 17,236 (57.9%) and 517 (1.7%). The population of exercise habits: over 3 days/weeks,
CKD. Altogether, these scales could be used to better stratify patient’s risk prior RRT 1-2 days/weeks and none were 5,138 (17.3%), 9,375 (31.5%) and 15,237 (51.3%),
decision making process and help clinicians to make more reproducible and consistent suggesting half of them did not have exercise habits. About smoking habits, the
decisions. Large-scale, multicenter validation studies could be the next step to prove population of current smoking, past smoking and never smoking were shown 6,445
their utility among advanced CKD patients. (21.6%), 8,459 (28.4%) and 14,876 (50.0%). In addition, about alcohol amount per day,
the population of over 60g, 40-60g, 20-40g and 0-20g were 1,840 (6.18%), 4,504
(15.1%), 6,727 (22.6%) and 16,709 (56.1%).
To investigate the impact of life-behavior for proteinuria, we obtained odds ratio of
adjusted multivariable logistic regression model. In multivariable regression, among
the life-behavior: skipping breakfast, current smoking, alcohol amount (ethanol over

10.1093/ndt/gfab087 | i321
Abstracts Nephrology Dialysis Transplantation

60 g/day), none of exercise habits and snacking were strongly associated with the
prevalence of proteinuria (skipping breakfast, adjusted odds ratio 1.45 [1.26, 1.68]; MO533 Table 1: AUC values to predict for positive COVID-19 status following hip
current smoking, 1.35 [1.14, 1.59]; alcohol amount (ethanol over 60 g/day), 1.35 [1.08, fracture in patients living with CKD
1.69]; none of exercise habits, 1.29 [1.07, 1.57]; snacking, 1.23 [1.04, 1.46]). In addition,
among the history of medical history, diabetes mellitus, hypertension and dyslipidemia Predictor AUC Value 95% Cl
were significantly associated with the prevalence of proteinuria (diabetes mellitus,
adjusted odds ratio 2.39 [1.93, 2.96]; hypertension, 1.83 [1.53, 2.17]; 1.22 [1.03, 1.45]). Clinical Frailty Scale 0.94 0.87-1.00
CONCLUSION: Among the unhealthy life-behaviors, skipping breakfast is the most Charlson’s Co-morbidity Index 0.92 0.86-0.99
impact factor for the presence of proteinuria.
Chronic Kidney Disease Frailty Index Laboratory Score 0.88 0.81-0.95
Estimated VO2 Peak 0.86 0.79-0.92
MO533 WHICH PARAMETERS BEST PREDICT POSITIVE COVID-19 Karnofsky Performance Status Scale 0.84 0.77-0.91
STATUS FOLLOWING HIP FRACTURE FOR PATIENTS LIVING Sernbo Score 0.80 0.74-0.87
WITH CKD?
Nottingham Hip Fracture Score 0.77 0.70-0.84
Henry Wu1,2, Reinier Van Mierlo3, Kirsty Challen4, George McLauchlan5, ASA Physical Status Classification System Score 0.74 0.67-0.81
Ajay Dhaygude1,2, Sandip Mitra1,6, Andrew Nixon1,6 Abbreviated Mental Test Score 0.65 0.58-0.72
1
University of Manchester, Faculty of Medical and Human Sciences, MANCHESTER,
United Kingdom, 2Lancashire Teaching Hospitals NHS Foundation Trust, Department of
Renal Medicine, PRESTON, United Kingdom, 3Lancashire Teaching Hospitals NHS
Foundation Trust, Department of Physiotherapy , PRESTON, United Kingdom,
4
Lancashire Teaching Hospitals NHS Foundation Trust, Department of Emergency
Medicine, PRESTON, United Kingdom, 5Lancashire Teaching Hospitals NHS Foundation MO534 VITAMIN D DEFICIENCY IN PATIENTS WITH CHRONIC
Trust, Department of Orthopaedics & Traumatology, PRESTON, United Kingdom and KIDNEY DISEASE OF UNCERTAIN ETIOLOGY IN
6
Manchester University NHS Foundation Trust, Department of Renal Medicine, WILGAMUWA, SRI LANKA
MANCHESTER, United Kingdom
Rivindi Godawita1, Ayesha Nayanamali2, Renuka Silva3, Nishantha Nanayakkara4
BACKGROUND AND AIMS: Patients living with chronic kidney disease (CKD) are 1
University of Peradeniya, Postgraduate Institute of Agriculture, Kandy, Sri Lanka,
at greater susceptibility of sustaining hip fractures compared to those without CKD 2
National Hospital, Nephrology and Transplant Unit, Kandy, Sri Lanka, 3Wayamba
due to higher falls risk. Post-trauma clinical outcomes for patients living with CKD University of Sri Lanka Makandura Premises, Department of Applied Nutrition, Sri
are exacerbated by frailty, co-morbidities and sarcopenia. Patients living with CKD Lanka and 4National Hospital - Kandy, Nephrology and Transplant Unit, Kandy, Sri
may require lengthy hospitalization following hip fracture, considering the Lanka
additional indications for extensive treatment and rehabilitation. A long hospital stay
may bring greater risks of contracting COVID-19, given the magnitude of this
current global pandemic. Complications from COVID-19 significantly increase BACKGROUND AND AIMS: Vitamin D deficiency (VDD) is a common, well known
mortality risks for older patients living with CKD after acute trauma, as a association in Chronic Kidney Disease (CKD). However, there are no published studies
considerable proportion will have a poor baseline health and functional status. Our on the prevalence of VDD among CKDu (Chronic Kidney Disease of uncertain
study aims to determine the most useful clinical and laboratory assessment tools to etiology) patients. This study aims to study on Vitamin D status of CKDu patients.
predict for a positive COVID-19 status following hospitalization with hip fracture in METHOD: This was a cross sectional survey conducted in Wilgamuwa area, in
patients living with CKD. Mathale located in Central province of Sri Lanka. Among the 39 GN (Grama
METHOD: Patients with CKDG3b-5 admitted from home to a tertiary hospital in Niladahri) divisions at Wilgamuwa, GN divisions where the CKD prevalence was high
North West UK with hip fracture between Feb and Dec 2020 were included. Each areas were taken for the study. Data were collected by using clinical examination and
patient included in this study received at least one COVID-19 nasopharyngeal swab interviewer administered questionnaire and analyzed using SPSS statistical software
during their hospitalization. Parameters assessed on hospital admission for each RESULTS: A total of 150 patients living in a CKDu endemic area in Sri Lanka was
patient included Clinical Frailty Scale (CFS), Charlson’s Co-morbidity Index (CCI), studied during the study period. Majority (n=118, 78.7%) of the CKDu patients were
Chronic Kidney Disease Frailty Index Laboratory Score (CKD FI-LAB), Estimated VO2 males. Mean age (years) was 56.7567.89 and 54.3467.87 for females and males
Peak, Karnofsky Performance Status Scale, Sernbo Score, Nottingham Hip Fracture respectively. More than half of the patients were middle aged outdoor workers.
Score, ASA Physical Status Classification System Score and Abbreviated Mental Test According to the BMI (Body mass index) results, majority (n= 87, 58%) of the CKDu
Score. Receiver Operating Characteristic (ROC) curve analyses were performed to patients were in the healthy weight category. More than one third of the patients were
evaluate the ability of individual parameters to predict for a positive COVID-19 status in the underweight category. VDD ( < 20ng/mL) was reported in 22.88% (n=27) of the
following hip fracture in patients living with CKD. Events of 30-day mortality were total males and 68.75% (n=22) of the total females. Vitamin D insufficiency (20-30ng/
recorded. mL) was identified among 45.76% (n=54) males and 25% (n=8) females. Rest of the
RESULTS: 92 patients met study inclusion criteria. The mean age was 84.667.8 years males (31.35, n=37) and females (6.25%, n=2) had normal vitamin D level (>30 ng/
and the female:male ratio was 1.6:1. 7 patients (7.6%) were on long-term dialysis and mL). As a summary the mean Vitamin D level was 24.85 67.93 ng/mL. There was a
the mean eGFR amongst non-dialysis patients was 36.5613.8 ml/min/1.73m2. The significant different in the prevalence of VDD between gender groups (p = 0.004).
median length of hospitalization was 17 days. 22 patients (23.9%) tested positive for VDD is more common (82%) during the early stages of CKDu while less common
COVID-19. Area under a Curve (AUC) values from ROC analyses are shown in Table during the late stage. However, there is no any significant association between the
1. The difference in 30-day mortality rate between patients who tested positive for prevalence of VDD and CKDu stage (p=0.183).
COVID-19 and those who tested negative was þ6.8% (p<0.001). CONCLUSION: VDD is more commonly encountered complication in during the
CONCLUSION: Frailty and co-morbidity assessment tools (CFS, CCI and CKD FI- early stages of CKDu and it was significantly high in male CKDu patients compared to
LAB) displayed the best predictive ability for positive COVID-19 status following hip females.
fracture in patients living with CKD. A continuous, holistic multi-disciplinary team
approach during hospitalization for comprehensive geriatric assessment and MO534 Table: Prevalence of VDD in early and late stages of CKDu
optimization of medical co-morbidities may improve outcomes, in anticipation of a
potential lengthy hospital stay. To improve prognosis, research efforts should
continue to explore avenues on reducing COVID-19 rates within this patient Vitamin D Normal
population.
deficiency Vitamin
D
Early Stage of CKDu(eGFR>45 ml/min/1.73m2) 32 (82%) 7 (17.9%)
Late Stage of CKDu(eGFR>45 ml/min/1.73m2) 79 (71.2%) 32 (28.8%)

i322 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Continued
Characteristic All Results
Participants for all
(%)
Age mean (sd) 355 63 (17)
Age category n (%) 355
<40 36 (10)
40-49 41 (11)
50-59 65 (18)
>60 213 (60)
Female n (%) 355 213 (60)
Hypertension n (%) 355 201 (58)
Diabetes n (%) 354 135 (38)
MO534 Figure: Gender wise prevalence of Vitamin D Deficiency
eGFR mean (sd) 355 81 (30)
eGFR <60 n (%) 355 90 (25)
MO535 PREVALENCE OF CHRONIC KIDNEY DISEASE AND eGFR <45 n (%) 355 42 (11)
ASSOCIATED RISK FACTORS ON THE ISLAND OF
MONTSERRAT
CKD stage n (%) among persons 90 -
Keniel Chrysostom1, Lori-Ann Fisher1, Everard Barton2, Adedamola Soyibo1, with eGFR < 60
Grethlyn West3, Georgette Skerritt3, Kyaw Hoe1 Stage 3 (estimated GFR 30-59) n (%) 73 (81)
1
University of the West Indies, Nephrology, Kingston, Jamaica, 2Caribbean Institute of Stage 4 (estimated GFR 15-29) n (%) 10 (11)
Nephrology, Kingston, Jamaica and 3Ministry of Health & Social Services, Glendon
Hospital, St. Johns, Montserrat Stage 5 (estimated GFR <15) n (%) 7 (8)

BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is a global health


problem with disproportionate burden in low- and middle-income countries in Latin
America and the Caribbean. Despite these disparities, little is known of the prevalence
and risk factors of CKD in the Caribbean. We sought to determine prevalence of CKD
among patients attending ambulatory centres in Montserrat, an island that to date, has MO536 CHINESE CHRONIC RENAL INSUFFICIENCY STUDY: BASED
no facilities for renal replacement therapy. ON SMARTPHONE PLATFORM (C- CRISS): DESIGN AND
METHOD: A cross-sectional observational study of Participants were individuals aged METHOD
18 years was performed. Random cluster sampling of at least 500 participants who
attended clinic from January 1 to July 1, 2020 across all primary health care facilities on Xiaohong Fan1, Peng Xia1, Xuehan Zhang1, Jiaying Li1, Ruilian You1,
island was performed. Patients without lab values for creatinine were excluded. The Yuanyuan Zhu2, He Liu3, Ling Qiu4, Yan Qin1, Xuemei Li1, Limeng Chen1
1
main outcome measures was estimated CKD prevalence (as defined based on KDIGO Peking Union Medical College Hospital, Nephrology, Beijing, P.R. China, 2Peking Union
2012 guidelines of eGFR < 60mL/min/1.73m2 using creatinine based CKD-EPI for Medical College Hospital, Cardiology, Beijing, P.R. China, 3Peking Union Medical College
blacks; and estimated prevalence of CKD risk factors (Self-reported diabetes or Hospital, Ultrasound, Beijing, P.R. China and 4Peking Union Medical College Hospital,
hypertension and obesity, BMI> 30kg/m2). Multivariate Logistic regression was used P.R. China
to determine independent predictors of CKD.
RESULTS: Three hundred and fifty-five participants (n = 355) were selected for BACKGROUND AND AIMS: Abnormal mineral bone metabolism of chronic kidney
participation. Participants’ mean age was 63 6 17 years, with 60% (n=213) being disease (CKD-MBD) is the most common CKD complication. However, fewer data
female. 38% (n=135) had self-reported diabetes and 58% (n=201) had hypertension; concerning the relationship between bone metabolic indexes, such as high serum
and 44% were obese. Mean6 SD estimated GFR was 81 6 30 ml/min/1.73 m2 . One phosphorus and cardiovascular diseases, bone mass reduction, and fracture, is available
quarter of the participants (25%) had an eGFR <60 ml/min/1.73 m2, indicating CKD. in Chinese adult patients. The Chinese Chronic Renal Insufficiency Study: Based on
Age [95% CI, OR 1.03 (1.01–1.07)], Self-reported hypertension [95% CI, OR 2.09, Smartphone Platform (C-CRISS) is established to explore the relationship between
(1.13–3.90)] and female gender [95% CI ,OR 0.20 (0.10, 0.39)] were independent bone metabolic markers and other non-traditional risk factors with renal function
predictors of reduced eGFR. progression, cardiovascular (CVD), and cerebrovascular diseases (BVD), and bone loss
CONCLUSION: CKD and its risk factors were prevalent among adults in Montserrat. in CKD patients.
Consideration must be made for infrastructural and/or policy changes to be mandated, METHOD/DESIGN: The C-CRISS study is a multi-center prospective cohort study in
to slow the progression of CKD. Primary prevention initiatives can be implemented to China. It will recruit 3360 pre-dialysis patients aged 18 to 74 years and follow up for at
reduce the associated morbidity, mortality and cost associated with CKD. There is least two years. The individuals with CKD G3b-5ND will account for over 70 percent
room for further longitudinal studies to identify etiology, as well as factors affecting of the study population. Active glomerulonephritis, rapidly progressing and advanced
CKD progression. This study will also propel creation of the Montserrat arm of the heart, liver, and tumor diseases will be excluded. The primary composite endpoints
Caribbean Renal Registry, to allow for future follow up of long-term effects, as well as include the events of progression to ESRD, cardiovascular events, and death. The
ascertain risk factors for CKD progression. participants will undergo the clinical evaluation at baseline and clinic visits at six-
monthly intervals in traditional consultation ways. The CVD, BVD, retinopathy, DXR,
and other complications will be measured annually. Data on the questionnaire, diet,
quality of life, and patients’ status during follow-up will be collected by the smartphone
platform developed for this study. The sample size will enable us to have 80% power to
Characteristic All Results detect a 2.0 risk ratio of CVD events in CKD G4 patients compared with CKD G3a
Participants for all patients.
(%) CONCLUSION: The C-CRISS study would provide evidence of the potential risk of
bone metabolic markers for progressive CKD and CVD/BVD. The study will also
Age mean (sd) 355 63 (17) provide a new management and complication monitoring model through smartphone
Age category n (%) 355 communication in chronic kidney disease patients.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04229485
<40 36 (10)
40-49 41 (11)
50-59 65 (18)
>60 213 (60)
Female n (%) 355 213 (60)
Hypertension n (%) 355 201 (58)

Continued

10.1093/ndt/gfab087 | i323
Abstracts Nephrology Dialysis Transplantation

vessels. It is possible that hyperhomocysteinemia may lead to intrarenal arteriosclerotic


lesions and decline in GFR or impaired renal function. Aim of this study was to
elucidate the association of plasma homocystiene level with renal function and
cardiovascular risk factors in rural population.
METHOD: A well defined rural area was selected. Study subjects were identified by
computer generated random numbers after entering household listings and then Kish
table was used to choose a participant. Adult subjects (18 years) were only included.
The approached participant was explained the purpose, if consented, then given an
appointment to be present at a research hospital on a separate date for clinical and
biochemical evaluation. A face to face interview was conducted. Clinical history,
physical examination anthropometrics were recorded on data sheet. Fasting blood
sample and morning spot urine was collected. Then serum tHcy was measured by
chemiluminescent microparticle immunoassay (CMIA) technology. Study population
were investigated with Spot urine ACR, Fasting glucose, serum lipid profile, creatinine,
homocysteinine , Folic acid and Vit B12.
RESULTS: Early results of 234 random subjects are presented here. The mean age was
41 6 13(18-92) years with male 33% and female 67%. Mean eGFR was 996 26 ml/min,
tHcy 11.6 6 5.9 lmol/l, Vit B12 329 6 187 pg/ml and Folic Acid 5.57 6 2.63 ng/ml. A
tHcy cut-off value in study subjects 15 lmol/l was seen in 17 % and <15 lmol/l in
83%. Serum creatinine, Uric Acid, Cholesterol, LDL was significantly higher and Vit
MO537 INTERACTION OF PLASMA HOMOCYSTIENE, RENAL B12, Folic acid lower in tHcy 15 lmol/l group. Further grouping showed tHcy level
FUNCTION AND CARDIO-METABOLIC RISK FACTORS- AN was significantly higher in Vit B12<200 pg/ml and Folic acid <3ng/l group.
OBSERVATION IN A RURAL POPULATION OF BANGLADESH Correlation studies showed homocystiene positively correlated with age, systolic blood
pressure, creatinine, LDL and negatively with Folic acid and Vit B12.
Md.Hafizur Rahman1, Kazi Shahnoor Alam1, Babrul Alam1, Sajal CONCLUSION: Our findings suggest that elevated plasma homocystiene level might
Krishna Banerjee2, SR Chaudhury3, MI Arslan4, MS Hassan5, MAA Chowdhury1, influence and are associated with altered markers of renal, cardiac and metabolic risk
Md M Iqbal1,6 factors in rural population. Preventive approaches are required towards this issue as
1
NIKDU, 2BSMMU, Bangladesh, 3NHFRI, 4BSMMU, 5BIRDEM and 6KDRG larger population segment belongs to rural areas.

BACKGROUND AND AIMS: Elevated plasma total homocystiene (tHcy) levels are
associated with atherosclerotic diseases in coronary, cerebral and peripheral blood

i324 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i325–i336, 2021
10.1093/ndt/gfab085

CKD. ANAEMIA baseline at 1 and 3 months. Bar heights represent mean change and error bars
represent standard deviations of the sample. FDI: Ferric derisomaltose.

MO538 THE SHORT-TERM IMPACT OF HIGH DOSE INTRAVENOUS


IRON USE ON RENAL FUNCTION IN PATIENTS WITH
CHRONIC KIDNEY DISEASE AND IRON DEFICIENCY
WITHOUT ANAEMIA - A POST-HOC ANALYSIS OF A
MULTICENTRE RANDOMIZED CONTROLLED TRIAL*

Xenophon Kassianides1, Adil Hazara1, Philip A. Kalra2, Iain Macdougall3,


Sunil Bhandari1
1
Hull University Teaching Hospitals NHS Trust and the Hull York Medical School,
Academic Renal Research Department, Kingston upon Hull, United Kingdom, 2Salford
Royal NHS Foundation Trust and the University of Manchester, Department of Renal
Medicine, Manchester, United Kingdom and 3King’s College Hospital, Department of
Renal Medicine, London, United Kingdom

BACKGROUND AND AIMS: High dose intravenous (IV) iron is commonly used in MO538 Figure 2: Change in cystatin C and creatinine relative to baseline in the two
patients with chronic kidney disease (CKD) but it remains unclear whether any short treatment arms, stratified by age and diabetes mellitus.
or long term impact on renal function exists. Studies using iron sucrose, a second
generation IV iron compound suggest effects on proteinuria while evidence with third
generation iron products revealed no impact on estimated glomerular filtration rate CONCLUSION: This post-hoc analysis of data from the Iron & Heart study indicates
(eGFR). These newer iron compounds have compact iron-carbohydrate cores, that high dose FDI did not cause any significant detriment in the short-term to renal
potentially limiting the nephrotoxic effects of labile free iron. function compared to placebo. This complements the safety profile of high dose third
As a part of the Iron & Heart study, we examined the impact of high dose ferric generation IV iron products and improves our understanding of their use in patients
derisomaltose (FDI), a third generation IV iron product, in patients with non-dialysis with CKD at their approved doses. There was a good correlation between cystatin C
dependent CKD and iron deficiency on markers of renal injury and function using and creatinine, which was not affected by various sub-groups such as age or presence of
both established (serum creatinine, eGFR, 24-hour excretion of protein) and novel diabetes mellitus. The analysis confirms the role of cystatin C as a robust biomarker of
methods (Cystatin C, Neutrophil gelatinase-associated lipocalin (NGAL)). measuring renal function at least when compared to other established methods.
In addition, correlations between the different markers of renal dysfunction were
examined alongside the impact of various confounders including age and diabetes
mellitus on the reliability of such markers. MO539 HEMATOLOGIC EFFICACY OF VADADUSTAT FOR ANEMIA IN
METHOD: This was a multicentre randomized double-blinded placebo-controlled PATIENTS WITH KIDNEY FAILURE ON DIALYSIS
study involving three tertiary renal centres in the United Kingdom. Patients with CKD
stages 3b-5 (non-dialysis), a serum ferritin <100 micrograms/L and/or transferrin Wolfgang Winkelmayer1, James A. Tumlin2, Steven Fishbane3, Youssef Farag4,
saturation <20% and a haemoglobin value of 110 – 150 g/L were enrolled. The Dennis Vargo4, Wenli Luo4, Mark Koury5
participants were randomized 1:1 to receive either 1000 mg of FDI or placebo. Cystatin 1
C, NGAL, serum creatinine eGFR and 24-hour urinary excretion of protein were Baylor College of Medicine, Nephrology, Houston, United States of America, 2Emory
measured at baseline and then repeated at 1- and 3- months. Changes in the levels of University School of Medicine, Lawrenceville,, United States of America, 3Hofstra
these were analysed both in terms of their absolute values and percentage change from Northwell Health School of Medicine, Division of Nephrology, Department of Medicine,
baseline. Pearson’s coefficient (r) was calculated as a measure of correlation between Great Neck, NY, United States of America, 4Akebia Therapeutics, Inc., Cambridge, United
changes in the follow-up values, and the level of statistical significance was set at less States of America and 5Vanderbilt University Medical Center, Nashville, United States of
than 0.05. America
RESULTS: 54 patients were randomized; 26 to FDI and 28 to placebo. Patients in the
two treatment arms were similar in age, gender, the prevalence of diabetes, baseline BACKGROUND AND AIMS: Vadadustat is a small-molecule inhibitor of hypoxia-
eGFR and urinary protein excretion (200mg vs 350mg/24hr in the FDI and placebo inducible factor prolyl hydroxylase being developed for treatment of anemia associated
groups respectively, p = 0.2713). Compared to baseline levels, serum creatinine, with chronic kidney disease (CKD). The vadadustat phase 3 program includes four
cystatin C and NGAL did not change significantly in either arm (figure 1). There were efficacy and cardiovascular safety outcome trials of vadadustat versus the
no significant changes in urinary protein excretion both within and between groups erythropoiesis-stimulating agent (ESA) darbepoetin alfa. Here we describe detailed
(median change in urinary protein excretion: FDI: -10mg and -39mg/24hr; placebo: results on hematologic efficacy in two of the four phase 3, randomized, open-label,
0mg and 0mg/24hr at 1- and 3- months respectively, p>0.05) There was a significant sponsor-blind trials (the INNO2VATE trials) in adult patients with dialysis-dependent
correlation between changes in cystatin C levels and serum creatinine (r = 0.6994, (DD) CKD and anemia, where vadadustat met prespecified noninferiority criteria
p<0.0001) during follow-up. This correlation persisted when patients were stratified by compared with darbepoetin alfa with respect to cardiovascular safety and correction/
an age of 65 years and presence of diabetes (figure 2). Changes in Cystatin C levels did maintenance of hemoglobin (Hb) target concentrations.
not correlate well with changes in NGAL. METHOD: The mean screening Hb range for the incident DD-CKD trial
(NCT02865850) was 8.0-11.0 g/dL; for the prevalent DD-CKD trial (NCT02892149), it
was 8.0-11.0 g/dL in the United States (US) and 9.0-12.0 g/dL for non-US. Patients in
the incident and prevalent DD-CKD trials had initiated dialysis within <16 weeks with
limited or no prior ESA exposure and >12 weeks with established ESA treatment prior
to screening, respectively. Vadadustat starting dose was 300 mg/day for all patients,
whereas initial darbepoetin alfa dose depended on each patient’s prior dose or product
label. Both vadadustat and darbepoetin alfa doses were titrated according to
prespecified dosing algorithms to achieve target Hb concentrations (US: 10-11 g/dL;
non-US: 10-12 g/dL) during the primary evaluation period (PEP; weeks 24-36) and the
secondary evaluation period (SEP; weeks 40-52). Herein, we present topline results
from PEP and SEP endpoints, as well as other, more detailed hematologic erythrocyte
parameters.
RESULTS: A total of 3923 patients (369 with incident DD-CKD and 3554 with
prevalent DD-CKD) were randomized 1:1 to vadadustat or darbepoetin alfa.
Vadadustat was noninferior to darbepoetin alfa in achieving target-range Hb
concentrations (primary efficacy endpoint) among patients who were new to, or
established on, dialysis. The respective proportions of patients (vadadustat vs.
darbepoetin alfa) with an average Hb value within the geography-specific target range
in the PEP and SEP were 43.6% versus 56.9% and 39.8% versus 41.0% in the incident
MO538 Figure 1: Percentage change in Creatinine, Cystatin C and NGAL relative to trial and 49.2% versus 53.2% and 44.3% versus 50.9% in the prevalent dialysis trial. The

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

proportion of patients who achieved an Hb increase >1.0 g/dL from baseline to week
52 was assessed only for the incident trial and was 84.0% (95% CI: 77.8%, 89.0%) for Table. Incidence Rates of Adjudicated MACE, MACEþ, and ACM Events/100 PEY in
vadadustat versus 89.9% (95% CI: 84.7%, 93.8%) for darbepoetin alfa. Patients Receiving Roxadustat
Hematologic erythrocyte parameters at time points within the PEP and SEP are
presented in Table 1. In the incident trial, reticulocyte count was slightly increased Achieved Hb Immediately Prior to Eventa Preliminary ROR of Hba.b
from baseline at 28 and 52 weeks for vadadustat, whereas for darbepoetin alfa, <10 g/dL 10 to <12 g/dL 12 to <13 g/dL 13 g/dL 2 g/dL/ >2 g/dL/
reticulocyte count was slightly decreased or unchanged in both trials. Erythrocyte PEY¼759.9 PEY¼2835.7 PEY¼664.3 PEY¼129.9 4 weeks 4 weeks
mean corpuscular volume and erythrocyte mean corpuscular Hb showed increases by PEY¼4247.6 PEY¼142.3
week 52 for both groups. MACE 17.4 5.1 5.0 6.2 7.2 2.8
CONCLUSION: Vadadustat demonstrated similar profiles across erythrocyte MACEþ 24.7 7.5 7.2 10.0 9.8 9.8
ACM 13.2 3.0 2.9 1.5 4.8 0.7
parameters compared with darbepoetin alfa in the treatment of anemia associated with a
CKD in adults in both incident dialysis and prevalent dialysis settings. Adjudicated events by Hb level that occurred during the treatment period and within 7 days of
the last dose of study medication in randomised subjects who took any dose of roxadustat.
b
Preliminary Hb ROR was defined as the maximum change at every moving 4-week window.
Total PEY for the ROR >2 g/dL per 4 weeks category includes a union of all windows that contain
ROR >2 g/dL; the complement set is defined as the PEY for ROR 2 g/dL per 4 weeks category.
Subjects with more than one event in each category were only counted once.
Incidence rate/100 PEY ¼ 100 x number of subjects with events/PEY.
Abbreviations: ACM, all-cause mortality; Hb, haemoglobin; MACE, major adverse cardiovascular
events; MACEþ, MACE plus heart failure and unstable angina requiring hospitalisation; PEY,
patient-exposure years; ROR, rate of rise.

MO541 HEMATOLOGIC EFFICACY OF VADADUSTAT FOR ANEMIA IN


PATIENTS WITH NON–DIALYSIS-DEPENDENT CHRONIC
KIDNEY DISEASE

Mark Koury1, Pablo E. Pergola2, Prabir Roy-Chaudhury3, Youssef Farag4,


MO540 CARDIOVASCULAR OUTCOMES ASSOCIATED WITH
Dennis Vargo4, Wenli Luo4, Wolfgang Winkelmayer5
ACHIEVED HAEMOGLOBIN LEVEL IN POOLED PHASE 3 1
STUDIES OF ROXADUSTAT IN NON-DIALYSIS-DEPENDENT Vanderbilt University Medical Center, Department of Medicine, Nashville, United States
PATIENTS WITH ANAEMIA of America, 2Renal Associates, P.A., San Antonio, United States of America, 3UNC School
of Medicine, W. G. (Bill) Hefner VA Medical Center, Chapel Hill, United States of America,
4
Jonathan Barratt1, Wladyslaw Sulowicz2, Elinor Cockburn3, Michael Reusch3, Akebia Therapeutics, Inc., Cambridge, United States of America and 5Baylor College of
James Young4, Nada Dimkovic5 Medicine, Houston, United States of America
1
University of Leicester, Leicester, Department of Respiratory Sciences, 2Collegium
Medicum of Jagiellonian University, Department of Nephrology, 3Astellas Pharma BACKGROUND AND AIMS: Vadadustat is a small-molecule inhibitor of hypoxia-
Europe B.V., 4Astellas Pharma, Inc. and 5School of Medicine, University of Belgrade, inducible factor prolyl hydroxylases under development to treat anemia associated
Clinical Department for Renal Diseases, Zvezdara University Medical Centre with chronic kidney disease (CKD). The vadadustat phase 3 program includes four
efficacy and cardiovascular safety outcome trials of vadadustat versus the
erythropoiesis-stimulating agent (ESA) darbepoetin alfa. Here we describe detailed
BACKGROUND AND AIMS: Randomised clinical trials evaluating anaemia
results on hematologic efficacy in two phase 3, randomized trials (the PRO2TECT
correction using erythropoietin-stimulating agents (ESAs) in chronic kidney disease
trials) in adult patients with non–dialysis-dependent (NDD) CKD and anemia, in
(CKD) patients have demonstrated an association between ESA use and increased risk
which vadadustat met prespecified noninferiority criteria compared to darbepoetin
of cardiovascular (CV) complications and mortality. Although the mechanism for this
alfa, with respect to hematologic efficacy (correction/maintenance of hemoglobin [Hb]
increased risk remains unclear, possibilities include rapid rates of rise (ROR) in
target concentrations).
haemoglobin (Hb), exposure to high ESA dose and dose escalation, a high Hb target
range, and off-target effects of ESAs. Thus, current recommendations generally state
that Hb levels should be maintained between 10 and 12 g/dL. Roxadustat, a hypoxia-
inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is used for the treatment of
anaemia of CKD; roxadustat stimulates endogenous production of erythropoietin and
enhances iron availability, thereby supporting red blood cell production. In this pooled
analysis, we explored the relationship between 1) achieved Hb levels and 2) preliminary
data for ROR of Hb and subsequent incidence rates of CV events in non–dialysis-
dependent (NDD) CKD patients who received roxadustat.
METHOD: We analysed pooled data from four phase 3 studies in NDD patients
(placebo-controlled: ALPS, ANDES, OLYMPUS; ESA-controlled: DOLOMITES) with
anaemia of CKD who received any dose of roxadustat. The reported events occurred
during the treatment period and within 7 days of the last dose of roxadustat. Incidence
rates of adjudicated major adverse CV events (MACE: all-cause mortality [ACM],
myocardial infarction, and stroke), MACEþ (MACE plus heart failure and unstable METHOD: The mean screening Hb level for the ESA-untreated NDD-CKD trial
angina requiring hospitalisation), and ACM were examined relative to 1) most recent (NCT02648347) had to be <10.0 g/dL, and for the ESA-treated NDD-CKD trial
Hb level before the event and 2) the preliminary data for ROR of Hb within the 4 weeks (NCT02680574), the range had to be from 8.0-11.0 g/dL in the United States (US) and
of treatment immediately prior to the event. from 9.0-12.0 g/dL non-US. In the ESA-untreated trial, patients received no ESA
RESULTS: Overall, 2709 patients were randomised and received roxadustat. Incidence within 8 weeks before randomization; in the ESA-treated trial, patients were
rates of MACE, MACEþ, and ACM were 3- or 4-fold higher in patients with lower maintained on ESA therapy, with 1 dose received within 6 weeks prior to or during
reported Hb levels (Hb <10 g/L) compared with those who achieved Hb 10 g/dL. screening. The vadadustat starting dose was 300 mg/day for all patients, whereas the
Incidence rates of MACE, MACEþ, and ACM were similar or lower in patients with a initial darbepoetin alfa dose depended on each patient’s prior dose or the product label.
maximum rise of >2 g/dL in Hb within the 4-week period prior to the event compared Both vadadustat and darbepoetin alfa doses were titrated according to prespecified
to those with a change of 2 g/dL within the same period (Table). However, it should dosing algorithms to achieve target Hb concentrations (US: 10-11 g/dL; non-US: 10-12
be noted that patient-exposure years (PEY) were low for the subgroup of patients with g/dL) both during the primary (PEP; weeks 24-36) and secondary (SEP; weeks 40-52)
ROR >2 g/dL (3.3% of overall PEY), and patients with a decreasing Hb were evaluation periods. Herein, we present topline results from the PEP and SEP endpoints,
included in the 2 g/dL/4 weeks subgroup. in addition to more detailed erythrocyte parameters.
CONCLUSION: In this analysis of roxadustat-treated patients with NDD CKD, RESULTS: A total of 3,476 patients (1751 ESA-untreated and 1725 ESA-treated) were
incidence rates of MACE, MACEþ, and ACM were lower in patients who achieved randomized 1:1 to vadadustat or darbepoetin alfa. In both trials, vadadustat was
target Hb levels of 10-12 g/dL compared with patients who achieved Hb <10 g/dL. noninferior to darbepoetin alfa with regard to the difference of mean change in Hb
Risk of MACE, MACEþ, or ACM did not appear to be associated with the proximal concentrations between baseline and PEP, as well as between baseline and SEP. The
preliminary data for ROR of Hb; however, further characterisation of the ROR of Hb respective proportions of patients (vadadustat vs. darbepoetin alfa) with an average Hb
and ROR in relation to baseline Hb are warranted. value within the geography-specific target range in the PEP and SEP were 50.4% versus
50.2% and 43.1% versus 43.5% in the ESA-untreated trial and 60.1% versus 60.7% and
50.7% versus 49.0% in the ESA-treated trial. The proportion of patients (vadadustat vs
darbepoetin alfa) who achieved an Hb increase >1.0 g/dL from baseline to week 52 was
assessed only for the ESA-untreated trial and was 87.7% (95% CI: 85.4%, 89.8%) for
vadadustat versus 88.0% (95% CI: 85.6%, 90.0%) for darbepoetin alfa.
Hematologic parameters at time points within the PEP and SEP are presented in Table
1. In both the ESA-untreated and ESA-treated trials, the reticulocyte count trended up

i326 | Abstracts
Nephrology Dialysis Transplantation Abstracts
from baseline through week 52 for vadadustat and trended down from baseline for might reduce CV events in this patient population. This study aimed to evaluate the
darbepoetin alfa. Trends in erythrocyte mean corpuscular volume and erythrocyte impact of anaemia and other risk factors on long-term CV risk in haemodialysis (HD)
mean corpuscular Hb were largely unremarkable by week 52 in both treatment groups. patients with CKD. A secondary aim was to establish a CV risk equation for this
CONCLUSION: Vadadustat demonstrated similar profiles across erythrocyte patient population.
parameters compared with darbepoetin alfa in the treatment of adults with anemia in METHOD: This retrospective study used data from the Phase 3 AURORA study
CKD not on dialysis, whether ESA-untreated or ESA-treated at study entry. (NCT04042350) of 2776 ESRD patients aged 50–80 years receiving regular HD/
haemofiltration, for a mean 3.2 year follow up.3 The primary endpoint of our analysis
was time to first major adverse cardiovascular event (CV MACE; non-fatal stroke, non-
fatal myocardial infarction, and CV mortality; n=804). Secondary endpoints included
MO542 MOLIDUSTAT FOR ANAEMIA IN JAPANESE PATIENTS
time to non-fatal stroke (ischaemic or haemorrhagic; n=98), coronary revascularisation
UNDERGOING PERITONEAL DIALYSIS: A SINGLE ARM,
therapy (n=300) and all-cause mortality (n=1296), and development of a CV risk
OPEN-LABEL, PHASE 3 STUDY
equation. Ferritin and transferrin baseline values were determined for this analysis
using the original frozen AURORA study patient samples (>10 years old). Statistical
Tadao Akizawa1, Kiyoshi Nobori2, Yoshimi Matsuda2, Kentaro Taki3,
analyses were performed using univariate and multiple Cox regression models. For
Yasuhiro Hayashi4, Takanori Hayasaki4, Hiroyasu Yamamoto6
1
each outcome a full model was estimated and then simplified by approximation with
Showa University School of Medicine, Department of Medicine, Tokyo, Japan, 2Bayer fewer factors. This was done using linear regression against the linear predictor of the
Yakuhin Ltd, Research & Development, Osaka, Japan, 3Bayer Yakuhin Ltd, Medical full Cox regression model. In a stepwise manner, the least contributing variable was
Affairs & Pharmacovigilance, Tokyo, Japan, 4Bayer Yakuhin Ltd, Medical Affairs & removed until the subset of variables approximated the full model to 95%. Model
Pharmacovigilance, Osaka, Japan and 6The Jikei University School of Medicine, performance was measured using the C-statistic, and internally validated using
Department of Internal Medicine, Tokyo, Japan bootstrap.
RESULTS: Incidence rates for CV MACE, non-fatal stroke, coronary revascularisation,
BACKGROUND AND AIMS: Erythropoiesis-stimulating agents (ESA) are the and all-cause mortality were 9.36, 1.11, 3.57, and 13.73 per 100 patient-years,
standard of care for anaemia due to chronic kidney disease (renal anaemia). respectively. Certain established risk factors among HD patients, such as age, gender,
Molidustat, a novel hypoxia-inducible factor prolyl hydroxylase (HIF–PH) inhibitor previous history of CVD, diabetes mellitus, smoking, blood pressure, high phosphate
for the treatment of renal anaemia, could offer an alternative to ESAs. Molidustat was and C-reactive protein levels, and low albumin levels, were also findings for this study,
evaluated in the “molidustat once daily improves renal anaemia by inducing although non-fatal stroke was underpowered to show significance (Table). Elevated
erythropoietin (MIYABI) program”, comprising five phase 3 studies. The present study haemoglobin levels (127 g/L) demonstrated a protective effect on the risk of all-cause
investigated the safety and efficacy of molidustat in Japanese patients with renal mortality (hazard ratio [HR] 0.916, p=0.010 for 127 g/L [upper quartile] versus 107 g/L
anaemia undergoing peritoneal dialysis (PD) and previously treated with ESAs or not. [lower quartile]), but were also associated with an increased risk of coronary
METHOD: This was a 36-week, open-label, single-arm, phase 3 study in Japanese revascularisations (HR 1.164, p=0.011 for 127 g/L versus 107 g/L). Haemoglobin levels
patients 20 years with renal anaemia undergoing PD and not expected to start 107 g/L were associated with an approximately 9% increased annual risk of mortality
maintenance haemodialysis. Molidustat was administered once daily at a starting dose (HR 1/0.916=1.092). Elevated ferritin and transferrin levels were significant and
of 75 mg. Doses were titrated every 4 weeks based on the patient’s haemoglobin (Hb) independent risk factors for CV MACE (HR [95% CI] 1.130 [1.025, 1.246] and 1.202
response to the previous dose during visits to maintain the Hb level within the target [0.987, 1.464], respectively), and all-cause mortality (HR [95% CI] 1.088 [1.008, 1.174]
range of  11.0 g/dL to < 13.0 g/dL (Japanese guidelines). The primary efficacy and 1.402 [1.198,1.641], respectively), but further analyses of iron metabolism markers,
outcome was the responder rate, defined as the proportion of patients who meet all of such as hepcidin, are needed to draw meaningful conclusions. The age of the samples
the following criteria: (1) mean Hb level during the evaluation period in the target may have also impacted the results. Risk prediction models were developed, and the
range from week 30 to week 36; (2) 50% of Hb values within the target range during predictive ability was 0.66–0.68 (C-statistic).
the evaluation period; (3) no rescue treatment before the end of the evaluation period. CONCLUSION: This analysis confirmed that this cohort is representative of a HD
Other outcomes included mean Hb level during the evaluation period and its change population. Moreover, elevated haemoglobin levels were associated with increased
from baseline, Hb level at each visit and the number of treatment-emergent adverse survival, concomitantly with coronary revascularisation. Elevated ferritin and
events (TEAEs). transferrin levels were identified as potential risk factors for CV MACE and all-cause
RESULTS: Overall, 51 patients received molidustat (49 ESA-treated; 2 ESA-untreated) mortality, but further studies are required to better understand their value in
and 36 (70.6%) completed treatment. Mean age was 63.3 years, mean body weight was estimating CV risk. Risk predication models were developed and performed well but
62.4 kg and 62.7% were male. Mean baseline Hb level was 11.19 g/dL and mean require validation against an independent patient cohort.
duration of peritoneal dialysis was 2.8 years. Over the study period, mean treatment
duration was 200.8 days with a mean dosage of 93.8 mg/day.
The responder rate (95% confidence interval [CI]) during the evaluation period was
54.9% (40.3, 68.9). The proportions of patients meeting criterion (1), (2) or (3) were
54.9%, 58.8% and 92.2%, respectively. The mean (95% CI) for mean Hb level during
the evaluation period was 11.18 (10.83, 11.54) g/dL and the mean (95% CI) for the
change in mean Hb level during the evaluation period from baseline was 0.00 (–0.41,
0.41) g/dL. Mean Hb level stayed in the target range from week 12–36.
Of the 15 patients who did not complete treatment, 9 discontinued because of a TEAE,
4 initiated rescue treatment and 2 progressed to maintenance haemodialysis. Overall,
98.0% of patients experienced 1 TEAE during the study; most TEAEs were mild
(49.0%) or moderate (37.3%) in intensity. The most common TEAEs were
nasopharyngitis (35.3%), constipation and medical device site infection (11.8% each).
No deaths were reported, and major adverse cardiovascular events occurred in 2.0% of
patients.
CONCLUSION: In this phase 3, single-arm, open-label study, over 70% of patients
completed the study and more than half of the patients met the responder criteria.
Molidustat maintained Hb in the prespecified range ( 11.0 g/dL to < 13.0 g/dL) and
was well-tolerated over the 36 weeks of treatment. Molidustat offers a potential
alternative to ESAs in patients with renal anaemia undergoing PD.

MO543 ASSESSMENT OF RISK FACTORS FOR CARDIOVASCULAR


EVENTS AND MORTALITY IN DIALYSIS PATIENTS IN THE
AURORA STUDY, A RETROSPECTIVE ANALYSIS

Bengt Fellström1, Niclas Eriksson2, Antonia Morga3, Wim Wilpshaar4,


James Young5, Alina Jiletcovici5, Knut Smerud6, Elinor Cockburn7, Ana
Filipa Alexandre4
1
Uppsala University Hospital, Sweden, 2Uppsala University, Uppsala Clinical Research
Center, 3Astellas Pharma Europe Ltd, Addlestone, United Kingdom, 4Astellas Pharma 1. Sud M et al. Circulation. 2014;130:458–465
Europe B.V., Leiden, The Netherlands, 5Astellas Pharma Inc., Northbrook, IL, United 2. Sarnak MJ. Am J Kidney Dis. 2003;41:S11–17
States of America, 6Smerud Medical Research International AS, Oslo, Norway and 3. Fellström BC et al. New Engl J Med. 2009;360:1395–1407
7
Astellas Pharma A/S, Kastrup, Denmark

BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) are at
higher risk of cardiovascular disease (CVD), which can also lead to end-stage renal
disease (ESRD).1 As anaemia is an independent risk factor for CVD,2 treating anaemia

10.1093/ndt/gfab085 | i327
Abstracts Nephrology Dialysis Transplantation

MO544 EFFECT OF DIFFERENT FREQUENCY OF FG-4592 ON


CHRONIC KIDNEY DISEASE

Di Yin1, Zuolin Li1, Zhao-ying Ding1, Bicheng Liu1


1
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine,
Nanjing, P.R. China

BACKGROUND AND AIMS: Hypoxia inducible factor-prolyl hydroxylase inhibitor


(HIF-PHI) is a novel small molecule inhibitor in clinical treatment for renal anemia.
Several studies have shown that sustained HIF activation may also have deleterious
effects, such as tubulointerstitial fibrosis. Here, the potential effects of different
treatment frequency of HIF-PHI (FG-4592) on CKD (chronic kidney disease) mice
were investigated.
METHOD: Male C57BL/6J mice were constructed by subtotal nephrectomy of 5/6 to
serve as a model for CKD. We then compared four different strategies based on the
frequency of FG-4592(intragastric administration, 30mg/kg) over 9 weeks: once a week
(qw), twice a week (biw), three times a week (tiw), and every day (qd).
In vitro, HK-2 cells were divided into three groups according to the different
administration methods of FG-4592(30lM): FG-4592 for 20h (FG0); FG-4592 for 8h,
followed by washing with medium for 12h(FG1); twice FG-4592 for 8h, followed by
washing twice with medium for2h(FG2).
RESULTS: Hemoglobin in the biw group, tiw group or qd group was significantly
higher than that in vehicle group. EPO, HIF-1a and HIF-2a of tiw group, biw group
and qd group were significantly higher than those in vehicle group. Makers of fibrosis
and inflammation in qd group were higher than that in vehicle group, while there was
no statistical difference in the changes of the above indicators in tiw group and biw
group. HIF-1a and HIF-2a were increased in intermittent administration, but the
expression of VEGF, makers of fibrosis or inflammation were not affected. In HK2,
HIF-1a and HIF-2a were activated by continuous administration of FG-4592. At the
same time, the expression of VEGF, inflammatory and fibrosis indicators were
increased significantly during continuous administration. In HepG2, EPO was
increased in intermittent administration in HepG2 cells without VEGF increasing. MO544 Figure 2: Intermittent administration of FG-4592 ameliorated the
CONCLUSION: Taken together, our studies demonstrated that FG-4592 inflammation and fibrosis in CKD mice.
administration 2-3 times a week can effectively improve renal anemia without side
effects on inflammatory and fibrosis.

MO544 Figure 3: Intermittent administration of FG-4592 activated HIF without


increasing inflammation and fibrosis in HK2 cells.

MO544 Figure 1: Intermittent administration of FG-4592 alleviated anemia in CKD


mice.

MO544 Figure 4: Intermittent administration of FG-4592 increased EPO but did


not affect VEGF in HepG2 cells.

i328 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO545 INSIDE ANEMIA OF CKD: ESTIMATING THE IMPACT OF METHOD: This was a multicentre double blinded randomized placebo-controlled trial
POLICY INTERVENTIONS ON ANAEMIA OF CKD IN THE USA in three tertiary renal centres in the United Kingdom. Patients with CKD stages 3b-5
BY MICROSIMULATION MODELLING (non-dialysis) and iron deficiency without anaemia (serum ferritin <100 micrograms/
L and/or transferrin saturation <20%) were enrolled. The participants were
Lise Retat1, Laura Webber1, Juan Jose Garcia Sanchez2, Claudia Cabrera3, randomized 1:1 to receive either 1000 mg of FDI or placebo and followed up at 1- and
Susan Grandy4, Naveen Rao2, Purav Bhatt4, Jill Davis4, K-H Yu5, Rachel Lai5, 3-month intervals. Biomarkers of inflammation (CRP, IL6, IL8 and IL10), oxidative
Navdeep Tangri6, Jay Wish7 stress (thiobarbituric acid reactive substances and F2-isoprostane) and cardiac stress
1
HealthLumen, London, United Kingdom, 2AstraZeneca, BioPharm Medical, Cambridge, (NT-proBNP) were analysed. Endothelial function was investigated through
United Kingdom, 3AstraZeneca, BioPharm Medical, Gothenburg, Sweden, 4AstraZeneca, biomarkers (E-selectin and P-selectin) and pulse wave velocity measurements.
BioPharm Medical, Wilmington, United States of America, 5FibroGen, San Francisco, Statistical analysis using repeated measure ANOVA with baseline, 1 month and 3-
United States of America, 6University of Manitoba, Chronic Disease Innovation Center, month data was performed with statistical significance inferred at p<0.05.
Winnipeg, Canada and 7Indiana University School of Medicine, Division of Nephrology, RESULTS: A total of 54 patients were randomized to receive FDI (n=26) or placebo
Indianapolis, United States of America (n=28). The two groups were comparable for baseline characteristics. Both pro and
anti-inflammatory cytokines (IL2, IL6 and IL10) were not affected by FDI at any study
BACKGROUND AND AIMS: Anaemia is a common complication in patients with point, nor there was any statistical difference was exhibited in CRP (FDI vs. placebo: 1-
chronic kidney disease (CKD) and is associated with increased mortality, month: 4.2 (2.7) vs. 6.9 mg/L (18.3), p=0.6; 3-months: 7.5 (6.8) vs. 10.3 mg/L (23.0);
cardiovascular complications, reduced quality of life and increased use of healthcare p=0.46). Markers of oxidative stress were not significantly altered following FDI
resources. Mathematical modelling based on robust epidemiological and clinical data is treatment or in comparison to placebo. A non-significant trend for a decrease in F2-
a useful approach for predicting the future burden of disease and the impact of isoprostane measurements was noted during the first month following FDI infusion
different intervention scenarios; this is important for health service planning. This compared to placebo (-77% vs. -66%; p=0.83). FDI caused a greater reduction in NT-
analysis uses a microsimulation model, Inside ANEMIA of CKD, to predict the effects proBNP compared to placebo (FDI: baseline: 422 (881.9) ng/l; 1-month: 242.5 (209.1)
of a hypothetical intervention scenario that reduces the prevalence of anaemia of CKD ng/l; placebo: baseline: 485.2 (1268.1) ng/l; 1-month: 436.4 (1383.4) ng/l), but this was
on related healthcare costs in the USA from 2020 to 2025. not statistically significant (p=0.37). Pulse wave velocity was not affected in either
METHOD: A virtual cohort representing the US population was created within the group while measurements of P-selectin remained unaltered. There was a statistically
Inside ANEMIA of CKD microsimulation model framework using demographics and significant increase in E-selectin at both follow-up points following infusion with FDI
epidemiological data drawn from the US Census Bureau, the Centers for Disease compared with placebo (1-month: p=0.03; 3 months: p<0.001).
Control and Prevention, and the National Health and Nutrition Examination Survey. CONCLUSION: High dose third generation iron treatment of CKD patients with iron
In the cohort, virtual individuals were ascribed an age–sex-stratified CKD status deficiency did not lead to either a pro-oxidant or a pro-inflammatory signal. The
(defined by estimated glomerular filtration rate and albuminuria levels, as per decrease in markers of oxidative stress following administration of FDI may represent
international guidelines) and anaemia status (defined by haemoglobin level as mild, the anti-oxidant effects following alleviation of iron deficiency. Although there was no
moderate or severe, as per WHO criteria) based on US prevalence data. Key increase in inflammatory markers there was an increase in E-selectin which might
comorbidities (type 2 diabetes, heart failure and hypertension) were also assigned, impact vascular function, as upregulation of selectins can be a sign of inflammation or
reflecting US-specific population statistics. Healthcare costs related to CKD and atherosclerosis but the unaffected pulse wave velocity and the reduction in NT pro-
anaemia of CKD were taken from the published literature. The study modelled the BNP are reassuring. Overall, the data confirm that high dose FDI therapy is
effects on healthcare costs of a hypothetical intervention scenario in which the mechanistically safe. Further larger studies are needed to confirm these findings and
prevalence of moderate and severe anaemia is reduced by 20% per year from 2020 to the longer term impact on cardiac and vascular function of high dose FDI
2025 compared with no intervention (baseline). In each scenario (i.e. intervention or administration.
baseline), the modelling analysis estimated healthcare costs related to CKD and
anaemia (including inpatient, outpatient, pharmacy costs) for patients with moderate
or severe anaemia of CKD. The model did not adjust for the potential costs of the MO547 ASSOCIATION BETWEEN SERUM INDICES OF IRON
intervention. METABOLISM AND CARDIOVASCULAR MORBIDITY IN
RESULTS: Preliminary results predict that, with the hypothetical intervention, there PATIENTS WITH PREDIALYSIS CHRONIC KIDNEY DISEASE
could be 1.40 million fewer patients with moderate or severe anaemia of CKD in the
USA in 2025 compared with no intervention (1.45 million versus 2.85 million). This Takeshi Hasegawa1,2, Takahiro Imaizumi3, Kenta Murotani4, Takayuki Hamano5,
represents a 49% reduction in cases of moderate or severe anaemia of CKD in 2025 Masafumi Fukagawa6
with the intervention versus no intervention. The intervention is projected to lead to a 1
reduction of approximately US$18 billion in annual direct healthcare costs in 2025 for Showa University, Showa University Research Administration Center (SURAC), Tokyo,
patients with moderate or severe anaemia of CKD compared with no intervention Japan, 2Showa University, Division of Nephrology, Department of Medicine, School of
(US$26 billion versus US$44 billion). Medicine, Tokyo, Japan, 3Nagoya University Hospital, Data Coordinating Center,
CONCLUSION: The Inside ANEMIA of CKD microsimulation model predicts that a Department of Advanced Medicine, Japan, 4Kurume University, Biostatistics Center,
hypothetical intervention which reduces the prevalence of moderate and severe Japan, 5Nagoya City University, Department of Nephrology, Graduate School of
anaemia of CKD would reduce direct healthcare costs. This suggests that interventions Medical Sciences, Japan and 6Tokai University School of Medicine, Division of
effective at reducing the prevalence of anaemia of CKD would help to reduce the Nephrology, Endocrinology and Metabolism, Japan
economic burden on healthcare services.
BACKGROUND AND AIMS: Patients with predialysis chronic kidney disease (CKD)
have a greater risk of developing cardiovascular disease (CVD) events than the general
population. Anaemia is the most frequent comorbidity in pre-dialysis CKD patients
MO546 THE SHORT-TERM EFFECT OF HIGH DOSE THIRD and is associated with an increase in CVD events. Iron deficiency is the most frequent
GENERATION INTRAVENOUS IRON ON PATIENTS IN cause of erythropoiesis-stimulating agents (ESAs) resistant anaemia in CKD patients
PATIENTS WITH CKD AND IRON DEFICIENCY ON OXIDATIVE and is modifiable by therapeutic intervention. However, the optimal ranges of iron
STRESS, INFLAMMATION, ENDOTHELIUM AND markers are uncertain in predialysis CKD patients. Therefore, we aimed to investigate
MYOCARDIAL STRESS the association between serum indices of iron metabolism and the incidence of CVD
events in patients with predialysis CKD using the CKD-Japan Cohort (CKD-JAC) data.
Xenophon Kassianides1, Adil Hazara1, Philip A. Kalra2, Iain Macdougall3, METHOD: We prospectively followed 1550 CKD patients aged 20-75 years with an
Sunil Bhandari1 estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 for a mean of 4.21
1
Hull University Teaching Hospitals NHS Trust and the Hull York Medical School, years. We set serum transferrin saturation (TSAT) and ferritin levels as the main
Academic Renal Research Department, Kingston upon Hull, United Kingdom, 2Salford exposures to be tested. Our main outcome measures were any of the CVD events
Royal NHS Foundation Trust and the University of Manchester, Renal Department, including fatal or non-fatal myocardial infarction, congestive heart failure (CHF),
Manchester, United Kingdom and 3King’s College Hospital, Department of Renal angina pectoris, arrhythmia, aorta dissection, cerebrovascular disorder, and peripheral
Medicine, London, United Kingdom artery diseases identified at each facility and adjudicated by the independent cardiac
function evaluation committee. Multivariable Cox proportional hazards regression
BACKGROUND AND AIMS: Intravenous (IV) iron administration in patients with models were employed to examine the association between serum TSAT or ferritin
chronic kidney disease (CKD) may lead to both pro-oxidant and pro-inflammatory levels with time to events. Death was considered as a competing risk with the Fine and
effects and thus secondarily compromise, potentially causing adverse cardiovascular Gray model. All models were stratified by facilities and adjusted for potential
outcomes. In-vitro and in-vivo studies suggest that these effects correlate with the confounders as follows: age, sex, systolic blood pressure, diabetes mellitus, history of
amount of labile free iron circulating following infusion of iron. Third generation IV CHF, haemoglobin, serum calcium, serum phosphorus, intact parathyroid hormone,
irons (e.g. ferric derisomaltose (FDI)) have been developed with more compact iron- eGFR, proteinuria, ESAs, iron supplementation, renin-angiotensin system inhibitors,
carbohydrate cores, enabling higher doses to be delivered in a single sitting with lower and beta-blockers. We also applied the multivariable fractional polynomial interaction
labile iron generation. (MFPI) approach to investigate whether TSAT levels are the effect modifier of the
The Iron & Heart study was a multicentre randomized placebo-controlled trial set out association between iron supplementation and the outcomes.
to examine the effect of high dose third generation iron (FDI) on the functional RESULTS: In the overall cohort, 208 (13.4 %) patients developed CVD events
capacity of patients with CKD and iron deficiency. A pre-specified secondary (including 97 CHF) during the follow-up period (26.6 events/1000 person-year). The
mechanistic endpoint was the effect of FDI on markers of oxidative stress, incidence rate of CVD events was the highest in the TSAT < 20% category (33.0
inflammation, endothelial function and cardiac stress. events/1000 person-year). Compared to patients in the TSAT > 40% category, those in

10.1093/ndt/gfab085 | i329
Abstracts Nephrology Dialysis Transplantation

the TSAT < 20% category demonstrated an increased risk of CVD events (adjusted
hazard ratio (AHR): 1.86, 95% confidence interval (CI): 1.06-3.26) and CHF events
(AHR: 2.82, 95% CI: 1.15-6.89), respectively. Meanwhile, there was no association
between serum ferritin levels and the risk of developing CVD or CHF events. MFPI
analyses showed a reduced risk of CVD in patients receiving iron supplementation
only in patients with TSAT <20% (P for interaction=0.02).
CONCLUSION: Maintaining TSAT >20% could be effective to reduce the risk of
developing CVD events (especially CHF) in patients with predialysis CKD. Our
analyses also suggest that iron-deficient patients with predialysis CKD may benefit
from iron supplementation for reduced risk of CVD events.

MO548 PREVALENCE AND INCIDENCE OF ANAEMIA IN PATIENTS


WITH NON-DIALYSIS DEPENDENT (NDD) CHRONIC KIDNEY
DISEASE (CKD), AND EVALUATION OF TREATMENT
PATTERNS WITH ERYTHROPOIESIS-STIMULATING AGENTS
(ESAS): A RETROSPECTIVE DATABASE STUDY IN ITALY

Paolo Di Rienzo1, Robert Snijder2, Luca Degli Esposti3, Valentina Perrone4,


Lora Todorova5
1
Astellas Pharma Italia S.P.A., Assago, Italy, 2Astellas Pharma Europe Ltd, Leiden, The
Netherlands, 3CliCon Srl Health, Economics & Outcomes Research, Addlestone, United
Kingdom, 4CliCon Srl Health, Economics & Outcomes Research, Ravenna , Italy and
5
Astellas Pharma Inc., Addlestone, United Kingdom

BACKGROUND AND AIMS: Anaemia is a common complication in patients with


NDD-CKD, and its prevalence increases with advancing CKD stage.1,2 It is a risk factor
for both CKD progression and other adverse outcomes, including major adverse
cardiac events, hospitalisation and all-cause mortality.1 We aim to report the
prevalence of NDD-CKD stage 3a–5 in Italy, and to evaluate the prevalence and
incidence of anaemia among patients with NDD-CKD. Of those patients with anaemia,
we seek to establish the size of the patient pool eligible for ESAs, and consequently, the
proportion of patients treated with ESAs.
METHOD: Patients 18 years of age with a record of NDD-CKD stage 3a–5 between 1. Palaka E et al. Int J Nephrol. 2020;2020:7692376
1 January 2014 and 31 December 2016 were identified from databases of five Local 2. Fishbane S et al. Am J Kid Dis 2019;73:309–315
Health Units (LHUs) across Italy. NDD-CKD stage 3a–5 in our study was defined as 3. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of
either 1 hospitalisation record with discharge diagnosis of CKD (ICD-9-CM 585.x, Chronic Kidney Disease. Kidney Int Supp. 2013;3:1–163
where x = 3, 4, or 5) or 1 record of estimated glomerular filtration rate (eGFR) <60 4. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney
mL/min. eGFR values were estimated using the Modification of Diet in Renal Disease Int Suppl. 2012;2:279–335
method and were as reported by LHUs. Patient classification into CKD stage 3a–5
based on eGFR was done according to KDIGO guidelines.3 Anaemia was defined as Hb
<13 g/dL (males) or <12 g/dL (females). Prevalence was defined as the presence of 1 MO549 INSIDE ANEMIA OF CKD: MICROSIMULATION MODELLING
record of NDD-CKD stage 3a–5 or anaemia in the entire period preceding the OF THE IMPACT OF POLICY INTERVENTIONS ON ANAEMIA
timepoint of interest, or as incident NDD-CKD/anaemia; incidence was defined as a OF CKD IN CANADA
first record of the condition in the year of interest (no record of the condition in the
patient’s history). Point prevalence (at 31 December of each reported year) and annual Lise Retat1, Laura Webber1, Juan Jose Garcia Sanchez2, Claudia Cabrera3,
incidence were age- and sex-standardised using census data from 1 January of the Susan Grandy4, Naveen Rao2, Purav Bhatt4, Deborah Wong5, Anna Parackal5,
following year. Among patients with anaemia of NDD-CKD stage 3a–5, eligibility for Jay Wish6, Navdeep Tangri7
ESA was defined as at least one record of Hb <10 g/dL,4 and patients with a record of 1
ESA prescription were categorised as ESA treated. HealthLumen, 2AstraZeneca, BioPharm Medical, Cambridge, United Kingdom,
3
RESULTS: For 2016, the prevalence of NDD-CKD stage 3a–5 in the population aged AstraZeneca, BioPharm Medical, Gothenburg, Sweden, 4AstraZeneca, BioPharm
18 years was 5.6% (83,625/1,507,391): CKD stage 3a was the most common (4.2%; Medical, Wilmington, United States of America, 5AstraZeneca, BioPharm Medical,
62,683/1,507,391), while the prevalence of each of the stages 3b–5 was 1.0% (Table). Mississauga, Canada, 6Indiana University School of Medicine, Division of Nephrology,
The prevalence and incidence of anaemia among patients with NDD-CKD stage 3a–5 Indianapolis, United States of America and 7University of Manitoba, Chronic Disease
in 2016 was 33.8% and 11.4%, respectively. The prevalence of anaemia increased with Innovation Center, Winnipeg, Canada
CKD stage: from 28.2% among patients with stage 3a to 78.9% among those with stage
5. A similar trend was observed for incidence, which increased from 9.3% for stage 3a BACKGROUND AND AIMS: Anaemia is common in patients with chronic kidney
to 32.8% for stage 5. The proportion of patients with NDD-CKD stage 3a–5 and disease (CKD) and is associated with increased mortality, cardiovascular
anaemia who were eligible for ESA treatment from 2014–2016 ranged from 51.9% to complications, reduced quality of life and increased use of healthcare resources. Based
75.6% across the CKD stages. In 2016, the proportion of patients with incident NDD- on robust epidemiological and clinical data, mathematical modelling is a useful
CKD anaemia who were eligible for ESAs but not treated was 42.3%. This proportion approach for predicting the future burden of disease and the effects of different
was similar across the CKD stages, except for stage 5, for which the proportion of intervention scenarios, which is essential for health service planning. This analysis uses
patients who were eligible but not ESA treated was 51.1%. a microsimulation model, Inside ANEMIA of CKD, to project the impact of a
CONCLUSION: In Italy, we found that higher CKD stages are associated with hypothetical intervention scenario that reduces the prevalence of anaemia of CKD on
increased prevalence and incidence of anaemia in NDD-CKD, a finding which is related healthcare costs in Canada from 2020 to 2025.
supported by previous research in other countries worldwide.1,2 Despite this, almost METHOD: A virtual cohort representing the Canadian population was created within
half of patients with anaemia of NDD-CKD stage 3a–5 were eligible for ESA treatment the Inside ANEMIA of CKD microsimulation model framework using national
but did not receive ESAs. This suggests that anaemia may not be adequately controlled demographics and epidemiological data drawn from Statistics Canada and a provincial
in patients with NDD-CKD stage 3a–5, and may need further attention and treatment. renal database. In the cohort, virtual individuals were ascribed an age- and sex-
stratified CKD status (defined by estimated glomerular filtration rate and albuminuria
levels, as per international guidelines) and anaemia status (defined as mild, moderate
or severe based on haemoglobin level, as per WHO criteria) based on Canadian
prevalence data. Key comorbidities (type 2 diabetes, heart failure and hypertension)
were also assigned, reflecting Canada-specific population statistics. Costs related to the
treatment of CKD were taken from the published literature, and are shown in
Canadian dollars (C$). This modelling analysis evaluated the effects on healthcare costs
of a hypothetical intervention scenario in which the prevalence of moderate and severe
anaemia is reduced by 20% per year from 2020 to 2025 compared with no intervention
(baseline). In each scenario (i.e. intervention or baseline), the modelling analysis
estimated CKD-related healthcare costs for patients with moderate or severe anaemia
of CKD. The modelling analysis did not adjust for the potential costs of the
intervention.

i330 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: Preliminary results predict that, with the hypothetical intervention, there MO551 A COST-OFFSET ANALYSIS OF THE ROXADUSTAT
could be approximately 435,000 fewer patients with moderate or severe anaemia of DIALYSIS-DEPENDENT GLOBAL PHASE 3 PROGRAM: A
CKD in Canada in 2025 compared with no intervention (approximately 497,000 versus CANADIAN HEALTHCARE PERSPECTIVE
932,000). The intervention is projected to lead to a reduction of C$4.4 billion in annual
direct healthcare costs in 2025 for patients with moderate or severe anaemia of CKD John Schneider1, Shawn Davies1, Amanda Howarth1, Juan Jose Garcia
compared with no intervention (C$9.1 billion versus C$13.5 billion), assuming that all Sanchez2, Naveen Rao2, Susan Grandy3, Purav Bhatt3, Deborah Wong4,
eligible patients are diagnosed and treated. Anna Parackal4, K-H Yu5, Rachel Lai5, Andrew Briggs1
1
CONCLUSION: The Inside ANEMIA of CKD microsimulation model predicts that a Avalon Health Economics, United States of America, 2AstraZeneca, BioPharm Medical,
hypothetical intervention which reduces the prevalence of moderate and severe Cambridge, United Kingdom, 3AstraZeneca, BioPharm Medical, Wilmington, United
anaemia of CKD would produce reductions in direct healthcare costs. This suggests States of America, 4AstraZeneca, BioPharm Medical, Mississauga, Canada and
5
that interventions effective at reducing the prevalence of anaemia of CKD would help FibroGen, San Francisco, United States of America
to reduce the economic burden on healthcare services.
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a costly public health
issue, which affects 13.4% of the population globally. Anaemia is a common
MO550 INDOXYL SULFATE AFFECTS ERYTHROPOIESIS DURING complication in patients with CKD resulting in reduced health-related quality of life
THE COURSE OF CHRONIC KIDNEY DISEASE: A and high healthcare costs. The objective of this analysis was to estimate the direct
MOLECULAR STUDY medical care cost offsets of the investigational agent roxadustat for the treatment of
anaemia in patients with dialysis-dependent (DD) CKD from a Canadian healthcare
Eya Hamza1, Hakim Ouled-Haddou1, Nicolas Jankovsky1, Yohann Demont1,2, perspective.
Benjamin Brigant3,4, Ziad Massy5,6, Stéphane Burtey 7,8, Gabriel Choukroun4,9, METHOD: Data from the roxadustat global phase 3 program were used to estimate the
Loı̈c Garçon1,2, Laurent Metzinger1, Valérie Metzinger-le Meuth1,10 incidence of rescue therapy or iron supplementation use (i.e. intravenous iron,
1 erythropoiesis-stimulating agents [ESAs] or red blood cell transfusions) and major
HEMATIM UR-UPJV 4666, C.U.R.S University of Picardie Jules Verne, Amiens, France,
2 adverse cardiovascular events (MACEþ) for roxadustat compared with ESAs in DD
Service Hématologie Biologique, Centre Hospitalier Universitaire (CHU) Amiens-
patients with anaemia of CKD. MACEþ included myocardial infarction, stroke,
Picardie, Amiens, France, 3NTNU Norwegian University of Science and Technology,
unstable angina requiring hospitalization, congestive heart failure (CHF) requiring
Faculty of Medicine and Health Sciences, Trondheim, Norway, 4UR-UPJV7517, MP3CV,
hospitalization, cardiovascular death and other death. Published Canadian cost data
C.U.R.S University of Picardie Jules Verne, Amiens, France, 5Inserm U-1018, Team 5,
were used to estimate event costs. Drug acquisition costs for roxadustat and ESAs were
Centre de recherche en épidémiologie et santé des populations, Versailles Saint-
not considered. A hypothetical cohort of 10,000 Canadian adult DD patients (90%
Quentin-en-Yvelines University (Paris-Ile-de-France-Ouest University), Villejuif, France,
6 undergoing haemodialysis, 10% undergoing peritoneal dialysis) with treatable anaemia
Division of Nephrology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de
was modelled to determine net medical care cost offsets annually and cumulatively
Paris, Paris, France, 7C2VN, Aix Marseille Univ, INSERM, INRAE, Marseille, France, 8Centre
compared with ESAs over a 4-year time horizon.
de Néphrologie et Transplantation Rénale, AP-HM, Hôpital de la Conception, Marseille,
RESULTS: Preliminary results for patients with DD CKD show that, compared with
France, 9Department of Nephrology, Dialysis and Transplantation, Centre Hospitalier
ESAs, roxadustat could produce sizeable net medical care cost offsets resulting from
Universitaire (CHU) Amiens-Picardie, Amiens, France and 10INSERM UMRS 1148,
reductions in rescue therapy or iron supplementation use, specifically red blood cell
Laboratory for Vascular Translational Science (LVTS), Bobigny, France
transfusions, and from reductions in MACEþ, specifically CHF hospitalizations. For
the entire cohort of patients with DD CKD, cumulative medical care cost offsets for
BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a global health roxadustat were an estimated $162,609 for rescue therapy or iron supplementation use
condition characterized by a progressive deterioration of renal function due to high and $1,027,070 for MACEþ compared with ESAs.
serum levels of uremic toxins. Anemia is a major trouble in CKD patients that CONCLUSION: This analysis provides evidence that treatment with roxadustat in DD
contributes to a faster deterioration of renal failure, leading to cardiovascular disease patients with anaemia of CKD could result in considerable medical care cost offsets for
and increasing morbimortality. Erythropoietin (EPO) is known to contribute to CKD- roxadustat compared with ESAs.
associated anemia. Thus, accumulation of uremic toxins in blood impairs EPO
synthesis, leading to a subsequent impairment of erythropoiesis in the bone marrow.
Very few molecular clues explain why erythropoiesis is affected in CKD or explain why
erythropoiesis-stimulating agents (ESA) are not efficient in some patients with CKD. MO552 PHARMACOLOGICAL HIF PROLYL HYDROXYLASE
The current study aims to characterize the impact of one of the most representative INHIBITION IMPROVES EXERCISE ENDURANCE CAPACITY
uremic toxins, Indoxyl Sulfate (IS), in CKD-related anemia. IS is a protein-bound IN CKD MICE
uremic toxin derived from the tryptophan dietary metabolism which is difficult to
remove by dialysis. Our study demonstrates the molecular effects of IS on the growth Koji Takemura1, Hiroshi Nishi1, Takaaki Higashihara1, Masaomi Nangaku1
1
and the differentiation of red blood cells in an erythroid cell line and in primary cell The University of Tokyo Hospital, Division of Nephrology and Endocrinology, Tokyo,
cultures CD34þ. Japan
METHOD: Firstly, we examined in vitro the time-courses of IS under clinically
relevant concentrations of IS (250 mM -1 mM) in a human leukemic cell line in which BACKGROUND AND AIMS: Erythropoietin (EPO) and hypoxia-inducible factor
proliferation is induced by EPO, the UT7/EPO cell line. Cell apoptosis, proliferation, (HIF) stabilizers (prolyl hydroxylase (PH) inhibitors) are efficient therapeutic
differentiation and cell cycle analysis were assessed by the MACSQuant flow modalities against anemia in chronic kidney disease (CKD). Compared to EPO and
cytometry. Erythroid gene expression analysis was assessed by RT-qPCR (Quantstudio EPO receptor system, extra-renal action of PH inhibitors has still not been fully
7 flex). The ratio A260/280 assessed the quality of nucleic acids. Western blotting investigated. Previous reports caution us about the actual misuse of PH inhibitors in
experiments were performed to study protein expression. Human primary CD34þ doped athletes, but the drug nonhematopoietic effects of PH inhibitors on skeletal
cells were obtained from mobilized peripheral blood mononuclear cells (MNC) of muscles remain controversial both in healthy subjects or in patients with CKD.
healthy subjects and were isolated by magnetic microbeads separation on MACS METHOD: To study direct pharmacological effects of PH inhibitors on skeletal
columns. muscles, one of PH inhibitors, roxadustat, was administered via oral gavage to healthy
RESULTS: IS at 250 mM and 1 mM increased apoptosis of UT7/EPO cell line at 48h 8-week-old C57BL6 mice. Plasma EPO levels and HIF-targeted gene expression were
compared to control condition. On the other hand, we found no significant effect of IS analyzed after a single administration. Exercise ability was assessed by treadmill
on the phenotype of UT7/EPO, when using CD235a (Glycophorin A), as a marker for exhaustion test after a single dose or chronic 5-week treatment. Roxadustat was also
the detection of the erythroid cell lineage. administered for 2 weeks to CKD mice with 2-week 0.2% adenine diet. Endurance
Ki67 cellular levels, a cell proliferation marker, was not altered between control and IS capacity was similarly assessed after 2-week roxadustat treatment.
experiments. This indicated that IS did not affect proliferation in UT7/EPO. At 48h, at RESULTS: Even a single administration of roxadustat increased plasma EPO levels and
the clinically relevant concentration of IS (250 mM), we observed an increase of the cell gene expression downstream of HIF in skeletal muscles. Healthy mice treated with
phase cycle Sub-G1. The analysis of erythropoiesis related genes shows that HIF2a was roxadustat for 5 weeks showed higher blood haemoglobin (Hb) levels and improved
deregulated with IS (250 mM). Finally, in the Epo-EpoR signalling pathway, we studied exercise endurance in treadmill exhaustion test, which was blunted by hemodilution
the activation of the Jak2/Stat5 proteins. procedure. Adenine-fed CKD mice showed lower blood Hb levels and worse endurance
Results in human primary CD34þ cells confirmed the apoptotic effect of IS observed capacity compared to control mice. Roxadustat treatment improved endurance
in UT7/EPO. capacity in CKD mice without significant increase in blood Hb levels compared to
CONCLUSION: Our findings suggest that IS, a representative protein-bound uremic control mice.
toxin, could affect cell viability, apoptosis and the cell cycle. This study suggests clues to CONCLUSION: Treatment with HIF-PH inhibitor, roxadustat, improves exercise
develop new therapies for CKD-associated anemia. endurance principally via pharmacological erythropoiesis. However, roxadustat shows
potential effects independent of erythropoiesis on endurance capacity in CKD.

10.1093/ndt/gfab085 | i331
Abstracts Nephrology Dialysis Transplantation

MO553 INSIDE ANEMIA OF CKD: MICROSIMULATION MODELLING addition, using a generalized linear mixed model, we divided the HF patients into three
OF THE FUTURE COST BURDEN OF ANAEMIA OF CKD IN groups with eGFR 60, 30–60, and <30, and examined whether the severity of CKD
CANADA was related to the Hb change and physical function.
RESULTS: The median age of the subjects in this study was 77 years (interquartile
Lise Retat1, Laura Webber1, Juan Jose Garcia Sanchez2, Claudia Cabrera3, range 72–82). Changes in Hb during hospitalization were independent determinants of
Susan Grandy4, Naveen Rao2, Purav Bhatt4, Deborah Wong5, Anna Parackal5, physical function (leg strength, b: 0.158, P < 0.001; gait speed, b: 0.023, P < 0.001;
Jay Wish6, Navdeep Tangri7 6MWD, b: 13.039, P < 0.001), even after accounting for factors related to severity of
1
Health Lumen , 2AstraZeneca, BioPharm Medical, Cambridge, United Kingdom, HF. Moreover, the group with more severe CKD showed significantly lower physical
3
AstraZeneca, BioPharm Medical, Gothenburg, Sweden, 4AstraZeneca, BioPharm function, although Hb improved (P < 0.001) with respect to leg strength and 6MWD
Medical, Wilmington, United States of America, 5AstraZeneca, BioPharm Medical, compared with the group with lower CKD stage.
Mississauga, Canada, 6Indiana University School of Medicine, Division of Nephrology, CONCLUSION: Hb change during hospitalization was an independent determinant of
Indianapolis, United States of America and 7University of Manitoba, Chronic Disease physical function in patients with HF. Patients with a more severe CKD showed lower
Innovation Center, Winnipeg, Canada leg strength values and 6MWD even if Hb improved.

BACKGROUND AND AIMS: Anaemia is a common complication in patients with


chronic kidney disease (CKD). Prevalence of anaemia increases with CKD severity and
ranges from 17% in patients with stage 3 disease to over 50% in patients with stage 5
CKD who are not on dialysis. Anaemia of CKD is associated with increased mortality,
cardiovascular complications, reduced quality of life and increased use of healthcare
resources. Mathematical modelling based on robust epidemiological and clinical data is
a useful approach for predicting the future burden of disease, which is important for
health service planning. This analysis uses a microsimulation model, Inside ANEMIA
of CKD, to project the economic burden of anaemia of CKD in Canada from 2020 to
2025.
METHOD: A virtual cohort representing the Canadian population was created within
the Inside ANEMIA of CKD microsimulation model framework, using Canadian
demographics and epidemiological data drawn from Statistics Canada and a provincial
renal database. In the cohort, virtual individuals were ascribed an age–sex-stratified
CKD status (defined by estimated glomerular filtration rate and albuminuria levels, as
per international guidelines) and anaemia status (defined as mild, moderate or severe
based on haemoglobin level, as per WHO criteria) based on Canadian prevalence data. MO554 Figure: Association between changes in hemoglobin and physical function
Key comorbidities (type 2 diabetes, heart failure and hypertension) were also assigned, with the severity of chronic kidney disease. Adjusted for age, sex, BMI, hemoglobin at
reflecting Canada-specific population statistics. Incidence rates for acute kidney injury admission, B-type natriuretic peptide, left ventricular ejection fraction, New York
and cardiovascular complications (heart failure, myocardial infarction and stroke) were Heart Association classification.
drawn from the literature. Costs related to CKD, anaemia of CKD and associated
complications were taken from Canadian government sources and the literature, and
are shown in Canadian dollars (C$).
RESULTS: Preliminary results show that, in Canada, the number of individuals with
anaemia of CKD is projected to increase by approximately 0.8 million between 2020
MO555 ASSESSMENT OF HEALTH-RELATED QUALITY OF LIFE
and 2025 (from 1.8 million to 2.6 million). Annual healthcare costs for patients with
(HRQOL) MEASURES FOR PAEDIATRIC PATIENTS WITH
anaemia of CKD are projected to increase by 17% by 2025 (from C$19.3 billion to
ANAEMIA OF CHRONIC KIDNEY DISEASE (CKD)
C$22.5 billion). Between 2020 and 2025, the costs associated with cardiovascular
complications in patients with anaemia of CKD are projected to increase by 28% for
Antonia Morga1, Ana Filipa Alexandre2, Patricia Koochaki3,
heart failure (from C$1.13 billion to C$1.45 billion), 26% for myocardial infarction
Alexandros Georgiadis4, Celine Desvignes-Gleizes5
(from C$0.83 billion to C$1.05 billion) and 29% for stroke (from C$0.99 billion to 1
C$1.29 billion). Astellas Pharma Europe Ltd, Addlestone, United Kingdom, 2Astellas Pharma Europe
CONCLUSION: Inside ANEMIA of CKD is the first microsimulation model to project B.V., Leiden, The Netherlands, 3ICON plc, Cincinnati, United States of America, 4ICON
the economic burden of anaemia of CKD in Canada. Based on the modelling plc, Buckinghamshire, United Kingdom and 5Mapi Research Trust, Lyon, France
projections, the increase in the number of individuals with anaemia of CKD over the
next 5 years will be accompanied by a parallel increase in associated healthcare costs BACKGROUND AND AIMS: Anaemia is a common complication of CKD in
and a marked rise in the cost of cardiovascular complications. Evidence-based children that is associated with adverse clinical outcomes, including poor physical
therapies for anaemia of CKD that lower cardiovascular complications are needed to functioning for patients and lower HRQoL for patients and caregivers.1 Given the
reduce the economic burden on healthcare services. subjective nature of the disease, instruments that measure patient- and/or observer-
reported outcomes (PROs/ObsROs), by collecting information about symptom severity
and HRQoL, could be of value to assess treatment benefit. We determined which
aspects of anaemia of CKD and its treatments are important for paediatric patients and
MO554 THE EFFECT OF HEMOGLOBIN CHANGES AND THE
their caregivers, and examined which PRO/ObsRO instruments comprehensively
SEVERITY OF CHRONIC KIDNEY DISEASE IN PHYSICAL
capture patients’ and caregivers’ experiences.
FUNCTION IN ELDERLY PATIENTS WITH HEART FAILURE
METHOD: A targeted literature review and database search were performed to find a)
qualitative and quantitative studies of symptoms and related health outcomes in
Takumi Noda1, Kentaro Kamiya1, Nobuaki Hamazaki2, Kohei Nozaki2,
paediatric patients with anaemia of CKD; b) related clinical practice guidelines; and c)
Takafumi Ichikawa2, Masashi Yamashita1, Shota Uchida1, Shun Yoshikoshi1,
HRQoL information in product labelling. Study outcomes were used to develop a
Emi Maekawa3, Minako Yamaoka-Tojo1, Atsuhiko Matsunaga1, Junya Ako3
1
structured representation of health outcomes concepts and issues (‘conceptual model’)
Kitasato University Graduate School of Medical Sciences, Department of Rehabilitation capturing the symptoms, perceptions of treatment and impact on HRQoL of anaemia
Sciences, Sagamihara, Kanagawa, Japan, 2Kitasato University Hospital, Department of of CKD, from the perspective of both paediatric patients and their caregivers. PRO and
Rehabilitation, Sagamihara, Kanagawa, Japan and 3Kitasato University School of ObsRO instruments were identified from published quantitative studies and ongoing
Medicine, Department of Cardiovascular Medicine, Sagamihara, Kanagawa, Japan clinical trials, and a selection was then critically assessed to determine their content
validity and whether their psychometric properties adequately covered the conceptual
BACKGROUND AND AIMS: Anemia is frequently observed in patients with heart model domains.
failure (HF) and causes increased hospitalization and mortality rates. Anemia is also RESULTS: The conceptual model captured shortness of breath, fatigue and headaches
associated with and is a major risk factor of impaired physical function and frailty. On as the most important symptoms experienced by paediatric patients with anaemia of
the other hand, a high percentage of elderly patients with HF have chronic kidney CKD. Concerns regarding disease management included medical interventions, fear
disease (CKD), which is an aggravating factor for anemia, and the combination of associated with interventions and the need for information about the disease. Disease
anemia and CKD has been reported to increase physical dysfunction and mortality. symptoms and their management impacted seven HRQoL domains, namely physical,
However, the relationship between hemoglobin (Hb) changes and physical function emotional and social functioning; activities of daily living; and effects on family, work
during hospitalization in elderly patients with HF is unclear, and the impact of CKD and caregivers (Figure).
severity on these relationships is also unclear. This study aimed to examine the The quantitative search of published studies identified 20 unique instruments; of these,
relationship between Hb changes and physical function during hospitalization in the most frequently used was Pediatric Quality of Life InventoryTM (PedsQL) Version
elderly patients with HF. We further examined the relationship when stratified by CKD 4.0. Ongoing clinical trials used 14 unique instruments, of which only EQ-5D-Y was
severity. used in more than one study. Two clinical practice guidelines (National Institute for
METHOD: Seven hundred and thirty-seven elderly patients with HF, who underwent Health and Care Excellence and Kidney Disease: Improving Global Outcomes)
changes in Hb and physical function test (leg strength, gait speed, and 6-min walking supported measurements of HRQoL, symptoms, patient preferences and school
distance [6MWD]), were included in this study. Using a multiple linear regression
model, associations between Hb changes and physical function were assessed. In

i332 | Abstracts
Nephrology Dialysis Transplantation Abstracts
attendance/performance, but they did not advocate use of any specific instruments. No 3238 IU and 20 lg, respectively. During their initial course of therapy, three-quarters
HRQoL product labelling information was identified. of patients had either an increase or decrease in ESA dose. Less than 10% of patients
Based on the conceptual model, the literature review results and age group coverage, switched ESAs, while approximately one-third discontinued within 2 years of
five instruments were selected for critical appraisal: PedsQL, PedsQL Infant Scales, initiation. At 3 and 6 months post-ESA initiation, only 64.7% of the sample had a
PedsQL Multidimensional Fatigue Scale, PedsQL v3.0 End Stage Renal Disease documented Hb measurement despite continuing ESA treatment; this proportion was
module, and EQ-5D-Y. Between them, these instruments provided complete coverage further reduced to 60.0% by 12 months after initiation.
of the impact of fatigue and headaches, and partial coverage of the effects on physical The Hb target was maintained by 88.7%, 74.6% and 49.4% of patients at 3, 6 and 12
functioning, activities of daily living, emotional functioning and social functioning. months, respectively. Mean ferritin levels were 167.3 ng/mL at initiation and 198.7 ng/
None of these instruments measured the impact of shortness of breath, and there was mL at 12 months (among the 85% and 48% of the sample, respectively, with recorded
no coverage of the consequences for work or the family’s/caregivers’ HRQoL. data). Mean TSAT was 22.1% at initiation and 25.6% at 12 months (among the 67%
CONCLUSION: Anaemia of CKD affects many HRQoL domains for paediatric and 38%, respectively, with recorded data).
patients and their caregivers. While current PRO/ObsRO instruments partially address Approximately three-quarters of patients (77.3%) received iron therapy concomitantly
these impacts, no single instrument in our assessment measured all symptoms and with ESA treatment; in the UK, most of these received IV iron, while in Germany and
domains of interest to patients and caregivers. Multiple instruments should be included Spain, a majority received oral iron (Table). Blood transfusions were more common in
in clinical studies to capture symptoms and HRQoL important to patients, and Spain (24.2%) than in Germany (5.1%) or the UK (8.4%). Approximately one-fifth of
adequate measurement of the effects of anaemia on work or the family’s/caregivers’ patients required dialysis.
HRQoL might require development of a new instrument. CONCLUSION: Initiation of ESAs to treat anaemia among patients with NDD-CKD
in Germany, Spain and the UK follows current guidelines. However, recommendations
to regularly monitor Hb were not routinely followed or were poorly documented. As
most patients with NDD-CKD anaemia were treated at home, oral therapies may be of
benefit to these patients

1. Atkinson MA & Warady BA. Pediatr Nephrol. 2018;33:227–38

MO556 TREATMENT OF ANAEMIA WITH ERYTHROPOIESIS


STIMULATION AGENTS (ESAS) AND CONCOMITANT
THERAPIES AMONG PATIENTS WITH NON-DIALYSIS
DEPENDENT CHRONIC KIDNEY DISEASE (NDD-CKD) IN
GERMANY, SPAIN AND THE UK: A RETROSPECTIVE CHART
REVIEW

Danilo Fliser1, Jose Portoles2, Katherine Houghton3, Claire Ainsworth3,


Martin Blogg4, Maria Mata Lorenzo4
1
Saarland University Medical Center, Homburg, Germany, 2Hospital Universitario Puerta
de Hierro, Madrid, Spain, 3RTI Health Solutions, Manchester, United Kingdom and
4
Astellas Pharma Europe Ltd, Addlestone, United Kingdom

BACKGROUND AND AIMS: Among patients with CKD, prevalence of anaemia


increases with CKD severity,1 and is accompanied by elevated risk of hospitalisation
and mortality.2 Treatment options include iron therapy and ESAs; international
guidelines recommend initiating ESA therapy when haemoglobin (Hb) declines <10 g/
dL, and to monitor Hb and iron status every 3 months during ESA treatment.3 This
study aimed to describe the routine clinical management of patients with NDD-CKD
and anaemia following ESA initiation, in Germany, Spain and the UK.
METHOD: This was a non-interventional, retrospective cohort study of adults with
NDD-CKD stages 3b–5 (as defined in KDIGO 2012 guidelines)1 diagnosed with
anaemia (Hb <13.0 g/dL [males] or <12.0 g/dL [females]), who began ESA treatment
01 Jan 2015–31 Dec 2015 inclusive. Data for 24 months after ESA initiation were
extracted from medical records: patient characteristics; anaemia diagnosis and
treatment (including iron and ESA use); Hb, serum ferritin and transferrin saturation
(TSAT) measurements; and CKD-related outcomes. Patients were excluded if they had
been diagnosed with end-stage kidney disease at baseline, or previously received a
kidney transplant or dialysis.
RESULTS: In total, 848 patient records (Germany, 211; Spain, 430; UK, 207) were
included. Average age was 66 years (Table). Most patients were white and almost half
had >2 comorbidities. Prior to ESA initiation, at least half of all patients in each
country received either oral or intravenous (IV) iron therapy. The average (mean 6
SD) number of months between anaemia diagnosis and initiation of ESA therapy was
8.4 6 19.2.
Hb levels were recorded at ESA initiation for almost all (91.3%) patients and averaged
9.8 6 1.0 g/dL for the total cohort; this initial Hb level was similar between countries
(Table). Mean 6 SD estimated glomerular filtration rate (eGFR) at ESA initiation was
28.0 6 10.4 ml/min/1.73m2. Across countries, 72–88% of patients received ESAs at
home. The mean 6 SD duration of therapy (at the time of data collection) was 41.2 6
18.2 months, and the median weekly dose of short-acting and long-acting ESAs was

10.1093/ndt/gfab085 | i333
Abstracts Nephrology Dialysis Transplantation

1. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of years). The mean Hb was 11.8 61.9 g/dL. Important cardiovascular comorbidities in
Chronic Kidney Disease Kidney Int Suppl. 2013;3:1–150 patients with anemia were arterial hypertension (86.7%), obesity (65.5%), Diabetes
2. Ogden L et al. J Kidney Care 2018;3:S3–S8 Mellitus (DM) (52%) and dyslipidemia (46%). In univariate analysis, mortality was
3. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease Kidney associated with anemia (36.9 vs 13.0%, p<0.001), obesity (30.1 vs 21.8%, p<0.001) and
Int Suppl. 2012;2:1–64 DM (30.1 vs 21.1%, p<0.001). Of the patients with anemia, 738 met the criteria for
CKD progression. In univariate analysis, CKD progression was associated with anemia
(49.6 vs 43.9%, p=0.002), male gender (49.5 vs 43.6% p= 0.001); DM (49.6 vs 44.8 %
MO557 EFFICIENCY OF FERRIC CARBOXYMALTOSE IN NON- p=0.009) and hypertension (47.9 vs 42.3% p=0.0018). In multivariate logistic
DIALYSIS CKD PATIENTS AND ITS IMPACT ON KIDNEY regression analysis, anemia emerged was an independent predictor of CKD
FUNCTION: A PROSPECTIVE OBSERVATIONAL STUDY progression (OR 1.435, CI 95% 1.21-1.71, p<0,001). Comparing hb values intervals (hb
10g/dl; hb10-12 g/dL; hb 12 g/dL), in the multivariate logistic regression analysis,
Marisa Rold~ao1, Rachele Escoli1, Hern^ ani Gonçalves1, Karina Lopes1 hb 10g/dl was not associated with CKD progression and hb value between 10-12 g/dL
1 was associated (OR 1,486, CI 95% 1.23-1.80, p<0,001), when compared with the group
Centro Hospitalar Médio Tejo, Nephrology, Torres Novas, Portugal with hb 12g/dL. In multivariate logistic regression analysis, the independent
predictors of mortality were: older age (OR per 1 year increase: 1.048, 95% CI 95%
BACKGROUND AND AIMS: Iron deficiency anemia occurs in the vast majority of 1.04-1.06, p<0.001); arterial hypertension (OR 0.699 CI 95% 0.51-0.96, p=0.0029);
patients with chronic kidney disease (CKD). The aim of this study was to investigate obesity (OR 0.741, CI 95% 0.60-0.91, p=0.004) and hb value (OR per 1 g/dL decrease:
the efficacy of ferric carboxymaltose (FCM) iron deficiency anemia’s treatment in non- 1.301, CI 95% 1.23-1.38, p<0.001). Cardiovascular events were correlated with Hb
dialysis CKD patients and to clarify its impact on kidney function. levels between 10-12 g/dL (univariate analysis: OR 2.021, CI 95% 1.27-3.22, P=0.003),
METHOD: Prospective observational study of non-dialysis CKD stage 3 to 5 patients, but not with the group with hb10 g/dL (univariate analysis: OR 1.837, CI 95% 0.96-
with anemia and iron deficiency treated with FCM from 01 January 2019 to 31 June 3.51, P=0.066), having the group with hb 12g/dL was reference. Anemia was strongly
2020. FCM was administrated as a single IV infusion of 500mg or 1000mg. Baseline associated with hospitalizations (multivariate logistic regression analysis: OR per 1 g/
clinical, analytical and demographic data were recorded. FCM efficacy was evaluated dL of Hb decrease: 1.256 CI 95% 1.12-1.32 p<0.001), and this strong association was
by comparing hemoglobin (Hb), serum ferritin and transferrin saturation index also observed on the groups with hb hb10 g/dL (multivariate logistic regression
(TSAT) 24 6 8 weeks after the infusion with analytical values at baseline. Renal analysis: OR 3.591 CI 95% 32.67-4.84 p<0.001) and between 10-12 g/dL (multivariate
function was also assessed at baseline and at 24 6 8 weeks using estimated glomerular logistic regression analysis: OR 1.678 CI 95% 1.40-2.02, p<0.001)
filtration rate (eGFR), calculated by CKD-EPI formula. Statistical analysis was executed CONCLUSION: Our study suggests that anemia, at first consultation, increases the
using SPSS (Version 23 for Mac OSX). risk for rapid CKD progression and global mortality. This study could guide us on the
RESULTS: The average age of 71 patients was 77.31 6 9.68 years, 29 (40.8%) were development of futures studies in order to prove if anemia correction can slow the
male, 46 (64.8%) were diabetic and 41 (57.8%) had congestive heart failure. Sixteen progression of CKD.
(22.5%) patients had CKD stage 3, 41 (57.7%) stage 4 and 14 (19.7%) stage 5. Twenty-
five (35.2%) patients were treated with 1000mg of FCM. At baseline, average
hemoglobin level (Hb) was 10.16 6 1.12g/dL, serum ferritin 83.25 6 96.55mg/L, TSAT
14.48 6 6.72mg/dL and eGFR 24.216 13.09ml/min/1.73m2. At 24 6 8 weeks, Hb MO559 ASCEND-ND: STUDY DESIGN AND BASELINE
showed an increase of 1.31 6 1.49 g/dL (p=0.001) and TSAT 10.68 6 10.40% CHARACTERISTICS
(p=0.001). Serum ferritin showed also an increase of 4.75 6 180.53mg/L but did not
reach statistical significance. The increase in Hb was observed uniformly across all Vlado Perkovic1, Allison Blackorby2, Borut Cizman2, Kevin Carroll3,
stages of CKD. A Pearson correlation revealed a positive correlation between the Alexander Cobitz2, Richard Davies2, Tara DiMino2, Vivekanand Jha4,5,6,
variation of Hb and eGFR during the study follow-up period (r=0.310, p=0.008). A Kirsten Johansen7, Renato Lopes8, Lata Kler2, Iain Macdougall9,
subgroup analysis was performed, patients were classified in 2 groups according to John McMurray10, Amy Meadowcroft2, Gregorio Obrador11, Scott Solomon12,
FCM dose. At baseline, there was no age, comorbidities or eGFR difference among Lin Taft2, Christoph Wanner13, Sushrut S Waikar14, David Wheeler15, Andrzej
groups. Patients treated with 1000mg had lower Hb (p=0.03) and serum ferritin Jan Wiecek16, Ajay Singh12
1
(p=0.01). At 2468 weeks both groups showed increases in Hb (p=0.001) and TSAT University of New South Wales, Medicine Department, Sydney, Australia,
2
(p=0.001). Patients treated with 1000mg showed also a significant increase in ferritin GlaxoSmithKline, Collegeville, United States of America, 3KJC Statistics, Cheadle Hulme,
(p=0.004). The Pearson correlation confirmed a positive correlation between the United Kingdom, 4George Institute for Global Health, New Delhi, India, 5Imperial
variation of Hb and eGFR in the group of patients treated with 1000mg (r=0.467, College, Faculty of Medicine, London, United Kingdom, 6Manipal Academy of Higher
p=0.019) but not in the group treated with 500mg. Education, Manipal, India, 7Hennepin Healthcare, University of Minnesota, Nephrology
CONCLUSION: FCM was effective in the treatment of iron deficiency anemia in non- Division, Minneapolis, United States of America, 8Duke Clinical Research Institute, Duke
dialysis CKD stage 3 to 5 patients. In our population, the increase of Hb levels Health, Durham, United States of America, 9King’s College Hospital, Renal Unit, London,
correlated with an improvement in eGFR in patients treated with higher doses of FCM, United Kingdom, 10Glasgow University, Institute of Cardiovascular and Medical
suggesting a positive impact of FCM on kidney function. Sciences, Glasgow, United Kingdom, 11Universidad Panamericana, School of Medicine,
Mexico City, Mexico, 12Brigham and Women’s Hospital, Renal Division, Boston, United
States of America, 13University of Würzburg, Division of Nephrology, Würzburg,
Germany, 14Boston Medical Center, Nephrology, Boston, United States of America,
MO558 ROLE OF ANEMIA ON PROGRESSION AND CLINICAL 15
University College London, Department of Renal Medicine, London, United Kingdom
OUTCOMES OF CKD: A PATIENT-LEVEL, RETROSPECTIVE, and 16Medical University of Silesia, Department of Nephrology, Endocrinology and
COHORT ANALYSIS OF A CKD OUTPATIENTS POPULATION Metabolic Diseases, Katowice, Poland
Sara Fernandes1, Beatriz Donato1, Adriana Paix~ ao Fernandes1, Luıs Falca
~o1,
Mario Raimundo1, Ana Cortesa ~o Costa1, Catarina Teixeira1, So
nia Silva1, BACKGROUND AND AIMS: The Anemia Study in Chronic kidney disease (CKD):
Edgar Almeida1 Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Non-
1 Dialysis (ASCEND-ND; NCT02876835) trial is evaluating the efficacy and safety of
Hospital Beatriz Ângelo, Nephrology, Loures, Portugal daprodustat when compared with darbepoetin alfa in CKD patients with anaemia not
requiring dialysis. We report the trial design as well as key baseline characteristics of
BACKGROUND AND AIMS: Anemia is a well-know complication of Chronic participants.
Kidney Disease (CKD) and it seems to contribute for deterioration of kidney function. METHOD: Eligible patients from 39 countries were adults with CKD stages 3–5 who
Experimental data suggest that anemia produces hypoxia of tubular cells which leads to were able to provide informed consent and demonstrated adherence to daprodustat
tubulointerstitial damage resulting on CKD progression. Other mechanism described placebo tablets and study procedures during the run-in period. Patients were eligible if
is that red blood cells have antioxidant properties that prevent the damage of (1) they were not using erythropoiesis stimulating agents (ESAs) and had a screening
tubulointerstitial cells and glomerulosclerosis from oxidative stress. There aren’t many haemoglobin (Hb) 8 to 10 g/dL or if (2) they were receiving ESAs with screening Hb of
observational studies that evaluated the association between anemia and progression of 8 to 12 g/dL. Patients were required to be iron replete [transferrin saturation (TSAT)
CKD. Therefore, our aim was to evaluate the association of anemia and CKD >20% and serum ferritin >100 ng/mL] at screening. Participants were randomised to
progression and its association outcomes in an outpatient ND-CKD population. daprodustat or darbepoetin alfa (1:1) in an open-label (sponsor-blind) trial design with
METHOD: We conduct a retrospective, patient-level, cohort analysis of all adult ND- blinded endpoint assessment. An IDMC conducts regular reviews of unblinded safety
CKD patients evaluated in an outpatient nephrology clinic over a 6 years period. The and efficacy data and makes recommendations for additions or adjustments. An
follow up time was at least 12 months. Anemia was defined according to the WHO external, independent and blinded Clinical Events Classification (CEC) group, led by
definition (hemoglobin [hb] < 13.0 g/dL in men and 12.0 g/dL in women). Progression the Duke Clinical Research Institute, in collaboration with George Clinical, adjudicate
of CKD was defined by one of the following criteria: decline in eGFR (CKD-EPI) predefined events.
superior to 5 ml/min/1.73 m2/year; duplication of serum creatinine or the need renal During the study, both groups had randomised treatment adjusted using a protocol-
replacement therapy. Demographics and clinical data were also accessed. defined algorithm targeting a Hb range of 10 to 11 g/dL. Participants also followed
RESULTS: Out of 3008 patients referred to the nephrology clinic, 49.9% had anemia protocol-defined iron management criteria to ensure they remained iron replete.
(mean age 71.9615.9 years; 50.4% male; 92% white; mean follow-up time of 2.361.2 Additionally, an anaemia rescue algorithm was in place to minimise the risk of

i334 | Abstracts
Nephrology Dialysis Transplantation Abstracts
extended periods of inadequate Hb response and to ensure consistent application of
rescue therapy across the study. Beta Exp(B) 95%CI p
The co-primary endpoints are mean change in Hb between baseline and Evaluation
Constant –2.54 0.08 - 0.006
Period (EP; Weeks 28 to 52, inclusive) and time to first adjudicated major adverse
cardiovascular event (MACE; composite of all-cause mortality, non-fatal myocardial eGFR 0.05 1.05 1.01 to 1.10 0.02
infarction, and non-fatal stroke). The study has more than 99% power for the Hb non- Serum Hep-25 0.02 1.02 1.00 to 1.03 0.05
inferiority (NI) test with an NI margin of -0.75 g/dL for the treatment difference of Nagelkerke R2 = 0.24
mean change in Hb between baseline and EP, and approximately 90% power to exclude Variables entered in the first step: estimated glomerular filtration rate (eGFR), serum
the NI margin of 1.25 for time to first adjudicated MACE, for daprodustat compared hepcidin-25 (Hep-25), percentage of medullary sideroblasts, reticulocyte index, and
with darbepoetin alfa. Conditional on both co-primary endpoints achieving NI at the mean corpuscular hemoglobin concentration
one-sided 2.5% level, statistical testing will progress to evaluate MACE and the
principal secondary endpoint of CKD progression for superiority. These tests will be
multiplicity adjusted.
RESULTS: A total of 3872 patients were randomised (median age 67 years, 56%
female; 55% white, 28% Asian, and 10% black). The median baseline Hb was 9.8 g/dL,
serum ferritin was 274 ng/mL, TSAT 30%, and eGFR 18 mL/min/1.73 m2. Among
randomised patients, 54% were ESA non-users, 57% reported a history of diabetes
mellitus and 36% a history of cardiovascular disease. Median blood pressure was 135/ MO561 PREFERENCES OF DIALYSIS-DEPENDENT PATIENTS FOR
74 mmHg. Sixty percent of participants were taking angiotensin converting enzyme TREATMENT OF ANAEMIA OF CHRONIC KIDNEY DISEASE IN
inhibitors or angiotensin II receptor blockers, while 57% were taking lipid modifying AUSTRALIA AND CANADA: A DISCRETE CHOICE
agents at baseline. The trial is expected to complete during 2021. EXPERIMENT
CONCLUSION: ASCEND-ND will define the efficacy and safety of daprodustat
compared with darbepoetin alfa in the treatment of patients with anaemia associated Simon Fifer1, Bronwyn West1, Juan Jose Garcia Sanchez2, Eric Wittbrodt3,
with CKD not requiring dialysis. Purav Bhatt4, Susan Grandy4, Naveen Rao2, Rita Karamy5, Deborah Wong6,
Anna Parackal6, Farhad Khan7, Karthik K Tennankore8, David W Johnson9
1
CaPPRe, Sydney, Australia, 2AstraZeneca, BioPharm Medical, Cambridge, United
MO560 IS SERUM ERYTHROPOIETIN CORRELATED WITH IRON Kingdom, 3AstraZeneca, BioPharm Medical, Gaithersburg, United States of America,
4
METABOLISM AND INFLAMMATION IN NON-DIALYSIS AstraZeneca, BioPharm Medical, Wilmington, United States of America, 5AstraZeneca,
CHRONIC KIDNEY DISEASE PATIENTS WITH ANEMIA? BioPharm Medical, Sydney, Australia, 6AstraZeneca, BioPharm Medical, Mississauga,
Canada, 7AstraZeneca, BioPharm Medical, Gothenburg, Sweden, 8Dalhousie University
Cristina-Stela Capusa1,2, Ana-Maria Mehedinti1,2, Ana Stanciu3, Gabriela- & Nova Scotia Health Authority, Department of Medicine, Halifax, Canada and
9
Adriana Talimba1, Liliana Viasu3, Gabriel Mircescu1,2 Princess Alexandra Hospital, Department of Nephrology, Brisbane, Australia
1
“Carol Davila” University of Medicine and Pharmacy, Nephrology, Bucharest, Romania,
2
“Dr. Carol Davila” Teaching Hospital of Nephrology, Nephrology, Bucharest, Romania BACKGROUND AND AIMS: Anaemia is a common complication of chronic kidney
and 3“Dr. Carol Davila” Teaching Hospital of Nephrology, Laboratory, Bucharest, disease (CKD) and is associated with reduced quality of life, cardiovascular
Romania complications, early mortality and a high economic burden for patients. Current
treatment options for anaemia of CKD include subcutaneous (SC) or intravenous (IV)
erythropoiesis-stimulating agents (ESAs) with or without supplementary iron and
BACKGROUND AND AIMS: Both the relative erythropoietin (Epo) deficiency and blood transfusions. New oral therapies for anaemia, such as hypoxia-inducible factor
its relationship with serum hemoglobin (Hb) are widely postulated in chronic kidney prolyl hydroxylase inhibitors, are in development and may have advantages for
disease (CKD), but the influence of chronic inflammation and iron status on serum patients compared with ESAs. It is therefore crucial to understand the treatment
Epo levels is still a matter of debate, with yet divergent reported results. Therefore, we attributes that patients consider most important. This study aimed to investigate
aimed to assess the determinants of serum Epo in non-dialysis CKD patients. patient preferences for potential anaemia of CKD treatments in adults with dialysis-
METHOD: Fifty-two adults with CKD and anemia (defined as Hb <12g/dL), in stable dependent (DD) CKD in Australia and Canada.
clinical condition, never treated with erythropoiesis-stimulating agents (ESA) entered METHOD: Adult patients with DD CKD completed a discrete choice experiment
this cross-sectional, single-center study. Diabetes mellitus, active infectious and (DCE) online survey. In each scenario, patients were asked to choose between three
inflammatory diseases, malignancy, anemia of other causes than CKD, current hypothetical treatment alternatives (‘oral pill’, ‘subcutaneous injection’ and
immunosuppressive therapy, iron supplementation and blood transfusions in the ‘intravenous injection’) with differing levels of attributes and an opt-out option (none
previous six months were exclusion criteria. The subjects were mostly men (56%), of these treatments/current treatment) to treat anaemia of CKD. Treatment attributes
elderly (two thirds over 60 years), with advanced CKD [71% in CKD stages G4-G5, focused on administration (where, how often and by whom), purchasing (where it is
median estimated glomerular filtration rate – eGFR 14.5 (95%CI 16 to 25) mL/min], collected and the cost per month), additional benefits (e.g. whether it reduces ‘bad’/
moderate anemia [Hb 9.8 (95%CI 9.2 to 9.9) g/dL], and mild to moderate LDL cholesterol), side effects (chance of hospitalization from a heart attack or stroke
inflammation [C-reactive protein 6 (95%CI 9.2 to 18.4) mg/L]. due to the medicine) and the need for rescue therapy (IV iron or blood transfusion).
Serum Epo was assessed by ELISA (AbcamV R 119522). Complete blood count,
The attributes and their levels were derived from existing market research, the
reticulocyte index, peripheral blood smear, bone marrow aspiration (Perls’ stain), literature and expert opinion. A mixed multinomial logit model, which allows for
serum ferritin, and transferrin saturation, were used to investigate anemia and iron preference heterogeneity, was used to quantify the overall value of such treatments and
metabolism. Parameters of kidney disease (CKD etiology, eGFR and proteinuria), the relative importance of each of the defining attributes. Australian patients were
demographic data (age, gender), C-reactive protein, serum albumin, and serum divided into those who were eligible for reduced prescription charges under the
hepcidin-25 (Hep-25, BachemV R commercial ELISA kit) were also analyzed.
Pharmaceutical Benefits Scheme, such as the elderly or those on low incomes (referred
RESULTS: The median serum Epo of the whole cohort was 4.8 (95%CI 5.1 to 9.9) mU/ to as concessions), and those who were not (general patients). Prescription charge
mL. According to median Epo, subjects were clustered in Group 1 (below median, G1) concessions did not apply for Canadian patients.
and Group 2 (above median, G2). Estimated GFR and serum Hep-25 were lower in G1 RESULTS: This preliminary analysis included 61 patients with DD CKD from
than in G2 [10.6 (95%CI 9.7 to 20.8) vs. 26 (95%CI 19.1 to 32.8) mL/min, p=0.004, and Australia (n = 22) and Canada (n = 39). The majority of patients were receiving
62.6 (95%CI 51.0 to 85.1) vs. 95.4 (95%CI 77.0 to 108.5) ng/mL, p=0.03, respectively]. haemodialysis (Australia, 72.7%; Canada, 61.5%), and more than half received their
All the other investigated parameters were similar in the two groups. dialysis in a clinic or hospital (Australia, 54.5%; Canada, 76.9%); 50% of the Australian
In bivariate analysis (Spearman rank correlation), serum Epo was positively associated patients were concessions. In both countries, patients were likely to choose a new
only with eGFR (rs=0.40, p=0.003). Marginal associations with the percentage of bone treatment alternative over the opt-out, with the greatest preference for oral treatment
marrow sideroblasts, as marker of the iron available for erythropoiesis (rs=0.25, among Australian general and Canadian patients, all else being equal. For Australian
p=0.08), erythrocyte mean corpuscular hemoglobin concentration (rs=0.26, p=0.07), concession patients, cost per month was the most important attribute across all
and reticulocyte index (rs=0.24, p=0.09) were observed. Conversely, serum Epo was not treatment options; the risk of side effects (i.e. hospitalization from a heart attack or
related to hemoglobin, indices of iron stores (e.g. serum ferritin and iron content in stroke) was the second most important attribute, with patients preferring treatments
bone marrow macrophages), inflammation and nutritional status (e.g. C-reactive with the lowest possible risk. For Australian general and Canadian patients, the risk of
protein and serum albumin). side effects and the cost per month were the two most important attributes, and had
In a model of multiple linear regression which explained 14% of serum Epo variation, similar levels of importance. Patients in both countries were also concerned about the
eGFR was the only determinant: Beta 0.14 (95%CI 0.05 to 0.23), p=0.004. Also, a binary risk of needing rescue therapy, and valued reductions in the amount of ‘bad’/LDL
logistic multiple regression model predicting serum Epo lower or higher than the cholesterol.
median retained the eGFR as an independent predictor, while serum hepcidin showed CONCLUSION: Results from this DCE study showed that the risk of side effects and
only borderline significance: the costs of treatment are the most important attributes for hypothetical anaemia of
CONCLUSION: Kidney function is the main determinant of endogenous CKD treatment for patients with DD CKD. Australian general and Canadian patients
erythropoietin level in moderately anemic patients with advanced CKD, ESA or iron showed a preference for oral therapy over SC or IV injection, all other factors being
naive, while serum hepcidin-25 seems to exert a limited influence. equal. These findings may help to guide clinicians when selecting treatments for

10.1093/ndt/gfab085 | i335
Abstracts Nephrology Dialysis Transplantation

anaemia of CKD for their patients, and may provide useful information when assessing glomerular filtration rate 24 (11;36) mL/min, 78% in the very high-risk category
the value of new or future treatments. according to KDIGO, 90% with hypertension and 40% with diabetes mellitus] were
included. The study was approved by Ethics Committee of the UMF “Carol Davila”
Bucharest. Pregnancy and breast feeding, anemia of other cause, history of
erythropoietin therapy, high-degree inflammation, active malignancies,
MO562 ACUTE IMPACT OF A SINGLE HIGH DOSE OF FERRIC
glomerulonephritis or liver diseases, immunosuppressive therapy, hemoglobin <7g/dl,
CARBOXYMALTOSE ON ENDOTHELIAL FUNCTION IN CKD
ferritin > 500 ng/ml and/or transferrin saturation > 50%, baseline flow mediated
NON-DIALYSIS PATIENTS
dilatation (FMD) < 7%, antioxidant supplements and active smoking were exclusion
criteria. The effect on endothelial function was clinically assessed by comparing FMD
Ana-Maria Mehedinti1,2, Liviu Iosif3, Irina Stoian3, Iuliana Andreiana1,2, Cristina-
at 15 minutes before and 15 minutes after 2 infusions: first, the comparator (250 mL
Stela Capusa1,2, Gabriel Mircescu1,2
1
0.9% saline), and 24 hours apart, FCM (1000 mg in 250 mL 0.9% saline). FMD was
“Carol Davila” University of Medicine and Pharmacy, Nephrology Department, measured using a Doppler ultrasound system according to guidelines
Bucharest, Romania, 2“Dr. Carol Davila” Teaching Hospital of Nephrology, Nephrology recommendations. Wilcoxon paired test was used to test the post- and pre-infusion
Department, Bucharest, Romania and 3“Carol Davila” University of Medicine and differences.
Pharmacy, Biochemistry Department, Bucharest, Romania RESULTS: Flow mediated vasodilatation and blood pressure at baseline was similar
before each intervention. Neither comparator nor FCM infusion had any effect on
BACKGROUND AND AIMS: Anemia is highly prevalent in CKD, and most acute changes in systolic and diastolic blood pressure. Arterial reactivity was not
frequently is caused by iron deficiency. Intravenous iron therapy is often and efficiently acutely affected after FCM [DFCM 0.01 (-0.35;0.15) versus saline solution 0.001 (-
used, even in non-dialysis CKD patients. Still, experimental data suggested that 0.4;0.5), p=0.9].
intravenous iron could alter endothelial function, rising concerns related to the CONCLUSION: A single high dose of ferric carboxymaltose did not acutely impaired
possible cardiovascular long-term effects. In this regard, we clinically assessed the acute endothelial function evaluated by flow mediated vasodilatation, in a CKD non-dialysis
impact of a high dose of iron ferric carboxymaltose (FCM), a commonly used iron cohort.
formulation, on endothelial function in CKD iron-naive non-dialysis patients.
METHOD: In this prospective crossover single center study, forty CKD iron-deficient
non-dialysis patients [median age 66.5 (56;73) years, 62% female, median estimated

i336 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i337–i350, 2021
10.1093/ndt/gfab086

CKD. BONE DISEASE

MO563 HIGH DIALYSATE MAGNESIUM AND CORONARY ARTERY


CALCIFICATION IN MAINTENANCE HEMODIALYSIS
PATIENTS*

Praopilad Srisuwarn1, Arkom Nongnuch1, Sethanant Sethakarun2,


Sutipong Jongjirasiri3, Chanika Sritara4, Sinee Disthabanchong1
1
Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Division of Nephrology,
Department of Medicine, Bangkok, Thailand, 2Bhumirajanagarindra Kidney Institute
Hospital, Bangkok, Thailand, 3Faculty of Medicine, Ramathibodi Hospital, Mahidol
University, Department of Radiology, Bangkok, Thailand and 4Faculty of Medicine,
Ramathibodi Hospital, Mahidol University, Division of Nuclear Medicine, Department of
Radiology, Bangkok, Thailand

BACKGROUND AND AIMS: Cardiovascular calcification is highly prevalent among


patients with end-stage renal disease (ESRD). Low normal serum magnesium has been
linked to a more severe degree of vascular calcification and a decrease in patient
survival. An inhibitory effect of extracellular magnesium on osteogenic transformation
of vascular smooth muscle cells and the upregulation of anti-calcification protein have
been confirmed in vitro. Increased dialysate magnesium concentration has also been
shown to lower calcification propensity of the serum of maintenance hemodialysis
(HD) patients.
METHOD: This study is an investigator initiated, single-blinded, parallel-group,
matched case-control clinical trial that investigated the effect of high dialysate
magnesium concentration for 24 weeks on the progression of coronary artery
calcification (CAC) in maintenance HD patients. The changes in laboratory data and
bone mineral density (BMD) were also examined. Seventy-six ESRD patients
underwent CAC screening by multi-slice computed tomography and BMD
measurement by dual-x-ray absorptiometry. Only patients with Agatston score>300
were included. They were matched according to the initial CAC score that fell within
20% of one another. Twenty patients were assigned to high dialysate magnesium MO563 Figure 1: Changes of CAC score during the study. All patients (a and b),
concentration of 1.75 mEq/L and the matched controls were kept on standard dialysate patients with baseline CAC score <1600 (c and d),and patients with CAC score >1600
magnesium concentration of 0.7 mEq/L. CAC and BMD measurements were repeated (e and f). Median (IQR) values of the CAC score are shown in each graph.
after 24 weeks. Laboratory data were obtained prior to dialysis at study entry, 8-week
intervals during the study and 2 weeks after the study ended.
RESULTS: There were no significant differences in age, sex, BMI, underlying diseases,
dialysis vintage, medications, baseline CAC scores and BMD. The median baseline
CAC Agatston score (Volume score) were 1923 (720) and 1672 (785) in the standard
and high dialysate groups, respectively. At the end of the study, a significant increase in
the CAC score was observed in both groups. Because majority of the included patients
had severe calcification burden at baseline, patients were categorized into 2 subgroups
using the median baseline CAC Agatston (1600) and Volume scores (700) as cut-offs.
Among patients with CAC Agatston score <=1600, CAC score increased significantly
in the standard dialysate magnesium group (P<0.01) but was stable in the high
dialysate magnesium group (P=0.33). Among patients with CAC Agatston score
>1600, the severity of CAC worsened in both groups. The progression of CAC was
analyzed by the difference between the follow-up and the baseline square root
transformed Agatston and Volume scores. In subgroup of patients with less severe
calcification, more patients in the standard dialysate magnesium group progressed
compared to the high dialysate magnesium group (P=0.03). In subgroup of patients
with more severe calcification, the number of progressors were comparable among the
2 groups. Serum and ionized magnesium levels increased substantially during the study
and returned to baseline after the return to standard dialysate magnesium
concentration. The highest predialysis serum magnesium was 3.8 mg/dL. Most patients
who received high dialysate magnesium reported the disappearance of symptoms of
muscle cramps (P=0.01) and requested the high dialysate magnesium be continued
after the end of the study. There were no significant changes in serum calcium,
phosphate or PTH levels. The decline in BMD was observed in both groups but the
difference did not reach statistical significance.
CONCLUSION: High dialysate magnesium was well tolerated and could ameliorate
the progression of CAC in maintenance HD patients with mild to moderate vascular
calcification.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

MO564 CHRONIC EXPOSURE TO INDOXYL SULFATE CHANGES


BONE PROPERTIES AND EXPRESSION OF SIRT2, SIRT3,
AND SIRT7 GENES*

Malgorzata Karbowska1, Beata Sieklucka1, Tomasz Domaniewski2,


Malgorzata Galazyn-Sidorczuk3, Krystyna Pawlak2, Dariusz Pawlak2
1
Medical University of Bialystok, Department of Pharmacodynamics, Bialystok, Poland,
2
Medical University of Bialystok, Department of Monitored Pharmacotherapy, Bialystok,
Poland and 3Medical University of Bialystok, Department of Toxicology, Bialystok,
Poland

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is connected with


accumulation of uremic toxins that leads to dysfunction of many systems including
skeletal system. Indoxyl sulfate (IS) is one of the most potent protein-bound uremic
toxin. However, its impact on bone and mineral disorders remains unclear. Sirtuins
(SIRT) are members of the class III type nicotinamide adenine dinucleotide-dependent
histone deacetylases. Their roles are commonly linked to aging, metabolism, and
antioxidant defense. However, SIRT1, SIRT3 and SIRT7 maintain also bone formation.
In turn, reduction of SIRT2 has a protective role due to reduced activation of
osteoclasts-mediated bone resorption. Thus, the aim of this work was to evaluate IS
impact on bone metabolism and bone properties, and SIRT genes expression.
METHOD: Male Wistar rats weighting 180 – 210 g were divided into 2 groups:
experimental receiving IS in the dose of 200 mg/kg of b.w. for four weeks (200IS), and
control receiving pure water (CON). After four weeks the femurs and tibiae were
collected, and geometrical parameters (CI – cortical index, CSA – cortical sectional
area, CSMI – cross sectional moment of inertia, MRWT – mean relative wall thickness)
were measured. The IS bone (cortical and trabecular), plasma and urine levels were
determined by high-performance liquid chromatography (HPLC). The concentrations
of Ca, Mg, Zn, Fe, Mn, and Cu in bone tissue were determined by the flame atomic
absorption spectrometry. Bone turnover markers (alkaline phosphatase – ALP, and
tartrate-resistant acid phosphatase - TRAP) were determined in homogenates from
trabecular and cortical left femurs. The expression of ALP, TRAP, SIRT1, SIRT2,
SIRT3 and SIRT7 gene was assessed by QRT-PCR in right femurs.
RESULTS: Plasma, urine, cortical and trabecular bone IS concentrations were
increased in 200IS compared to CON. Geometrical properties of femur (CI, CSA,
CSMI and MRWT) were significantly reduced in 200IS. There were no differences in
relative femur weight and length between studied groups. The activity of ALP and
TRAP in bone tissue were significantly lower in 200IS compared to CON. In turn, the
expression of TRAP gene was increased in 200IS. There were no difference in
concentrations of Ca, Mg, Fe, Mn, and Cu in bone tissue. Only Zn concentration in
cortical bone was reduced in 200IS. The expressions of SIRT3 and SIRT7 were
decreased in 200IS, whereas SIRT2 was increased in 200IS. Chronic exposure to IS did
not affect expression of SIRT1.
CONCLUSION: Obtained results suggest that IS affects bone properties and bone
metabolism, and has impact on expression of SIRT2, SIRT3, and SIRT7 genes. Our
findings may help to better understand mechanisms leading to dysfunction of skeletal
system during CKD.
This work was supported by Polish National Science Centre (Grant No. 2017/27/N/
NZ4/00033).

MO565 M2 MACROPHAGES REGULATE MOUSE AORTIC SMOOTH


MUSCLE CELL CALCIFICATION BY TRANSMITTING
SENESCENCE INFORMATION

Yaping Fang1, Xiaodong Zhu1,2, Yu Zhao1, Xiao liang Zhang1


1
institute of nephrology, Zhongda Hospital, Nanjing, P.R. China and 2institute of neph-
rology, Zhongda Hospital, Nanjing,

BACKGROUND AND AIMS: Vascular calcification is highly prevalent in chronic


kidney disease (CKD)with high morbidity and mortality. Complex pathological
mechanisms are involved in the development of vascular calcification, including aging.
Previous work have indicated that M2-macrophage promote mouse aortic smooth
muscle cells (MAoSMCs) calcification. The present study aimed to understand the
contribution of M2-macrophage to MAoSMCs calcification by focusing on the
mechanisms underlying the transmitting senescence information
METHOD: The expression of IFITM3 and P16, marker of aging, in aging
macrophages were confimed by RT-qPCR, western blotting and immunofluorescence
staining. Then, the MAoSMCs were co-cultured with the supernatant of M2
macrophages. The expression of IFITM3 and P16 in MAoSMCs also were detected.
Alizarin red staining and calcium content assay were used to analyse MAoSMCs
calcification. We modulated the expression of IFITM3 using siRNAs to study M2-
macrophages function in regulating MAoSMCs calcification.We detected the
expression of IFITM3 and P16 in co-cultivate MAoSMCs and validate intracellular
calcium contents by calcium test kit.
RESULTS: In the present study, we observed a significant increase in the expression of
IFITM3 and P16 expression in M2 macrophages.Compared with M0 and M1
macrophages, the expression of IFITM3 and P16 at lowlevel. Alizarin red staining and
calcium content assay revealed that M2 macrophage-mediated IFITM3 and P16
overexpression led to an apparent VSMC calcification in the presence of M2
macrophages medium.By contrast, inhibition of IFITM3 by siRNAs significantly
blocked calcification of VSMCs in vitro. Moreover, we found that aging macrophages
that overexpressed of IFITM3 and P16 increased in rats with CKD. Furthermore,

i338 | Abstracts
Nephrology Dialysis Transplantation Abstracts
pharmacological inhibition of aging signal was shown to block IFITM3-induced VSMC without differences in later groups. Osteoblast SOST expression was also higher in SO6
calcification. These findings demonstrate for the first time that M2 macrophage- vs SO2 (Figure).
mediated IFITM3 contributes to vascular calcification through a mechanism involving
transmitting Senescence signalling.
CONCLUSION: Collectively, our present study demonstrated that the functional
importance of M2 macrophage-IFITM3 dependent vascular calcification and provided
a novel mechanistic insight to the macrophage senescence in CKD.

MO566 THE BONE EXPRESSION OF WNT INHIBITORS IN THE


EXPERIMENTAL MODEL OF EARLY CHRONIC KIDNEY
DISEASE

Evdokia Bogdanova1, Natalia Semenova2, Olga Galkina1, Irina Zubina1,


Olga Beresneva1, Galina Ivanova3, Marina Parastaeva1, Vladimir Dobronravov1
1
Pavlov University, Nephrology Research Institute, Saint Petersburg, Russia, 2Almazov
National Medical Research Center, Institute of Experimental Medicine, Saint Petersburg,
Russia and 3Pavlov Institute of Physiology, Laboratory of cardiovascular and lymphatic
systems physiology, Saint Petersburg, Russia
MO566 Figure: – a) Representative micro pictures of bone anti-SOST and OKK1
BACKGROUND AND AIMS: Molecular mechanisms implicated in the IHC and b) quantitative morphometry of bone DkK1 and SOST expression
initial stages of inorganic phosphate (Pi) imbalance in chronic kidney disease CONCLUSION: Increased serum levels of sclerostin and Dickkopf-1 and their bone
(CKD) remain poorly understood.The aim of the study was to evaluate whether expression are apparent in early stages of experimental CKD associating with
canonical Wnt pathway inhibitors (iWnt) involved in early response to Pi retention hyperphosphatemia. Alterations of bone resorption and osteoblast depopulation
in CKD. occurred before the increase of serum Pi likely reflecting incipient stages of renal Pi
METHODS: Mild CKD was induced by 3/4 nephrectomy (NE) in spontaneously retention. These molecular and cellular events seem to be independent of systemic
hypertensive rats (SHR) fed rat chow diet containing 0.6 % phosphate. Controls were FGF23 and PTH response.
sham operated SHR (SO). Duration of experimental exposure (NE or SO) was 2 and 6
months. Serum levels of creatinine (Cr), inorganic phosphate (Pi), fractional Pi
excretion (FEPi), intact parathyroid hormone (PTH), fibroblast growth factor 23
MO567 PILOT STUDY OF BONE RESISTANCE MEASURED IN VIVO
(FGF23), alfa-Klotho (KL), sclerostin (SOST) and Dickkopf-1 (DKK1) were measured.
BY IMPACT MICROINDENTATION IN KIDNEY
The following morphological characteristics by light microscopy of bone metaphysis
TRANSPLANTATION
and kidney tissues: the area of renal interstitial fibrosis (RF) (Masson’s trichrome),
bone matrix volume (MV), the active osteoblasts to trabecular cells number ratio (aOB/
Maria Jesus Lloret1, Cristina Canal1, Silvana Di Gregorio2, Carmen Facundo
cells), eroded surface to bone surface ratio (ES/BS) (hematoxylin & eosin), and bone
Molas1, Ana Vila Santandreu1, Nuria Serra Cabanas1, Rosana Gelpi1,
SOST and DKK1 proteins expression (by IHC) were analyzed and calculated
Leonor Fayos De Arizon1, Carolt Arana1, Daniel Montolio3, Beatriz Bardaji1,
quantitatively. Statistical comparisons among groups were performed using Mann–
Lluis Guirado1, Jordi Bover1
Whitney U-test and Kruskal-Wallis H-test.
RESULTS: Serum Cr, RF and indices of Pi exchange in the experimental model
1
o Puigvert, Nephrology, Barcelona, Spain, 2CETIR CENTRE MEDIC, Barcelona,
Fundaci
corresponded to early CKD (Table). Pi elevated in NE6 suggestive for its renal Spain and 3Universitat de Barcelona School of Economics, Economics, Barcelona, Spain
retention. KL level decreased (Table) in all experimental groups vs control. No
differences were observed in serum levels FGF23 (p=0.62) and PTH (p=0.63). Serum BACKGROUND AND AIMS: Impact microindentation (IMI) is a new technique
SOST and DKK1 levels were significantly higher in NE6 group compared to SO6 that measures bone material strength (BMS). Results are expressed as a BMS index
(Table). The bone SOST and DKK1 expression increased in NE6 compared to SO6 (BMSi) which represents the ratio between the IMI distance [penetration of the needle-
(Figure). aOB/cells were lower in NE2, SO6 and NE6 vs SO2 (all p-values<=0.041). ES/ probe in patient’s bone (mid-shaft tibia)] versus a reference material
BS increased in NE2 (vs SO2) while being lowest in NE6 and SO6 animals (Table). (polimethylmethacrylate).
SOST and DKK1 metaphyseal expression increased in NE6 compared to SO2, SO6, METHOD: Observational, prospective, single-center study. Baseline IMI
R
V
NE2 (Figure). Osteocyte SOST expression increased in SO6 compared to SO2 and NE2 (Osteoprobe , Active Life Scientific, USA) and bone densitometry (iDXA, Lunar

MO566 Table Parameters studied in SO and NE SHR

Parameters SO2 (n=8) NE2 (n=8) SO6 (n=8) NE6 (n=8)


Kidney function
Cr, mmol/l 73.0 (67.5-77.0) 92.5 (91.0-97.0)p=0.001 83.2 (80.5-85.5)p=0.005 106.5 (101.5-
110.0)p=0.001
RF, % FOV 1.8 (0.1-3.3) 6.4 (3.8-7.6)p=0.001 5.8 (3.5-7.2)p=0.001 14.5 (13.2-17.2)p=0.001
Bone turnover
aOB/cells, % 23.3 (20.0-26.0) 10.0 (7.8-15.6)p=0.008 10.8 (8.4-14.2)p=0.013 12.1 (10.4-16.2)p=0.025
ES/BS, % 4.8 (3.4-5.3) 8.3 (7.5-10.7)p=0.002 2.7 (1.5-3.3)p=0.025 2.6 (2.4-2.7)p=0.025
MV, %BV 39.7 (36.7-42.0) 34.1 (33.5-34.9) 33.7 (26.5-39.0) 38.0 (28.5-42.5)
Inorganic phosphate exchange
Pi, mmol/l 1.89 (1.79-1.95) 1.60 (1.50-1.84)p=0.015 1.90 (1.80-1.98) 2.21 (2.15-2.28)p=0.002
FEPi, % 32.7 (27.1-42.0) 63.3 (47.9-64.8 p=0.002 38.1 (32.4-43.7) 46.8 (42.6-49.3)
PTH, pg/ml 76.6 (18.4-111.0) 45.9 (21.2-76.6) 45.5 (12.6-67.1) 33.5 (9.6-84.9)
FGF23, pg/ml 361.7 (330.8-3530.3) 676.0 (330.9-793.7) 468.0 (326.9-694.9) 630.7 (330.8-953.1)
Klotho, pg/ml 2916 (2520-5374) 2304 (2074-2524)p=0.020 2043 (1676-2663)p=0.020 2259 (1428-2696)p=0.034
Circulating Wnt inhibitors
DKK1, ng/ml 1290 (929-2209) 1454 (1236-1687) 686 (629-853) 999 (811-1157)p=0.028
SOST, ng/ml 428.2 (240.6-675.6) 339.9 (263.5-479.3) 261.3 (230.7-335.4) 361.4 (342.8-
479.3)p=0.028

P-values: NE6 vs SO6,SO6 vs SO2

10.1093/ndt/gfab086 | i339
Abstracts Nephrology Dialysis Transplantation

Health Care GE) were performed and data collected in the peritransplantation period METHOD: Bone biopsies with prior tetracycline labeling of sufficient quality for a full
of kidney transplant (KT) patients from May 2019 to May 2020, following our current histomorpometric analysis were included (n = 205). Mean age of participants was
clinical bone and transplant protocols. Based on the individual risk of fracture and 56613 years, 67% were men, and 22% had diabetes mellitus. Diagnostic accuracy of
current Spanish Society of Rheumathology/Nephrology guidelines, antirresorptive static histomorphometric parameters for bone turnover was evaluated by area under
treatment (bisphosphonates or denosumab) was added on top of calcium and vitamin the receiver operator characteristics curve (AUC) statistics, against the full set of static
D supplements. We hereby present preliminary results of the control IMI performed 6 and dynamic histomorphometric parameters. The cohort was randomly split to allow
months after KT. calculation of optimal diagnostic cutoffs in an exploration cohort (n=105), with
RESULTS: Baseline IMI was performed in 45 patients, 62% men, 56614 y/o, and a subsequent validation in a separate subset of patients (n=100).
BMI of 24.963.5 kg/m2, reasonably controlled for classical serum bone mineral RESULTS: All histomorphometric parameters were significantly different across
parameters. 70% were on dialysis prior to KT, 20% were diabetic, and 33.3% of women categories of low (24%), normal (60%), and high (16%) bone turnover (p < 0.01), and
suffered from early menopause. 15.9% had a history of previous fragility fracture, 13% all were significant predictors of both high and low bone turnover (Figure 1).
had a parent history of hip fracture, and 14% fell more than twice during the last year. Calculated optimal cutoffs and their sensitivities and specificities in the validation
R V
Mean baseline FRAX (https://www.sheffield.ac.uk/FRAX/tool.aspx?lang=sp) for a cohort are shown in Table 1.
major osteoporotic fracture and hip were 4.3% and 2.3%, respectively. Baseline lumbar, Diagnostic accuracy was very good for high turnover, as the combination of presence
femoral neck, hip and ultradistal radius DXA T-score were respectively -0.9, -1.7, -1.5, of fibrosis with ObPm>5.4%, OcPm>1.5%, and OAr>2.4% provided a correct
-2.0 SD. Mean BMSi was 78.567.6. Osteopenic/osteoporotic patients had a diagnosis in 94% of patients, with positive (PPV) and negative (NPV) predictive values
significantly lower BMSi than those who were not (76.3 vs 83; r = 0.37; p = 0.012). A of 80% and 96%, respectively. Using the same predefined combination, an accuracy of
statistically significant positive correlation was observed between BMSi and the 80% was achieved for low turnover (no fibrosis, ObPm1.9% OcPm0.9% and
trabecular bone score [(TBS), r = 0.346 ; p = 0.036). On a visual-analogic scale of pain, OAr1.6%), with a PPV of 71% and a NPV of 82%.
puncture was rated on average 1.161.6 over 10 (82% 0-2). 37.2% of patients began CONCLUSION: Static histomorphometric parameters provide an acceptable
bisphosphonates (alendronic acid) and 9.3% denosumab. Control IMI was performed alternative for the diagnosis of high and low bone turnover. In the absence of successful
at 6 months in 24 patients, with a mean BMSi of 76.9610.5. Mean difference between tetracycline labeling, the proposed cutoffs may provide a suitable alternative for the
baseline and 6 months BMSi in this subgroup was 1.18611.5. The group of patients evaluation of bone turnover in renal osteodystrophy.
treated with antiresorptives showed on average an increase in BMSi at 6 months,
compared with a decrease in the control group (þ5.2 vs -5.3; p = 0.054).
CONCLUSION: IMI is a technique with excellent tolerance that may offer
complementary information on bone quality in the global assessment of bone
resistance. IMI may allow the detection of EARLY changes in bone resistance in
corticosteroid-treated KT patients with/without antiresorptives added to prophylactic
treatment with calcium and vitamin D.

MO568 STATIC PARAMETERS OF HISTOMORPHOMETRY FOR THE


EVALUATION OF BONE TURNOVER IN RENAL
OSTEODYSTROPHY

Hanne Skou Jørgensen1,2, Geert Behets3, Patrick D’Haese3, Pieter Evenepoel1,4


1
KU Leuven, Microbiology, Immunology and Transplantation; Nephrology and Renal
Transplantation Research Group, Leuven, Belgium, 2Aarhus University, Institute of
Clinical Medicine, Nephrology, Aarhus N, Denmark, 3University of Antwerp, Institute of
Pathophysiology, Biomedical Sciences, Wilrijk, Belgium and 4University Hospitals
Leuven, Medicine, Division of Nephrology, Leuven, Belgium

BACKGROUND AND AIMS: A full histomorphometric analysis of a transiliac bone


biopsy with prior tetracycline labeling remains the gold standard to diagnose renal
osteodystrophy. Bone turnover is primarly evaluated by the dynamic parameter bone
formation rate, calculated from the incorporation of tetracycline in bone. In cases of
failed tetracycline labels, however, an evaluation of bone turnover based on static
parameters is warranted. This study investigates the diagnostic accuracy of static
histomorphometric parameters for the diagnosis of high and low bone turnover.

Exploration cohort (n=105) Validation cohort (n=100)


High turnover AUC Cutoff Sensitivity Specificity
Fibrosis 0.81 (0.70, 0.92) Yes 92% 90%
Osteoclast perimeter (OcPm) % 0.81 (0.69, 0.92) >1.46 75% 76%
Eroded perimeter (EPm) % 0.80 (0.70, 0.91) >4.51 83% 69%
Osteoblast perimeter (ObPm) % 0.79 (0.69, 0.89) >5.37 100% 73%
Osteoid area (OAr) % 0.77 (0.67, 0.87) >2.44 92% 57%
Osteoid perimeter (OPm) % 0.77 (0.67, 0.86) >22.33 83% 53%
Osteoid width (OWi) lm 0.73 (0.61, 0.85) >10.41 50% 76%
Low turnover AUC Cutoff Sensitivity Speci˚city
Osteoid width (OWi) lm 0.87 (0.79, 0.95) <5.81 45% 87%
Osteoid area (OAr) % 0.86 (0.77, 0.95) <1.63 59% 79%
Osteoid perimeter (OPm) % 0.81 (0.70, 0.92) <8.10 31% 90%
Eroded perimeter (EPm) % 0.76 (0.66, 0.86) <2.68 83% 68%
Osteoblast perimeter (ObPm) % 0.74 (0,63, 0,84) <1.88 72% 72%
Osteoclast perimeter (OcPm) % 0.63 (0.52, 0.74) <0.89 86% 49%
Fibrosis 0.61 (0.56. 0.65) No 97% 27%
AUCs, calculated cutoffs by Liu’s method, and corresponding sensitivity and specificity

i340 | Abstracts
Nephrology Dialysis Transplantation Abstracts
days incubation with high level Ca/P, fiber tube and vesicle structure of M-mig showed
rupture or fragmentation and the expression of M-mig surface integrin a5b1 increased.
Pre-treatment with integrin a5b1 antagonist or block by integrin a5 antibody
significantly reduced the calcifying M-mig formation. Further investigation showed
that M-mig induced stray mice artery microcalcification while M-migintegrin a5-
exhibited a reduce microcalcification.
CONCLUSION: Our finding revealed an association between microcalcification and
integrin a5b1 signalling in the fiber tube and vesicle structure of M-mig and provide a
new insight into vascular calcification in CKD.

MO570 PULSE PRESSURE: A PREDICTOR OF CARDIOVASCULAR


CALCIFICATION AND CARDIOVASCULAR MORTALITY IN
HEMODIALYSIS PATIENTS.

Merita Rroji (Molla)1, Saimir Seferi1, Majlinda Cafka2, Erjola Likaj1, Vilma Cadri1,
Myftar Barbullushi1
1
UHC “Mother Tereza”, Department of Nephrology, Tirana, Albania and 2UHC “Mother
Tereza”, Deaprtment of cardiology, Tirana, Albania

BACKGROUND AND AIMS: The mortality rate is extremely high in chronic kidney
disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD).
Increased pulse pressure (PP), defined as the difference between inappropriately
elevated systolic blood pressure (SBP) and reduced diastolic blood pressure (DBP) at
any value of mean arterial pressure (MAP), is a surrogate measure of increased arterial
stiffness of central elastic arteries (aorta and its major branches). CKD-MBD anomalies
leading to calcification contribute to increased arterial stiffness and pulse pressure. This
study aimed to evaluate the relationship of pulse pressure parameter with valve
calcification and abdominal aortic calcification in hemodialysis patients and its impact
on cardiovascular mortality.
METHOD: We performed a prospective case series study with 3 years follow- up. Plain
X-ray images of the lateral lumbar spine from all subjects were studied to obtain images
of the lower abdominal aorta using semiquantitative scores as described by Kauppila et
al. Cardiac valve calcifications were evaluated by two-dimensional echocardiography
with an HDI 5000 Sono CT echocardiographic machine with a 3.3-MHz multiphase
array probe in subjects lying in the left decubitus position an according to the
recommendations of the European Association of Echocardiography. The patient was
evaluated as having vascular calcification if he had the presence of calcification in at
least one of the site examined: a mitral valve, aortic valve or abdominal aorta.
RESULTS: We studied 85 chronic stable hemodialysis patients. Mean age and
meantime is therapy was 49.9612.4 years and 51.5628.7 months, respectively. Mean
pulse pressure was 55.72614.2 mmHg. Fifty-nine patients (69.4%) were identified with
aortic abdominal calcification, and the mean Kauppila score was 4.91 6 4.05. Sixty
patients (70.5%) had at least one valve calcified, while thirty-three patients (38.8%) had
both valves calcified. Univariate analysis revealed that every 1 mmHg increase in pulse
pressure was associated with increased cardiovascular calcification risk p=0.020. In
multivariate analysis, after adjustment for age, gender, diabetes mellitus, cholesterol,
and triglyceride serum levels, the association also remained strong, where every
increase of 1 mm Hg in pulse pressure was associated with increased risk for
cardiovascular calcification (HR 1.02, 95% CI (1.00-1.03), p= 0.038). Besides, pulse
pressure was an independent predictor for cardiovascular mortality (HR 1.03, 95% CI
(1.02-1.05), p=0.002).
CONCLUSION: Pulse pressure may identify hemodialysis patients with subclinical
cardiovascular calcification who need further evaluation. Wide pulse pressure is
MO569 MACROPHAGE PROMOTE VASCULAR CALCIFICATION VIA associated with increased cardiovascular mortality.
THE MIGRASOMES/ INTEGRIN A5B1 PATHWAY IN CKD

Xiaodong Zhu1, Yuqiu Liu1, Xin Yang1, Yaping Fang1, Xiao liang Zhang1 MO571 PRACTICE PATTERNS ON THE MANAGEMENT OF
1 SECONDARY HYPERPARATHYROIDISM IN THE UNITED
Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine,
Nanjing, P.R. China STATES: RESULTS FROM A MODIFIED DELPHI PANEL

BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) have a David E. Henner1, Beatrice Drambarean2, Teresa M. Gerbeling3, Jessica
predisposition to develop vascular calcification due to dysregulated homeostatic B. Kendrick4, William T. Kendrick5, Lisa Koester Wiedemann6, Thomas Nickolas7,
mechanisms. Macrophages can promote vascular calcification by releasing diverse Anjay Rastogi8, Anis A. Rauf9, Brenda Dyson10, Michael C. Singer11,
extracellular vehicles including the newly found migrasomes (M-mig). Our previous Pooja Desai12, Kathleen Fox12, Sunfa Cheng12, William Goodman12
1
research had found that M-mig provide nucleating foci for calcific mineral formation Berkshire Medical Center, Division of Nephrology, Pittsfield, Massachusetts, United
and initiating bone mineralization process. However, the specific mechanism by which States of America, 2University of Illinois Hospital & Health Sciences System, Chicago,
M-mig influence the formation of vascular calcification remains incompletely Illinois, United States of America, 3Dialysis Center of Lincoln, Lincoln, Nebraska, United
understood. States of America, 4University of Colorado, Division of Renal Diseases and Hypertension,
METHOD: To study calcifying M-mig, we exposed M-mig to high Ca/P (Ca/P=3 Aurora, Colorado, United States of America, 5Eastern Nephrology Associates, Greenville,
mmol/L calcium/2 mmol/L phosphate) and/or with LPS for 1, 3, 5,7 days. The North Carolina, United States of America, 6Washington University School of Medicine,
expression of M-mig surface integrin a5b1 was determined by fluorescence staining. Division of Nephrology, St. Louis, Missouri, United States of America, 7Columbia
To block the M-mig-integrin a5b1 mediated calcification, we modulated the University Irving Medical Center, Division of Nephrology, New York, New York, United
expression of integrin a5 using siRNAs to produce M-migintegrin a5- or using 20 nM States of America, 8UCLA School of Medicine, Division of Nephrology, Los Angeles,
ATN-161 (small peptide antagonist of integrin a5b1) or integrin a5 antibody under California, United States of America, 9Nephrology Associates of Northern Illinois,
high Ca/P stimulation. The stray mice artery co-cultivate with M-mig integrin a5- under Oakbrook, Illinois, United States of America, 10Mississippi, United States of America,
11
high level Ca/P. Then the calcifying M-mig were assessed by TEM, Fluo-3 staining and Henry Ford Hospital, Department of Otolaryngology–Head and Neck Surgery, Detroit,
calcium content assay. Michigan, United States of America and 12Amgen, Inc., Thousand Oaks, California,
RESULTS: We discovered that Ca/P-stimulated macrophages released M-mig capable United States of America
of mineralization. Amorphous calcium phosphate mineral deposit the surface or
internal of M-mig. The M-mig exhibited increased Ca/P mineral content, implying BACKGROUND AND AIMS: The 2017 Kidney Disease Improving Global Outcomes
aggregate larger calcifying M-mig that develop over time. Significantly, following a 7 (KDIGO) Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) guidelines

10.1093/ndt/gfab086 | i341
Abstracts Nephrology Dialysis Transplantation

inform clinical practice for the management of secondary hyperparathyroidism MO572 BONE BIOPSY AND MINERAL METABOLISM,
(SHPT) internationally; however, many recommendations lacked high or moderate CARDIOVASCULAR DISEASE AND PATIENT SURVIVAL IN
clinical evidence as defined by KDIGO. An expert panel was convened to establish END-STAGE RENAL PATIENTS
clinical consensus for the current management of SHPT in the United States (US).
METHOD: The panel comprised 10 US healthcare providers (HCPs; [6 nephrologists, Ana Carina Ferreira1,2, Patrıcia Cotovio1, Ine^s Aires1,2, Marco Mendes1,
1 surgeon, 1 nurse practitioner, 1 pharmacist, 1 dietician]) and 1 patient. HCP panelists David Navarro1, Cecılia Silva1, Fernando Caeiro1, Rute Salvador3, Bruna Correia3,
participated in a modified Delphi process over 3 phases, addressing 126 questions Guadalupe Cabral3, Fernando Nolasco1,2, Manuel Anibal A. Ferreira1,2
1
based on a review of the literature and published guidelines. The threshold for Hospital Curry Cabral, Nephrology, Lisboa, Portugal, 2Nova Medical School,
consensus was 66%. In phases 1 and 2, panelists anonymously completed electronic Nephrology, Lisboa, Portugal and 3CEDOC, Tissue Repair and Inflammation Lab, Lisboa,
surveys considering a ‘typical’ patient with SHPT unless otherwise specified. In phase 1, Portugal
panelists answered 126 questions based on their own knowledge and experiences. In
phase 2, panelists were reminded of their answers to closed-ended questions that did BACKGROUND AND AIMS: Chronic kidney disease-mineral and bone disorder
not achieve consensus in phase 1 and were asked if they would change their responses (CKD-MBD) is frequent in end-stage renal disease (ESRD) patients, increasing
in light of the most common response. For open-ended questions, they were asked if morbid-mortality. The aim of this study was to determine the prevalence and
they agreed with summary statements that captured the most common answers. Phase phenotype of bone disease before transplantation; and to correlate FGF23, klotho and
3 was an unblinded virtual meeting where panelists reviewed the consensus reached in sclerostin serum levels with bone histomorphometric parameters and CV disease. The
phases 1 and 2, and through active discussion, resolved those questions that had not secondary aim was to correlate bone biopsies data with other bone related parameters,
reached consensus. The patient completed a separate electronic survey, which as PTH, bone alkaline phosphatase, 25-hidroxivitamin D3, calcitonin, calcium,
complemented key points in the HCP survey, and provided perspective during the phosphorus, and magnesium.
virtual meeting. METHOD: We performed a prospective cohort study of a sample of ESRD patients
RESULTS: All 11 panelists completed the entire modified Delphi process. Sixty-three listed for renal transplant. All patients were submitted to renal transplant and were
out of 126 (50%) and 116/126 (92.1%) questions reached consensus or addressed followed for 12 months. Patient and graft survival were recorded. At inclusion,
practice-specific information not requiring consensus by the end of phase 1 and 2, demographic and clinical data were collected, laboratorial evaluation; bone biopsy and
respectively; all questions reached consensus by the end of phase 3, including X-ray of the pelvis and hands (Adrag~ao score) were performed. Continuous variables
modification of 2 questions and the addition of 1 question. The panel unanimously are presented as medians and categorical variables as frequencies. Associations between
agreed that SHPT treatment is often started too late and suggested additional markers variables were performed using Wilcoxon rank sum test, Fisher and Kruskal Wallis
for early identification of patients requiring treatment are needed. Serum levels of test. Multivariate analysis was performed using logistic regression. STATA software
calcium, phosphate, and parathyroid hormone (PTH) should be monitored starting at was used and p < 0.05 was considered statistically significant.
CKD stage G3a at intervals of every 6 months, 3–6 months for CKD G3b, and at least RESULTS: We included 84 patients. Median age 53.5 (IQ range: 40.5 – 61.5) years, 59
every 3 months at CKD G4 and above. Thresholds for interventions could not be men (70.2%), 65 caucasian (77.4%). The median left ventricular mass index was 108.5
defined in absolute terms for all patients due to patient-and practice-specific factors. (92 – 129) g/m2, with 32 patients presenting left ventricular hypertrophy and 19 valve
However, in patients on dialysis, serum levels of phosphate > 5.5 mg/dL (1.8 mmol/L) calcifications. Median Adrag~ao score was 1 (0 – 2). We diagnosed adynamic bone
and calcium > 9.5 mg/dL (2.4 mmol/L), warrant increased monitoring and disease in 15 patients; hyperparathyroid bone disease in 19 patients; osteomalacia in 1
consideration of therapeutic interventions. Serum intact PTH > 300 pg/mL (32 pmol/ patient and mixed renal osteodystrophy in 3 patients. At the end of 12 months, 4
L) typically indicates a need for SHPT treatment, with a consensus preferred target of patients died, 5 had graft failure (non-primary function) and 4 had a cardiovascular
150–300 pg/mL (16–32 pmol/L); patients on dialysis were considered out of PTH event. Sclerostin was found to be a risk factor for low bone volume; whereas low
target at  8 times the upper limit of normal (> 520 pg/mL [55 pmol/L] intact PTH). phosphorus, low FGF23 and high bAP risk factors for abnormal mineralization. High
HCPs were concerned about vascular calcification in all patients with CKD 3a–G5D. turnover was mainly present in patients with high bAP and phosphorus and low
The panel reached consensus on the use of several SHPT interventions, including a sclerostin levels. The presence of valve calcifications was associated with low volume
consensus preference for the intravenous calcimimetic etelcalcetide over the oral and with low or high turnover disorder. FGF23 appears as an important independent
calcimimetic cinacalcet in appropriate in-center dialysis patients requiring PTH- factor for vascular calcifications [as well age (p=0.009), BMI (p=0.02), presence of
lowering therapy; cinacalcet was agreed to be first-line therapy in appropriate patients diabetes (p=0.01)], and for cardiovascular events. Sclerostin emerged as a risk factor for
on home dialysis (Table 1). Factors such as formularies and dialysis center protocols vascular calcifications and lower levels of sclerostin were associated with patient
were recognized to influence therapeutic choices. survival at the end of 12 months.
CONCLUSION: Ten US HCPs reached consensus on many aspects of SHPT CONCLUSION: From the bone-derived hormones, sclerostin and FGF23 seem to act
management, further defining therapeutic strategies and highlighting the need to be as risk factors for vascular calcifications and worse outcomes.
proactive. While the panel expressed evidenced-based preferences for certain therapies,
factors such as cost and dialysis center protocols may affect decision making.
MO573 CNI AND MTORI-BASED REGIMENS ON FIVE-YEAR COURSE
OF BONE MINERAL DENSITY SCORES AFTER RENAL
TRANSPLANTATION

Berfu Korucu1, Hasan Haci Yeter1, Galip GUZ € 1


1
Gazi University Faculty of Medicine, Nephrology, Ankara, Turkey

BACKGROUND AND AIMS: Since glucocorticoids are used in low maintenance


doses today, the relationship between calcineurin inhibitors (CNI) and osteoporosis
after solid organ transplantation has gained clinical significance. In contrast,
(mammalian target of rapamycin inhibitors) mTORi agents are shown to have an
antiresorptive effect on bone by reducing osteoclastic activity in vitro and in vivo. We
investigated the bone mineral density (BMD) changes on an extremely selective group
of incident renal transplant recipients under CNI or mTORi-based maintenance
treatment regimens during the first five-year posttransplant course.
METHOD: This study consists of renal allograft recipients with a dialysis history of
less than one year. Patients older than 50 years old, using CNI - mTORi combinations,
patients with a history of a prior renal transplant, acute rejection, CNI – mTORi switch
after posttransplantation first three months, bisphosphonate treatment,
parathyroidectomy, diuretic use, and malignancy excluded to eliminate all
confounding factors for bone mineral loss. First and fifth-year BMD scores and
simultaneous laboratory parameters were evaluated.
RESULTS: CNI (n=21) and mTORi (n=17) groups had similar demographics, dialysis
vintages, cumulative steroid doses, first and fifth-year parathormone, calcium,
phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D levels. The femur
neck scores of the CNI group decreased from -0.82(60.96) to -1.52(60.92) (p=0.020).
We observed a significant decrease in the CNI group compared to the mTORi group [-
0.70(60.68) and 0.30(60.36), respectively; p<0.01] when BMD score changes
evaluated among years. The mean femur neck score of the mTORi group
insignificantly increased from -1.13(60.65) to -0.82(60.56) at the fifth-year DXA scan
(p=0.230). Although statistically insignificant, similar trends were also observed in L1-4
scores.
CONCLUSION: Our study suggests that CNI-based treatment is associated with
decreased femur neck and L1-4 BMD scores, and mTORi-based treatment tends to be
beneficial presumably due to their antiresorptive effects in the posttransplant five-year

i342 | Abstracts
Nephrology Dialysis Transplantation Abstracts
follow-up. Our findings may shed light on long-term maintenance therapy RESULTS: We recruited 84 patients in a 28 month-period. At the end of 12 months, 69
management in renal transplant patients with bone disease if supported by future patients performed a 2nd evaluation. Median age 53 years, 48 men, 53 caucasian,
studies. median dialysis vintage 55 months. We observe a significant reduction on phosphorus,
magnesium, PTH, calcitonin, sclerostin, bone alkaline phosphatase and FGF23. Both
calcium and alpha-klotho serum levels increase, with no significant changes in vitamin
D levels. 68% of the patients presented renal osteodystrophy at the 2nd bone biopsy,
and we observed a significant increase in the development of low turnover bone
disorder, with no major changes in volume or mineralization. Changes in alpha-klotho,
bAP and sclerostin (from T0 to T1) were important determinants of changes in
turnover, mineralization and volume, respectively. Despite not being statistically
significant, we were able to observe an improvement in the cortical bone porosity.
Vascular calcifications and echocardiographic findings weren’t different comparing to
the baseline (Median Adrag~ao score was 1 in both evaluations, and valve calcifications
were present in 22% and 23% of patients, with no changes in LVMI). The median
Agatston score was 48.5, being the median adjusted percentile of 82%. FGF23 and
sclerostin were found to be independent risk factors for extra-osseous calcifications, as
well as low bone volume, cortical porosity and osteoid volume. Adrag~ao score and
valve calcifications correlated well with the increased severity of coronary calcifications
determined by Agatston score (absolute and percentile).
CONCLUSION: In conclusion, renal transplantation improves two of the three
components of CKD-MBD (biochemical and bone disorders), slowing the progression
of vascular calcifications. FGF23, sclerostin and bAP seemed to be key parameters in
understanding the bone changes observed in post transplant period, and these
hormones also interfere with extra osseous calcification severity. Adrag~ao score seems
to be a good tool to access vascular calcifications in renal transplanted patients.

MO575 SEX DISPARITY IN THE ASSOCIATION BETWEEN DIETARY


SODIUM INTAKE AND THE RISK OF INCIPIENT
OSTEOPOROSIS

Mi-yeon Yu1, Jong Wook Choi2, Sang-Woong Han1, Chang Hwa Lee1, Joon-
Sung Park1
1
Hanyang University College of Medicine, Department of Internal Medicine, Seoul,
Korea, Rep. of South and 2Konkuk University School of Medicine, Research Institute of
Medical Science, Chungcheongbuk-do, Korea, Rep. of South

BACKGROUND AND AIMS: Rationale & Objective: Dietary nutrition is closely


related with bone health, but there is wide controversy on the association of dietary
sodium intake with bone densitometry (BMD) and risk of incipient osteoporosis.
METHOD: Study Design: Community-based retrospective cohort study
MO573 Figure: Changes in the posttransplantation bone mineral density scores
Measurement: We used Tanaka method for estimating 24-h urinary sodium excretion
CNI: calcineurin inhibitors, mTORi: mammalian target of rapamycin inhibitors (e24hUNaETanaka) as candidate indicator of dietary sodium intake.
CNI: calcineurin inhibitors, mTORi: mammalian target of rapamycin inhibitors Setting & Participants: Using long-term follow-up cohort data from the Korean
Genome Epidemiology Study, we identified 4310 participants without osteoporosis and
classified them into quartile according to their e24hUNaETanaka.
Outcome: Participants were followed up for 12 years of less for a new diagnosis of
MO574 MINERAL AND BONE DISORDERS CHANGES IN RENAL osteoporosis.
TRANSPLANTED PATIENTS Analytical Approach: Multiple Cox-proportional hazard model was performed to
estimate hazard ratio (HR) of osteoporosis and survival curve analysis was utilized to
Ana Carina Ferreira1,2, Marco Mendes1, Cecılia Silva1, Patrıcia Cotovio1, compare cumulative survivals.
^s Aires1,2, David Navarro1, Fernando Caeiro1, Ru
Ine ben Ramos3, Rute Salvador4,
RESULTS: Decreased dietary sodium intake was deeply related with low BMD
Bruna Correia4, Guadalupe Cabral4, Fernando Nolasco1,2, Manuel Anibal parameters. Multiple Cox-proportional hazard model, adjusted for various
A. Ferreira1,2 conventional risk factors of decreased BMD, demonstrated that e24hUNaETanaka had
1
Hospital Curry Cabral, Nephrology, Lisboa, Portugal, 2Nova Medical School, inverse association with the risk of osteoporosis (adjusted HR = 0.868, 95% CI = 0.768-
Nephrology, Lisboa, Portugal, 3Santa Marta Hospital, Cardiology, Lisboa, Portugal and 0.981). Interestingly, our RCS analysis revealed that there was wide variation in the
4
CEDOC, Tissue Repair and Inflammation Lab, Lisboa, Portugal relation between dietary sodium intake and the risk of incipient osteoporosis according
to sex and female hormone status: negative curvilinear relationship in male
BACKGROUND AND AIMS: Successful renal transplant restores many physiologic participants; positive linear relationship in premenopausal female participants; and
abnormalities, including improvement of chronic kidney disease- mineral and bone negative linear relationship in postmenopausal female participants.
disorder (CKD-MBD) syndrome. The primary aims of this study were: analyse the CONCLUSION: Our findings suggest that decreased sodium intake was a significant
changes and evolution of the 3 components of CKD-MBD pre and 1 year post renal predictor of osteoporosis progression and there was some sex disparity in the relation
transplantation: the mineral abnormalities, the bone disorders and the vascular dietary sodium intake and the risk of incipient osteoporosis.
calcifications; and to correlate fibroblast grow factor 23 (FGF23), klotho and sclerostin
serum levels with bone histomorphometric parameters and CV disease. The secondary
aims were to study the evolution of other bone related parameters and correlate those MO576 ASSOCIATION OF BONE MATERIAL STRENGTH WITH BONE
with bone biopsies data, as well as to validate Adrag~ao vascular calcification score in a DENSITY IN PATIENTS WITH END-STAGE RENAL DISEASE
population of renal transplant patients.
METHOD: We performed a prospective cohort study of a consecutive sample of de Matilda Johnsson1, Abdul Rashid Tony Qureshi1, Magdalena Jankowska2,
novo single renal transplanted patients in our unit. At inclusion, demographic, clinical Bengt Lindholm1, Mathias Haarhaus1,3
and transplant-related data were collected, X-ray of the pelvis and hands (for Adrag~ao 1
score) and echocardiographic findings were recorded. All patients were submitted to a Karolinska Institute, Division of Renal Medicine and Baxter Novum, Department of
bone biopsy and laboratorial evaluation at baseline (time 0 – T0). Patients were Clinical Science, Internvention and Technology, Stockholm, Sweden, 2Medical University
followed for 12 months (time 1 – T1), after which performed laboratorial evaluation, a of Gdansk, Department of Nephrology, Transplantology and Internal Medicine, Poland
2nd bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry and and 3Diaverum Sweden AB, Malmö, Sweden
non-contrast cardiac CT (Agatston score). Continuous variables are presented as
medians and categorical variables as frequencies. Differences between T0 and T1 were BACKGROUND AND AIMS: Patients with end-stage renal disease (ESRD) have an
accessed by Wilcoxon matched-pairs test and paired McNemar test. Correlations increased risk of skeletal complications, including an increased fracture risk, which is
between bone histomorphometric findings and severity of vascular calcifications with only partially identified by determination of bone mineral density (BMD).
demographic and laboratorial parameters were obtained with Wilcoxon rank-sum test Experimentally, the complex bone-and mineral disorders in ESRD cause disturbances
or Kruskall Wallis test. STATA software was used and p < 0.05 was considered of bone material properties, but these have not been studied in vivo. Determination of
statistically significant. bone material strength index (BMSi) by reference point indentation (RPI) is a novel
method to determine bone material quality in vivo and can identify patients at

10.1093/ndt/gfab086 | i343
Abstracts Nephrology Dialysis Transplantation

increased fracture risk, even in the presence of normal BMD. We determined BMSi in matched healthy controls were recruited. Serum vitamin K2 and osteocalcin both intact
ESRD patients and investigated its association with BMD and serum markers of and undercarboxylated were measured. Transthoracic echocardiography was done for
mineral metabolism. valvular calcification and thickening, and carotid duplex was done for carotid intimal
METHOD: 15 Adult patients with ESRD, scheduled for a living-donor kidney medial calcification and thickening.
transplantation, were included in this cross-sectional study. Laboratory analyses RESULTS: Hemodialysis patients have higher median serum vitamin K2 (p<0.001),
included calcium, phosphate, PTH 1-84 and alkaline phosphatase. BMSi was higher undercarboxylated osteocalcin (p<0.001). Only older age, duration of
determined by RPI with the OsteoProbe RUO in the tibia. Bone mineral density was hypertension, and duration of established cardiovascular disease are associated with
measured by dual X-ray absorptiometry. carotid media-intimal calcification. Old age is a strong predictor of carotid media
RESULTS: Patients with bone mineral strenght index above median had higher bone intimal thickening. Female sex is associated with valvular thickening.
mineral density of the right hip and total body than patients below median (p = 0.04). CONCLUSION: Functional vitamin K deficiency is present in maintenance
Alkaline phosphatase was lower in patients with BMSi below the median (47 (35-71) hemodialysis patients and serum osteocalcin is not associated with cardiovascular
U/L vs. 103 (53-318) U/L, p = 0.009). There was a trend towards a significant calcification.
relationship between length and BMSi (p = 0.09).
CONCLUSION: We identified for the first time an association of BMSi with BMD and
alkaline phosphatase in patients with ESRD. Our findings of an association of BMSi
MO578 Table1. Simple regression analysis for prediction of carotid intima-
media thickness:
with BMD are in accordance with findings in other populations with increased fracture
risk.
OR 95% CI P
value
MO577 EXPANDING THE POTENTIAL BENEFITS OF FERRIC Age (years) 1.072 1.024-1.123 0.003*
CITRATE FOR IMPROVING IRON-DEFICIENCY ANAEMIA AND
HTN Duration (years) 1.168 1.045-1.305 0.006*
MINERAL BONE DISORDER PARAMETERS IN NON-
DIALYSIS-DEPENDENT CHRONIC KIDNEY DISEASE DM Duration (years) 1.241 0.979-1.572 0.075
PATIENTS: A META-ANALYSIS OF RANDOMIZED eCVD Duration (years) 1.525 1.027-2.265 0.036*
CONTROLLED TRIALS

Boby Pratama Putra1, Felix Nugraha Putra2


1 MO578 Table 2. Simple regression analysis for prediction of valvular thickening:
Medical doctor, Blitar, Indonesia and 2Faculty of Medicine, Universitas Airlangga,
Surabaya, Indonesia
OR 95% CI P
BACKGROUND AND AIMS: Most of non-dialysis-dependent chronic kidney value
disease (NDD-CKD) patients will suffer from iron-deficiency anaemia (IDA) also Sex Male Female Ref.2.935
mineral and bone disorders (CKD-MBD) as consequences of CKD progression. Ferric 1.011-8.519 0.048*
citrate (FC) is an iron-based phosphate binder that based on previous studies showed
efficacies in improving IDA and CKD-MBD parameters although the results were still
inconclusive. This study aims to establish the overall efficacies of FC in improving IDA MO578 Table 3. Simple regression analysis for prediction of CIMT >7.5 mm
and CKD-MBD parameters in NDD-CKD patients.
METHOD: We did comprehensive searching using predefined keywords in online
databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include OR 95% CI P
all relevant studies from 2000-2020. We included all randomized controlled trials value
(RCTs) accessing the efficacies of FC in improving IDA and CKD-MBD parameters
compared with standard care (SC) in NDD-CKD patients. The CKD-MBD parameters Age (years) 1.143 1.082-1.207 <0.001*
analysed in this study are changes in serum phosphorus (P), serum calcium ions (Ca), Diabetes History NA NA NA
alkaline phosphatase (ALP), intact fibroblast growth factors-23 (iFGF-23), C-terminal HTN Duration (years) 1.096 0.983-1.221 0.099
fibroblast growth factors-23 (cFGF-23), and intact parathyroid hormone (iPTH), while
the IDA parameters analysed are changes of haemoglobin (Hb), serum iron (Fe),
transferrin saturation (TSAT), and ferritin. Bias risk was accessed by using the revised
Cochrane Risk-of-bias (RoB-2) tool. Analysis was performed to provide standard mean
difference (SMD) with 95% confidence interval (CI) using random-effect heterogeneity MO579 POST-TRANSPLANT HYPERCALCEMIA AND VITAMIN D
test. SUPPLEMENTATION
RESULTS: We included six RCTs with total of 1,082 participants met our inclusion
criteria. The FC significantly improve CKD-MBD parameters of P (SMD = -0.84. 95% Andrey Vatazin1, Ekaterina Parshina2, Rusudana Kantaria1, Vadim Stepanov1,
CI = -1.21 to -0.07, p<0.00001, I2 = 74%), iFGF-23 (SMD = -0.43. 95% CI = -0.73 to - Aleksei Zulkarnaev1
0.13, p = 0.005, I2 = 73%), cFGF-23 (SMD = -0.74. 95% CI = -1.12 to -0.35, p = 0.0002, 1
Moscow Regional Research and Clinical Institute, Surgical department of transplanta-
I2 = 78%), and iPTH (SMD = -0.23. 95% CI = -0.40 to -0.06, p = 0.008, I2 = 0%), while tion and dialysis, Moscow, Russia and 2Saint Petersburg State University Hospital,
the improvement of Ca (SMD = 0.16. 95% CI = -0.07 to 0.38, p = 0.17, I2 = 0%) and Department of outpatient dialysis, Saint-Petersburg, Russia
ALP (SMD = 0.03. 95% CI = -0.22 to 0.28, p = 0.81, I2 = 14%) are not statistically
significant compared with the SC group. The FC also significantly improve IDA BACKGROUND AND AIMS: Post-transplant hypercalcemia is common after
parameters of Hb (SMD = 1.10. 95% CI = 0.06 to 2.14, p = 0.04, I2 = 97%), TSAT (SMD successful kidney transplantation in patients with chronic kidney disease (CKD) and
= 1.18. 95% CI = 0.67 to 1.69, p<0.00001, I2 = 72%), and ferritin (SMD = 1.10. 95% CI can be partially explained by the side effects of concomitant therapy. We aimed to
= 0.34 to 1.86, p = 0.004, I2 = 87%) compared with the SC group, unless the evaluate the prevalence of hypercalcemia among recipients of kidney transplant and its
improvement of Fe is not statistically significant (SMD = 1.34. 95% CI = -0.28 to 2.95, p relationship with vitamin D supplementation.
= 0.11, I2 = 97%). METHOD: We performed a cross-sectional study of 236 patients underwent successful
CONCLUSION: The ferric citrate shows potential benefits for improving iron- kidney transplantation in our clinic. Median age was 49 [Q1-Q3: 39; 58] years, mean
deficiency anaemia and CKD-MBD parameters in NDD-CKD patients. Nevertheless, estimated glomerular filtration rate (eGFR) was 51,1621,8 ml/min/1,73 m2. Most of
further trials are needed to establish the efficacies. the patients received hemo- or peritoneal dialysis treatment, pre-emptive
transplantation was performed in 6% cases. For those previously received dialysis,
median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months. Median time
MO578 OSTEOCALCIN AND VASCULAR CALCIFICATION IN after transplantation reached 42 [Q1-Q3: 19; 75] months. Target range for total serum
HEMODIALYSIS PATIENTS: AN OBSERVATIONAL COHORT Ca was defined according to National guidelines on CKD-MBD as 2,1 - 2,5 mmol/l.
STUDY RESULTS: In our cohort median serum total Ca level was 2,41 [Q1-Q3: 2,36; 2,56]
mmol/l. Hypercalcemia was encountered in 21% (7 of 33) cases during the first year
Hesham Kamal Habeeb Keryakos1, Ahmed Salama1, Nagwa Okaily2, after transplantation and in 30% (61 of 203) – after first year. Serum total Ca weakly
Mariam Boulis1 correlated with iPTH (q= 0,282 [95%CI: 0,15; 0,4], h<0,0001), alkaline phosphatase
1 (q=0,181 [95%CI: 0,05; 0,31], h=0,006) and total duration of renal replacement therapy
Faculty Of Medicine - Minia University, Internal Medicine and Nephrology Department,
(dialysis þ transplantation) - q=0,2 [95%CI: 0,07; 0,32], h=0,002. We did not observe
Egypt and 2Faculty Of Medicine - Minia University, Clinical Pathology Department,
statistically significant correlations between serum total Ca and eGFR (p=0,132), total
Egypt
Ca level and time after transplantation (p=0,06). Total Ca levels did not differ in groups
with different eGFR (p=0,04 in Kruskall-Wallis test, but no statistically significant
BACKGROUND AND AIMS: Vascular calcification contributes to morbidity and differences after correction for multiply comparisons). Data on concomitant therapy
mortality in patients with ESRD on maintenance hemodialysis. to study the were available for 230 patients. 173 of 230 recipients received any therapy of CKD-
relationship between osteocalcin and vascular calcification. MBD. Of them, 123 patients took only active vitamin D (alfacalcidol), 33 patients
METHOD: 160 patients with ESRD on maintenance hemodialysis and 60 age-and sex- received monotherapy with inactive vitamin D (cholecalciferol). 57 patients not taking

i344 | Abstracts
Nephrology Dialysis Transplantation Abstracts
any medications were the control group. Serum total Ca level varied significantly MO580 HYPOPROTEIC DIET SUPPLEMENTED WITH
between groups (p=0,0006, Kruskall-Wallis test), being higher in patients KETOANALOGUES IN PATIENTS WITH ADVANCED DIABETIC
supplemented with cholecalciferol - fig.1. Meanwhile, iPHT (p=0,171), serum KIDNEY DISEASE – EFFECTS ON MINERAL BONE
phosphorus (p=0,563) and alkaline phosphatase levels did not differ in these three DISORDERS
groups. Fraction of patients with normocalcemia was the lowest in cholecalciferol
group (v2, h=0,0018) - fig. 2. Liliana Garneata1,2, Carmen-Antonia Mocanu1, Tudor Petrisor Simionescu2,
Andreea Elena Mocanu2, Gabriel Mircescu1,2
1
“Carol Davila" Univesity of Medicine and Pharmacy, Internal Medicine and
Nephrology, "Dr C Davila” Hospital of Nephrology, Bucharest, Romania and 2“Dr Carol
Davila” Teaching Hospital of Nephrology, Nephrology, Bucharest, Romania

BACKGROUND AND AIMS: Dietary protein restriction is rediscussed as mainstay


approach in advanced Chronic Kidney Disease (CKD), both in diabetics and non-
diabetics to defer renal replacement therapy (RRT), mainly by better metabolic control;
improvements in mineral bone disorders (MBD) were also suggested, but less studied
in Diabetic Kidney Disease (DKD).
An unicentric prospective interventional trial aimed to assess the effects of
ketoanalogue-supplemented low protein diet (sLPD) on proteinuria and CKD
progression (data already presented). The parameters of MBD were also evaluated.
METHOD: Adult diabetic patients (452) with stable CKD stage 4þ, proteinuria>3g/g
creatininuria and SGA A were enrolled in a run-in phase (3 mo), with LPD (0.6g/kg
dry ideal bw). Those who proved adherent (92, 64% males, median age 55.7 yrs, 65%
on insulin) received sLPD (KetosterilV R , 1 tablet/10kg) for 12mo. Monitoring and

treatment followed the Best Practice Guidelines.


The primary endpoint was proteinuria during intervention as compared to pre-
enrolment. Serum levels of calcium, phosphates and iPTH were considered to assess
MBD. Nutrition, inflammation (SGA, BMI, serum albumin, CRP) and compliance
were safety parameters.
RESULTS: In patients with advanced DKD and severe proteinuria, sLPD was
associated with a 69 (63; 82) % reduction in proteinuria (data presented).
Significant amelioration in MBD was noted: serum levels of calcium and phosphates
were significantly ameliorated at the end of the study as compared to enrolment - 4.3
(4.2-4.9) vs 3.2 (3.1-3.5) mg/dL and 5.4 (4.9-6.1) vs 8.2 (7.8-8.9) mg/dL, respectively.
Serum iPTH significantly decreased: 185 (168-212) vs 375 (354-585) pg/mL. The need
for calcium supplementation decreased: 6.5 (6.0-6.7) vs 7.0 (6.8-7.3) g/day. Vitamin D
was required by only 35% vs 65% of patients.
Nutritional status was preserved and dietary compliance was very good throughout the
MO579 Figure 1: Serum total calcium level in groups of renal graft recipients study.
receiving or not vitamin D analogues. AC – alfacalcidol, CCF – cholecalciferol. CONCLUSION: In patients with advanced DKD ketoanalogue supplemented low
Kruskall-Wallis test, p=0,0006. FDR-adjusted for multiply comparisons p-values (q- protein diet seems to be effective and safe as part of MBD management.
values) are shown for significant differences between two groups.

MO581 ASSOCIATION OF ETELCALCETIDE WITH ADYNAMIC BONE


DISEASE IN DIABETIC PATIENTS : A MULTI-CENTRIC
STUDY

Giuseppe Leonardi1, Alessio Montanaro1, Alessandra Spinelli1, Patrizia Covella1,


Cosima Balestra1, Antonio Flores1, Brigida Di Renzo1, Palmira Schiavone1,
Amalia Mariotti1, Annarita De Giorgi1, Irma Figlia2, Emanuela D’Anello2,
Giuseppe Coppolino3, Luigi Vernaglione1
1
“A.Perrino Hospital" Brindisi, Nephrology and Dialysis Unit, Brindisi, Italy, 2“G. Iannelli
Hospital” Cetraro, Nephrology and Dialysis Unit, Cetraro, and 3AOU “ Magna Graecia
University” Catanzaro, Nephrology and Dialysis Unit, Catanzaro, Italy

BACKGROUND AND AIMS: Several dialysis patients frequently suffer of different


mineral and bone disorders (CKD-MBD) associated with secondary
hyperparathyroidism (sHPT). Among CKD-MBD, adynamic bone disease (ABD) is an
alteration characterized by reduced osteblasts and osteoclasts, no accumulation of
osteoid and low bone turnover. The histologic pattern of ABD is generally associated to
low levels of PTH.
MO579 Figure 2: Fraction of patients within or above target range for serum total Etelcalcetide is a novel second-generation calcimimetic given intravenously after each
calcium level in groups of renal graft recipients receiving or not vitamin D analogues. hemodialysis session that has a longer elimination half-life than cinacalcet. Plasmatic
AC – alfacalcidol, CCF – cholecalciferol. Omnibus test result (marked in red) and concentration remains stable from 24 h to 48 h after injection. One potential risk of
FDR-adjusted for multiply comparisons p-values (q-values) are shown. calcimimetics, such as etelcalcetide, is the dramatic and sustained PTH lowering, which
CONCLUSION: We observed a high prevalence of hypercalcemia in kidney transplant could lead to the induction of adynamic bone disease (ABD). ABD and elevated serum
patients, that was not associated with transplant function or time after transplantation. levels of advanced glycation end products (AGEs) often are found in patients with
Our data suggest usage of active vitamin D to be safer than cholecalciferol to prevent renal failure caused by diabetic nephropathy since AGEs are involved in the
hypercalcemia development in renal allograft recipients. pathogenesis of ABD by inhibiting osteoblastic activity and by parathyroid hormone
secretion in response to hypocalcemia. So, diabetic patients treated with etelcalcetide
could be considered at increased risk of developing ABD.
Aim of our study was to verify the incidence of adynamic bone disease, (defined by low
PTH levels) in prevalent diabetic and non-diabetic HD patient of three large
community Hospital.
METHOD: Data were collected from 3 dialysis units with n = 130 patients on the
charge for a period of 1 year from start of the calcimimetic. A total of 40 patients ( 23
male, 17 female) on etelcalcetide were enrolled (21 Diabetic, 19 non diabetic patients).
Time points of assessment included 1-3-6-12 months. Patients were 18-years-old or
older; they were on stable doses of active vitamin D analogs, phosphorus binders, a
supplement of oral calcium, and calcium concentration in dialysate (1.25–1.50
mmol/L)
RESULTS: Median age was 55,9 years and dialysis vintage was 4.6 year. 59,5% percent
of patients switched from cinacalcet to etelcalcetide (90 days from last cinacalcet
prescription); the remaining patients were calcimimetic naive. 40% of patients had a

10.1093/ndt/gfab086 | i345
Abstracts Nephrology Dialysis Transplantation

MO581 Table 1: PTHi, Ca, P laboratory values

PTHi (pg /mL)


M1 ( p:0,789) M3 ( p:0,363) M6 (p:0.966) M12 (
p:0.042)
DIABETIC PATIENTS 701,22 þ 577 402,304 þ 204 430,236 þ 235 473 þ 340,08
NON DIABETIC PATIENTS 618,41 þ701,22 465,34 þ 280,71 425 þ 239 253,13 þ 98,87
Ca21 (mg)
M1 (p:0,194) M3 (p: 0,987) M6 (p:0,124) M12 (p:0,982)
DIABETIC PATIENTS 9,1760,53 8,5560,39 9,0160,88 8,5860,61
NON DIABETIC PATIENTS 8,55 þ 0,55 8,5560,57 8,3360,75 8,4560,86
P (mg/dl)
M1 (p:0,734) M3 (p:0.218) M6 (p:0.599) M12(p:0,388)
DIABETIC PATIENTS 5,3161,12 5,260,75 4,761,27 5,6860,8
NON DIABETIC PATIENTS 5,0860,82 4,561,18 5,261,70 5,1361,24

history of at least one cardiovascular event 61.5% had a starting etelcalcetide dose of
5 mg and the median weekly dose was 7.5 mg (range: 2.5-15 mg).
On Diabetic Group: mean PTHi, Ca2þ and P before calcimimetic start was
respectively 8446479,30 pg /mL , 9,9560,97 mg/dl , 5,0260,99 mg/dl. In non diabetic
patients: mean PTHi, Ca2þ and P before calcimimetic start was: 793,366534,41 150
pg /mL, 9,3360,70 mg/dl, 5,961,17 mg/dl
CONCLUSION: Results of our study show that after 1 year of etelcalcetide treatment,
levels of PTHi are lower more in non-diabetic patients, ( M12: 4736340,08 vs
253,13 þ 98,87 p:0.042) despite scientific evidence currently supporting hypothesis
that osteoblastic activity is reduced by AGES and ABD risk is increased in diabetic
nephropathy. Therefore, etelcalcetide could be used safely in diabetic patients and
could even protect from the risk of development ABD. However, further studies are
required to validate this hypothesis.
Results are shown in the following table:

MO582 LONGITUDINAL STUDY TO FIND THE ASSOCIATION OF


SERUM PHOSPHORUS LEVEL WITH FGF 23 IN THREE
DIFFERENT HYPERPHOSPHATEMIA MANAGEMENTS
GROUPS OF STAGE 3 AND 4 CHRONIC KIDNEY DISEASE
(CKD) PATIENTS

Navjot Kaur1, Himansu Mahapatra1, Neera Sharma2, Lalit Pursnani1,


Muthukumar B1, Neeraj Inamdar1, Mansi Singh1, Tannu Arora3
1
ABVIMS, DR. RML Hospital, Nephrology, New Delhi, India, 2ABVIMS, DR. RML Hospital,
Biochemistry, New Delhi, India and 3ABVIMS, DR. RML Hospital, Dietetics, New Delhi,
India

BACKGROUND AND AIMS: There were paucity of clinical evidence on target


serum phosphorus levelsin early CKD. Present longitudinal study finds target
phosphorus level and its association with FGF 23 in three different hyperphosphatemia
managements groups.

MO582 Figure 1: Bar diagram showing relation of different phosphorus levels with
progression of disease
METHOD: This one year, prospective, randomised controlled, open labelled study was
conducted among three equally allocated treatment groups in 120 screened early CKD
patients.Group1 Dietary phosphorus modificationn40; Group2 calcium-based
phosphate bindersn40 and Group3 non calcium-based phosphate bindersn40.Three
monthly dietary assessment, MDRD e-GFR, phosphorus, calcium, iPTH, Alkaline
phosphatise and six monthly FGF23, 2D Echocardiography, X ray of chest and
abdomen were performed. Association of three categories of phosphorus level up to 3.9
mg/dl, 4 to 5mg/dl and >5mg/dl, rate of progression of all parameters and correlation
with FGF 23among all three groups were studied.
RESULTS: At baseline, all clinical and biochemical parameters were equally
distributed with a controlled nutritional phosphate among all groups. There was no
significant difference of FGF23 in all the three categories of phosphorus level among all
groups. Association of serum phosphorus at the level of 5 mg/dl was there with iPTH
and e-GFR at one year. Over one year there were significant decline in serum
phosphorus levels in Group1 p 0.02, Group2 p 0.00,Group3p 0.05;FGF23 was declined
significantly only in group3p 0.00.Correlation of FGF23 was positive and negative with
iPTH r 0.19,p 0.03 and e-GFR r-0.30, p 0.00respectively but not with phosphorus p0.13

i346 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Serum phosphorus levels up to 5mg/dl has no effect on FGF 23 at
early CKD stages. Although different treatment groups have significant phosphorus
reduction, non-calcium phosphate binder has major impact on FGF23 reduction.

MO583 IN VITRO AND EX VIVO EXPERIMENTS OF VASCULAR


CALCIFICATION

Jana Holmar1, Heidi Noels1, Joachim Jankowski1,2, Setareh Orth-Alampour1


1
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University,
Aachen, Germany and 2School for Cardiovascular Diseases, Maastricht University,
Maastricht, The Netherlands

BACKGROUND AND AIMS: Vascular calcification (VC) is one major complication


in patients with chronic kidney disease whereas a misbalance in calcium and phosphate
metabolism plays a crucial role. The mechanisms underlying VC have not been entirely
revealed to date. Therefore are the studies aiming at the identification and
characterization of the mediators/uremic toxins involved in VC ongoing and highly
relevant. However, currently many different protocols being used in the studies of
vascular calcification processes. This complicates the comparison of study outcomes,
composing systematic reviews, and meta-analyses. Moreover, the reproducibility of
data is hampered, and the efficiency in calcification research through the lack of a
standardized protocol is reduced. In this study, we developed a standardized operating
protocol for in vitro and ex vivo approaches to aiming at the comparability of these
studies.
METHOD: We analysed in vitro and ex vivo experimental conditions to study VC.
Vascular smooth muscle cells (HAoSMCs) were used for in vitro experiments and
aortas from Wistar rats were used for ex vivo experiments.
The influence of the following conditions was studied in detail:

• Phosphate and calcium concentrations in calcifying media.


• Incubation time.
• Fetal calf serum (FCS) concentration.

The degree of calcification was estimated by quantification of calcium concentrations


that were normalized to protein content (in vitro) or to the dry weight of the aortic ring
(ex vivo). Additionally, the aortic rings were stained using the von Kossa method.
Optimal conditions for investigating medial vascular calcification were detected and
summarized in the step-by-step protocol.
RESULTS: We were able to demonstrate that the degree and the location of VC in
vascular smooth muscle cells and aortic rings were highly dependent on the phosphate
and CaCl2 concentration in the medium as well as the incubation time. Furthermore,
the VC was reduced upon increasing fetal calf serum concentration in the medium.
An optimized protocol for studying vascular calcification in vitro and ex vivo was
developed and validated. The final protocol (Figure 1) presented will help to
standardize in vitro and ex vivo approaches to investigate the processes of vascular
calcification.

MO583 Figure 1. A standardized calcification protocol to study medial calcification


in vitro (A) and ex vivo (B).
CONCLUSION: In the current study, we developed and validated a standardized
operating protocol for systematic in vitro and ex vivo analyses of medial calcification,
which is essential for the comparability of the results of future studies.

MO584 TRABECULAR BONE SCORE AND BONE


MICROARCHITECTURE IN HEMODIALYSIS PATIENTS. ITS
POTENTIAL RELATIONSHIP WITH PTH-RESISTANCE : A
PILOT STUDY

Luciano De paola1, Chiara Ciaccio2, Laura Saturno1, Maria antonietta Mascaro1,


Giovanni Ruotolo3, Marco Vatrano4, Paolo Puntieri5, Federica De paola6
1
Complex Operational Structure of Nephrology, Department of Medicine, CATANZARO,
Italy, 2Magna Graecia University (UMG ), Department of Internal medicine,
CATANZARO, Italy, 3Geriatric Section, Medicine Department, CATANZARO, Italy, 4cardi-
ology, Department of Medicine, CATANZARO, Italy, 5Complex Operational Structure of
Nuclear Medicine, Department of Medicine, CATANZARO, Italy and 6University of
Modena and Reggio Emilia(UNIMORE), Department of Medicine, modena, Italy

BACKGROUND AND AIMS: To explore:i)differences in predictive variables between


TrabecularBoneScore(TBS)-derived and LumbarT-score derived bone types.ii)the
relationship difference of TBS and LumbarT-score with various ranges of PTH levels in

10.1093/ndt/gfab086 | i347
Abstracts Nephrology Dialysis Transplantation

order to identify the levels of PTH that overcome PTH resistance iii) to conform metabolism. Results must not be extended to higher or lower levels of PTHi compared
normal upper limit of PTHi levels in hemodialysis patients recommended by K-DIGO to those considered in the study for which there is a clear evidence of increase in the
guidelines. relative risk of mortality.
METHOD: In twenty-five hemodialysis patients,following variables were
recorded:biochemical variables,DXA derived variables(including TBS),FRAX-tool
derived HRs.The relationship of variables with TBS-derived and LumbarTscore-
MO585 EFFECTS OF LANTHANUM CARBONATE AND CALCIUM
derived bone types was tested by univariate analysis. The association of
CARBONATE ON CARDIOVASCULAR CALCIFICATION IN
TBS,LumbarTscore and fracture HRs with PTHi was tested by univariate analysis and
HEMODIALYSIS PATIENTS: A SYSTEMATIC REVIEW AND
regression curve fitting(maximizing R2).
META-ANALYSIS
RESULTS: Using univariate analysis,the predictive variables of lumbarT-score derived
and TBS-derived bone types are different.By curve fitting regression TBS vs PTHi had a
Junlan Yang1, Xiao liang Zhang1, Lina Wang3
sinusoidal pattern with higher values,correlating to PTHi values in the 4th quartile(462 1
pg/ml (341 -696)corresponding to the normal levels recommended by K-DIGO Institute of Nephrology, Zhong Da Hospital,, Southeast University School of Medicine,
guidelines.In the same range of values,LumbarT-score vs PTHi for BMD-derived bone Nanjing, Jiangsu, P.R. China and 3Department of Epidemiology & Biostatistics, School of
type has a progressively increasing trend for osteopenia and osteoporosis,with a Public Health, Southeast University, Nanjing, Jiangsu, P.R. China
statistically significant difference(P0.008).
BACKGROUND AND AIMS: Commonly used phosphorus-lowering drugs include
calcium-containing phosphate-binding agents and non-calcium-containing
phosphate-binding agents, the latter mainly including lanthanum carbonate (LC). In
recent years, some studies have explored the effect of lanthanum carbonate compared
with calcium carbonate on serum calcium. However, the results are different.
Therefore, we conducted this review to systematically review and meta-analyze
evidence on the efficacy of lanthanum carbonate and calcium carbonate (CC) and the
risk of cardiovascular calcification in hemodialysis (HD) patients, and to provide
reference for phosphorus-lowering drugs in HD patients.
METHOD: The Cochrane library, PubMed, Web of Science, Chinese journal full-text
database (CNKI), WANGFANG DATA and Sino Med were searched between January
1946 and December 2020. The literatures with respect to the randomized controlled
clinical trial comparing lanthanum carbonate and calcium carbonate in HD patients
were selected. The two evaluators independently collected the data according to the
retrieval strategy, screened the literatures according to the inclusion criteria and
exclusion criteria, and summarized the literatures that met the criteria. The risk ratio
(RR) and 95% confidence interval (CI) were used to represent the counting data. The
standard deviation from mean (SMD) and 95%CI were used to represent the
continuous variables. Forest plots, sensitivity analysis, Egger regression test and TSA
were used to summarized the test performance characteristics.
RESULTS: Of 388 original titles screened, data was extracted from 9 studies included
625 participants (Table 1). There was moderate-certainty evidence from 9 trials (625
participants) that LC can significantly reduce the progression of coronary artery
calcification than CC (SMD= -0.59, 95%CI -0.94 to -0.25, P< 0.01) (Figure 2). The
serum phosphorus level in the LC group was significantly lower than that in the CC
group (SMD= -1.35, 95%CI: -2.33 to -0.36, P< 0.01), and the serum calcium level was
significantly reduced (SMD= -1.03, 95% CI: -1.83 to -0.23, P= 0.012). The fibroblast
growth factor 23 (FGF-23) level in the LC group was significantly lower than that in the
CC group (SMD= -4.80, 95%CI: -7.96 to -1.64, P= 0.003). The Egger regression test of
coronary artery calcification score (CACS) showed no potential publication bias
(P= 0.72).

MO585 Figure 2: Forest plots of main effects of LC and CC on CACS according to


duration of follow-up
CONCLUSION: In this systematic review, compared with calcium carbonate,
lanthanum carbonate can significantly delay the process of coronary artery
calcification, and at the same time reduce the patient’s serum phosphate, serum
MO584 Figure 2: calcium and FGF-23. Therefore, we recommend LC as phosphorus-lowering drugs for
Opposite relationship between TBS and lumber T score vs PTHi HD patients.
CONCLUSION: The predictive variables of TBs-derived and LumbarT-score derived
bone types are different.Bone microarchitecture(MA),measured by TBS,correlates
oppositely than LumbarT-score with higher PTHi values in the normal range of PTHi
levels recommended by the K-DIGO-CKD-MBD2009-2017 guidelines.Within this
range,PTHi values overcome PTH-resistance and improve the bone mineral

i348 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO585 Table 1. Characteristics of included studies.

Study (year) Sample size Mean age (LC/CC, years) Dialysis vintages (LC/CC) DN (LC/CC, %) Outcomes Follow-
(LC/CC) up
Ohtake, T. (2013) 26/26 67.8066.31 124.4647.5months 42.9 abcde 6 months
Wei, Y.(2014) 32/32 50.3569.42/50.1869.31 48.1166.31/47.9866.26months —— acde 3 months
Yu, M. (2015) 26/26 55.66615.34/59.53614.85 10.2168.53/15.33611.75 months 15/20 abcde 12 months
Zhang, C. (2015) 30/30 48.8767.48/49.9066.71 45.63616.63/42.20614.39 months 0/0 acdef 12 months
Peng, F. (2016) 35/21 57.2064.20/58.4063.40 25.8614.8/28.3611.9 months 26/28 abcdef 36 months
Li, H. (2017) 54/54 51.2865.76/50.2464.67 22.1564.75/23.1164.23 months —— abcdef 36 months
Zhang, C. (2017) 46/46 48.1768.91/51.0169.46 56.774617.542/60.732 100/100 acdef 12 months
615.762 months
Fujii, H. (2018) 53/55 65614/63613 —— 52/41.8 ab 18 months
Gao, Y. (2019) 16/17 56.8615.8 —— —— ab 24months

DN: diabetic nephropathy, (a) CACS, (b) cardiovascular events, (c)serum phosphate, (d) serum calcium, (e) iPTH, (f) FGF-23.

MO586 RISK OF OSTEOPOROSIS IN OBESE PATIENTS WITH TYPE 2 (corresponding chronic kidney diasease (CKD) stage 3T) was defined as 35-70 pg/ml,
DIABETES: A SYSTEMIC REVIEW AND META-ANALYSIS for eGFR corresponding CKD 4T – as 70-110 pg/ml, for CKD 5T – as 70-150 pg/ml.
RESULTS: In our cohort normal iPTH level was observed only in 13% cases, whereas
Yen-Chung Lin1 84% of the patients had hyperparathyroidism. iPTH inversely correlated with eGFR
1
Taipei Medical University Hospital, Taipei, Taiwan, R.O.C. (q= -0,454 [95%CI: -0,55; -0,34], h<0,0001 – fig.1) and its level differed significantly
between groups with different CKD stage (h<0,0001, Kruskall-Wallis test) – fig.2.
BACKGROUND AND AIMS: The aim of this study is to evaluate the alterations in However, fraction of patients with target iPTH did not differ in recipient groups with
bone marrow density and other surrogate markers for osteoporosis in obese patients normal and decreased eGFR (p=0,118). Hypercalcaemia was observed in 29% cases;
with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) there was a weak correlation of serum total Ca level with iPTH (q= 0,282 [95%CI: 0,15;
versus medical treatment as control. 0,4], h<0,0001) and AP (q=0,181 [95%CI: 0,05; 0,31], h=0,006) – fig.3.
METHOD: We searched four electronic databases and reference lists of relevant Hypophosphatemia was seen much more frequently during the first year after
studies for eligible research published before December, 2019. After quality assessment, transplantation than in long-term period (30,3% vs 6,4% respectively, h=0,0002).
eligible studies were synthesized for relevant outcomes, including lumbar spine bone Serum P level varied significantly in groups with different eGFR (p<0,0001, Kruskall-
mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C- Wallis test), increasing in parallel with declining of transplant function – fig.4. The
terminal telopeptide (CTX) level and parathyroid hormone (PTH) level. percentage of patients within a target range of AP amounted to 54%, above the target
RESULTS: Three randomized clinical trials and two observational studies concerning range – 40,7%. In total, only 6,8% of our cohort had all laboratory parameters within
307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. the target range.
Patients underwent RYGB surgery were associated with both higher L-spine BMD loss
(mean difference: -2.90, 95% CI: -2.99-2.81, p<0.00001 )and total hip BMD loss
(mean difference: -5.81, 95% CI: -9.22-2.40, p=0.0008). As to biochemical markers of
bone metabolism, we found signifcantly higher osteocalcin level in medical treatment
(control) group compared with RYGB group (mean difference: 11.16, 95% CI:
8.5713.75, p<0.00001). However, higher CTX level and PTH level were noted in
medical treatment group (control) compared with RYGB group (mean difference: 0.29,
95% CI: 0.110.48, p=0.002; mean difference: 1.56, 95% CI: 0.842.27, p<0.0001).
CONCLUSION: RYGB surgery is associated with negative impact on bone metabolism
and increase the risk of osteoporosis in obese patients with T2DM. We suggest that
clinicians acknowledge the adverse effects of surgery and keep monitoring bone
mineral components in post-RYGB populations. Further studies regarding the optimal
amount of peri-operative and post-surgical supplementation should be evaluated.

MO587 PREVALENCE OF MINERAL AND BONE DISORDERS


MAKERS AMONG RECIPIENTS OF KIDNEY TRANSPLANT:
SINGLE-CENTER EXPERIENCE

Andrey Vatazin1, Ekaterina Parshina2, Rusudana Kantaria1, Vadim Stepanov1,


Aleksei Zulkarnaev1
1 MO587 Figure 1: Correlation between PTH level and eGFR of transplant recipients.
Moscow Regional Research and Clinical Institute, Surgical department of transplanta-
tion and dialysis, Moscow, Russia and 2Saint Petersburg State University Hospital,
Department of outpatient dialysis, Saint-Petersburg, Russia

BACKGROUND AND AIMS: Mineral and bone disorders (MBD) are common after
successful kidney transplantation in patients with chronic kidney disease (CKD). We
aimed to evaluate the prevalence of biochemical abnormalities among recipients of
kidney transplant.
METHOD: We performed a cross-sectional study of 236 patients underwent successful
kidney transplantation in our clinic between 2007 and 2019. Median age was 49 [Q1-
Q3: 39; 58] years, mean estimated glomerular filtration rate (eGFR) was 51,1621,8 ml/
min/1,73 m2. Most of the patients received hemo- or peritoneal dialysis treatment, pre-
emptive transplantation was performed in 6% cases. For those previously received
dialysis, median duration of any type of dialysis was 21 [Q1-Q3: 11; 36] months.
Median time after transplantation reached 42 [Q1-Q3: 19; 75] months. We evaluated
serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P) and
alkaline phosphatase (AP) levels. Target ranges were defined according to National
guidelines on CKD-MBD as follows: 2,1 - 2,5 mmol/l for total Ca, 0,87 – 1,49 mmol/l
for P; normal AP level is defined considering a gender (53-128 ð/l for men, 42-98 ð/l
for women). Target iPTH level for optimal and slightly decreased transplant function

10.1093/ndt/gfab086 | i349
Abstracts Nephrology Dialysis Transplantation

MO587 Figure 2:
PTH level in groups of transplant recipients with different CKD stage (h<0,0001,
Kruskall-Wallis test). Horizontal lines show significant differences between two groups
(h<0,0001 for all comparisons).

MO587 Figure 4:
Serum P level in groups of transplant recipients with different CKD stage (h<0,0001,
Kruskall-Wallis test). Corrected p-values (q) are shown for significant differences
between two groups.
CONCLUSION: We observed a high prevalence of biochemical abnormalities in
kidney transplant patients confirming that transplantation itself does not cure mineral
and bone disorders in CKD patients.
MO587 Figure 3: Correlation between serum total calcium of transplant recipients
with PTH level (left side) and alkaline phosphatase level (right side).

i350 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i351–i360, 2021
10.1093/ndt/gfab089

CKD. NUTRITION, INFLAMMATION AND OXIDATIVE undetermined. Here we aimed to investigate the clinical utility of TMAO and its
dietary determinants for graft failure prediction in renal transplant recipients (RTRs).
STRESS METHOD: We included 448 RTRs who participated in the TransplantLines Cohort
Study. Cox proportional-hazards regression analyses were performed to study the
association of plasma TMAO with graft failure. Net Benefit, a decision analysis
method, was performed to evaluate the clinical utility of TMAO and dietary
MO588 DECREASED IL-15 PRODUCTION INDUCED BY information in the prediction of graft failure.
HYPERPHOSPHATEMIA AS A POSSIBLE MECHANISM OF RESULTS: Among RTRs (age 52.7 6 13.1 years; 53% males), baseline median TMAO
AGED-RELATED SARCOPENIA* was 5.6 (3.0–10.2) mmol/L. In multivariable regression analysis, the most important
dietary determinants of TMAO were egg intake (Std. b = 0.10 [95%CI, 0.01;0.19];
Elena Alcalde-Estévez1, Ana Asenjo-Bueno2, Gemma Olmos1,3, Diego Rodrıguez- P=0.03), fiber intake (Std. b = -0.13 [95%CI, -0.22, -0.05]; P =0.002), and fish and
Puyol3,4,5, Susana Lo pez-Ongil2,3, Maria Piedad Ruiz-Torres1,3 seafood intake (Std. b = 0.11 [95%CI, 0.02,0.20]; P=0.01). After a median follow-up of
1
Universidad de Alcal a: Facultad de Medicina y Ciencias de la Salud, Biologıa de 5.3 (4.5–6.0) years, graft failure was observed in 58 subjects. TMAO was associated
Sistemas, Alcala de Henares, Spain, 2Hospital Universitario Prıncipe de Asturias, with increased risk of graft failure, independent of age, sex, BMI, blood pressure, lipids,
Fundacion para la Investigaci on Biomédica, Meco, Spain, 3Instituto Reina Sofıa de albuminuria and eGFR (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95%
Investigacion Nefrol
ogica (IRSIN) y Red Renal (REDinREN) del ISCIII, Madrid, Spain, confidence interval (CI): 1.22; 2.14, P<0.001). A TMAO and dietary enhanced
4
Universidad de Alcal a: Facultad de Medicina y Ciencias de la Salud, Medicina y prediction model offered approximately double Net Benefit compared to a previously
Especialidades Médicas, Alcala de Henares, Spain and 5Hospital Universitario Prıncipe reported, validated prediction model for future graft failure, allowing the detection of
de Asturias, Servicio de Nefrologıa, Meco, Spain 21 RTRs per 100 RTRs tested with no false positives versus 10 RTRs respectively.
CONCLUSION: A predictive model for graft failure, enriched with TMAO and its
dietary determinants yielded a higher Net Benefit compared with an already validated
BACKGROUND AND AIMS: The loss of muscle mass and function, termed
model. This study suggests that TMAO and its dietary determinants are associated
sarcopenia, is an aging-related condition associated to some important diseases such as
with an increased risk of graft failure and that it is clinically meaningful.
chronic kidney disease (CKD). Hyperphosphatemia has been related to both
pathologies. A chronic subclinical inflammation and a dysregulated immune system
function are associated to aging affecting to multiple pathways in the skeletal muscle,
and this fact has been linked to the development of sarcopenia. Interleukin-15 (IL-15)
is a skeletal muscle-derived cytokine which promotes muscle regeneration. The aim of
this work was to analyze the role of hyperphosphatemia on the IL-15 production of the
skeletal muscle and its implication in aging-related sarcopenia.
METHOD: Cultured C2C12 myoblasts were used for in vitro experiments. Cells were
treated with 10 mM beta-glycerophosphate (BGP) as a phosphate donor for 2, 4, 6, 8
and 24 hours. IL-15 mRNA levels were assessed by RT-qPCR. Three groups of C57BL6
male mice were used for the in vivo studies: 5-months-old mice (young), 24-month-old
mice fed with a standard diet containing 0.6 % of phosphate (old) and 24-month-old
mice fed with a hypophosphatemic diet, containing a 0.2% of phosphate (oldþlowPi),
for the last three months before sacrifice. Muscle force was measured by a grip test.
Serum phosphate levels were analyzed with a commercial kit. Quadriceps muscle
samples were collected to evaluate in them the IL-15 mRNA expression by RT-qPCR.
RESULTS: C2C12 cells treated with BGP show a significant decrease in the IL-15 mRNA
expression. On the other hand, in vivo studies showed that old mice had an increase in
serum phosphate concentration and a reduction in forelimb strength and muscle mass,
compared to young mice. Old animals fed with the hypophosphatemic diet displayed lower
levels of phosphate serum linked to an improvement in the muscle mass and function. IL-15
expression of quadriceps muscle was reduced in old mice compared to young mice, whereas
those values were increased in old mice fed with the low phosphate diet. Furthermore, there
was a negative correlation between IL-15 expression levels and serum phosphate
concentrations and a positive correlation between IL-15 and forelimb strength and muscle
mass, suggesting that a decreased IL-15 expression affects muscle function.
CONCLUSION: High extracellular phosphate concentrations decrease IL-15 mRNA
expression in myoblasts, and it is correlated with low IL-15 mRNA expression in the
quadriceps muscle isolated from old mice. This reduction was associated to a decreased
muscular strength and muscle mass, whereas the dietary restriction of phosphate
improved these features. These results point to a role of hyperphosphatemia in the
impaired immune system function, disrupting the skeletal muscle function, and this
could be involved in aging and CKD-related sarcopenia.
MO590 GUT HEALTH INTERVENTIONS IN CHRONIC KIDNEY
DISEASE: ACCEPTABILITY AND FEASIBILITY OF OF
SYNBIOTIC SUPPLEMENTATION

Catherine McFarlane1,2, Rathika Krishnasamy1,3, Tony Stanton1, Emma Savill1,


MO589 PLASMA CONCENTRATIONS OF TRIMETHYLAMINE N- Jaimon T Kelly4, Matthew Snelson5, Gabor Mihala4,6, Mark Morrison7, David
OXIDE, AND ITS DIETARY DETERMINANTS ARE W Johnson3,8, Katrina L Campbell2,3,4
1
ASSOCIATED WITH INCREASED RISK OF GRAFT FAILURE Sunshine Coast University Hospital, Birtinya, Australia, 2The University of Queensland,
School of Medicine, Saint Lucia, Australia, 3Australasian Kidney Trials Network (AKTN),
Jose L Flores-Guerrero1, Maryse C.J. Osté1, Paula B. Baraldi1, Margery Woolloongabba, Australia, 4Menzies Health Institute Queensland, Southport, Australia,
5
A. Connelly2, Erwin Garcia2, Gerjan Navis1, Stephan Bakker1, Robin P.F. Dullaart3 Monash University, Department of Diabetes, Clayton, Australia, 6Griffith University,
1
University Medical Center Groningen, Internal Medicine, Groningen, The Netherlands, Nathan Campus, Centre for Applied Health Economics, Nathan, Australia, 7Diamantina
2
Laboratory Corporation of America Holdings (LabCorp), Morrisville, North Carolina, institute, Woolloongabba, Australia and 8Princess Alexandra Hospital, Department of
United States of America and 3University Medical Center Groningen, Endocrinology, Nephrology, Woolloongabba, Australia
Groningen, The Netherlands
BACKGROUND AND AIMS: Synbiotics, co-administered prebiotics and probiotics,
BACKGROUND AND AIMS: Due to the critical shortage of kidneys for have emerged over the last decade as an innocuous intervention targeting the microbial
transplantation, the identification of modifiable factors related to graft failure is highly generation of the uraemic toxins, indoxyl sulphate (IS) and p-cresyl sulphate (PCS).
desirable. The role of trimethylamine-N-oxide (TMAO) in graft failure remains However, most trials to date are of short duration (2-24 weeks). In order to inform
translation into clinical practice, it is imperative to consider the efficacy of synbiotic

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

supplementation as a long-term intervention. The aims of this study were to evaluate in age (77.5 vs. 68, p=0.068), comparing with patients without sarcopenia. The group of
the feasibility and acceptability (including symptoms and adherence) of long-term the sarcopenic patients had lower BMI (24.4 vs. 28.4 Kg/m2, p=0.008) and height (65.9
synbiotic supplementation in adults with chronic kidney disease (CKD), as well as vs. 77.6, p=0.01), although BMI > 30 Kg/m2 (1 vs. 9, p=0.052) and visceral obesity (7
explore the perspectives of these patients on nutrition supplementation for gut health, vs. 19, p=0.084) were not significantly different between the two groups. Moreover, we
including strategies to optimise adherence in practice. observed that patients with sarcopenia tended to have lower albumin levels (2.9 vs. 3.7,
METHOD: SYNERGY II was a double-blind randomised controlled trial in adults p=0.034) and higher LDL levels (135 vs. 67.5, p=0.04). Regarding mortality, 18 patients
(>18years) with stage 3-4 CKD over 12 months. The intervention comprised of daily (41,9%) died during follow-up and the frequency of sarcopenia was significantly higher
prebiotic powder (2 x 10g/day resistant starch) and probiotic supplementation (single among non-survivors (68.8% vs. 25.9%, p=0.006). In the univariate logistic regression,
sachet of 6g/day multi strain 4.5x1011CFU) or placebo control (waxy maize powder for every decrease of one unit in the SMI, mortality increased by 10% (p=0.012).
and a sachet of maltodextrin). Adherence to nutrition supplementation was defined as CONCLUSION: Sarcopenia is common in patients with non-dialysis dependent CKD,
participants consuming >80% of the prescribed sachets/powder. Symptoms were particularly in advanced stages, and is strongly associated with mortality in this
monitored via Gastrointestinal Symptom Rating Scale (GSRS) and Bristol Stool Score population. Our study highlights the importance of early diagnosis and
(BSS). Semi-structured interviews were conducted in person or by telephone with a implementation of therapeutic strategies to minimize the adverse outcomes in CKD
sample of 30 participants at the completion of the intervention. The interviews patients.
explored experiences and perspectives regarding frequencies, timing and difficulties
experienced with each aspect of the intervention and overall perceptions of the
intervention as a strategy to improve gut health.
MO592 INTERLEUKIN-1A (IL-1A) IS A CENTRAL REGULATOR OF
RESULTS: Sixty-eight participants [66% male, median age 70 (IQR 58-75) years] were
INFLAMMATION IN CARDIOVASCULAR AND KIDNEY
consented and randomised to either intervention or control groups, with a mean
DISEASES
estimated glomerular filtration rate of 34 6 11 mL/min/1.73m2. A total of 56
participants (82%) completed the 12-month intervention with no differences in
Stefan Schunk1, Triem Sarah1, Rafael Kramann2, Peter Boor2,
withdrawals between groups (p=0.6). One participant from each group withdrew at
Emmanuel Ampofo1, Danilo Fliser1, Thimoteus Speer1
week 2, citing palatability of the study product as the reason for withdrawal. Overall 1
adherence to study supplementation was excellent in both intervention and placebo Saarland University, Saarbrücken, Germany and 2RWTH Aachen University, Aachen,
groups [median intake 92.1% (85.9-95.2%) placebo versus 89.5% (84.4-94.5%) Germany
synbiotic; P=0.4)]. Overall, there was no significant change from baseline to end of
study visit for mean BSS (3.6 6 1.4 to 3.6 6 1.4 placebo versus 3.6 6 1.1 to 4.1 6 1.2 BACKGROUND AND AIMS: Cardiovascular diseases (CVD) and chronic kidney
synbiotic, P=0.13), mean bowel movements (1.3 6 0.6 to 1.6 6 0.9 placebo versus 1.3 disease (CKD) are highly prevalent, aggravate each other, and account for substantial
6 0.6 to 1.8 6 1.0 synbiotic, P=0.70) or GSRS [1.3 (1.1 - 1.9) to 1.3 (1.1 - 1.5) placebo mortality. Both conditions are characterized by activation of the innate immune
versus 1.1 (1.1 - 1.5) to 1.3 (1.1 - 1.5) synbiotic, P=0.83]. Acceptability components system. The alarmin IL-1a is expressed in a variety of cell types promoting (sterile)
described by participants were appreciating convenience and improving health and systemic inflammation. The aim of the present study is to examine the role of IL-1a in
well-being. Participants discussed the following feasibility components: integrating mediating inflammation in the setting of cardiorenal diseases.
easily into lifestyle and social accountability. Tablets or capsules were the preferred METHOD: We assessed the expression of IL-1a on the surface of monocytes from
supplement formulation with a probiotic drink made from a SCOBY (synbiotic culture patients with acute myocardial infarction (AMI) and patients with CKD and
of bacteria and yeast) the least preferred. determined its association with atherosclerotic CVD events during follow-up in an
CONCLUSION: Among adults with stage 3-4 CKD, synbiotic supplementation is a explorative clinical study. Furthermore, we assessed the inflammatory effects of IL-1a
well-tolerated and acceptable form of nutrition supplementation. People with CKD in several organ injury models in Il1a-/- and Il1b-/- mice and investigated the
would prefer nutrition supplements to be formulated as a tablet or capsule, which is an underlying mechanisms in vitro in monocytes and endothelial cells.
important consideration when translating into clinical practice. RESULTS: IL-1a is strongly expressed on the surface of monocytes from patients with
AMI and CKD compared to healthy controls. Higher IL-1a surface expression on
monocytes from patients with AMI was associated with a higher risk for atherosclerotic
CVD events, which underlines the clinical relevance of IL-1a. In mice, IL-1a, but not
MO591 THE EVALUATION OF SARCOPENIA IN NON-DIALYSIS
IL-1b, mediates leukocyte-endothelial adhesion as determined by intravital
CHRONIC KIDNEY DISEASE STAGES BY COMPUTED
microscopy. IL-1a promotes accumulation of macrophages and neutrophils in
TOMOGRAPHY
inflamed tissue in-vivo. Furthermore, IL-1a on monocytes stimulates their homing at
sites of vascular injury. A variety of stimuli such as free fatty acids or oxalate crystals
Beatriz Donato1, Adriana Paixa ~o Fernandes1, M ario Raimundo2, Luis Falcao2,
nia Velho3, Ana Primitivo4, Sara Fernandes2, Catarina Teixeira2, Ana induce IL-1a surface expression and release by monocytes, which then mediates their
So
~o Costa2, So nia Silva2, Edgar Almeida2 adhesion to the endothelium via IL-1 receptor-1. Besides, IL-1a promotes expression of
Cortesa
1
the vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells thereby fostering
Hospital Beatriz Ângelo, Nephrology, Loures, Portugal, 3Hospital Beatriz Ângelo, the adhesion of circulating leukocytes. IL-1a induces inflammatory injury after
Nutrition, Loures, Portugal and 4Hospital Beatriz Ângelo, Radiology, Loures, Portugal experimental AMI and abrogation of IL-1a prevents the development of CKD in
oxalate or adenine-fed mice.
BACKGROUND AND AIMS: Sarcopenia is common in chronic kidney disease CONCLUSION: IL-1a represents a key mediator of leukocyte-endothelial adhesion
(CKD) and it has been reported a correlation between the increased prevalence of and inflammation in cardiorenal diseases. Inhibition of IL-1a may serve as a novel
sarcopenia and worsening kidney function. Computed tomography (CT) is the gold anti-inflammatory treatment strategy.
standard for studying sarcopenia because of its capacity to identify quantitative and
qualitative changes in muscle mass. Our major aim was to evaluate the prevalence of
sarcopenia ant its association with renal function, in non-dialysis CKD patients, using
MO593 CONTROLLING DIETARY PHOSPHORUS IN CHRONIC
a diagnostic criterion that has not been applied before in this population.
KIDNEY DISEASE STAGES 1 AND 2 DECREASES
METHOD: We conducted a longitudinal retrospective analysis on a cohort of non-
PROTEINURIA AND PREVENTS DECLINE IN RENAL
dialysis CKD patients who visited an outpatient Nephrology clinic between January
FUNCTION
2012 and December 2012 and continued follow-up until December 2018. We selected
those who underwent a CT scan as part of their clinical workup and simultaneously
Anita Saxena1, Amit Gupta2, Trisha Sachan1, Vishwas Kapoor4, Anup Kumar5,
had a serum creatinine determination within 90 days of the scan. CT images were
Sachin Sharma6
obtained and evaluated for body composition analysis by one investigator blinded to 1
clinical data. Images were selected by radiologists at the third lumbar vertebra (L3). Sanjay Gandhi Post Graduate Institute Of Medical Sciences, Nephrrology, LUCKNOW,
Segmentation of tissue cross-sectional areas was conducted according to the following India, 2Apollo Medics, Nephrrology, Lucknow, India, 4Sanjay Gandhi Post Graduate
Hounsfield unit thresholds: -29 to 150 for skeletal muscle, -190 to -30 for subcutaneous Institute Of Medical Sciences, Bioinformatics and Biostatistics, LUCJNOW, India, 5Sanjay
and intramuscular adipose tissue and -50 to -150 for visceral adipose tissue. Skeletal Gandhi Post Graduate Institute Of Medical Sciences, Bioinformatics and Biostatistics,
muscle area (SMA) was normalized for stature to calculate the skeletal muscle index Lucknow, India and 6Sanjay Gandhi Post Graduate Institute Of Medical Sciences,
(SMI). Sarcopenia was defined as SMI lower than 41 cm2/m2 in women and 43 cm2/m2 Bioinformatics and Biostatistics, LUCKNOW, India
in men with body mass index (BMI) < 25 kg/m2 and < 53 in men with BMI > 25 kg/
m2, as described by Martin et al, based on the International Consensus of Sarcopenia. BACKGROUND AND AIMS: High phosphorus intake is known to cause renal and
Visceral obesity was defined as visceral fat area > 130 cm2. Diagnosis and classification vascular calcification and renal tubular injury and albuminuria. Dietary phosphorus
of CKD were based on the Kidney Disease Improving Global Outcomes criteria and the restriction is therapeutic for controlling disordered phosphorus homeostasis and for
glomerular filtration rate was estimated from the serum creatinine levels using the improving cardiovascular outcomes in CKD. However, early restriction of dietary
CKD Epidemiology Collaboration equation. phosphorus is not advocated Aim: To evaluate if early control of dietary phosphorus
RESULTS: Out of the 521 non-dialysis CKD patients referred to the nephrology clinic, ameliorates proteinuria, prevents decline in glomerular filtration rate and prevents
43 patients met the inclusion criteria. Mean age was 71.0 6 14.6 years, 55.8% were increase in FGF-23
male and 97.7% were caucasian. The mean follow-up time was 4.3 6 2.3 years. Most METHOD: One year longitudinal study on 79 CKD patients in stages 1 and 2. eGFR,
patients had CKD stages 3 to 5 (67.4%) and the mean GFR was 45.4 6 32.6 ml/min/ serum creatinine , phosphorus, calcium, FGF-23, soluble a-Klotho iPTH FGF 23, blood
1.73m2. In our entire cohort, 16 patients were sarcopenic (37.3%; median age: 77.5 pressure, were evaluated and compared with 35 controls. 3 days dietary intake was
years; 9 female and 7 male) and a high prevalence of sarcopenia was observed in stages taken using standard methodology on first visit, 6 and 12 months. CKD patients were
3 and 4 of CKD (54,5% and 50%, respectively). There was a non-significant difference grouped based on dietary phosphorus intake: Group 1 (n 42): normal phosphorous

i352 | Abstracts
Nephrology Dialysis Transplantation Abstracts
intake (<1000mg/day) and Group 2 (n=37; 17 in CKD 1; 20 CKD 2): high
phosphorous intake (>1000mg/d). Patients in Group 2 were educated on high and low
phosphorus foods and counselled to avoid fresh and frozen and processed meat, eggs,
nuts and seeds, chocolates, packaged food, phosphorus-containing food additives and
counselled to adopt a plant-based diet, for low phosphorus availability/absorption diet
with directed diet plan. Lentils and pulses, milk and milk products (hard cheese, ice-
creams, custards, cottage cheese, pudding, yoghurt), bran and whole wheat cereals were
restricted up to 1-2 servings a day Data were analysed using SPSS.
RESULTS: At baseline there was no significant difference in the GFR (group1
85.00618.64 ml/min vs group 2 82.53616.30ml/min), serum creatinine between
groups. In group2 ; GFR, sKlotho, serum phosphorus and FGF-23 correlated
significantly with dietary phosphorus intake. In group 2, FGF-23, Serum phosphorus,
dietary protein and phosphorus intake were significantly higher and sKlotho was
significantly lower than group 1. There was significant difference in serum phosphorus
(p 0.000), iPTH, (p 0.004), FGF23 (p0.000), Klotho (p0.000), urinary protein (p0.000),
dietary protein (Group 1 37.5763.40; Group 248.7965.86 p 0.000) and phosphorus
(Group 1868.96669.99 mg/d and Group 2 1312.266137.57 mg/d p 0.000) intake and
dietary phosphorous to protein ratio (p 0.000) between groups 1 and 2.. After dietary
intervention in group 2 GFR increased from 80.93615.34 to 84.11615.38 in six
months and to 87.43618.27 ml/min at 12 months p 0.012, and urinary protein
declined to 22.0163.39 mg/mL. FGF 23 declined from 60.6766.26 to 58.0067.07 to
53.2969.48 pg/mL at 12 months. Urinary phosphorus excretion increased from
574.376214.22 to 624.646137.67 at 12 months. Dietary phosphorus protein to ratio
reduced from 27.1664.35 to24.7564.34 p 0.000 at 12 months MO594 Figure 1: Flow-chart of the study.
CONCLUSION: CKD patients should be cautioned and counselled on their first visit
on the impact of dietary phosphorus intake on the progression of CKD and Abbreviations: FORD, Free Oxygen Radical Defence; FOR7; Free Oxygen Radicals Test;
development of CVD. IPAQ, International Physical Activity Questionnaire; PREDJMED, Prevention con
dieta Mediterranea; SF-36, Short-Form 36items health survey.
The study was inserted in the projects: "MioMenu: nuova filiera dell’agro-industria e
MO594 POTENTIAL BENEFICIAL EFFECT OF EXTRA VIRGIN OLIVE una cucina tracciata natura/benessereLazio Region" and "BioSynOLOil and Legumes:
OIL WITH HIGH MINOR POLAR COMPOUNDS CONTENTS IN biodynamic and synergistic crops for naturally fortified foods and innovative products
NEPHROPATHIC PATIENTS: PRELIMINARY DATA for health and sport - G.O. Tuscany Region".

Annalisa Noce1, Francesca Di Daniele1,2, Giulia Marrone1,2, Anna Pietroboni


Zaitseva1, Silvia Urciuoli3, Manuela Di Lauro1,4, Nicola Di Daniele1, RESULTS: Preliminary data highlight a reduction of the inflammatory state,
Annalisa Romani4,4 monitored by CRP (p=0.0299), ESR (p=0.0063), TNF-a (p=0.0001), IL-6 (p=0.0219),
1 an improvement of renal function (azotemia, p=0.0256) and of lipid profile
University of Rome Tor Vergata, UOC of Internal Medicine-Center of Hypertension and (triglycerides, p=0.0476) after 9 weeks of EVOO assumption (Fig 2). Moreover, we
Nephrology Unit, Department of Systems Medicine, Rome, Italy, 2University of Rome Tor observed a significant improvement of the C-ITM (p=0.0146) and a significant
Vergata, PhD School of Applied Medical, Surgical Sciences, Rome, Italy, 3University of reduction of oxidative stress monitored by FORT (p=0.0144). The results of the
Florence, PHYTOLAB (Pharmaceutical, Cosmetic, Food Supplement, Technology and PREDIMED and IPAQ questionnaires showed no significant differences. This data
Analysis), DiSIA, Sesto Fiorentino, Florence, Italy and 4University of Florence, QuMAP indicates that patients have not changed their lifestyle and the results obtained are
Laboratory, PIN Polo Universitario Citt a di Prato, Prato, Italy attributable to EVOO assumption. At the end of the study, there was an improvement
of quality of life, in the domains of emotional well-being (p=0.0340) and general health
BACKGROUND AND AIMS: Chronic degenerative non-communicable diseases (p=0.0405) of SF-36 questionnaire (Fig 3).
represent one of the main causes of death in the world. Among these, chronic kidney
disease (CKD) has an estimated prevalence of 7-12% worldwide. CKD is related to
numerous comorbidities, especially these cardiovascular. Furthermore, its progression
is characterized by a low-grade inflammatory status and oxidative stress, factors that
negatively influence quality of life. In recent years, numerous in vitro and in vivo
studies have analysed the beneficial effects of natural bioactive compounds on health.
Extra virgin olive oil (EVOO) is rich in minor polar compounds (MPCs), capable of
exerting a cardioprotective, anti-inflammatory and antioxidant action. The 98-99% of
EVOO total weight is made up by fatty acids, in particular, monounsaturated ones such
as oleic acid, and a small percentage 1-2% by MPCs. Among MPCs, hydroxytyrosol,
tyrosol, oleacin and oleocanthal are of particular importance for their heathy effects. In
our study, we analysed the potential healthy effects of EVOO MPCs in CKD patients.
METHOD: The EVOO selected for the study (Ophenoil), was previously characterized
for its high content of MPCs through quantitative and qualitative analysis performed
using HPLC-DAD-MS and Oxitester. We enrolled 20 CKD patients undergoing
conservative therapy (stages I-IV according to K-DIGO guidelines). All enrolled
patients have been instructed to assume 40 ml per day of EVOO, for 9 weeks.
Laboratory parameters have been collected at two different time-points of the study (at
baseline T0 and after 9 weeks T1) (Fig 1). At T0 the patients have been undergo to a
detailed medical history. All CKD patients have been unstructured to follow a
conventional Mediterranean diet (which adherence is assessed by PREDIMED
questionnaire), containing a controlled protein intake according to CKD stage, in
which the EVOO Ophenoil represent the main source of plant-based fats. In both
time-points of the study, all patients have been undergoing to blood sampling to MO594 Figure 2: Preliminary result of the study.
evaluate renal function, lipid profile, inflammatory parameters (C-reactive protein-
CRP, erythrocyte sedimentation rate-ESR, Interleukin(IL)-6, Tumor necrosis
factor(TNF)-a) and oxidative stress (Free Oxygen Radicals Test-FORT and Free
Oxygen Radical Defence-FORD by CR4000). Moreover, we evaluated the
cardiovascular risk indices (Carotid intima-Media Thickness (C-ITM) monitored by Abbreviations: C-ITM, Carotid lntima-Media Thickness. CRP, C-reactive protein; e-
eco(color)Doppler ultrasound). Each patient has been interviewed with Quality of Life GFR, estimated glomerular filtration rate; ESR, erythrocyte sedimentation rote; FORD,
Assessment Questionnaire (Short-Form 36 items health Survey- SF-36) and Free Oxygen Radical Defence; FORT, Free Oxygen Radicals Test; HDL-C, high-
International Physical Activity Questionnaire (IPAQ). density lipoprotein- cholesterol; IL-6,interleukin-6; LDL-C, Low-density lipoprotein-
cholesterol; TNF-a, Tumor necrosis factor-a.

10.1093/ndt/gfab089 | i353
Abstracts Nephrology Dialysis Transplantation

aging and CKD, it has been described a decline lung function, however, relationship
between high serum levels of phosphate and lung damage has not been described yet.
The aim of this work was to evaluate if phosphate could induce inflammation in lung,
studying the mechanisms implied.
METHOD: In vitro studies were performed on a cell line from human lung fibroblasts
(Wi-38) which were treated with a phosphate donor termed b-glycerophosphate (BGP,
10 mM) and also with endothelin 1 (ET-1, 10 nM) at different times. To assess
inflammation, the expression of several cytokines such as TNF-a,IL-1b, IL-6 and MCP-
1 were measured by real time PCR. mRNA expressions of prepro-ET-1 and
endothelin-converting enzyme-1 (ECE-1) were also analyzed by real time PCR.
Reactive oxygen species (ROS) production was evaluated by confocal microscopy in
live cells using the fluorogenic probe CellROX as oxidative stress reagent.
RESULTS: Treatment with BGP induced a significant rise of the pro-inflammatory
cytokines expression, TNF-a, IL-1b, IL-6 and MCP-1, on lung fibroblasts. Moreover,
MO594 Figure 3: Results of Sf.36 questionnaire. BGP was able to regulate ET-1 system, as we found a significant increase of mRNA
expressions not only of prepro-ET-1 but also of ECE-1, reaching a peak around 2 and 6
hours, respectively. Later, it was checked whether ET-1 could induce inflammation
CONCLUSION: The consumption of EVOO with high MPCs content would seem to itself in lung fibroblasts. Cells incubated with ET-1 show similar results as BGP,
exert an anti-inflammatory (due to high content of oleocanthal) and antioxidant (due increasing expressions of all cytokines, TNF-a, IL-1b, IL-6 and MCP-1.ET-1 response
to high content of hydroxytyrosol, oleacin and oleuropein aglicone) action in CKD was earlier than BGP, around at 2 hours with ET-1 instead of at 8 hours with BGP. In
patients. Therefore, once again it is highlighted how the diet therapy plays a pivotal order to elucidate a possible mechanism, ROS production was assessed after BGP
role in the clinical management of CKD patients and that it allows an improvement of treatment. BGP induced ROS production at 15 min in lung fibroblasts.
their quality of life. CONCLUSION: BGP induces the synthesis of pro-inflammatory cytokines as well as
the system of synthesis of ET-1, besides to rise ROS production.ET-1 itself also
increases pro-inflammatory cytokines expression. ET-1 could contribute to the
MO595 FREQUENCY OF INTAKE OF DIETARY FIBER SOURCES NOT inflammation observed in lung fibroblast after BGP treatment. We propose oxidative
ASSOCIATED WITH HYPERKALEMIA IN HEMODIALYS stress as a potential mechanism implied, as it is well known that ROS can mediate in
PATIENTS IN A MULTICENTER STUDY inflammation and in the ET system. However, more studies are necessary to confirm
this role. All in all, these results relate hyperphosphatemia with a higher inflammation
Rafaela G. Dos Santos1, Juliana Malinovski2, Nat alia Scatone1, Jorgiane De in lung fibroblasts which could decline lung function in chronic diseases associated to
Oliveira2, Andrea Sczip1, Jyana Moraes2, Marcos Vieira2, FABIANA NERBASS2 aging as CKD.
1
Centro de Tratamento de Doenças Renais, Brazil and 2Fundaç~
ao Pr
o-Rim, Brazil

BACKGROUND AND AIMS: Patients undergoing hemodialysis (HD) treatment MO597 ESTIMATING INDIVIDUAL-LEVEL SODIUM INTAKE WITH
usually have a low intake of food groups rich in dietary fiber to avoid hyperkalemia. REPEATED SPOT URINE SAMPLING
However, dietary potassium is not associated with serum potassium or hyperkalemia in
recent studies, and higher intake of fiber food groups such as fruits and vegetables is Gina Ginos1, Liffert Vogt1, Petra Frings-Meuthen2, Martina Heer3, Rik Olde
associated with lower mortality and other complications in HD populations. This Engberink1
multicenter cross-sectional study aimed to investigate the frequency of intake of dietary 1
Amsterdam UMC, University of Amsterdam, Department of Nephrology, Amsterdam
fiber sources, its determinants, and the relationship with hyperkalemia in HD patients. Cardiovascular Sciences, Amsterdam, The Netherlands, 2Institute of Aerospace
METHOD: Prevalent HD patients from four dialysis clinics in Southern Brazil were Medicine, German Aerospace Center (DLR), Köln, Germany and 3Institute of Nutritional
invited to participate (at least 80% of eligible patients from each clinic). Patients were and Food Sciences, University of Bonn, Bonn, Germany
interviewed by the researchers and answered a food frequency questionnaire (FFQ)
with the main dietary fiber sources (fruits, vegetables, legumes, whole grains cereals BACKGROUND AND AIMS: In daily clinical practice, individual-level sodium (Na)
and seeds) with seven frequency possibilities (from never to more than twice a day). To intake is often estimated by measuring Na excretion in a single 24h urine collection,
estimate the weekly frequency of intake, answers were transformed into a score. Every but long-term Na balance studies indicate that 7 consecutive 24h urine collections are
score point corresponded to one time per week (ex.: score 7 = seven times per week). needed. However, this approach is not feasible in clinical settings. In this study, we
The sum of the five scores was calculated to determine the total score. Demographical investigate whether the use of repeated spot urine sampling is an appropriate
and laboratory data were obtained from medical records. Univariate analysis was used alternative for repeated 24h urine collections.
to assess total score associations, and the variables with P<0.20 were included in the METHOD: We performed a post-hoc analysis of a metabolic ward study in 8 healthy
regression analysis model. male adults who consumed a 7-day diet with a fixed amount of Na (200 mmol/d).
RESULTS: 305 HD patients were included (male: 51%; age: 52.2 6 14.7 years old; HD Urine was collected in four daily intervals: 7-13h, 13-19h, 19-23h and 23-7h. After
vintage: 46 (19 – 82) months; hyperkalemia: 29%). Median (interquartile) FFQ scores reaching steady state, we estimated Na intake with 1 and 3 consecutive 24h urine
were: fruits: 6 (2-14); vegetables: 6 (3-10); legumes: 3 (1-7); whole-grain: 0 (0-1) and collections and 3-day spot urine sampling, using the Kawasaki formula with measured
seeds: 0 (0-0). Total score was 19 (14-28) and correlated with age (r=0.15; P=0.01), HD 24h urine creatinine excretion.
vintage (r=-0.22; P=<0.001) and body mass index (BMI) (r=0.15; P=0.007). Patients RESULTS: ON: day 5, mean 24h Na excretion matched intake, indicating that steady
with diabetes had a higher total score (22 (15-31) versus 18 (13-27) P=0.03). Only the state was achieved (Fig A). Mean and standard deviation of absolute differences
vegetables score correlated with serum potassium (r=0.17; P=0.03) and no difference between estimated and measured Na intake (DNa) for each method were: 18.8 614.6
was found between dietary fiber food groups scores and total score with hyperkalemia. mmol (3 x spot urine 7-13h), 32.3 618.7 mmol (3 x spot urine 13-19h), 74.6 630.0
The linear regression analysis model also included gender and education (years at mmol (3 x spot urine 19-23h), 28.2 619.8 mmol (3 x spot urine 23-7h), 29.8 623.9
school) (all with P<0.20 in the univariate analysis). The independent predictors of mmol (1 x 24h urine) and 22.9 611.3 mmol (3 x 24h urine) (Fig B). With the exception
dietary fiber total score were age (OR=0.1 (95%IC 0.01-0.20);P=0.04), HD vintage of the 19-23h spot urine collection period, the accuracy of 3-day spot urine sampling
(month) (OR=-0.03 (95%IC -0.06 - -0.01);P=0.02) and years at school (OR=0.27 did not significantly differ from accuracy of 1 and 3 consecutive 24h urine collections.
(95%IC 0.85-0.46);P=0.005). When combining the pre-night and morning spot urine collections (19-7h), the
CONCLUSION: The usual frequency of intake of fiber sources was low, and its accuracy of the estimation did not improve (DNa 28.7 619.6 mmol).
independent determinants were age, HD vintage and education. The lack of association CONCLUSION: 3-day spot urine sampling did not perform significantly different
with hyperkalemia suggests that other dietary sources and clinical factors should be than 1 and 3 24h urine collections for estimation of individual-level Na intake.
considered to manage hyperkalemia in this population. Adequately powered studies need to confirm whether repeated spot urine sampling is
an accurate and low burden alternative to repeated 24h urine collections.

MO596 HYPERPHOSPHATEMIA INDUCES ENDOTHELIN-1


SYNTHESIS AND INFLAMMATION IN LUNG FIBROBLASTS

Ana Asenjo-Bueno1, Elena Alcalde-Estevez2, Gemma Olmos2, Diego Rodrıguez-


Puyol3, Maria Piedad Ruiz-Torres2, Susana Lo pez-Ongil1
1
Hospital Prıncipe de Asturias, Fundaci
on para la Investigaci on Biomédica, Alcal
a de
Henares, Spain, 2Universidad de Alcal a, Biologıa de Sistemas, Alcal
a de Henares, Spain
and 3Hospital Prıncipe de Asturias, Servicio de Nefrologıa, Alcal
a de Henares, Spain

BACKGROUND AND AIMS: Hyperphosphatemia is an aging-related condition


associated to chronic diseases such as chronic kidney disease (CKD). In both cases,

i354 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO597 Figure: (A) Mean 24h Na excretion during 7-day diet. (B) Comparison of
absolute differences between measured and estimated Na intake (DNa). Estimates are
based on 3-day spot urine samples for each collection period (blue), 1 (green) and 3
(red) consecutive 24h urine collection. Data are mean and standard deviation.

MO598 COMPARISON OF GUT MICROBIOTA COMPOSITION


BETWEEN PERITONEAL DIALYSIS PATIENTS AND HEALTHY
HOUSEHOLD CONTACTS

Renata Rodrigues Teixeira1, Laila S. Andrade1, Natalia Barros Ferreira Pereira1,


Christian Hoffmann4, Lilian Cuppari5
1
Universidade Federal de S~ao Paulo (UNIFESP), Nutrition Program, S~
ao Paulo, Brazil,
4
University of Sao Paulo, School of Pharmaceutical Sciences, Sao Paulo, Brazil and
5
Universidade Federal de S~ao Paulo (UNIFESP), Division of Nephrology, S~
ao Paulo, Brazil

BACKGROUND AND AIMS: According to some studies, it seems that advanced


chronic kidney disease (CKD) has the potential to cause alterations in the composition
of patients gut microbiota. Most of these data have been provided by comparing the
microbiota profile between patients and healthy individuals. However, well-known
factors that influence the microbiota composition such as age, environment and diet
were not considered in the majority of these comparative studies. In the present study,
we aimed to compare the gut microbiota composition between patients on peritoneal
dialysis (PD) and age-paired healthy household contacts.
METHOD: This is a cross-sectional study. Patients undergoing automated PD for at
least 3 months, aged 18 to 75 years and clinically stable were enrolled. Those who were
using prebiotics, probiotics, symbiotics and antibiotics within a period of 30 days
before the study, were not included. A healthy control group was composed by
individuals living in the same home and with similar age of the patients. Participants
received sterile materials to collect the feces sample and were instructed to keep it
refrigerated and bring to the clinic within a period of 12h. To evaluate the microbial
profile, 16S ribosomal DNA was PCR-amplified and sequenced on an IlluminaMiSeq
platform. Diet was evaluated using a 3-day food record and the diet quality was
analyzed by a Brazilian Diet Quality Index. Rome IV questionnaire was applied to
diagnose constipation. Nutritional status was assessed by 7-point subjective global
assessment (SGA) and body mass index (BMI). Fasting blood samples were collected
and clinical data were obtained from interviewing the participants and from the
patient’s charts. Data are presented in percentage, mean 6 standard deviation or
median (interquartile range).
RESULTS: Twenty patients (PD group) and 20 healthy household contacts (control
group) were studied. In PD group: 70% were men, 53.5 (48.2 - 66) years old, 50% had
diabetes, BMI 25.9 6 4.8 kg/m2, 95% well-nourished, 40% constipated, 14 (5.2 – 43.5)
months on dialysis and 80% had residual diuresis. In control group: 30% were men,
51.5 (46.2 - 59.7) years old, BMI 28.7 6 3.5 kg/m2 and 20% constipated. Except of sex
(p = 0.01) and BMI (p = 0.04), there were no other differences between groups. MO598 Figure 2: Genera differential abundance between groups (p>0.05)
Comparing dietary intake between groups, no difference was found in daily energy
[PD: 20.8 6 5.4 kcal/kg/d vs. control: 22.0 6 5.6 kcal/kg/d, p = 0.51], protein (PD: 0.8
6 0.2 g/kg/d vs. control: 0.9 6 0.2 g/kg/d, p = 0.23) and fiber [PD: 14.1 (10.7 – 21.1) g/ CONCLUSION: In the present study, no difference in the gut microbiota composition
d vs. 13.7 (10.4 – 18.0) g/d, p = 0.85]. In addition, the Diet Quality Index was also not was found between patients on PD and healthy household contacts sharing a similar
different between groups (PD: 52.3 6 15.6 vs. control: 54.5 6 14.8, p = 0.65). environment and diet. This result suggests that CKD and PD seem not to alter
Regarding microbiota composition, no difference was found between groups in alfa significantly gut microbiota composition.
diversity (Figure 1), beta diversity (p>0.05), and genera differential abundance (Figure
2).
MO599 COMPARISON OF TOTAL BODY WATER MEASURED BY
BIOIMPEDANCE SPECTROSCOPY TO UREA DISTRIBUTION
VOLUME ESTIMATED FROM UREA KINETIC MODELING IN
HEMODIALYSIS PATIENTS

Ariella Mermelstein1, Ulrich Moissl1, Bernard Canaud1, Jeroen Kooman1,


Rachel Lasky1, Lemuel Rivera-Fuentes1, Stephan Thijssen1, George Kaysen1,
Jochen Raimann1, Peter Kotanko1
1
Fresenius Medical Care

BACKGROUND AND AIMS: Monitoring of fluid, body composition and nutritional


changes is important in clinical nephrology. The Body Composition Monitor (BCM;
Fresenius Medical Care, Bad Homburg, Germany) measures whole-body
MO598 Figure 1: Alfa diversity between groups according to Shannon and Simpson bioimpedance and determines extracellular and intracellular resistance by using the
indexes Cole-model to estimate total body water (TBW-BCM) and its partition into
extracellular and intracellular water. Both can then be used to define body composition
and separate body weight into lean tissue mass, adipose tissue mass, and fluid overload.
Urea kinetic modeling (UKM) allows the estimation of dialysis dose (double-pooled
Kt/V), urea distribution volume (V-UKM) and dietary protein intake. We studied the
bias between estimated V-UKM to anthropometric and measured TBW-BCM (Vant,
TBW-BCM).
METHOD: Pre-hemodialysis (HD), electrodes for the BCM assessments were placed
on the non-arteriovenous access arm and ipsilateral leg, respectively, with the patient
in a supine position. Vant was calculated using the Watson equation. In addition to
these assessments we entered the specified values from the most recent urea kinetic
modeling (UKM) treatment into the online solute-solver calculator (http://
ureakinetics.org). We chose a baseline ratio of modeled/anthropometric volume of 0.6
to 1.3 L to exclude values with data entry errors and/or UKM sampling errors. We
calculated the post HD TBW-BCM by subtracting the intradialytic weight loss and

10.1093/ndt/gfab089 | i355
Abstracts Nephrology Dialysis Transplantation

adjusted these estimates by the differences in post HD weight between sessions to make MO600 DIFFERENCES IN BODY COMPOSITION, MUSCLE
both estimates comparable. We depicted the comparison between the estimated V- STRENGHT AND BIOCHEMICAL PARAMETERS IN CKD
UKM versus the TBW-BCM in a scatter- and Bland-Altman (BA) plot (Figure). For PATIENTS WITH AND WITHOUT PROTEIN ENERGY WASTING
the purpose of error investigation we studied the computed bias (V-UKM minus (PEW)
TBW-BCM) as a function of body mass index (BMI) and stray capacitance (td) in a BA

Guillermina Barril1, Angel Nogueira1, Graciela Alvarez1, Paula Romasco1,
plot. We then calculated the difference between Vant and V-UKM and illustrated the
comparison in a scatter and BA plot. Yohana Gil1, Almudena Nun ~ez1, Carmen Sanchez Glez1, Natalia Tromborelli1
1
RESULTS: In a cross-sectional design, we studied 161 stable prevalent HD patients Hospital Universitario de la Princesa, Nephrology, Madrid, Spain
(61.3614.7 years, 98 (60.9%) males, height of 167.5610.7 cm) prior to their treatment.
The regression plot showed slight agreement (R2= 0.69) and the Bland-Altman plot no BACKGROUND AND AIMS: PEW sometimes produces irreversible alterations in
systematic trends or proportional error in the main analysis (Figure 1a and b). Neither nutritional status, and early diagnosis could mark the sindrome reversibility.
BMI or td explained bias and variance in the bias between both estimates. Vant and V- Aim.-To establish the prevalence of PEW in an advanced CKD unit in a sample of 325
UKM plots showed agreement (R2 of 0.68) with a mean bias of -2.365.1 and no patients with CKD and to establish the differences in nutritional parameters, body
proportional error. composition and muscle strength.
METHOD: The patients treated in Advanced CKD Unit (ACKD) nutritional status
monitoring is performed every 3 months, will be assessed through a cross-sectional ,
with the frequency being able to increase if malnutrition is detected in the screening.
The ISRNM criteria are applied to diagnose PEW, and the patients are classified
according to whether or not they have PEW and the differences in nutritional
parameters are analyzed: albumin, transferrin, CRP, linphocytes, Hb, body
composition with Akhern HD-01 monofrequency BIA and anthropometric
measurements and muscular strength with dynamometer (baseline).
RESULTS: We have evaluated 325 patients with CKD xage 70.88 6 12.55 years, 66.8%
217pac are men with xCKD-EPI of 19.19 6 9.28ml / min / 1.73m2 PEW prevalence
8.9% (29 patients) aged 74.06 6 12.79 years, with no significant difference between
sexes with and without PEW (18/215 men and 11/108 women). We found significant
differences between the groups with PEW vs without PEW in protein intake (nPNA)
0.73 6 0.21 vs 0.93 6 0.26, p0.003, albumin 3.74 6 0.66 vs 4.21 6 0.41, CRP 1.20 6
2.09 vs 0.68 6 1.20, p0.05, Hb 11.33 6 1.52 vs 11.90 6 1.50, p0.023, transferrin 199.71
6 48.38 vs224.95 6 48.85, p0.013.
Data on anthropometric and body composition measures as showing in the table. The
values of biochemical parameters and body composition in patients with PEW are
striking, as some are close to the low limit of normality, which suggests the possible
reversibility if action is taken on time.
CONCLUSION: The monitoring of nutritional status in a protocolized way provides
low prevalences of PEW and allows its early detection, which favors its reversibility
with the appropriate intervention.

MO600 Table: Differences in body composition and hand grip strength

Parameter PEW Mean Standard desv. p


Phase Angle Yes 3.43 1.23 0.001
No 4.23 1.17
Na/k Yes 1.84 0.67 0.001
No 1.39 0.46
BCMpct Yes 33.08 10.21 0.001
No 39.14 9.26
TBW% Yes 57.57 8.00 0.001
No 53.36 6.84
IBW% Yes 38.41 10.38 0.001
No 43.91 8.20
Fat mass% Yes 25.76 11.42 0.01
No 32.20 9.13
BMI Yes 24.94 4.98 0.01
No 27.60 5.01
BCMI Yes 5.87 2.77 0.01
No 7.02 2.11
Muscle arm circ. Yes 25.97 4.39 0.01
No 28.33 4.08
Wirst circunference Yes 90.90 22.41 0.05
No 99.98 15.04
MO599 Figure: Comparison of urea distribution volume (V-UKM) to total body BSA Yes 1.74 0.21 0.04
water (TBW-BCM) from the body composition monitor (BCM) in a) a Bland-Altman No 1.83 0.22
plot and b) a scatter plot.
Hand grip strenght Yes 20.58 11.52 0.01
No 25.37 10.35
CONCLUSION: Both TBW-BCM and the V-UKM as the “bronze standard” of TBW
estimation seemed to agree reasonably well. Neither body composition measurement
or kinetic modeling approach showed any significant influence on the accuracy and
precision of the estimate. According to BCM availability, estimated V-UKM or
measured TBW-BCM could be used alternatively in practice to support clinical
decision when pharmacokinetic considerations are concerned.

i356 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO601 THE ASSESSMENT OF NUTRITIONAL STATUS AND mean value of AOPP increased concomitantly with intima-media thickness (P < 0.05).
MORTALITY IN GERIATRIC PATIENTS WITH CKD 3B-5 Furthermore, AOPP mean value was relatively higher in patients with atherosclerotic
STAGES plaques (P < 0.05) compared to those without plaques. Vit-E treatment stabilized the
levels of AOPP but had no effect of atherosclerotic progression.
Elina Borkhanova1, Adelya Maksudova2 CONCLUSION: AOPPs were proved to be effective markers of oxidative stress and
1
UK “Clinica Dialysa”, UK “Clinica Dialysa”, Kazan, Russia and 2Kazan State Medical their high levels help to predict the progression of the atherosclerosis process. As a
Univercity, Hospital Therapy Department, Kazan, Russia powerful antioxidant, Vit-E stabilized the AOPP levels.

BACKGROUND AND AIMS:.: the prevalence of chronic kidney disease (CKD)


increases with age–almost 50% of people over the age of 70 have stage 3-5 CKD.
Geriatric patients with pre-dialysis stages of CKD are recommended to assess the risk
of absolute probability of death of the patient both in the case of starting dialysis and
without it. Malnutrition in this group of patients is the risk factor of mortality. The
EQUAL study, a European Quality Study on treatment in advanced chronic kidney
disease, showed that according to the Subjective Global Assessment Scale the
majority of the geriatric patients with with incident glomerular filtration rate <20mL/
min/1.73m 2 (nondialysis) had a normal nutritional status (SGA 6-7), 26% had
moderate PEW (SGA 3-5), and less than 1% had severe PEW (SGA 1-2). The aim is to
assess prevalence of protein-energy wasting (PEW) and the absolute risk of death over
5 years in the geriatric patients with advanced chronic kidney disease (CKD).
MO602 Figure 2: Evolution of AOPP levels in the Vit-E treatment and the non Vit-
METHOD: Materials and methods: a study of 151 geriatric patients with stage 3B-5
E treatment groups between the onset of treatment (T0) and after two years (T1). *.
CKD, average age 77 68.6. Patient inclusion criteria: age 60-90 years, CKD stage 3B-5
Difference between the two times point was significant at P < 0.01.
(GFR in CKD-EPI <= 45 ml / min / 1.73 m2.
Patient exclusion criteria: oncological diseases; acute infections; severe mental illness
(including alcoholism), any serious somatic diseases, according to the researcher.
The patients were assessed by Subjective Global Assessment; to assess the estimated 5- MO603 PREVALENCE AND PROGNOSTIC SIGNIFICANCE OF
year mortality rate, patient indicators were evaluated on the Banzal scale. All patients MALNUTRITION IN DIALYSIS PATIENTS UNDERGOING
were evaluated for laboratory data (absolute number of lymphocytes, hemoglobin, red ENDOVASCULAR THERAPY FOR PERIPHERAL ARTERY
blood cells, creatinine, urea, total protein, blood albumin, total cholesterol, blood DISEASE
potassium, and proteinuria); The study group consisted of 105 patients with stage 3B
CKD, 35 patients with stage 4 CKD, and 11 patients with stage 5 CKD. Ting-Yun Lin1, Szu-Chun Hung1
RESULTS: according to the SGA 66,7% of patients with CKD 3b stage have normal 1
Taipei Tzu Chi Hospital, Division of Nephrology, New Taipei City, Taiwan, R.O.C.
nutritional status, 26,6% patients are mild to moderate malnourishment, 6,7 % are
malnourished. 60% of patients with CKD 4 stage have normal nutritional status,
31,2% patients had moderate PEW, 8,8% had severe PEW. In patients with CKD 5 BACKGROUND AND AIMS: Malnutrition often coexists with inflammation and
72,7% had moderate PEW, 27,3% had severe PEW. atherosclerosis and is associated with adverse clinical outcomes in dialysis patients.
The level of total protein in the blood serum is correlated with nutritional disorders on However, both prevalence and prognostic significance of preexisting malnutrition in
the SGA scale(r=-0.52) in geriatric patients with predialysis stages of CKD. dialysis patients with peripheral artery disease (PAD) referred for endovascular therapy
During assessing the absolute risk of death within 5 years (Bansal Score) in 20.9% of are not well known.
patients with CKD3B, the estimated mortality rate was 40%, in 12.4% 54%, in 25.7% METHOD: A prospective cohort of 395 dialysis patients undergoing endovascular
69% and higher. All patients with stage 5 CKD had a mortality risk of 40% or higher. therapy for PAD between 2005 and 2019 was studied. Nutritional status was assessed at
Indicators of the the Bansal scale significantly increased with a decrease in GFR (r= - admission by using the Controlling Nutritional Status (CONUT) score, a simple tool
0.68, r=-0.46). The Banzal mortality index (r=0.32) significantly increased with incorporating serum albumin concentration, total peripheral lymphocyte count, and
increasing the level of serum phosphorus and uremia. total cholesterol concentration. Patients were divided into 4 groups based on the
CONCLUSION.: The prevalence of nutritional disorders are observed in 33-40% of CONUT score: normal nutrition (0–1), mild malnutrition (2–4), moderate
elderly patients with stage 3B-4 CKD and until 75% with stage 5CKD. During malnutrition (5–8), and severe malnutrition (9–12). We examined the associations
assessing the absolute risk of death over 5 years in the study population of geriatric between malnutrition and all-cause mortality as well as major adverse limb events
patients with CKD stages 3B-5, a high risk on the Bansal scale (69% or higher) was (MALE) and major adverse cardiovascular events (MACE) using Cox proportional
observed in 25.7% with CKD stage 3B, 60% hazards models.
RESULTS: According to the CONUT score, 40.8% patients were moderately or
severely malnourished. During a median follow-up of 2.1 years, 218 (55.2%) patients
died, 211 (53.4%) patients had MALE, and MACE occurred in 135 (34.2%) patients.
MO602 HIGH LEVELS OF ADVANCED OXIDATIVE PROTEIN Severely malnourished patients, as compared to patients with normal nutritional
PRODUCTS (AOPP) HELP TO PREDICT THE PROGRESSION status, had significantly increased risk for all-cause death (adjusted hazard ratio [HR],
OF ATHEROSCLEROSIS IN CHRONIC KIDNEY DISEASE WITH 4.83; 95% confidence interval [CI], 2.56 to 9.12) and in particular non-cardiovascular
VITAMINE E TREATEMENT MIGHT STABILIZE AOPP LEVELS death (adjusted HR, 7.20; 95% CI, 3.22 to 16.08) and MALE (adjusted HR, 2.42; 95%
CI, 1.23 to 4.74) but not MACE (adjusted HR, 1.81; 95% CI, 0.74 to 4.40). Similar
Leila Azouaou toualbi1, Mounir Adnane2, Wafa Ballouti3, Medina Arab4, results were found when the CONUT score was analyzed as a continuous variable.
Khelfi Abderrezak5, Chahine Toualbi6, Henni Chader7, Abdelghani Benoui8, CONCLUSION: Malnutrition is common and is strongly associated with increased all-
Atmane Seba1 cause mortality and MALE among dialysis patients with PAD requiring endovascular
1
university algiers 1,CHU nephrology hussein dey, medecine, nephrology, algiers algeria, therapy. Clinical trials are needed to evaluate whether nutritional interventions
Algeria, 2Institute of Veterinary Sciences, University of Tiaret, Tiaret, Algeria, Department improve outcomes for dialysis patients with PAD.
of Biomedicine, Tiaret, Algeria, 3university algiers 1, CHU nephrology hussein dey, mede-
cine, biochimy, algiers algeria, Algeria, 4university algiers 1, CPMC, Department of
Biochimy, algiers, Algeria, 5university algiers 1, toxicology, algiers algeria, Algeria, 6uni-
MO604 DIFFERENCES IN THE EXTRACELLULAR BODY WATER/
versity of bedjaia, medecine, surgy , bedjaia, Algeria, 7university algiers 1, pharmacol-
TOTAL BODY WATER (EBW/TBW) IN HEMODIALYSIS AND
ogy, algiers algeria, Algeria and 8university algiers 1, medecine, nephrology, algiers,
CHRONIC KIDNEY DISEASE PATIENTS. RELATIONSHIP
Algeria
WITH NUTRITIONAL PARAMETERS

BACKGROUND AND AIMS: Advanced Oxidation Protein Product (AOPP) are 


Guillermina Barril1, Angel Nogueira1, Graciela Alvarez1, David Sapiencia1,
created during oxidative stress and are considered as markers of this phenomenon and Natalia Andres1, Martin Giorgi1, Almudena Nun ~ez1, Paula Romasco1
of inflammation. Vitamin E (Vit-E) is a powerful antioxidant, whoever no consensus 1
Hospital Universitario de la Princesa, Nephrology, Madrid, Spain
on its effectiveness on the level of AOPP or the process of atherosclerosis have been
made. The aim of the present study was to determine AOPP levels in patients with
chronic kidney disease (CKD) at different stages and their relationship with the BACKGROUND AND AIMS: Knowing the hydration status of CKD patients is one
progression of atherosclerosis in patients under Vit-E treatment. of the basic objectives in CKD patients considering the Ratio of EBW(TBW) as
METHOD: A longitudinal study has been conducted on 205 patients with CKD and 40 indicator of them.
controls. the correlations between AOPP and glomerular filtration rate (GFR) and AIM: Determine the cut-off point of the EBW/TBW ratio using Bioimpedance in
different biological markers were analyzed. Doppler of the supraoptic trunks was patients with global CKD and divided into advanced CKD and hemodialysis (HD) as a
conducted to assess the correlation of AOPP with intima-media thickness. The hydration marker in relation to MIS scale (malnutrition inflammation score), cut-off
effectiveness of Vit-E treatment on AOPP levels and atherosclerosis progression was point 5.
also investigated.
RESULTS: AOPP levels were significantly higher in CKD patients compared to the
control group (P < 0.05) and increased with the alteration of renal functions. The

10.1093/ndt/gfab089 | i357
Abstracts Nephrology Dialysis Transplantation

METHOD: We value 199 CKD patients by setting the EBW/TBW cut-off points using In univariate time-dependent analysis, patients with zero mGPS had better kidney
Inbody S10 multifrequency bioimpedance with global ROC curve and for advanced survival than those with the score of one and two (99.9 (95%CI 96.9, 102.9) vs 92.1
CKD (ACKD) and HD analyzing differences according to age ranges (<65,65,1-75 and (95%CI 85.2, 99.0) vs 78.1 (95%CI 60.4, 95.4) months, log rank p=0.02). However, the
>75 years) and differences in nutritional parameters (visceral proteins, MIS scale and kidney survival differences were not present after adjusting for CKD progression risk
body composition). factors (HR 1.12 (95%CI 0.78, 1.62), p 0.5).
RESULTS: We have evaluated 199 patients with ACKD, 143 male and 56 female, 74 in CONCLUSION: The inflammation-based mGPS score was associated with eGFR
CKD xage72.27 ?11.98years and 125 in HD, xage 70.76 ?12.73 years. Overall EBW / decline in CKD patients. Therefore, could prove useful in improving risk stratification
TBW ratio: AUC 0.657, p0.006, cut-off point 0.3965 60% sensitivity, 64% specificity. of CKD patients.
Advanced CKD: AUC 0.648, p0.071, cutoff point 0.397, 64% sensitivity, 61%
specificity. HD: AUC 0.706, p0.012, cutoff point 0.391, 71% sensitivity, 63% specificity.
The results in relation to age strata and MIS with 5 as the cut-off point in the table. No
MO606 FUNCTIONAL CAPACITY AND NUTRITION-INFLAMMATION
greater hydration in men than in women overall.
BINOMIUM IN PATIENTS WITH ADVANCED CHRONIC
The nutrition-inflammation parameters according to the cut-off point are different:
KIDNEY DISEASE (ACKD)
Advanced CKD: age 0.001, albumin 0.024, prealbumin 0.013, trasferrin 0.078, CRP
0.432. HD: albumin 0.014, prealbumin 0.001, transferrin 0.939, lymphocytes 0.030, 
Angel Nogueira1, Graciela Alvarez2, Guillermina Barril1
CRP 0.342, age 0.000. 1
CONCLUSION: 1. We have found slightly higher cut-off points between ACKD and Hospital Universitario de la Princesa, Nephrology, Madrid, Spain and 2Hospital
hemodialysis in the assessed sample. 2. The EBW / TBW ratio appears higher in Universitario de la P^rincesa, Nephroogy, Madrid, Spain
patients > 65 years in both ACKD and HD, in contrast to what is observed in the
healthy population. 3. A greater malnutrition appairs in a greater hyperhydration in BACKGROUND AND AIMS: There are differents factors that will influence the
HD and ACKD. functional capacity of ACKD patients, among them the nutritional condition.
AIM: to assess the functional capacity of ACKD patients with the Short Physical
Performance test Battery (SPPB), and its relationship with the malnutrition-
MO604 Table 1: Differences according HD and ACKD inflammation binomium.
METHOD: We have evaluated 216 ACKD patients, 66.2% (143) male. xage 70.85
?12.01 years, being female older than male (72.58 ?13.19 vs 69.96 ?11.32, p = 0.129). We
have determine plasma proteins indicators of nutritional status such as albumin,
MIS EBW/TBW Age Total prealbumin and CRP as a marker of the status of inflammation. And we have applied
< 65 65 – 75 > 75 malnutrition inflamation score (MIS).
RESULTS: In the univariate analysis, we found an association between the
ACKD MIS<5 EBW/TBW 0,397 3 8 3 14 functionality determined with the test and the age (RR95% 0.866 p = 0.000), sex
>0,397 1 4 4 9 (RR95% 0.387 p = 0.005). albumin (RR95% 2,222 p = 0.035), prealbumin (RR95%
MIS>5 EBW/TBW 0,397 4 3 3 10 1.065 p = 0.018), CRP (RR95% 0.733 p = 0.022) and the state nutritional value
determined with the MIS scale (RR95% 0.791 p = 0.000). We donot any found any
>0,397 0 4 14 18 association with DM, transferrin and total lymphocytes. Albumin values were
Total EBW/TBW 0,397 7 11 6 24 established as 3.8g / dl, and CRP at 1g / dl, obtaining 4 groups: (G1: alb> 3,7-PCR <1,
G2: alb> 3,7-PCR> 1, G3: alb <3,7-PCR <1 and G4: alb <3,7-PCR> 1 ).
>0,397 1 8 18 27 The table shows the results of the relationship between groups and the limitations
HD MIS<5 EBW/TBW 0,391 7 4 1 12 determined with SPBB. Group 1 was the most numerous, also being the one with the
>0,391 1 1 5 7 best nutrition-inflammation profile, observing that in this group 68 patients (78.2%)
presented minimal / no limitations.
MIS>5 EBW/TBW 0,391 7 2 2 11 CONCLUSIONS: 1. The nutritional-inflammation status will influence the functional
>0,391 5 11 11 27 capacity of the patient with ERCA.
Total EBW/TBW 0,391 14 6 3 23 2. The SPPB test, in addition to being a good choice to evaluate the functional capacity
of patients with ACKD, can provide guidance on the nutritional status of patients.
>0,391 6 12 16 34 3. Maintaining a good nutritional status will also have a positive influence on the
functional capacity of ACKD patients.

MO606 Table 1: Transplant Kidney Biopsy Findings from Positive COVID-19


MO605 INFLAMMATION-BASED MODIFIED GLASGOW PROGNOSTIC Cases
SCORE AND CHRONIC KIDNEY DISEASE PROGRESSION

Gabriel Stefan1,2, Simona Stancu1,2, Adrian Dorin Zugravu1,2, Cristina- G1: G2: G3: G4: *p
Stela Capusa1,2 Alb>3.8 Alb>3.8 Alb<3.8 Alb<3.8
1
University of Medicine and Pharmacy Carol Davila, Nephrology and 2Dr Carol Davila * CRP<1 * CRP>1 * CRP<1 * CRP>1
Teaching Hospital of Nephrology, Nephrology
Severe limitations 66.7% (8) 0,0% (0) 25% (3) 8.3% (1) 0.012
BACKGROUND AND AIMS: The modified Glasgow prognostic score (mGPS), based Moderates 64.9% (24) 27% (10) 0,0% (0) 8.1% (3)
on combination between albumin (sAlb) and C-reactive protein (CRP), has been Limitations
derived from oncology and validated in multiple diseases. Since chronic kidney disease
Mild Limitations 83.3% (65) 7.7% (6) 6.4% (5) 2.6% (2)
(CKD) progression is related to inflammation, we aimed to evaluate the relationship
between the mGPS and CKD outcome. M?mal Limitations 78.2% (68) 10.3% (9) 5.7% (5) 5.7% (5)
METHOD: The present retrospective unicentric cohort study included 547 CKD * P<0.05 (sig.) (Fisher test)
patients (age 60.2 years, 53% male, eGFR 42.0 mL/min, mean change -2 mL/min/year)
admitted between January 1, 2007 and December 31, 2012.
The mGPS assessment: zero points if CRP 10 mg/L and sAlb 3.5 g/dL; one point if
CRP >10 mg/L and sAlb 3.5 g/dL, two points if CRP >10 mg/L and sAlb <3.5 g/dL.
MO607 THE EFFECT OF VITAMINE E ON OXIDATIVE STRESS AND
Patients records were reviewed from the CKD diagnosis to one of the four outcomes:
CARDIOVASCULAR COMPLICATIONS IN HEMODIALYSIS
end-stage kidney disease (ESKD), death, loss to follow-up, or until July 31, 2017.
PATIENTS
RESULTS: The mGPS score was 0 for 420 (78%), 1 for 110 (19%), and 2 for 17 (3%)
patients. Rapid progression defined as a sustained decline in eGFR of more than 5 mL/
Leila Azouaou toualbi1, Medina Arab2, Chahine Toualbi3, Khelfi Abderrezak4,5,
min/year was found in 17% of the studied patients. More patients with rapid CKD
Henni Chader6, Abdelghani Benoui7, Atmane Seba8
progression were found in the group with the highest mGPS (30% vs 17%, vs 16%, 1
p=0.05). university algiers 1,CHU nephrology hussein dey, medecine , nephrology, algiers alge-
In the multivariate analysis, mGPS was associated with the eGFR slope (OR 1.42 ria, Algeria, 2university algiers 1,, 3, medecine ,surgy , 4, 5university algiers 1,, toxicology,
6
(95%CI 0.29, 2.55), p 0.01). Moreover, mGPS was negatively correlated with baseline , medecine , nephrology, 7university algiers 1,, medecine , nephrology and 8university
eGFR (OR -3.74 (95%CI 7.8, 0.33), p 0.05) and positively with albuminuria (0.87 algiers 1,CHU nephrology hussein dey, medecine , nephrology, Algeria
(95%CI 0.51, 1.23), p 0.001).
During the study period, 130 patients (24%) died and 109 (20%) reached ESKD. The BACKGROUND AND AIMS: Oxidative stress represents a risk factor for
mean kidney survival time was 8.1 (95%CI 7.9, 8.4) years. Kidney survivals at 12, 24, cardiovascular complications . The aim of the work is to evaluate the effectiveness of
36, 48, 60, and 72 months were 96, 95, 89, 86, 83 and 82%, respectively. vitamin E on cardiovascular complications in hemodialysis patients.

i358 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: a study including 420 patients on hemodialysis and 360 controls.
Treatment with Vit E at a rate of 300 mg / day for 2 years. All patients benefited from a
blood sample of oxidative stress markers as well as paraclinical explorations in search
of cardiovascular complications.
RESULTS: The study grouped together 780 cases. We find that there is a significant
relationship between cardiovascular complications and Advanced Oxidation Protein
Product (AOPP), Low Density Oxidized Lipoprotein (LDLox), Malondialdehydes
(MDA) and Gluthations), we did not find any correlation with nitrogen monoxide
(NO) and myeloperoxidases (MPO) .Concerning gluthations (IU / ml ) we observe that
the mean values clearly increased after treatment (P-value <0.05) . The mean value of
MDA mmol / l significantly decreased after treatment .we note that the cardiovascular
complications have decreased (11.03% versus 16.04%) with the decrease in certain
markers of oxidative stress. (p > 0.05)
CONCLUSION: Regarding cardiovascular complications, we have certainly noticed a
drop in their frequency after treatment with vit E without the difference being
significant.
MO608 Figure 1: Total intuitive eating and subscales scores pre and post
intervention (n=23). [*p-value derived obtained with Wilcoxon test].

CONCLUSION: The intervention approaching IE principles was effective to improve


IE attitudes in the studied patients. With exception for “body-food choice congruence”,
all IE subscales improved after intervention. These results are promising and may
contribute to a paradigm change in the strategies aiming to enhance motivation and
adherence to dietary recommendations in CKD population.

MO609 PREVALENCE OF MALNUTRITION AND INFLAMMATION IN


NONDIALYZED PATIENTS WITH CHRONIC KIDNEY DISEASE:
MO607 Figure: Cardiovascular complications and markers of oxidative stress. A CLINICAL STUDY

Manzoor Parry1, Hamad Jeelani2


1
Sheri Kashmir institute of medical sciences, Nephrology, Srinagar, India and
MO608 INTUITIVE EATING CHANGES AFTER A BEHAVIORAL MULTI- 2
Narayana hospital, Guwahati, Nephrology, Guwahati, India
SESSION GROUP INTERVENTION FOR DIETARY
MANAGEMENT OF WOMEN WITH CKD
BACKGROUND AND AIMS: The prevalence of chronic kidney disease (CKD) in
Raıssa Antunes Pereira1, Marle Alvarenga2, Laila S. Andrade1, Renata R. India varies from 0.16–0.78%. The reported incidence of malnutrition in CKD patients
Teixeira1, Paula C. Teixeira3, Wanderson R. da Silva4, Lilian Cuppari1,5 is 37–84%. There is a paucity of data on the quantification of malnutrition and
1 inflammation in undialyzed patients of CKD from north east of India. This study
Federal University of S~ao Paulo, Nutrition Program, S~ ao Paulo, Brazil, 2University of
analyzed the prevalence and causes of malnutrition and inflammation in patients with
S~ao Paulo, Public Health School, Nutrition Department, S~ ao Paulo, Brazil, 3University of
CKD before the initiation of dialysis treatment.
S~ao Paulo, Clinical Hospital of Medicine School, Eating Disorders Program, Psychiatry
METHOD: This study was conducted from May 2017 to May 2019 in the department
Institute, S~ao Paulo, Brazil, 4S~
ao Paulo State University, School of Pharmaceutical
of nephrology Guahati medical college hospital. Assessment of nutritional and
Sciences, Department of Food and Nutrition, Araraquara, Brazil and 5Federal University
inflammatory status was carried out in patients with CKD before initiation of dialysis.
of S~ao Paulo, Division of Nephrology, S~ ao Paulo, Brazil
Serum albumin; body mass index (BMI); triceps skin fold thickness (TST); mid-arm
muscle circumference (MAMC); and subjective global assessment (SGA) scoring were
BACKGROUND AND AIMS: Approaches promoting eating guided by internal cues, used for assessment of nutritional parameters. Serum C-reactive protein; serum
such as intuitive eating (IE), have emerged as an alternative to decrease the impact of albumin and serum ferritin level were used to assess the inflammatory status in these
external cues on eating behavior while simultaneously avoiding the risk for patients.
dysfunctional eating. IE helps to connect with internal cues (i.e. hunger and satiety) RESULTS: A total of 528 (male:female= 359:169) patients with CKD participated in
and feelings rather than relying on external strategies to regulate what, how much and this study. Diabetic Nephropathy (35%) was the most common; followed by;
when to eat. In obese women, IE-based approaches have shown to enhance motivation hypertension (23%) and chronic glomerulonephritis (20 %). The evidence of
and adherence to lifestyle changes, hence improving metabolic and psychological malnutrition was noted in 344 (65%). The mean age of patients with malnutrition was
parameters, quality of life and diet quality. However, studies evaluating IE in chronic 52.8612.45 years with a male predominance (68%). On the basis of SGA score;
kidney disease (CKD) patients are scarce. Thus, we aimed to evaluate the impact of a malnutrition was noted in 344 patients (mild moderate [36%]; severe; [30%]);
behavioral multi-session group intervention on IE scores of overweight non-dialysis- remaining (34%) were well nourished. Thus; evidence of Malnutrition was noted in
dependent (NDD) CKD women. 65% of patients with CKD.). Serum total protein & albumin were higher in the non-
METHOD: This is a prospective non-controlled clinical trial of a behavioral multi- malnourished patients in comparison to malnourished (5.8361.0 vs 5.3161.12
session group intervention for dietary management. It was conducted with overweight p<0.05; 3.6560.7 vs 2.6260.74) The inflammatory markers (serum ferritin & C
women with chronic kidney disease (CKD). Each group comprised 5-8 participants in reactive protein) were elevated significantly in patients with malnutrition in
fifteen weekly or biweekly sessions lasting about 90 minutes. Most of IE principles were comparison to those without malnutrition (308.15660.18 mg/dL vs. 251.64663.14
discussed throughout the meetings. IE scale 2 (IES2) translated and adapted to mg/dL; p < 0.001; 77% vs. 50%; p < 0.01).
Brazilian population and composed of 23 questions with 5-point Likert response scale CONCLUSION: Malnutrition and inflammation are common in patients with CKD
ranging from 1=“strongly disagree” to 5=“strongly agree” and four-factor model before the commencement of dialysis. This indicates that an emphasis should be placed
(Unconditional Permission to Eat, Eating for Physical Rather than Emotional Reasons, on the assessment and prevention or correction of malnutrition and inflammatory
Reliance on Hunger and Satiety Cues, and Body-Food Choice Congruence) was burden in these patients with CKD.
applied before and after the intervention. The higher the score, the higher the intuitive
eating attitudes.
RESULTS: Of the 33 patients that initiated the study, 23 patients [age=62.0 (58.0-68.0)
years; schooling= 9.0 (7.0-12.0) years of study; BMI=32.6 (30.2-39.3); eGFR=28.0 MO610 NUTRITIONAL PARAMETERS OF PATIENTS WITH END-
(22.0-31.0) ml/min/1.73m2] completed the intervention. Figure 1 shows the results STAGE RENAL DISEASE IN THE GENERAL UNIVERSITY
regarding IES2. HOSPITAL AREA

Christian Man~as1,2, Angel Palacios Castillo2, Sergio Bea Granell2,


Antonio Galan Serrano2
1
Miguel de Cervantes European University - UEMC, Nutrition, Valladolid, Spain and
2
Consorci Hospital General Universitari de València, Servicio de Nefrologıa, València,
Spain

BACKGROUND: Malnutrition is one of the problems that patients can develop


during the later stages of kidney disease. These problems are derived from uraemia and
acidosis that can present due to the decrease in glomerular filtration and added to an
accumulation of urine levels. During the months of January 2019 and May 2020 were

10.1093/ndt/gfab089 | i359
Abstracts Nephrology Dialysis Transplantation

collected information of 564 patients about age, weight, height, BWI, glomerular CONCLUSION: In the General University Hospital area, the patients in ESRD have a
filtration rate, use of oral nutrition supplements and albumin, protein, phosphorous high BWI, which can impair the renal disease. Also, we found that BWI decrease in end
and potassium biochemical levels. All of patients were had a GFR below 45 mL/min/ stages of ESRD worsening the nutritional status before start the renal replacement
1,73m2 and any of them have been started a renal replacement therapy when the data therapy. About albumin, the worst levels were found at stage 4 of the kidney disease
was collected. A descriptive and frequency analysis has been carried out with all the and older patients have more risk of present low albumin levels. The mean values of
parameters obtained. The T of Student for a related sample test was used due to the albumin show that most of our patients meet one of three conditions to diagnose PEW.
normality of the data and the participants condition of intervention – control. The protein level was lower at the 5 stage of the disease, and as the albumin, the older
RESULTS: The results indicate that the mean values for ESRD patients in our area are: patients show lower values of this parameter. Concerning phosphorous and potassium
age (75,3612,5 years old), weight (74,7615,6 kg), height (1,660,1 m), IMC (28,865,4 the patients at the end stage of renal disease present higher values of both of them due
kg/m2), glomerular filtration rate (19,969,1 mL/min/1,73m2), albumin (3,760.5 g/dL), possibly to the impaired renal function. About the use of nutritional supplements, a
protein (6,860,7 g/dL), phosphorous (4,261,1 mg/dL) and potassium (4,660,5 mEq/ low percentage of patients used this as nutritional therapy, but mean levels of
L). 41 patients (7,3%) used oral nutrition supplements. We found statistical biochemical parameters such as albumin, protein, phosphorous and potassium were
significance between the stages 4 and 5 of kidney disease and albumin (p-value 0.03 higher than the patients who did not use them. However, we did not find statistical
and 0.04) and potassium (p-value 0.04 and 0.04) levels. Only at stage 4 we found significance between the use of ONS and better status of biochemical parameters.
statistical significance between the levels of protein (p-value 0.04) and phosphorous (p- We can say that older patients in end stage of renal disease have a higher risk of
value 0.04). Also were found increased levels of albumin (3,73 vs 3,7 mg/dL), proteins malnutrition in comparison with young patients due to a decrease in BWI, albumin
(6,87 vs 6,8 mg/dL), phosphorous (4,4 vs 4,3 mg/dL) and potassium (4,8 vs 4,6 mg/dL) and protein levels. To conclude, the nutritional treatment to these patients should
in the group who use oral nutrition supplements, however, we did not reach statistical consist, on the one hand, the decrease of the BWI to prevent a quickly loss of renal
significance between groups. About correlations, we found that the albumin levels have function and, on the other hand, prevent the malnutrition, especially in the older
a statistical significance with age, protein, phosphorous and potassium levels, but not patients with lower BWI.
with BWI.

i360 | Abstracts
Nephrology Dialysis Transplantation 35 (Supplement 3): i361–i364, 2021
10.1093/ndt/gfab091

MO612 THE ROLE OF MECHANICAL MUSCLE POWER IN PHYSICAL


CKD. REHABILITATION DYSFUNCTION: A MODEL FOR TAILORING RESISTANCE-
BASED REHABILITATION IN CHRONIC KIDNEY DISEASE

MO611 CARDIOPULMONARY RESERVE EXAMINED WITH Thomas Wilkinson1, Eleanor Gore1, Jared Palmer1, Luke Baker1, Emma Watson2,
CARDIOPULMONARY EXERCISE TESTING IN INDIVIDUALS Alice Smith1
1
WITH AND WITHOUT CHRONIC KIDNEY DISEASE; A Leicester, Department of Health Sciences, Leicester, United Kingdom and 2Leicester,
SYSTEMATIC REVIEW AND META-ANALYSIS Department of Cardiovascular Sciences, Leicester, United Kingdom

Eva Pella1, Marieta Theodorakopoulou1, Afroditi Boutou2, Maria BACKGROUND AND AIMS: Individuals living with CKD are characterised by
Eleni Alexandrou1, Dimitra Bakaloudi1, Aristi Boulmpou3, adverse changes in physical function. Knowledge of the factors that mediate
Christodoulos Papadopoulos3, Aikaterini Papagianni1, Pantelis Sarafidis1 impairments in physical functioning is crucial for developing effective interventions
1 that preserve mobility and future independence. Mechanical muscle power describes
Hippokration Hospital, Aristotle University of Thessaloniki, Department of Nephrology,
Thessaloniki, Greece, 2G. Papanikolaou Hospital, Department of Respiratory Medicine, the rate of performing work and is the product of muscular force and velocity of
Thessaloniki, Greece and 3Hippokration Hospital, Aristotle University of Thessaloniki, contraction. Muscle power has been shown to have stronger associations with
Third Department of Cardiology, Thessaloniki, Greece functional limitations and mortality than sarcopenia in older adults. In CKD, the role
of mechanical muscle power is poorly understood and is overlooked as a target in
BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) often many rehabilitation programmes, often at the expense of muscle mass or strength. The
present with reduced physical activity and exercise performance due to a number of aims of this study were to 1) explore the prevalence of low absolute mechanical power,
factors relevant to co-existing disturbances of the cardiac, nervous and muscular low relative mechanical power, and low specific mechanical power in CKD; and 2)
systems. Cardiopulmonary exercise testing (CPET) is widely applied in daily clinical investigate the association of mechanical power with the ability to complete activities of
practice used for clinical evaluation of exercise intolerance and related symptoms (i.e. daily living and physical performance.
dyspnea, fatigue), as well risk stratification, and other applications in several medical METHOD: Mechanical muscle power (relative, allometric, specific) was calculated
fields. using the sit-to-stand-5 (STS5) test as per previously validated equations. Legs lean
METHOD: This is a systematic review and meta-analysis of studies which used CPET mass was derived from regional analyses conducted using bioelectrical impedance
technology in adult patients with CKD to examine cardiopulmonary reserve in analysis (BIA). Physical performance was assessed using two objective tests: usual gait
individuals with versus individuals without CKD. The primary outcome was peak speed and the ‘time-up-and-go’ (TUAG) test. Self-reported activities of daily living
oxygen uptake (VO2peak). Literature search involved PubMed, Web of Science and (ADLs) were assessed via the Duke Activity Status Index (DASI). Balance and postural
Scopus databases; manual search of article references and of grey literature was also stability (postural sway and velocity) was assessed using a FysioMeter. Sex-specific
performed. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved tertiles were used to determine low, medium and high levels of relative STS power and
studies. its main components.
RESULTS: From an initial 4944 literature records, we identified 29 studies fulfilling the RESULTS: 102 participants with non-dialysis CKD were included (mean age: 62.0
inclusion criteria; of these, 25 studies with complete data including 2213 participants (614.1) years, n=49 males (48%), mean eGFR: 38.0 (621.5) ml.min.1.73m2). The
were included in final meta-analysis. Peak oxygen uptake (VO2peak) was significantly mean estimated relative power was 3.1 (61.5) W.kg in females and 3.3 (61.3) W.kg in
lower in CKD patients compared to controls without CKD (standardized-mean- males. Low relative power was found in 35/102 (34%) patients. Relative power was a
difference, SMD:-1.40, 95%CI[-1.68, -1.13]) (Figure). Oxygen consumption at significant independent predictor of self-reported ADLs (via the DASI) (B=.413,
anaerobic threshold (VO2AT) (SMD:-1.06, 95%CI[-1.34, -0.79]), maximum workload P=.004), and performance on the TUAG (B=-.719, P<.001) and gait speed (B=.404,
(weighted-mean-difference, WMD:-58.26, 95%CI[-74.14, -42.38]) and respiratory P=.003) tests. Skeletal muscle mass was not associated with the DASI or any of the
exchange ratio (RER) (WMD:-0.02, 95%CI[-0.05, 0.01]) were also impaired in CKD objective function tests
patients compared to non-CKD individuals. In 3 studies comparing patients with CKD CONCLUSION: Patients presenting with low muscle power would benefit from
versus patients with heart failure without CKD VO2peak was higher in the former participation in appropriate interventions designed to improve the physiological
(WMD:6.60, 95%CI[3.02, 10.18]). Sensitivity analyses confirmed the robustness of components accounting for low relative muscle power. Assessment of power can be
these findings. used to tailor renal rehabilitation programmes as shown in Figure 1. Incorporation of
CONCLUSION: VO2peak and other commonly analyzed CPET variables were lower power-based training, a novel type of strength training, designed by manipulating
in CKD patients compared to controls, indicating reduced functional cardiopulmonary traditional strength training variables and primarily movement velocity and training
reserve in the former. In contrast, CKD patients performed better when compared intensity may present the best strategy for improving physical function in CKD.
patients with heart failure.

MO611 Figure:VO2peak in CKD patients vs Controls

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

MO613 EFFECT OF 12 WEEK TRAINIG ON PHYSICAL ACTIVITY ON a target in less than 2s, the custom software provides both visual (the target explodes)
PATIENT ON A LOW PROTEIN DIET and auditory (positive sound) feedback as a reward (success).
The three outcome measures (Exergame-slowness, frailty, and cognitive performance)
Durdona Saipova1 were analyzed. Exergame-slowness was computed as an average of the ranges of ankle
1
Tashkent Medical Pediatric Institute, Internal disease, Tashkent, Uzbekistan angular velocity measured by wearable sensors. Linear regression analysis was
conducted for the three outcome measures to examine correlations between each
BACKGROUND AND AIMS: Symptoms such as fatigue, muscle weakness and outcome measure. Binary logistic regression model was conducted, and its area-under-
impaired nutritional status are common in CKD and lead to decreased exercise curve (AUC) was calculated to determine the ability of Exergame-slowness to identify
tolerance. CF. An independent t-test was conducted to compare the differences of Exergame-
The aim of the study was to study the effect of 12-week training on physical activity in slowness for CF and non-CF conditions. Significance was defined at the 2-sided p <
patients with pre-dialysis stages of CKD on a low-protein diet. 0.05 level.
METHOD: The study included 119 patients with CKD C3 and C4 stages. Clinical data RESULTS: Five out of 28 participants were identified with CF. Significant correlations
included anthropometric data: body mass index (BMI), mid-thigh circumference and were observed between Exergame-slowness and frailty (p = 0.004, R = -0.531),
mid-shoulder circumference, laboratory data: urea, creatinine, electrolytes, albumin, Exergame-slowness and cognitive performance (p = 0.023, R = 0.437), and frailty and
total protein, hemoglobin. All patients underwent instrumental research methods: cognitive performance (p = 0.015, R = -0.463). The model was significantly reliable (p =
ECG, EchoCG, cardiopulmonary stress test. The patients included in the study were 0.012) and its AUC was 0.90. Results indicated that Exergame-slowness was
offered three dietary options - with a low protein content (0.6 g / kg / day;) and a significantly higher (lower velocity) for participants with CF than for those with non-
limited protein content (0.6-0.8 g / kg / day;), and low protein diet with keto analogs (1 CF (CF: 27.41 6 3.58 degree/s, non-CF: 34.25 6 5.24 degree/s, p = 0.010).
tab / 5 kg body weight / day). The physical exercise program was designed for CONCLUSION: To our knowledge, this is the first study to investigate the feasibility
independent home use and included cardiovascular exercises (primarily walking, and accuracy of intradialytic-exergame with wearable sensors, as a practical tool for
morning exercises) and strength training exercises with dumbbells 1 and 3 kg. The routine screening CF assessment in hemodialysis patients. The results of this study
training frequency was at least 3 times a week and had a duration of at least 20–30 indicate that speed of ankle rotation, measurable using a wearable sensor during a
minutes. The patients kept exercise diaries, which were reviewed by the doctor at each simple intradialytic cognitive-demanding exercise, can be used as a practical digital
subsequent visit. The training exercise was adjusted depending on the self-perception biomarker for screening CF in hemodialysis patients.
of the patients; if necessary, the training time was increased to 60 minutes.
RESULTS: The 1 group 24% of patients received a diet with a low protein content, the
second group consisted of 40% of patients, the third group consisted of 37% of patients
receiving a diet with a limited protein content. The male to female ratio, mean
glomerular filtration rate, daily proteinuria and BMI did not differ significantly
between groups. In the dynamics of 12 weeks of training, an increase in the mid-thigh
and upper arm circumference was recorded. The study of physical activity of patients
with different types of diet showed that in patients of the 1st group, even with a low
nutritional status in the dynamics of 12 weeks of training, there was an improvement in
such physical indicators as the circumference of the mid-thigh and upper arm, and also
a slight improvement in the BMD. When comparing the groups of patients who
received and did not receive ketoanologs (groups 2 and 3, respectively), physical
training for 12 weeks instilled a significant improvement in indicators such as mid-arm
circumference and maximum oxygen consumption(peak VO2). However, in the group
receiving keto analogs, there was a significantly greater improvement in maximum
oxygen consumption (peak VO2).
CONCLUSION: Regular dosed exercise has a positive effect on physical fitness in CKD
patients on a low-protein diet. Correction of nutrition with keto analogs improves the
cardiorespiratory status of patients.
MO615 SUPPORT FOR CHRONIC KIDNEY DISEASE PATIENTS
DURING COVID-19: PERSPECTIVES FROM PATIENTS,
FAMILY AND HEALTHCARE PROFESSIONALS
MO614 A PRACTICAL SOLUTION TO SCREEN COGNITIVE FRAILTY
AMONG HEMODIALYSIS PATIENTS USING A GAME-BASED Archontissa Kanavaki1, Jared Palmer2, Courtney J Lightfoot2,
INTRADIALYTIC EXERCISE WITH WEARABLE SENSORS Thomas Wilkinson3, Roseanne E Billany4, Alice Smith2
1
University of Leicester, Leicester Kidney Lifestyle Team, Health Sciences, United
Catherine Park1, Fadwa Al-Ali2, He Zhou3, Abdullah Hamad2, Talal Talal4, Kingdom, 2University of Leicester, Health Sciences, United Kingdom, 3University of
Rania Ibrahim2, Bijan Najafi1 Leicester, Health Sciences and 4University of Leicester, Cardiovascular Sciences, United
1
Baylor College of Medicine, Department of Surgery, Houston, United States of America, Kingdom
2
Hamad General Hospital, Department of Nephrology, Doha, Qatar, 3BioSensics LLC,
Newton, United States of America and 4Hamad Medical Co, Diabetic Foot and Wound BACKGROUND AND AIMS: Patients with non-dialysis chronic kidney disease
Clinic, Doha, Qatar (CKD patients) require specialised management, including routine clinical visits,
laboratory measures, and medication adjustments. Inevitably, the COVID-19
BACKGROUND AND AIMS: Assessing and monitoring cognitive frailty (CF; pandemic has resulted in changes to delivery of care in a bid to prevent virus
coexistence of physical frailty and cognitive impairment) are critical for hemodialysis transmission in this clinically vulnerable group. The extent of the impact of any
patients. For administering physical frailty and cognitive assessments, however, clinical changes in support provision for patients is largely unknown. The study aimed to
settings need to address challenges (e.g., cost, human and technical resources, patient’s capture the views of CKD patients, family or other significant person in their lives
fatigue, etc.). This study aims to investigate the feasibility and accuracy of a novel (SO), and nephrology healthcare professionals (HCPs) on how patients’ healthcare
intradialytic cognitive-demanding exercise program based on wearables, called, needs were and could be supported during this time.
intradialytic-exergame for screening CF in hemodialysis patients. METHOD: CKD patients, their SO (e.g., family member, friend) and HCPs from 10
METHOD: Individuals diagnosed with diabetes and end-stage renal disease requiring secondary care sites across England were invited to take part in a bespoke online
hemodialysis (n=28, age: 61.36 6 6.85 years, 54% female) participated. All participants survey, as part of the DIMENSION-KD portfolio adopted study. Participants
were assessed for physical frailty using the Fried frailty phenotype method and responded to yes/no and free-text questions about their satisfaction with available
cognitive impairment using the Mini-Mental State Examination (MMSE). The Fried healthcare support (CKD, SO) and patients’ need for additional support (CKD, SO,
frailty phenotype method assesses physical frailty, which ranges between 0 and 5 based HCP). Thematic analysis was applied to the free-text responses.
on five criteria (unintentional weight loss, weakness, slowness, exhaustion, and low RESULTS: 230 CKD patients (mean age 63.8, SD 13.8 years), 67 SO (74% spouses),
physical activity). CF was determined with a frailty phenotype greater than or equal to and 59 HCP of various specialties completed the survey between August and December
1 and a MMSE score less than or equal to 24. 2020. 84% of CKD participants felt they could get the support they needed. The most
The intradialytic-exergame system consists of an inertial wearable sensor and an frequent explanation (25%) was that direct contact with a member of their renal team
interactive software installed on a standard laptop. A clinician attaches one wearable was available when needed. Other explanations included 1. being monitored by the
sensor to each foot after the participant sits or lies down on a bed (Figure A). While renal team, 2. continuation of regular appointments and having additional treatment
undergoing hemodialysis treatment, the participant performs 15 non-weight-bearing when necessary, 3. an accessible local General Practice (GP), and 4. a particularly
cognitively-demanding dorsiflexion and plantarflexion exercises for each foot. For each “helpful” nephrologist or “good relationships” with their doctors. All SO felt the patient
exercise, the laptop’s screen displays a target (solid yellow circle) and a cursor (solid red could get the help they required. Their explanations were in line with those of CKD
square), which the participant points down for a dorsiflexion motion or up for a patients, i.e., readily available contact and access to the renal team (25%), followed by
plantarflexion motion (Figure B). When the participant successfully puts the cursor in good relationship or highly positive experience with member(s) of the renal team,
the target, the target disappears, and a new target appears in a different location on the regularity of contact/ appointments, and GP accessibility. When asked about additional
screen (dashed yellow circle shown in Figure B). If the participant moves the cursor to healthcare information and support they would like, “none” was the most common
response by CKD patients (28%), followed by the need for reliable information around

i362 | Abstracts
Nephrology Dialysis Transplantation Abstracts
COVID-19 and renal conditions, access to local GP, and a reliable point of contact MO617 EFFECTS OF 12 WEEK PHYSICAL EXERCISES ON ECHO-
when kidney condition deteriorates. Similarly, for many SO there was no need for GEOMETRIC PARAMETERS IN PATIENTS WITH CKD
additional support, whilst the most often suggested type of support was provision of
reliable information on COVID-19 and renal health. For HCP, accessible service and Durdona Saipova1
1
guidance (36%) and psychosocial support for patients (25%) were most frequently Tashkent Medical Pediatric Institute, Internal disease, Tashkent , Uzbekistan
cited types of additional support that would benefit patients.
CONCLUSION: An accessible point of contact for renal care and continuation of BACKGROUND AND AIMS: Structural and functional changes in the cardiovascular
regular monitoring of some form emerged as key factors in CKD patient support across system in patients with chronic kidney disease (CKD) will lead to decreased exercise
the three stakeholder groups. Some needs raised, such as limited access to GP, are tolerance, decreased quality of life, and, ultimately, premature death.
relevant to local primary or secondary healthcare services, while practices adopted by The aim of this study was to study morphometric changes in the left ventricle of the
some renal teams, such as a number for patients to ring when needed, seemed to offer heart depending on the direction of therapeutic physical training.
reassurance and satisfaction among patients and their SO. METHOD: The study involved 60 patients with CKD stage C3. The average age of the
patients was 54.2 6 3.40 years. The average level of GFR for the sample as a whole was
79.1 6 9.4 ml / min / 1.73 m2. The control group (CG) consisted of 20 people (10 men
and 10 women) comparable to the main group in terms of gender and age. The
MO616 GAIT SPEED AND BODY COMPOSITION IN HAEMODIALYSIS examination of patients included a general examination, assessment of complaints,
PATIENTS collection of anamnestic data, anthropometry with calculation of BMI
cardiopulmonary stress test, echocardiography.
Barbara Cancho Castellano1, Cristina Lo pez Arnaldo1, Jorge Alberto Rodriguez According to the data of the cardiopulmonary stress test, 3 groups were formed on the
Sabillon1, Rafael Arago 
n Lara2, Alvaro 
Alvarez pez1, Rosa Maria Diaz
Lo basis of the predominant manifestation of any physical quality in the course of
Campillejo1, Julia n Valladares Alcobendas1, Marıa Victoria Martın Hidalgo therapeutic training: group 1 (n = 20) - with a respiratory orientation of the training
Barquero1, Rosa Marıa Ruiz Calero Cendrero1, Nicolas-Roberto Robles Perez- process; 2nd group (n = 20) - with a focus on cardio loads; 3rd group (n = 20) -
Monteoliva1 development of predominantly endurance.
1
Badajoz University Hospital, Nephrology, Badajoz, Spain and 2Badajoz University RESULTS: Of all groups of patients with CKD, the LVMM indicator reached the
Hospital, Internal Medicine, Badajoz, Spain highest values in men in group 2 (with a cardio-load orientation of the treatment-
training process), as well as in women in group 3 (predominantly endurance
development). It is this orientation of the training process that has the greatest effect on
BACKGROUND AND AIMS: Gait speed is a predictor of disability, mobility the increase in the mass of the left ventricular myocardium in patients with CKD. The
limitation and mortality. Buchner et al. the first to observe a non-linear relationship 2nd group of patients with CKD stage CKD had the highest values of LVTD in diastole
between leg strength and normal gait speed. This relationship was explained as small both among men and women. In addition, men in this group had the highest RTI per
changes in physiological capacity. The objective of this study is to assess the systole. In patients of the 2nd group, undergoing mainly cardio load, the change
relationship between gait speed and body composition in haemodialysis. concerned a slightly more pronounced increase in the wall thickness of the left
METHOD: Cross-sectional study in 40 subjects with CKD in hospital haemodialysis, ventricle.
70.5613.03 years, 62.5% male. 40% Diabetic Nephropathy, 10% Glomerulopathies, In the 3rd group of patients with CKD stages C3, both men and women had the
7.5% Nephroangiosclerosis, 2.5% Chronic Tubule-Interstitial Nephropathies, 32.5% maximum values of TMV in diastole, as well as LVTD in systole. Types of
Unknown, 2.5% Others. 35% arteriovenous fistula, 10% arteriovenous graft, 55% physiotherapy exercises with a predominance of endurance in physical exertion are
central venous catheter. Haemodialysis type: 40% High Flux, 45% Online distinguished by the most pronounced signs of left ventricular myocardial
postdilutional Haemodiafiltration, 10% Acetate Free Biofiltration. Gait seed was hypertrophy.
measured on the middle day of the week, predialysis. CONCLUSION: The present study has shown that patients with pre-dialysis CKD
Body composition was estimated by monofrecuency bioimpedance measurement (50 have decreased maximal and submaximal exercise tolerance. Analysis of the data
KHz) on the middle day of the week, posthemodialisis. obtained made it possible to reveal the peculiarities of adaptation of the cardiovascular
Statistical analysis was performed with SPSS 13.0. system of patients with CKD stages CKD to a specific type of therapeutic training and
RESULTS: Average gait speed 0.660.38 m/s, median 0.65 (IQR 0.18) m/s, range (0, to determine the quantitative values of echocardiographic parameters in patients with
1.23) m/s. The prevalence of a gait speed less than or equal to 0.8 m/s was 67.5%, while CKD.
32.5% of the patients presented a gait speed less than or equal to 0.8 m/s. Gait speed
was lower among diabetics (0.7760.3 vs 0.4660.39, p=0.0074). A positive and
significant correlation was observed between gait speed and phase angle. No
correlation was observed between gait speed and body fat. A positive linear relationship MO618 BIBLIOMETRIC ANALYSIS OF SCIENTIFIC PRODUCTION ON
or dependence was observed between gait speed and muscle mass and cell mass. In PHYSICAL REHABILITATION IN PATIENTS UNDERGOING
relation to body water, a negative linear relationship is observed with the EW/IW ratio. DIALYSIS IN THE LAST 24 YEARS
Table 1.
Camila Salazar1, Maryorie Sandoval1, Paula Moscoso1, Cristian Salazar2
1
MO616 Table 1. Gait speed and body composition in Haemodialysis patients. Universidad Austral de Chile, Physiotherapy, Valdivia, Chile and 2Universidad Austral
de Chile, Administration Institute, Valdivia, Chile

BACKGROUND AND AIMS: Patients with end stage renal disease (ESRD) exposed
r Pearson Sig. to renal replacement therapy (RRT) have many consequences, both physical and
Phase angle 0.6455 0.0000 psychological. Dialysis patient rehabilitation is a way to improve the well-being and
quality of life of users, but it is an area that has not been commonly explored and where
Exchange Na/K -0.4576 0.003 there is much to know. The participation of the Physiotherapist in the rehabilitation of
Total body water(L)% -0.18250.0198 0.25970.9144 these patients has increased mainly in the last period. The present study aims to carry
Extracellular water EW(L)% -0.18870.6648 0.24350.0000 out an analysis of how the scientific field has behaved in relation to rehabilitation in
Intracellular water (L)% 0.61880.6638 0.00000.0000 patients undergoing dialysis, exploring the existing bases for new studies and knowing
EW/IW -0.6072 0.0000 how it has varied between the years 1996 to 2020.
METHOD: The present study is a bibliometric analysis. Through this type of study, it
Fat Free Mass (kg) 0.26 0.09 is possible to analyze the scientific production and how is the activity on some subject.
Muscle Mass(kg) 0.56 0.0002 It allows, among others, the development of research topics that are little studied, in
Fat Mass(kg)% 0.07-0.0326 0.660.8417 addition to evaluating the countries, institutions and authors in a certain period. A
Body cell mass index 0.5707 0.0001 search for scientific articles was carried out using the web of science (WOS) page,
obtaining 236 articles. The search key was TS = (“rehabilitation”) AND TS = (physical
CONCLUSION: There is a dependent relationship between gait speed and diabetes in exercise or haemodialysis or renal dialysis or peritoneal dialysis) AND TS =
haemodialysis patients. The decrease of the phase angle, the increase of the ratio EW/ (hemodialysis) NOT TS = (fistula). In the same WOS platform, a filter was carried out
IW changes with the decrease the cell mass index are inversely related to the gait speed where only articles, reviews and conference articles were included, excluding editorial
in haemodialysis patients. These items and the gait speed, which provide information material, book chapters and early accesses, articles that are in the range of years
on the state of vulnerability of the patient, could be markers of frailty. between 1990 and 1995 were also excluded. These years were chosen because it was
observed that from 1996 an increase in the trend on the subject under study can be
observed. With this filtration the articles decrease to 191 results. The Scimat and
Bibliometrix biblioshiny softwares were used for their analysis.
RESULTS: A total of 191 records were compiled among which we have been able to
identify different bibliometric indicators that allow us to know the scientific
performance and how it has behaved over the years. Figure 1 shows a descriptive graph
obtained from biblioshiny bibliometrix where it was shown the annual scientific
production of the documents, with dates that fluctuate between 1996 and 2020. It is
observed that the scientific production on this issue of rehabilitation in dialysis patients

10.1093/ndt/gfab091 | i363
Abstracts Nephrology Dialysis Transplantation

through the years has been developing exponentially since 1996. However, there are MO619 GOODRENAL: HOLISTIC PATIENT CARE INTRADIALYSIS
years in which production decreased significantly. It was also found the authors who PROGRAM IN HEMODIALYSIS THROUGH A VIRTUAL
have published the most, the journals and their categorizations, and the network of HEALTH PLATFORM
collaborations that exist between authors from different countries, being the United
States the pioneer country in scientific production. Finally, emerging studies on the Eva Segura-Ortı1, Naomi Clyne2, Alicia Garcia-Testal3, Evangelia Kouidi4,
subject were found. Amaryllis Van Craenenbroeck5, Carla Avesani6, Patricia Mesa-Gresa7, José
Antonio Lozano-Quilis8, Bengt Lindholm6, Paula Moscoso9, Maycon
Moura Reboredo10, Andreas Lauer1
1
Universidad Cardenal Herrera-CEU, CEU Univerisities, Physiotherapy, Alfara del
Patriarca, Spain, 2Sk€
ane University Hospital, Nephrology, Lund, Sweden, 3Hospital de
Manises, Nephrology, Manises, Spain, 4Aristotle University of Thessaloniki, Laboratory of
Sports Medicine, Thessaloniki, Greece, 5Katholieke Universiteit Leuven,, Department of
Microbiology, Immunology and Transplantation, Leuven, Belgium, 6Karolinska Institute,
Department of Clinical Science, Intervention and Technology; Division of Renal
Medicine, Baxter Novum, Stockholm, Sweden, 7Universistat de València, Psychobiology
department, Valencia, Spain, 8Universitat Politècnica de Valéncia, DSIC, Valencia, Spain,
9
Universidad Austral de Chile, Physiotherapy, Valdivia, Chile and 10Federal University of
Juiz de Fora, School of Medicine, Juiz de Fora, Brazil

BACKGROUND AND AIMS: There is wide evidence that weak points of the care of
end-stage Chronic kidney disease (CKD) patients in hemodialysis include three aspects
that are suitable for intervention: exercise, nutrition and psychological support.
Evidence shows that exercise for patients on hemodialysis results in increased
functional capacity and strength and improved health-related quality of life and
survival. Additionally, earlier studies have shown the benefits of psychological
MO618 Figure 1: Annual productivity of scientific articles interventions and the positive effect of educational programs on nutritional status for
patients on hemodialysis. Despite the well-known benefits of exercise, these programs
are not being implemented in the routine clinical care of hemodialysis patients. Thus,
CONCLUSION: In this study we have addressed different points to show and the GoodRENal project aims to promote a healthy lifestyle among hemodialysis
publicize the issue of rehabilitation in dialysis patients, with its greatest contributors in patients using a holistic pedagogical approach that, addressing adult learners, combines
recent years. We can say that many studies are still missing to be able to have a solid exercise, nutrition and psychological well-being as well as cognitive functioning.
base in the rehabilitation of these patients, who are increasing more every day in the METHOD: GoodRENal is a project funded by the European Community, Erasmus þ
world population. Although, we have compiled a significant number of studies, it is program (336.327 euros). The project will last 3 years, from September 2020 to August
probably not all of them, studies that complement the information are needed with 2023 and the Partners of the consortium include institutions from five European
other search engines. This study can serve as a starting point for future research, which countries: Spain (Universidad CEU Cardenal Herrera, Hospital de Manises, Univesitat
is necessary in the field of dialysis, although the production rate has increased over the de Valéncia, Universitat Politécnica de Valéncia), Sweden (Skane University Hospital
years it is still quite low, it is important that new authors appear who can work among and Karolinska Institutet), Greece (Aristotles University of Thessaloniki) and Belgium
them to advance and thus obtain knowledge that allows us to help and benefit patients (Katholieke Universiteit Leuven). Other supporting institutions are located in the UK,
around the world. In addition, we have considered it very important to mention and Chile and Brazil.
suggest so that Latin American countries can become more interested in this topic, RESULTS: The project will develop a virtual platform comprising three aspects of care:
since they are part of the countries that produce the least, however, their population on physical activity/exercise, nutrition, psychological well-being/cognition. In summary,
dialysis increases progressively over the years. the project outputs will be: 1. A didactic content on a modular platform with an
educational program for integrated treatment in patients on hemodialysis; 2. A
guideline to promote a healthy lifestyle among patients on hemodialysis for healthcare
providers; 3. A guideline to promote a healthy lifestyle among patients on
hemodialysis for patients, and their formal- and non-formal carers. At the present
stage exploratory questionnaires regarding physical activity/exercise-nutrition-
psychological well-being/cognition have been developed in consensus with all the
partners. Data from this first exploratory study regarding needs and barriers of the
stakeholders (patients, health professionals, carers) will be presented at the ERA-EDTA
congress.
CONCLUSION: GoodRENal aims at improving the overall health, and thus the
health-related quality of life, of patients on hemodialysis through a holistic and
pedagogical approach that will target especially improvements of patient reported
outcomes including quality of life.

i364 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i365–i370, 2021
10.1093/ndt/gfab093

DIABETES. BASIC RESEARCH participants without diabetes and with diabetes type 1 (T1D), and type 2 (T2D). In
addition, the effect of different treatments for T2D on KPV was investigated.
METHOD: KPV was estimated in 35,703 UKBB participants (52% women, age = 45-
82 years) with a deep-learning-based segmentation of both kidneys (Dice = 0.956, error
MO620 ANTIFIBROTIC EFFECTS OF SGLT2 INHIBITION IN THE < 4%). The cohort was classified into Control, T1D and T2D subjects using an
KIDNEY AND PROXIMAL TUBULAR CELLS* algorithm developed on UKBB clinical data (Eastwood et al 2016). Individuals with
T2D were further divided into groups related to treatment: Lifestyle (no
Dora Balogh1,2, Judit Hodrea1,2, Adam Hosszu1,2, Tamas Lakat1,2, pharmaceuticals, i.e. light treatment, mean disease duration of 6.2 years), Metformin
Adar Saeed1,2, Lilla Lenart1,2, Laszlo Wagner3, Attila Szabo2,4, Andrea Fekete1,2 (metformin as the only pharmaceutical, i.e. intermediate treatment, mean disease
1
Semmelweis University, Diabetes Research Group, Budapest, Hungary, 2Semmelweis duration of 8.3 years), and Other (more potent treatment, combination of
University, 1st Department of Pediatrics, Budapest, Hungary, 3Semmelweis University, pharmaceuticals, mean disease duration of 14.1 years). KPV was studied as a function
Department of Transplantation and Surgery, Budapest, Hungary and 4Semmelweis of age in the different groups, divided according to sex. The statistical difference in
University, MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary mean KPV between groups was tested. For each group, the association between KPV
and age was assessed by linear regression. Comparison of line slopes was conducted to
investigate whether age-related patterns in KPV differed statistically between groups.
BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is a major cause of RESULTS: The moving average curve of KPV vs age, in controls and subjects with
chronic kidney disease and end stage renal disease, therefore identification of novel T1D and T2D, is shown in Fig 1A (with a 15-year sliding window). The corresponding
therapeutic strategies that reduce the risk of DKD is a research priority. Recent large curve for different T2D treatment groups is depicted in Fig 1B. Fig 2A-D presents
clinical trials suggest that improved renal outcomes by sodium-glucose cotransporter 2 results for the comparison of KPV and regression line slope between the subject
inhibitors (SGLT2i) are partly beyond their glucose lowering effects. Enhanced glucose groups. According to Fig 1A and 2A, KPV is usually higher in subjects with T1D and
reabsorption in diabetes leads to tubular hypoxia triggering fibrotic response. T2D than in controls. As shown in Fig 1B and 2B, T2D subjects with longer disease
Hyperglycemia is in strong association with increased protein O-GlcNAcylation, a duration and on pharmaceutical treatment (Metformin or Other) are generally more
post-translational modification contributing to renal fibrosis. Considering the proximal prone to large KPV than subjects with adapted lifestyle as treatment. The decreasing
tubular involvement in DKD pathogenesis and the key role of SGLT2 in glucose KPV pattern with age is faster in T2D subjects than controls but not significantly
metabolism, here we investigated the effects of SGLT2i on tubular hypoxia and O- different between T1D subjects and controls (Fig 1A and 2C). Women in group Other
GlcNAcylation. also show a pattern of steeper age-related decline in KPV compared to remaining
METHOD: Diabetes (D) was induced by streptozotocin (65 mg/bwkg, ip.) in adult, women with T2D treatment (Fig 1B and 2D).
male Wistar rats. Following the onset of diabetes rats were treated for six weeks with
dapagliflozin (DþDAPA, 1 mg/bwkg/day, po.). Metabolic parameters and renal
function were evaluated. Novel urinary biomarkers of extracellular matrix remodeling
(Pro-C3, uC3M, tumstatin) and profibrotic growth factors (TGF-b, CTGF, PDGF)
were determined. Histological evaluation of glomerular damage (PAS),
tubulointerstitial fibrosis (Masson’s trichrome, Picrosirius red) and fibronectin
accumulation were performed. The effect of hyperglycemia was tested in human
proximal tubular epithelial cells (HK-2) kept under normal glucose (5.5 mM), high
glucose (35 mM) or high mannitol (osmotic control, 35 mM) conditions for 24 hours.
HG cells were treated with 10 mM DAPA. O-GlcNAc, O-GlcNAc transferase (OGT)
and O-GlcNAcase (OGA) were measured. To test the effect of hypoxia cells were
treated with 10 mM DAPA and were placed in a hypoxic chamber (1% O2) for 2 hours.
Hypoxic injury was investigated using three different methods (qRT-PCR, Western
blot, immunofluorescence analysis). HIF-1a, EPO, VEGFA and profibrotic factors MO621 Figure 1: KPV mean average curves vs age in (A) controls, T1D, and T2D
were measured. subjects, and (B) T2D subjects with different treatments (Lifestyle = no
RESULTS: DAPA decreased blood glucose levels (D: 3762.7 vs. DþDAPA: 1865.6 pharmaceuticals, Metformin = metformin only, Other = other treatments)
mmol/L; p<0.05) and improved renal function (creatinine clearance: D: 3.860.4 vs.
DþDAPA: 8.961.0 mL/min; p<0.01). In parallel, novel urinary biomarkers of
extracellular matrix remodeling, profibrotic growth factor expressions and extensive
fibrotic tissue accumulation were reduced in the kidney. DAPA minimized
hyperglycemia-induced total protein O-GlcNAcylation in HK-2 cells. Hypoxia-
induced HIF-1a elevation was suspended by DAPA treatment. Moreover, DAPA
treatment prevented HIF-1a translocation to the nucleus, thereby confirming abolished
HIF-1a activation. EPO, VEGFA and profibrotic factor levels were also increased in
hypoxia and DAPA prevented EPO, TGFB and PDGF elevation.
CONCLUSION: These data highlight the role of ameliorated O-GlcNAcylation and
diminished tubular hypoxia as important benefits of SGLT2i treatment. Our results
support the link between glucose toxicity, tubular hypoxia and fibrosis, a vicious trio,
which seem to be targeted by SGLT2i. All these mechanisms are important parts in the
puzzle of the complex system behind the protective effect of SGLT2i.
OTKA-FK124491-K135398, 2017-1.3.1-VKE-2017-00006, 2020-4.1.1.-TKP2020-
6183169273, 2020-4.1.1.-TKP2020-6183069269

MO621 AGE-RELATED PATTERNS OF KIDNEY PARENCHIMAL


VOLUME IN T1D, T2D AND DIFFERENT TREATMENT
GROUPS OF T2D: A CROSS-SECTIONAL STUDY OF 35,703
UK BIOBANK PARTICIPANTS

Andrés Martınez Mora1, Elin Lundström1, Taro Langner1, Paul Hockings2,


Lars Johansson2, Håkan Ahlström1,2, Joel Kullberg1,2
1
Uppsala University, Surgical Sciences, Radiology, Uppsala, Sweden and 2Antaros
Medical AB, Mölndal, Sweden

BACKGROUND AND AIMS: Kidney parenchymal volume (KPV) presents a natural


variation with respect to sex, age, and body size, and is also affected by diseases such as
diabetes. The UK Biobank (UKBB) is a large-scale study including clinical and MRI
data. The current project investigated the association between KPV and age in UKBB

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

MO621 Figure 2: KPV distributions in (A) subjects with different diabetes status,
and (B) T2D subjects with different treatments. Distributions of line slopes of KPV vs
age in (C) subjects with different diabetes status, and (D) T2D subjects with different
treatments. Mean value and standard deviation of distributions are represented by
horizontal lines inside boxes and box widths, respectively. Significant p values
indicated by bold font and *

CONCLUSION: Compared to controls, T1D subjects show enlarged KPV similar to


that of T2D subjects, which is in line with previous literature. Subjects with T2D show
a pattern of steeper age-related decline in KPV compared to controls. Female T2D
subjects with longer disease duration, usually on a more potent treatment (beyond
adaption of lifestyle and metformin as the only pharmaceutical), are more prone to
enlarged KPV and exhibit a pattern of steeper age-related decline in KPV. This may be
due to hyperfiltration caused by diabetes, resulting in increased kidney size. The
normal loss of glomeruli with age could be accelerated by diabetes, leading to a greater
loss in KPV per year in diabetics. Steeper KPV decline patterns in disease could also be
caused by selection bias where old subjects with large KPV and related complications
are less likely to participate in the study.

MO622 IMPAIRED PROTEIN-BOUND UREMIC TOXIN EXCRETION


SUGGESTS TUBULAR DYSFUNCTION IN DIABETIC
NEPHROPATHY

Karin Gerritsen1, Sabbir Ahmed2, Rolf Sparidans2, Silvia Mihaila1,2,


Roel Broekhuizen3, Roel Goldschmeding1, Tri Nguyen3, Rosalinde Masereeuw2
1
University Medical Center Utrecht, Department of Nephrology and Hypertension,
Utrecht, The Netherlands, 2Utrecht University, Division of Pharmacology, Utrecht
Institute for Pharmaceutical Sciences, Utrecht, The Netherlands and 3University Medical
Center Utrecht, Department of Pathology, Utrecht, The Netherlands

BACKGROUND AND AIMS: Kidney tubular damage is an important prognostic


determinant in diabetic nephropathy (DN) (1). Proximal tubular secretion is a vital
homeostatic function that is responsible for excretion of waste, such as protein bound MO622 Figure 1: Plasma concentration (A-C), urinary concentration (normalized
uremic toxins (PBUTs) that are minimally eliminated via glomerular filtration. PBUTs to creatinine) (D-F) and urinary excretion (normalized to respective plasma
are potentially harmful waste products of endogenous metabolism that are efficiently concentration) (G-I) of protein bound uremic toxins in diabetic nephropathy mice
excreted by tubular secretion via organic anion transporters (OATs). Currently after 6 months. Data are presented as mean 6 SD. Non-parametric Mann-Whitney U
available diagnostic methods cannot accurately detect tubular dysfunction. We test or unpaired t-test was performed for statistical analysis. *** P < 0.001, ** P < 0.01,
hypothesize that renal PBUT clearance may be a sensitive tubular function marker. * P < 0.05. (IS = indoxyl sulfate, HA = hippuric acid, KA = kynurenic acid, Cr =
Here, we measured PBUTs in long-term streptozotocin (STZ)-induced murine diabetic Creatinine).
nephropathy (DN), which was characterized by severe tubular atrophy and interstitial
fibrosis (2).
METHOD: Diabetes mellitus was induced in C57Bl/6 mice by a single intraperitoneal
injection of 200 mg/kg STZ which resulted in substantial kidney damage after 6
months evaluated by histopathology and conventional markers (2). Indoxyl sulfate
(IS), hippuric acid (HA), kynurenic acid (KA), kynurenine (Kyn), p-cresol glucuronide
(pCG), p-cresol sulfate (pCS) and indole acetic acid (IAA) were measured in plasma
and urine after 6 and 8 months by LC-MS/MS.
RESULTS: Among the PBUTs with the highest OAT affinity, viz. IS, HA and KA,
plasma concentrations were 2.2-, 2.3- and 1.5-fold higher (p=0.005, 0.0006, 0.03; Fig
1A-C) after 6 months and 1.9-, 2.1- and 2-fold higher (p=0.008, 0.0005, 0.001; Fig 2A-
C) after 8 in DN, and urinary excretions (normalized for plasma concentrations) were
3.3-, 2.3- and 3.0-fold lower (p=0.012, 0.16, 0.03; Fig 1G-I) after 6 months and 2.5-, 1.6-
, 2.3-fold lower (p=0.028, 0.046, 0.0005; Fig 2G-I) after 8 months in DN. Other PBUTS,
viz. IAA, Kyn, pCS and pCG, were not significantly affected.

MO622 Figure 2: Plasma concentration (A-C), urinary concentration (normalized


to creatinine) (D-F) and urinary excretion (normalized to respective plasma
concentration) (G-I) of protein bound uremic toxins in diabetic nephropathy mice
after 8 months. Data are presented as mean 6 SD. Non-parametric Mann-Whitney U

i366 | Abstracts
Nephrology Dialysis Transplantation Abstracts
test or unpaired t-test was performed for statistical analysis. *** P < 0.001, ** P < 0.01, METHOD: Female db/db mice were injected with a renin-encoding adeno-associated
* P < 0.05. (IS = indoxyl sulfate, HA = hippuric acid, KA = kynurenic acid, Cr = virus construct (reninAAV) to induce hypertension and uninephrectomized (UNx) at
Creatinine). 7-8 weeks of age. At 12 weeks of age, daily dosing with vehicle, lisinopril, empagliflozin,
or the combination (combo) was initiated. Blood glucose (BG) was measured every
third week, while urine albumin-to-creatinine (ACR) and KIM1 were measured in spot
CONCLUSION: Our findings suggest that OAT function is compromised in murine urine samples collected before termination at 24 weeks of age. Cystatin C was
long-term DN. Renal clearance of IS, HA and KA may be a marker of tubular function measured in terminal plasma, while terminal kidney samples were collected for 3D
in DN. Future studies should focus on correlations with histology and validation in light sheet microscopy and 2D histology: Glomerulosclerosis scoring was performed by
other species. AI-assisted automized scoring, whereby glomeruli were given scores from 0 (normal
glomerulus) to 4 (glomerulus with global glomerulosclerosis), and morphometric
quantification of kidney collagen 3, CD11b, and KIM1 load was performed.
References RESULTS: In reninAAV UNx db/db mice, 12 weeks treatment with empagliflozin and
combo reduced fed BG (12.361.5 and 13.160.9 mM, vehicle: 18.061.9 mM) and
1. Gilbert RE. Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in
HbA1c (5.560.2 and 5.860.2%, vehicle: 7.460.03%). Treatment with lisinopril and
Diabetic Kidney Disease Diabetes. 2017;66(4):791–800.
combo reduced urine ACR (811061320 and 25086346 mg/mg, vehicle: 26,13861820
2. Falke LL, Dendooven A, Leeuwis JW, Nguyen TQ, van Geest RJ, van der Giezen DM
mg/mg) and KIM1-to-creatinine (7.561.1 and 3.960.6 ng/mg, vehicle: 24.863.2 ng/
et al. Hemizygous deletion of CTGF/CCN2 does not suffice to prevent fibrosis of the
mg), while treatment with empagliflozin alone worsened urine ACR (41,52364670 mg/
severely injured kidney Matrix Biol. 2012;31(7-8):421–31.
mg). Glomerular hypertrophy as assessed by 3D imaging was reduced in reninAAV
UNx db/db mice combo treated animals compared to vehicle (glomerular volume:
MO623 EFFECT OF PLANTAR ELECTRICAL NERVE STIMULATION 1.46*10564.3*103 and 1.65*10564.3*103 mm3), while treatment with empagliflozin
DURING ROUTINE HEMODIALYSIS PROCESS ON THE DAILY alone worsened glomerular hypertrophy (1.83*105 mm3). The total number of
PHYSICAL ACTIVITY IN ADULTS WITH DIABETES AND END- glomeruli per kidney was not affected by treatments. Compared to vehicle treatment,
STAGE RENAL DISEASE - A RANDOMIZED DOUBLE- lisinopril and combo treatment reduced the fraction of score 3 þ 4 glomeruli (% GS
BLINDED CONTROLLED TRIAL 3 þ 4 glomeruli: 0.3860.06 and 0.2760.03%, vehicle: 0.5460.05%) Glomerulosclerosis
index (GSI) was also reduced by lisinopril and combo treatment (GSI: 2.2960.10 and
Ram kinker Mishra1, Fadwa Al-Ali2, Abdullah Hamad2, Rania Ibrahim2, 2.0460.05, vehicle: 2.6260.09). Treatment with empagliflozin alone worsened GSI
Mincy Mathew2, Bijan Najafi1 (2.9560.11). Whereas treatments did not significantly affect collagen 3, lisinopril and
1 combo treatment reduced CD11b (total CD11b mass: 0.2560.03 and 0.2460.04 mg,
Interdisciplinary Consortium on Advanced Motion Performance (iCAMP), Michael E.
vehicle: 0.5760.07 mg) and KIM1 (total KIM1 mass: 0.2560.06 and 0.1760.09 mg,
DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United
vehicle: 2.0160.37 mg), whereas empagliflozin did not affect CD11b and KIM1.
States of America and 2Department of Nephrology, Hamad General Hospital, Doha,
CONCLUSION: Responses to the combination treatment with lisinopril and
Qatar
empagliflozin showed improvement of urine and histological markers of DKD.
Together, these data confirm the translatability of the ReninAAV UNx db/db mouse
BACKGROUND: Physical inactivity among patients undergoing hemodialysis (HD) is model of DKD in type 2 diabetes.
a long-standing clinical problem. While exercise could be beneficial, post-dialysis
fatigue, limited time availability, and severe frailty to travel often lead to poor
adherence to conventional exercise programs. To address this gap, we proposed testing
an alternative therapy using intradialytic plantar electrical nerve stimulation (IPENS) MO625 INHIBITION OF SGLT-2 CANNOT RESCUE NEPHRIN
provided during the routine hemodialysis process. EXPRESSION IN DIABETIC NEPHROPATHY
METHODS: Participants were randomized into either an intervention group (IG:
n=16, age=57.663.6 years, BMI=29.761.5 kg/m2, female=31%) or a control group Ahmed Kotb1, Bernd Klanke1, Jens Kroll3, Mario Schiffer1
1
(CG: n=15, age=63.561.6 years, BMI=29.961.6 kg/m2, female=41%). The IG received University of Erlangen-Nuremberg, Department of Nephrology and Hypertension,
1-hour IPENS during routine hemodialysis process (3 sessions/week) for 12 weeks. The Erlangen, Germany and 3Medizinische Fakult€ at Mannheim, Arbeitsgruppe Vascular
CG was provided with an identical but non-functional device for the same period. Signaling Abteilung für Vaskul€
are Biologie und Tumorangiogenese, Mannheim,
Participants and therapy-providers were blinded to the group allocation. Daily life Germany
physical activity (e.g., cumulative postures including sitting, standing, lying, and
walking; walking characteristics including step count, number of unbroken walking BACKGROUND AND AIMS: Early glomerular damage in diabetes is induced by high
bout, and postural transitions including sit to stand and stand to sit) was monitored blood glucose level (hyperglycemia) which affects the glomerular filtration barrier and
remotely at baseline and 12-week for a period of 48h using a validated pendant sensor. leads to proteinuria. Podocyte-specific proteins like the transmembrane protein
To determine the effect of intervention, we estimated Cohen’s effect size d. In addition, nephrin form the slit diaphragm that is important for proper function of the
time effect, group effect, and timegroup effect were estimated using general linear glomerular filtration barrier. Sodium-glucose co-transporter 2 (SGLT2) specific
model. proteins are involved in glucose reabsorption in the kidney and maintain the normal
RESULTS: All participants in the IG tolerated the IPENS and completed all therapy glucose level in the blood. Recent studies showed remarkable success of SGLT2-
sessions, indicating the feasibility. In the IG, we observed significant increase in time inhibition in patients with diabetic nephropathy. Therefore we wanted to study if
spent in standing (Cohen’s d=0.8, p=0.039) and walking (Cohen’s d=0.82, p=0.034), hyperglycemia induced reduction of nephrin expression is affected bySGLT-2
number of walking episodes (d=0.88, p=0.024), and number of postural transitions inhibition. Therefore we induced hyperglycemia in zebrafish larvae by knockdown of
(d=0.93, p=0.018) with a decrease in the average duration for sit to stand transition Pancreatic duodenal homeobox 1 (Pdx1) transcription factor and treated zebrafish
(d=0.87, p=0.032) compared to the CG. larvae with Empagliflozin. In parallel we treated Bl/6 mice with streptozotozin and
CONCLUSIONS: This is an ongoing study and our target sample is 100 eligible treated them with Empagliflozin. We then analyzed nephrin expression in both model
participants. This study provides earlier results on IPENS therapy’s feasibility and systems.
effectiveness as an alternative to exercise programs to improve daily life physical METHOD: Zebrafish is an ideal model to study glomerular diseases, because the
activity among people undergoing routine hemodialysis process. If the results were zebrafish larvae develops a pronephros with high homology to the human glomerulus.
held at a larger sample, we could recommend routine In order to inhibit SLGT-2 after Pdx1-knockdown, we treated both control and
diabetic zebrafish larvae with 10mM Empagliflozin from 1dpf to 5dpf. We used a
zebrafish line that expresses a fluorescent Vitamin D binding plasma protein Tg(l-
MO624 COMBINATION TREATMENT WITH LISINOPRIL AND fabp:DBP:eGFP) to measure proteinuria by measuring the GFP signal in both retinal
EMPAGLIFLOZIN IMPROVES BIOCHEMICAL AND and glomerular vessels of 120 hpf larvae. Immunohistochemistry against nephrin was
HISTOLOGICAL MARKERS OF DIABETIC NEPHROPATHY IN performed using a specific zebrafish antibody.
HYPERTENSIVE UNINEPHRECTOMIZED DB/DB MICE RESULTS:
Pdx1 knockdown induces a glomerular phenotype We found that Pdx1 knockdown
Mette Viberg Ostergaard1, Michael Christensen1, Thomas Secher1, Jacob Lercke
larvae developed pericardial edema and proteinuria two hallmarks for kidney dis-
Skytte1, Urmas Roostalu1, Casper Gravesen Salinas1, Frederikke
ease. To investigate the efficiency of the glomerular filtration barrier, we measured
Emilie Sembach1, Jacob Jelsing1, Lisbeth N Fink1, Niels Vrang1
1
the clearance of the GFP-vitamin D-binding protein by measuring fluorescence
Gubra, Hørsholm, Denmark activity of the retinal blood vessel plexus and in glomerular vessels. We found that
GFP signal in the retinal (Eye assay) and glomerular (Cryosections) vessels was
BACKGROUND AND AIMS: Emerging treatments of diabetic kidney disease (DKD) markedly decreased after Pdx1 knockdown indicating a leakage of the filtration bar-
include SGLT2 inhibitors and GLP-1 receptor agonists that are nephroprotective rier compared to control injected larvae. In contrast to control, Pdx1 knockdown
beyond their blood glucose lowering effects. Despite this progress, patients with resulted in significant changes of the morphology of the glomerulus. Pdx1 knock-
diabetes are still at risk of developing DKD, and drug discovery remains impeded by down glomeruli display a dilated Bowman’s space and capillaries. Immunostaining
the lack of reproducible rodent models exhibiting features of human DKD. To confirm with a specific antibody for zebrafish nephrin, a podocyte-specific protein essential
the translatability of an advanced mouse model, we tested standard of care in the for blood filtration, revealed that the expression of nephrin was significantly
setting of type 2 diabetes and hypertension. decreased in podocytes of Pdx1 knockdown larvae in contrast to podocytes of the
control larvae.

10.1093/ndt/gfab093 | i367
Abstracts Nephrology Dialysis Transplantation

SLGT-2 inhibitor could not rescue the diabetic glomerular phenotype In order to MO627 ASSOCIATION OF OXIDIZED LDL CHOLESTEROL WITH
investigate the SLGT-2 inhibitor effect on the diabetic phenotype, we treated dia- MORTALITY AND PROGRESSION OF PROTEINURIC
betic zebrafish larvae with Empagliflozin. 5 dpf Empagliflozin treated larvae still DIABETIC KIDNEY DISEASE
continuously develop pericardial edema. In addition, Empagliflozin treated larvae
showed low GFP signal in the retinal vessels (Eye assay) compare to control, con- Stefanos Roumeliotis1, Athanasios Roumeliotis1, Aikaterini Stamou2,
firming that Empagliflozin treated larvae still have a leaky glomerular filtration Dimitrios Divanis1, Marios Theodoridis3, Stylianos Panagoutsos3,
barrier. Vassilios Liakopoulos1
A confirmatory experiment with SLGT-2 inhibitor treatment of mice after STZ 1
AHEPA Hospital, School of Medicine, Aristotle Univeristy of Thessaloniki, Division of
induced diabetes showed similar results. Nephrology and Hypertension, 1st Department of Internal Medicine, Thessaloniki,
Greece, 2AHEPA Hospital, School of Medicine, Aristotle Univeristy of Thessaloniki,
CONCLUSION: Despite the promising effects of SLGT-2 inhibitor treatment in Department of Microbiology, Thessaloniki, Greece and 3University Hospital of
patients with diabetic nephropathy the early effects on nephrin expression are not Alexandroupolis, School of Medicine, Democritus University of Thrace, Department of
addressed and remain an unchanged problem by this novel treatment option. Nephrology, Alexandroupolis, Greece

BACKGROUND AND AIMS: Oxidative modification of low-density lipoprotein


MO626 EFFECTS OF RAMIPRIL IN LUNG AND KIDNEY ANGIOTENSIN (oxLDL) contributes to the pathogenesis and progression of oxidative stress (OS) and
CONVERTING ENZYME 2 (ACE2) EXPRESSION IN A TYPE 2 atherosclerosis in both Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease
DIABETIC MURINE MODEL: LESSONS FOR COVID-19 (CKD). Compared to normo-and micro-albuminuric, T2DM patients with
INFECTION macroalbuminuria have significantly higher plasma oxLDL levels. In this study we
aimed to assess the possible predictive role of oxLDL for mortality and deterioration of
Ander Vergara Arana1,2, Conxita Jacobs Cacha 2, Mireia Molina2, renal function in a cohort of patients with proteinuric diabetic CKD.
Pamela Dominguez2, Begon ~a Benito3, Sheila Bermejo1,2, Daniel Seron Micas1,2, METHOD: 91 patients with diabetic retinopathy, persistent proteinuria and eGFR
Maria Jose Soler Romeo1,2 below 90ml/min were recruited. At baseline, oxLDL, proteinuria and eGFR were
1 assessed and patients were categorized according to median oxLDL (above or below
Vall d’Hebron University Hospital, Nephrology, Barcelona, Spain, 2Vall d’Hebron
66.22 U/L). All patients were prospectively followed for a period of 10 years or the
Research Institute, Nephrology Group, Barcelona, Spain and 3Vall d’Hebron University
occurrence of a combined outcome of mortality or at least 30% decline in eGFR and/or
Hospital, Cardiology, Barcelona, Spain
progression to end stage renal disease (ESRD), requiring renal replacement therapy. At
the end of the follow-up period, renal function was re-assessed with a new estimation
BACKGROUND AND AIMS: Angiotensin converting enzyme 2 (ACE2) is one of the of eGFR, using the CKD-EPI formula. We performed a statistical analysis with receiver
components of the renin-angiotensin system (RAS) that mainly degrades angiotensin operation curves (ROC) to further examine the possible effect of oxLDL on the
II to angiotensin-(1-7). ACE2 is predominantly expressed in the kidney and the heart, percentage change in eGFR and proteinuria over time (calculated as DeGFR/baseline
but it has been evidenced in type 2 alveolar lung cells, where it acts as a receptor for the eGFR and Dproteinuria/baseline proteinuria respectively) and divided by the follow-up
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this context, a time.
controversy arose as to whether the use of RAS blockers could increase ACE2 lung RESULTS: The mean age of the patients was 67.0268.2 years, and the mean duration
expression and the risk infection by COVID-19. This study aimed to investigate the of T2DM was 14.568.0 years. At baseline, compared to the low, patients with high
effect of an ACE inhibitor (Ramipril) on ACE2 expression in experimental diabetes. circulating oxLDL levels had significantly higher levels of triglycerides, higher diastolic
METHOD: 12 weeks old diabetic db/db mice (n=7) were given ramipril (8 mg/Kg/day) blood pressure and lower eGFR (P=0.001, P=0.04 and P-0.013, respectively, Mann-
during 8 weeks or the respective vehicle. db/m (n=7) vehicle-treated non-diabetic mice Whitney test). After a 10-year follow up, 10/46 patients in the low and 20/45 patients in
were included as controls. ACE2 mRNA expression and enzymatic activity were the high ox-LDL group presented the composite outcome. Kaplan-Meier curves
studied in kidney, heart and lung samples of these animals to identify if the diabetic (Figure 1) showed that patients with oxLDL levels above median (>66.22 U/L)
condition or treatment with ramipril modulated ACE2 expression. presented a significantly higher risk for the outcome compared to the low oxLDL group
RESULTS: In vehicle-treated diabetic db/db animals, ACE2 mRNA expression was (P=0.001, log-rank test). Univariate Cox proportional hazard analysis revealed that
significantly increased in the kidney (p<0.001) and ramipril treatment reversed this high circulating oxLDL levels were independent predictors of the composite endpoint
effect (p=0.026). In the heart, ACE2 expression decreased in db/db when compared to (HR=3.42, 95%CI: 1.55-7.56, P=0.002). After adjustment for all factors that were
db/m littermates (p=0.035) and ramipril had no effect. We found no differences in associated with the outcome in univariate models (baseline proteinuria, serum
ACE2 gene expression in the lung. Besides, ACE2 enzymatic activity was increased in albumin, duration of T2DM and triglycerides), multivariate Cox analysis showed that
the kidney (29%) and also in the lung (16%) of db/db mice when compared to controls. the association between high oxLDL levels and the study endpoint remained significant
Ramipril treatment decreased ACE2 activity a 19% in the lung and had no effect in the (HR=3.76, 95%CI: 1.52-9.27, P=0.004). At ROC analysis the area under the curve
kidney when compared to untreated db/db (see figure). In the heart, ACE2 activity (AUC) for oxLDL to identifying progressor patients was 0.68 (95% CI: 0.56-0.80,
tended to decrease in db/db mice (29%) when compared to db/m and ramipril P=0.005). Of note, this AUC was virtually identical to that of baseline proteinuria.
increased ACE2 activity (18%) but did not exceed the cardiac ACE2 activity of the db/ OxLDL failed to show any association with the change of proteinuria over time.
m.

MO626 Figure: ACE2 mRNA expression and activity. ACE2 mRNA expression in
the kidney (A), lung (B) and heart (C). ACE2 enzymatic activity in the kidney (A), lung MO627 Figure: Kaplan-Meier curves for mortality or at least 30% decline in eGFR
(E) and heart (F). and/or progression to end stage renal disease, requiring renal replacement therapy in
patients with high and low circulating levels of oxLDL (according to the median value
of 66.22 U/L).
CONCLUSION: ACE2 is increased in the kidney and the lung, and decreased in the
heart of diabetic mice. Ramipril treatment restores ACE2 levels. The results suggest
that ACE inhibitors do not increase ACE2 expression and the activity decrease exerted CONCLUSION: Circulating ox-LDL might play an important role in the progression
in the lung may be protective against COVID-19 infection. of proteinuric DKD.

i368 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO628 IMPACT OF INDUCTION OF AUTOPHAGY BY RAPAMYCIN MO630 SNOGO-B IS AN IMPORTANT CONTRIBUTOR TO
AND METFORMIN ON NATURAL HISTORY OF DIABETIC GLOMERULAR ENDOTHELIAL CELL STABILITY AND
NEPHROPATHY IN RATS VASCULAR REMODELLING INTERVENING ON VEGFA/
VEGFR2 SIGNALLING
Samar Ahmed1, Emad Samaan2, Dina Abdallah Ibrahim3, Nagy Sayed-Ahmed4,
Hussein Sheashaa5 Carlo Alberto Ricciardi1, David Long2, Luigi Gnudi3
1 1
Faculty of Medicine - Suez Canal University, Nephrology, Ismailia, Egypt, 2Mansoura king’s College London, Section Vascular Biology and Inflammation, School of
Nephrology and Dialysis Unit, Faculty of Medicine, Mansoura University , Mansoura, Cardiovascular Medicine & Sciences, British Heart Foundation Centre for Research
Egypt, Nephrology, Mansoura, Egypt, 3Mansoura Faculty of Medicine, Pathology, Egypt, Excellence, Faculty of Life Sciences & Medicine, King’s College of London., London,
4
Mansoura Nephrology and Dialysis Unit, Faculty of Medicine, Mansoura University, United Kingdom, 2University College London, Developmental Biology & Cancer Dept
Mansoura, Egypt, Nephrology, Egypt and 5Urology & Nephrology Center, Mansoura UCL GOS Institute of Child Health, London, United Kingdom and 3king’s College
University, Egypt, Egypt London, Section Vascular Biology and Inflammation, School of Cardiovascular
Medicine & Sciences, British Heart Foundation Centre for Research Excellence, Faculty of
BACKGROUND AND AIMS: Impaired autophagy in the kidney resulted in podocyte Life Sciences & Medicine, King’s College of London.
loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by
activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic BACKGROUND AND AIMS: Nogo-B is an endoplasmic reticulum protein present as
option for the suppression of diabetic nephropathy. a full length and circulating soluble isoform (sNogo-B) corresponding to the first
METHOD: This experimental work was carried out on 48 adult male Sprague dawely 200aa of the N-terminus. Nogo-B is expressed in glomerular endothelial cells (GECs)
rats. The total duration of the study was 10 weeks. All investigation and intervention and is downregulated in the diabetic glomeruli; its repletion, ameliorates diabetic
were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly glomerulopathy. However, the precise biological role of Nogo-B and its soluble form in
divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 GEC is not well understood.
each), the three groups were the non-treated, treated with rapamycin and treated with We hypothesise that sNogo-B could modulate VEGFA/VEGFR2 signalling, and
rapamycin and metformin. To study autophagy, we use electron microscopy and vascular remodelling resulting in improved GECs health and vascular remodelling
immunohistochemical staining of kidney tissue with LC3 antibody (vessel repair/new vessel formation). We predict that this effect may be mediated by
RESULTS: Diabetic rats treated with rapamycin alone or rapamycin and metformin changes in VEGFA/VEGFR2 signalling; a critical signalling pathway which regulates
showed lower level of proteinuria and almost normal serum creatinine through all blood vessel function in physiology and disease.
intervals of the study. Also, their Kidney tissue showed increased autophagosomes and METHOD: For this experiment we used human conditionally immortalised GECs.
high expression of LC3 compared to diabetic rats. There are no significant differences Cells were used after differentiation at 37 . GECs were infected with adenovirus vector
between both treated groups in terms of induction of autophagy during the experiment expressing sNogo-B or identical vector lacking sNogo-B cDNA (control vector). Cells
period. were serum starved (4 hours, FBS 2%) and exposed to VEGFA (50 ng/ml) for 5’ 10’ 15’
CONCLUSION: we concluded that using a small dose of rapamycin for short duration min and VEGFR2 phosphorylation assessed with western immunoblotting.
in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding RESULTS: VEGFA-Mediated VEGFR2 phosphorylation was upregulated in wild-type
metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less GECs after 15 min VEGFA incubation (P<0.05) n=4. sNogo-B overexpression upregulated
beneficial. the sNogo-B protein level in the supernatant by 10 fold and prevented VEGFA/VEGFR2
phosphorylation in human immortalized glomerular endothelial cells(P<0.05).
CONCLUSION: sNogo-B prevents the VEGFA mediated VEGFR2 phosphorylation in
GECs. Upregulation of VEGFA/VEGFR2 signalling has been implicated in diabetic
MO629 XANTHINE OXIDASE INHIBITOR ATTENUATES RENAL glomerulopathy. sNogo-B inhibition of VEGFA/VEGFR2 signalling opens new
OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION investigations looking at the potential role of sNogo-B as therapeutic target in diabetic
THROUGH THE INHIBITION OF VEGF-NADPH OXIDASES IN nephropathy.
DIABETIC NEPHROPATHY

Yu Ah Hong1, Keum-Jin Yang2, Wonjung Choi1, Yoon-Kyung Chang1, Cheol


Whee Park1, Suk Young Kim1
1
College of Medicine, The Catholic University of Korea, Department of Internal
Medicine, Seoul, Korea, Rep. of South and 2Clinical Research Institute, Daejeon St.
Mary’s Hospital, Daejeon, Korea, Rep. of South

BACKGROUND AND AIMS: Xanthine oxidase (XO) is one of major source of


reactive oxygen species, and a XO inhibitor, febuxostat has been reported to the
protection of kidney diseases. We investigated whether febuxostat exerts
renoprotective effects against diabetic nephropathy (DN).
METHOD: Eight-week Male C57BL/6 mice were divided into four groups: Control
group (Cont), Febuxostat control group (FEB), streptozotocin treated group (STZ) and
a febuxostat and STZ-treated diabetes group (STZþFEB). STZ was used to induce
diabetes (50 mg/kg/day, 5 days), and 5 mg/kg of febuxostat was treated to experimental
mice for 8 weeks.
RESULTS: STZ-treated diabetic mice were significantly decreased in serum and kidney
XO levels, serum cystatin C and albuminuria by febuxostat treatment. Febuxostat
treatment decreased renal hypertrophy and mesangial matrix expansion in STZ-treated
diabetic mice. Febuxostat treatment suppressed the expression of vascular endothelial
growth factor (VEGF)1 and 3, NADPH oxidase (NOX)1, 2, and 4, and the levels of
their catalytic subunit mRNA in in STZ-treated diabetic mice. Febuxostat treatment
was accompanied by the downregulation of Akt phosphorylation, followed by the
suppression of transcription factor forkhead box O3a phosphorylation and the
enhancement of endothelial nitric oxide synthase. Finally, febuxostat improved
oxidative stress and resulted in decreased 8-hydroxy-2’-deoxyguanosine and kidney
malondialdehyde levels, and increased superoxide dismutase activity in STZ-treated
diabetic mice.
CONCLUSIONS: Febuxostat attenuated DN by modulating oxidative stress and
endothelial function through VEGF–NADPH oxidase signaling pathway.
MO631 XANTHINE OXIDASE INHIBITOR AMELIORATES HIGH
GLUCOSE-INDUCED OXIDATIVE STRESS BY ACTIVATING
AMPK VIA THE ACTIVATION OF PURINE SALVAGE PATHWAY
IN GLOMERULAR ENDOTHELIAL CELLS

Yu Ah Hong1, Keum-Jin Yang2, Won Jung Choi1, Yoon-Kyung Chang1, Cheol


Whee Park1, Suk Young Kim1
1
College of Medicine, The Catholic University of Korea, Department of Internal
Medicine, Seoul, Korea, Rep. of South and 2Clinical Research Institute, Daejeon St.
Mary’s Hospital, Daejeon, Korea, Rep. of South

BACKGROUND AND AIM: Oxidative stress plays a crucial role in the pathogenesis
of diabetic nephropathy (DN). Xanthine oxidase (XO) contribute to reactive oxygen

10.1093/ndt/gfab093 | i369
Abstracts Nephrology Dialysis Transplantation

species (ROS) production, and XO inhibitor, febuxostat has been reported to the brought to increase of this morbid condition. Nowadays, with a galloping rise, we have
protection of kidney diseases. However, the mechanism of renoprotective effects for a prevalence of 11,1 % of DM in the adult population and nearly 22% of hemodialysis
febuxostat remained unclear. We investigated the renoprotective mechanism patients whose primary diagnosis is diabetes. Despite this, data of EUROSTAT put us
associated with purine salvage pathway of febuxostat against DN. in the first place for mortality due to diabetes. It’s time to act!
METHOD: Glomerular endothelial cells (GEnCs) exposed to high glucose (HG) were METHOD: We analyzed the number of diabetic patients in Albania second the IDF
treated with or without febuxostat for 72 hours, and then the changes of purine salvage data and the number of diabetic nephropathy patients hospitalized during this decade
pathway and the phosphorylation of 5’ AMP-activated protein kinase (AMPK) and its in our Departement of Nephrology according the Statistical Department of UHC
related signaling pathway were evaluated. "Mother Theresa".
RESULTS: Cell survival was significantly decreased in HG-treated GEnCs, and RESULTS: In 2010 there were 4.5% diabetics in the adult population in Albania and in
febuxostat treatment enhanced cell survival in a dose-dependent manner. The 2019 there were 9%, so doubling of numbers. Diabetic nephropathy is increasing too
expressions of xanthine/hypoxanthine, and the levels of xanthine oxidoreductase were and now is our everyday clinical practice challenge, in 2010 there were 54 patients
significantly increased in HG-treated GEnCs, and these findings were attenuated by hospitalized for DN and its complications and in 2019 this number increased to 164
febuxostat. The AMP/ATP ratio was inhibited in in HG-treated GEnCs and enhanced patients. Diabetics on hemodialysis are now more and more present with their
by febuxostat treatment. Febuxostat treatment enhanced phosphorylation of AMPK, problems and difficulties that need not only nephrologists but a multidisciplinary
peroxisome proliferator-activated receptor (PPAR)-a, PPAR-gamma coactivator approach. Diabetic nephropathy in 2011 had only 11,3% of the hemodialytic pie and
(PGC)-1a, and dephosphorylation of the Forkhead box O (FoxO)3a in HG-treated now is reaching 17,2% of the primary cause of ESRD in our hemodialytic population,
GEnCs. Febuxostat treatment also suppressed NADPH oxidase expressions and their regarding ERA EDTA registry, but our 2020 numbers rise to 22%. We are below the
catalytic subunits and oxidative stress in HG-treated GEnCs. AMPK inhibition using European and North American data but in incident patients it is becoming the second
small interfering RNA blunted the antioxidative effects of febuxostat in HG-treated predominant cause of renal failure, after the hypertensive nephrosclerosis, reaching
GEnCs. 25%-27%. Mortality in this population is a crucial point, we stand first in Europe with
CONCLUSIONS: Febuxostat attenuated HG-induced oxidative stress through the 110 deaths/ million inhabitants despite the reimbursement range is three-fold
activation of purine salvage pathway and AMPK–PGC-1a–NADPH oxidase signaling. compared to 10 years ago An increasing number is translated into increased
problems especially in vascular access, cardiovascular problems, diabetic foot
problems, glycemic control, etc.
CONCLUSION: Nephrology Units and Hemodialysis Units too are being invaded by
MO632 FIRST PLACE IN MORTALITY DUE TO DIABETES IN EUROPE
diabetics Caring about the glycemic levels, type of hypoglycemia drugs, time and
BRINGS TO ALERT OF MULTIDISCIPLINARY TREATMENT IN
dosage, eating or not during the hemodialysis session, are every session challenges.
ALBANIA. ROLE OF NEPHROLOGISTS
Cardiovascular problems with frequent hypotensions, coronary heart disease, and
cardiac heart failure are other difficult to manage fields. But the most important and
Erjola Likaj1,2, Larisa Shehaj1,2, Alma Idrizi3, Myftar Barbullushi3
1
continuous care is that of vascular access, the "Achille’s Heel" of our patients. Results
UHC Mother Theresa, Tirana, Albania, 2, Nephrology Dialysis Transplantation and from our studies reveal diabetes like the second cause of arteriovenous fistulas failure,
3
UHC Mother Theresa, Tirana, Albania, Nephrology Dialysis Transplantation after the age of patients so we are reinforcing the whole medical chain for referring
patients in the fourth stage of CKD for the creation of permanent vascular access,
BACKGROUND AND AIMS: Diabetes mellitus was prevalent in nearly 0.8 % of the especially diabetics.
adult population and assent in our modest hemodialytic population in 1990. Changing
of lifestyle and nutrition, increase in longevity, aging population, and stress have

i370 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i371–i380, 2021
10.1093/ndt/gfab094

DIABETES. CLINICAL STUDIES eGFR>15ml/min/1.73m2. Our aims are to analyse the changes in metabolic and renal
parameters in chronic diabetic patients after 12 months of treatment in real life
practice with semaglutide.
METHOD: Retrospective observational study. Inclusion criteria: Patients over 18 years
MO633 GLYCAEMIC MARKERS IN PATIENTS WITH TYPE 2 old with DM2 and eGFR(CKD-EPI)>15 ml/min/1.73m2. We selected cases with
DIABETES UNDERGOING HAEMODIALYSIS EVALUATED BY eGFR<60 ml/min/1,73m2 and/or albuminuria/Creatinineu (albu/creatu)>30 mg/g
LONG-TERM CONTINUOUS GLUCOSE MONITORING* treated with semaglutide in real life practice for 12 months. Our main objectives were
to assess the changes in HbA1c and weight. Secondary objetives to analyse evolution of
Tobias Bomholt1, Marianne Rix1, Thomas Peter Almdal2, Filip K. Knop3, albuminuria (albu/creatu), eGFR(CKD-EPI), blood pressure (BP), lipidic profile and
Susanne Rosthøj4, Niels Søndergaard Heinrich5, Morten Jørgensen1, adverse events. Statistics anlysis: we used descriptive, student’s t, McNemar (paired
Anders Larsson6, Linda Hilsted7, Bo Feldt-Rasmussen1, Mads Hornum1 data), method by steps forward; SPSS v 19.0.
1
Rigshospitalet, University of Copenhagen, Nephrology, Copenhagen, Denmark, RESULTS: We included 122 patients, 62% males, mean age 51,43 6 33 years, time of
2
Rigshospitalet, University of Copenhagen, Endocrinology, Copenhagen Ø, Denmark, DM2 12.3 6 3.4 years, body mass index (BMI) 35.8 6 4.79, 25% had retinopathy,
3
Gentofte Hospital, University of Copenhagen, Endocrinology, Gentofte, Denmark, 93.4% hypercholesterolemia and 97% were hypertensive, 18% were active smokers.
4
University of Copenhagen, Section of Biostatistics, Copenhagen K, Denmark, 5Steno Mean Albu/Creatu: 349.49 6 863.16 mg/g and mean eGFR (CKD-EPI): 50.32 6 31.47
Diabetes Center Copenhagen, Complication Research, Gentofte, Denmark, 6Uppsala ml/min/1.73m2. Previous cardiovascular events: 36.5% myocardial infarction, 41%
University, Medical Sciences, Clinical Chemistry, Uppsala, Denmark and 7Rigshospitalet, congestive hearth failure, 10% peripheric arteriopathy and 6% strokes. 42.6% were
University of Copenhagen, Clinical biochemistry, Copenhagen Ø, Denmark already on iSGT2 who were kept and 64.8% were switched from other GLP-1ar. After
12 months of treatment with semaglitude HbA1c reduced -0.74 6 0.41% obtaining a
mean objective <7% (from 7.5761.36 to 6.8360.85, p<0.0001). Patients decreased
BACKGROUND AND AIMS: The reliability of haemoglobin A1c (HbA1c) as a weight in -6.95 6 6.0 Kg (from 98.48616.6 to 91.53616.42 p<00001) more than -5%
glycaemic marker in patients receiving haemodialysis (HD) remains unknown. To of total body weight in 69% of cases. Albuminuria reduced in -162,21 mg/g 6 365,77
assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose (from 349.496863.16 to 187.2876897.39 p<0.0001, 53% reduction). eGFR(CKD-EPI)
levels measured by continuous glucose monitoring (CGM) in patients with type 2 remained with a low increased of 2,2 ml/min/1.73m2. Systolic and Diastolic BP
diabetes receiving HD. decreased -9.85 6 13.34 mmHg (from 129.95611,27 to 120.09609 p < 0.0001) and -
METHOD: The HD group (maintenance HD and type 2 diabetes) comprised 30 patients 5.92 6 7.43 mmHg (from 77.0568.95 to 71.1267.83 p< 0.0001) respectively. LDL-
who completed the study period of 17 weeks; the control group (type 2 diabetes and an cholesterol and triglyceridemia decreased in -10.79 6 28.21.09 mg/dl (p <0.0001) and
estimated glomerular filtration rate >60 mL/min/1.73 m2) comprised 36 individuals. CGM -29,15 mg/dl 6 91,47 (p <0.0001) respectively. 5 % of patients on insulin had
RV
(Ipro2 , Medtronic) for periods up to seven days was performed five times (with four weeks mild hipoglycemic episodes. Our patients needed 25% less units of rapid insulin
intervals) during a 16-week period. HbA1c and fructosamine were measured at week 17. (p<0.01). Semaglutide was stopped in 5% of cases (65% because digestive intolerance).
The mean sensor glucose from CGM was compared with the measured HbA1c, its CONCLUSION: Chronic kidney diabetic patients with grade 3 albuminuria after 12
estimated mean blood glucose (eMBGA1c) and fructosamine levels. months of treatment in real life practice with semaglutide improved their glycemic
RESULTS: In the HD group, the mean sensor glucose from CGM was 1.4 (95% confidence control (mean final HbA1c <7%), with 25% less needs of rapid insulin. 69% of them
interval [CI]: 1.0–1.8) mmol/L higher than the eMBGA1c, whereas the difference was 0.1 decreased their total body weight in > 5%. We observed 53% reduction of albuminuria
mmol/L (95% CI: -0.1–[0.4]; P<0.001) in the control group. Adjusted for the mean sensor and better control of blood pressure.
glucose, HbA1c was -7.3 (95% CI: -10.0–[-4.7]) mmol/mol lower in the HD group than in
controls (P<0.001), whereas no difference was detected for fructosamine (P=0.64).
CONCLUSION: HbA1c evaluated by CGM underestimates mean blood glucose levels
in patients receiving maintenance HD; fructosamine appears to be more accurate.
CGM-assessed blood glucose could complement or replace HbA1c in patients where MO635 PRO-INFLAMMATORY CYTOKINES IL-6 AND IL-17 DISPLAY
HbA1c underestimates blood glucose levels. A PARTICULAR MOLECULAR PATTERN IN ASSOCIATION
WITH DYSREGULATED MIRNAS IN PATIENTS WITH TYPE 2
DIABETES MELLITUS IN THE EARLY STAGES OF DIABETIC
KIDNEY DISEASE

Golea Alina-Emanuela1,2,3, Florica Gadalean1,2,3, Adrian Vlad1,3,4,5,


Mihaela Vlad1,3,6, Dumitrascu Victor1,3,7, Daliborca Vlad1,3,7, Silvia Velciov1,2,3,
Gluhovschi Cristina1,2,3, Flaviu Bob1,2,3, Sorin Ursoniu1,3,5,8,9, Catalin Jianu1,3,5,10,
Petru Matusz1,11, Agneta Pusztai1,11, Motoc Andrei1,11, Octavian Cretu1,12,
Livia Oana Milas1,2,3, Anca Simulescu1,2,3, Mogos-Stefan Maria1,2,3,
Mihaela Patruica1,2,3, Balint Lavinia1,2,3, Ienciu Silvia1,2,3, Roxana Popescu1,3,13,
Ligia Petrica1,2,3,5,9
1
Victor Babeş University of Medicine and Pharmacy, Timis, oara, Romania, 2County
MO633 Figure 1: Bland–Altman plot illustrating the difference between the mean Emergency Hospital, Nephrology, Timisoara, Romania, 3Centre for Molecular Research
sensor glucose from CGM and the estimated mean blood glucose (eMBGA1c) for the in Nephrology and Vascular Disease, 4County Emergency Hospital, Diabetes and
haemodialysis (HD) group (A) and the control group (B). Y-axis is mean sensor Metabolic Diseases, Timisoara, Romania, 5Center for Cognitive Research in Neurologic
glucose from which the eMBGA1c has been subtracted. X-axis is calculated as the mean and Psyhiatric Disease, 6County Emergency Hospital, Endocrinology, Timisoara,
of the two with limits of agreement (LoA). A: HD group (bias = 1.4 (LoA: –0.6 to 3.5); Romania, 7Pharmacology, 8Public Health Medicine, 9Victor Babeş University of Medicine
B: control group (bias: 0.1 mmol/L;LoA –1.3 to 1.6; P<0.001). and Pharmacy, Center for Translational Research and Systems Medicine, Timisoara,
Romania, 10County Emergency Hospital, Neurology, Timisoara, Romania, 11Anatomy
and Embriology, 12Municipal Emergency Hospital, Surgery I, Timisoara, Romania and
13
Cellular and Molecular Biology

MO634 SEMAGLUTIDE IN REAL LIFE PRACTICE DECREASES BACKGROUND AND AIMS: Glomerular injury and proximal tubule (PT)
ALBUMINURIA IN HIGH RISK PROGRESSION CHRONIC dysfunction have intricate mechanisms in diabetic kidney disease (DKD). Pro-
KIDNEY DIABETIC PATIENTS inflammatory cytokines are involved in the initiation and progression of DKD through
mediating the inflammatory response, both at glomerular and proximal tubular level.
Beatriz Aviles1, Maria Dolores Garcıa de Lucas2, Luis Perez Belmonte3, miRNAs are able to modulate cellular and biochemical functions, thus intervening in
Anabel Jiménez Milla n4, Francisco Rivas Ruiz5 the pathogenesis of DKD.
1 The aim of the study, performed on patients with type 2 diabetes mellitus (DM), was to
Hospital Costa del Sol, Nephrology, Marbella, Spain, 2Hospital Costa del Sol, Internal
evaluate selective pro-inflammatory cytokines in relation to biomarkers of podocyte
Medicine, Marbella, Spain, 3Hopsital Regional University School of Medicine, Internal
lesion and of PT dysfunction. Particular molecular pathways, such as specific miRNA
Medicine, Malaga, Spain, 4Hospital Puerto Real, Endocrinology, Cadiz, and 5Hospital
profiles operating in this relation, have also been studied.
Costa del Sol, Research Unit, Marbella , Spain
METHOD: A number of 126 patients with type 2 DM, staged by albuminuria [39
normoalbuminuric – urinary albumin/creatinine ratio UACR)<30mg/g; 45
BACKGROUND AND AIMS: Semaglutide has shown safety and efficacy in type 2 microalbuminuric–UACR-30–300mg/g; 42 macroalbuminuric–UACR>300mg/g],
diabetic patients (DM2) in extensive clinical studies including patients until

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

and 23 healthy control subjects were included in a cross-sectional study. All patients interventions to prevent disease progression and premature death.
were evaluated concerning biomarkers of podocyte injury (nephrin, podocalyxin, METHOD: We have analyzed the prevalence of DKD according to lab criteria and the
synaptopodin) and of PT dysfunction [Kidney injury molecule-1(KIM-1), N-acetyl- rate of identification of DKD and/or chronic kidney disease (CKD) on 516,578 hospital
beta-D-glucuronidase (NAG), alpha 1- microglobulin]. Also, serum and urinary levels care electronic medical records (EMR) in a tertiary hospital-based population using
of specific interleukins (IL-6, IL-17), serum cystatin C, and eGFR were determined. Savana ManagerV R.

Serum and urinary miRNAs (miRNA-21, miRNA-124, miRNA-146a, miRNA-192) RESULTS: Out of 24,129 T2DM patients, 15,304 met inclusion criteria. DKD was
were assessed by RT-PCR. defined as eGFR<60 ml/min/1.73m2 or urinary albumin to creatinine ratio (UACR)
RESULTS: The biomarkers of podocyte lesion and of PT dysfunction were increased, >30 mg/g or urinary protein to creatinine ratio (UPCR) >0.3 g/g after excluding acute
even in normoalbuminuric type 2 DM patients. Serum and urinary IL-6 and IL-17 kidney injury (AKI). A total of 4,526 (29.6%) T2DM patients had DKD according to
showed increased levels in type 2 DM patients, across all groups studied. The model lab criteria. However, the terms “CKD” or “DKD” were only present in 33.1% and 7.5%
provided by univariable regression analysis showed that IL-6 and IL-17 correlated of the 4,526 EMR, with a hidden prevalence of CKD and DKD of 66.9% and 92.5%,
directly with biomarkers of podocyte injury (nephrin, podocalyxin, synaptopodin), of respectively. Less severe kidney disease (lower UACR or UPCR, higher eGFR values),
PT dysfunction (KIM-1, NAG, alpha 1-microglobulin), as well as with UACR. female sex, and lack of insulin prescription were associated with the absence of “DKD”
Negative correlations have been identified regarding eGFR. or “CKD” terms in EMR (p<0.001) in the patients fulfilling laboratory criteria for
In multivariable regression analysis, serum IL-6 correlated directly with synaptopodin, DKD. However, while younger age (<70 years) was associated with a missing CKD
NAG, and negatively with eGFR (p<0.00001, R2=0.805); serum IL-17 correlated diagnosis, older age (70 years) was associated with a missing DKD diagnosis in EMR.
directly with synaptopodin, NAG, KIM-1, UACR, and negatively with eGFR CONCLUSION: In conclusion, the prevalence of DKD among T2DM patients
(p<0.00001, R2=0.941); urinary IL-6 correlated directly with synaptopodin, NAG, and according to laboratory data is higher than prevalence based on specific diagnosis
negatively with eGFR (p<0.00001, R2=0.889); urinary IL-17 correlated directly with written in EMR. This could imply underdiagnosis of DKD, especially in patients with
synaptopodin, nephrin, NAG, and negatively with eGFR (p<0.00001, R2=0.905). less severe disease who may benefit the most from optimized therapy
Also, important associations were found between specific interleukins and miRNAs. In
univariable regression analysis, IL-6 and IL-17 correlated directly with miRNA-21 and
miRNA-124, and negatively with miRNA-146a and miRNA-192. The models provided
by multivariable regression analysis showed that urinary IL-6 correlated directly with
urinary miRNA-21, and negatively with urinary miRNA-192 (p<0.00001, R2=0.886). MO638 ANEMIA IN DIABETIC PATIENTS REFLECTS SEVERE
Urinary IL-17 displayed direct correlations with urinary miRNA-21, and negative TUBULOINTERSTITIAL INJURY AND ASSISTS CLINICALLY IN
correlations with urinary miRNA-192 (p<0.00001, R2=0.860). Serum IL-6 correlated PREDICTING DIAGNOSIS OF DIABETIC NEPHROPATHY
directly with serum miRNA-21, miRNA-124, and indirectly with serum miRNA-146a,
miRNA-192 (p<0.00001, R2=0.862). Serum IL-17 showed direct correlations with Soichiro Yokota1, Kenji Ito1, Maho Watanabe1, Koji Takahashi1, Naoko Himuro1,
serum miRNA-21, miRNA-124, and negative correlations with serum miRNA-192 Tetsuhiko Yasuno1, Katsuhisa Miyake1, Kosuke Masutani1, Hitoshi Nakashima1,
(p<0.00001, R2=0.745). Yori Inoue1, Noriko Uesugi2
CONCLUSION: In the early stages of DKD, there is an association of pro- 1
Faculty of Medicine, Fukuoka University, Division of Nephrology and Rheumatology,
inflammatory cytokines with specific miRNAs, and with biomarkers of podocyte injury Deparatment of Internal Medicine, Fukuoka, Japan and 2Fuculty of Medicine, Fukuoka
and of PT dysfunction. IL-6 and IL-17, as well as dysregulated miRNA-21, miRNA- University, Department of Pathology, Fukuoka, Japan
124, miRNA-146a, and miRNA-192 display a particular molecular pattern, in relation
to complex mechanisms that can initiate and maintain the chronic inflammatory
BACKGROUND AND AIMS: Diabetic nephropathy (DN) is currently a leading cause
response in DKD. Routine detection of these interleukins may provide biomarkers to
of end-stage kidney disease worldwide. Kidney biopsy is generally performed in
refine the diagnosis of early renal involvement in the course of type 2 DM,
diabetic patients to discriminate between DN and non-diabetic kidney disease
independently of albuminuria and level of renal function.
(NDKD), and to provide more specific treatments. In addition to conventional
predicting factors of DN, recent studies suggested the predictive value of anemia in the
diagnosis of DN, however detailed pathophysiology and the significance of anemia in
renal pathology are not fully understood. This study aimed to investigate the impact of
anemia on renal pathology and clinical course in patients who underwent kidney
MO636 THE ROLE OF DIFFUSION-WEIGHTED MRI AND APPARENT
biopsy.
DIFFUSION COEFFICIENT IN ASSESSMENT OF DIABETIC
METHOD: We reviewed 81 patients (60.4 6 13.7 years, 54 men and 27 women) with
KIDNEY DISEASE: PRELIMINARY EXPERIENCE STUDY
type 2 diabetes who underwent percutaneous kidney biopsy in Fukuoka University
Hospital from January 2001 through March 2020. DN was diagnosed by mesangial
Mohamed Taha1
1
expansion or nodular glomerulosclerosis observed under a light microscope, and
Faculty Of Medicine - Minia University, internal medicine, El Minya, Egypt immunofluorescence assisted in differentiating NDKD from DN. Anemia was defined
as hemoglobin level <13 g/dL in males and <12 g/dL in females in accordance with the
BACKGROUND AND AIMS: Diabetic kidney disease is the most common cause of World Health Organization standards. Laboratory and pathological findings, and
ESRD. There is poor correlation between the degree of renal fibrosis and current clinical courses were investigated.
screening markers. A noninvasive imaging technique is needed to assess the degree RESULTS: According to their pathological findings, patients were classified into two
of structural changes in the kidney. groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD
METHOD: Forty adult diabetic patients with chronic kidney disease as well as 20 group, n=51). There were 11 types of NDKD. Of these, membranous nephropathy was
age- and sex-matched adult healthy controls were recruited from Nephrology the most common (23.5%), followed by IgA nephropathy (17.6%), and crescentic
Department of our University Hospital. All patients underwent renal MR-DWI and glomerulonephritis (13.7%). In multiple logistic regression analysis, absence of severe
ADC mapping on a 1.5-T scanner (Philips Achieva) using phased array body coil. hematuria (odds ratio (OR) 11.66, 95% confidence interval (CI) 1.68 - 89.9) and
RESULTS: Among the studied 40 diabetic patients, five groups of patients were presence of anemia (OR 11.38, 95% CI 2.51 - 51.52) were significantly related with the
resulted 8 patients for each and the ADC values were inversely correlated with diagnosis of DN. Akaike’s information criterion (AIC) and net reclassification
advancement in renal parenchymal affection, ie, in late stages of the disease the improvement (NRI) analyses revealed improved predictive performance by adding
ADC values were lower than in early stages. The mean ADC values of renal anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of
parenchyma in patients with diabetic kidney disease were considerably lower than patients in the DN group demonstrated more severe interstitial fibrosis and tubular
that of healthy controls with normal renal function (2.16 0.3x102 3 mm2/s vs atrophy (IF/TA) than the NDKD group (p<0.05) regardless of the rate of global
2.46 0.1x102 3 mm2/s with p< 0.001). glomerulosclerosis (figure), and IF/TA was related to the prevalence of anemia (odds
CONCLUSION: ADC value is a possible noninvasive technique in evaluating the ratio: 7.31, 95% confidence interval: 2.33 - 23.00) in multivariate regression analysis.
stage of renal dysfunction with assessment of disease progression. These results suggest DM-associated severe IF/TA (compared with NDKD) impaired
erythropoietin production, resulting in earlier anemia, independent of glomerular
injuries and renal function. Furthermore, the renal prognosis was significantly better in
the NDKD group than in the DN group using Log-rank test (p<0.05).
CONCLUSION: DN is associated with anemia because of severe IF/TA regardless of
MO637 THE HIDDEN PREVALENCE OF DIABETIC KIDNEY DISEASE renal function, and anemia helps clinician discriminate clinically between isolated DN
IN A HOSPITAL-BASED REAL-WORLD DATA ANALYSIS and NDKD.

Maria Marques Vidas1, Alba Maroto1, Ester Domenech1, Paula Lo pez1,


Fernando Tornero Molina2, Jose’ M. Portoles1
1
Puerta de Hierro Majadahonda University Hospital, Majadahonda, Spain and
2
Hospital Arganda del Rey, Arganda del Rey, Spain

BACKGROUND AND AIMS: Correct identification of diabetic kidney disease (DKD)


in type 2 diabetes mellitus (T2DM) patients is crucial to implement therapeutic

i372 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO639 Figure 1: Comparison of serum IL-1b among the T2DM group, the T2DN
group and the controls.

MO638 Figure a: The percentage of glomeruli which showed global sclerosis in the
DN group (black line) and NDKD group (gray line); the error bar means standard
deviation. Figure b: The distribution of the grade of tubulointerstitial damage in the
DN group (black dots) and NDKD group (gray dots) *Result of v2 test is statistically MO639 Figure 2: Comparison of serum HS among the T2DM group, the T2DN
significant (p<0.05) group and the controls.

MO639 THE ASSOCICATION BETWEEN SERUM INTERLEUKIN 1


BETA AND HEPARAN SULFATE IN DIABETIC NEPHROPATHY
PATIENTS

Liqiong Jiang1
1
Affiliated Suzhou Hospital of Nanjing Medical University, nephrology, Suzhou, P.R.
China

BACKGROUND AND AIMSThe global diabetes mellitus (DM) prevalence in 2019 is


estimated to be 9.3%. Approximately 20% to 40% of patients with DM develop
diabetic nephropathy (DN). DN is the leading cause of end stage renal disease (ESRD).
Inflammation is considered to be an important mechanism in the development of DM
and persists for a long time before the occurrence of DN. Many studies demonstrated
that decrease of endothelium glycocalyx (EG) was negatively correlated with
proteinuria. Whether EG damage induced by inflammasome in DM patients leads to
the occurrence of micro albuminuria (MA) and accelerating the progress of DKD is
rarely studied.Method:This prospective, observational cohort study screened 300
diagnosed diabetic patients from departments of nephrology and endocrinology of our MO639 Figure 3: ROC curves analyses of HS, HGB and the combined model of HS
hospital. The exclusion criteria were: type 1 diabetes; acute infections; usage antibiotics and HGB for prediction of T2DN in diabetic patients.
within 3 months; kidney disease before; heart failure; malignancy. Finally 70 patients
were invited to this study and were divided into type 2 DM (T2DM) group and type 2
diabetic nephropathy (T2DN) group. T2DM group were defined as patients with
normal MA and without diabetic retinopathy (n=35). T2DN group were defined as
patients with increased MA and diabetic retinopathy (n=35). Laboratory data were
measured via routine laboratory methods. Heparan sulfate (HS) and interleukin 1 beta
(IL-1b) were noted as EG biomarker and inflammasome biomarker respectively.
Serum samples of patients were collected, and serum IL-1b and HS were measured by
ELISA. SPSS 18.0 was used for all statistical analyses.Results:T2DN patients had higher
serum IL-1b (27.85 vs. 21.35 pg/ml), higher HS (2.17 vs. 1.47 ng/ml), higher urea
nitrogen (6.30 vs. 5.33 umol/L), higher CRP (2.03 vs. 0.81 mg/L), higher hemoglobin
(128 vs. 141 g/L), higher neutrophil (4.1 vs. 3.4  109/L) and higher
neutrophilic granulocyte percentage (63% vs. 56%) compared with T2DM patients (all
MO639 Figure 4: Correlation of serum HS with IL-1b, fasting blood glucose and
P<0.05). Logistic regression analyses demonstrated serum HS was independently
glycolated hemoglobin in T2DN patients.
associated with T2DN. Furthermore in T2DN patients, serum IL-1b was positively
correlated with HS (r = 0.6, P<0.01) and was and independent associated factor. The
relationship of HS and IL-1b was not significant in T2DM patients.ConclusionT2DN
patients had higher serum IL-1b and HS than T2DM patients in our study. In T2DN
patients IL-1b was an independent associated factor of HS. The results suggested that
the inflammasome may damage the EG in diabetic patients, which induced the MO640 LASER DOPPLER FLOWMETRY IN STUDYING OF
occurrence of MA and accelerating the progress of DN. MICROVASCULAR DISORDERS IN PATIENTS WITH
DIABETIC NEPHROPATHY

Petr Vasilev1, Alexander Shishkin1, Nikolai Erofeev2, Mikhail Erman3, Ivan Pchelin1
1
Saint Petersburg State University, Department of Academic Course in Internal
Medicine, Sankt-Peterburg, Russia, 2Saint Petersburg State University, Department of
Physiology, Sankt-Peterburg, Russia and 3Saint Petersburg State University, Department
of Pediatrics, Sankt-Peterburg, Russia

BACKGROUND AND AIMS: According to various research, vascular complications


of type 2 diabetes mellitus are the main reason for patients’ mortality. The most specific
one, observed in patients with diabetes only, is diabetic microangiopathy, especially
diabetic nephropathy. This complication accounts for more than 20% of cases of
chronic kidney disease. So, the development of non-invasive methods for the diagnosis
of vascular complications of type 2 diabetes mellitus is critically important. There is a
perspective method for this problem - Laser Doppler flowmetry (LDF). It is currently

10.1093/ndt/gfab094 | i373
Abstracts Nephrology Dialysis Transplantation

used in the diagnosis of diabetic microangiopathy, but the limiting factor is the lack of pacemakers and changes of basal vascular tone pattern. It causes an increase in the role
a unified algorithmic approach to the data interpretation. This work aimed to analyze of neurogenic modulation of the micro-vascular bloodstream. These data can be an
changes in the amplitude indicators of the low-frequency part of the LDF signal additional argument in favor of the further development of improving laser Doppler
spectrum in patients with chronic kidney disease and type 2 diabetes and to identify flowmetry using for the tasks of early (preclinical) non-invasive diagnosis of
their correlations with the glomerular filtration rate. microvascular disorders in patients with type 2 diabetes mellitus, as well as for
METHOD: The study included 42 patients (20 men and 22 women) with type 2 monitoring the effectiveness of the therapy.
diabetes mellitus chronic kidney disease (stage C3-C4). The age of patients was 58-77 The reported study was funded by RFBR, project number 19-315-90080.
years (66 years on average). The duration of diabetes was more than 5 years (on
average 7 years). All patients had diabetic nephropathy with a decrease in glomerular
filtration rate, chronic kidney disease stage C3-C4. Laser Doppler flowmetry was done
using the "LAZMA MC-1" system ("Lazma", Russia). Each patient had a 10-minute
LDF registration. The sensor was placed on the skin of the rear of the foot. After
MO641 IMPACT OF MAGNESIUM AND L-CARNITINE
recording the LDF curve, the special software has calculated amplitudes of endothelial,
ADMINISTRATION ON 3-YEAR SURVIVAL IN DIABETIC
myogenic, neurogenic, respiratory, and pulse flux motions. Then we assessed the
PATIENTS WITH END-STAGE RENAL DISEASE
amplitude contribution of every frequency range to the total power of the local flux
motion region. The next step was a correlation analysis with the estimated glomerular
Oleksandr Susla1, Zoriana Litovkina1, Olha Bushtynska1
filtration rate. For statistical analysis, we used the GraphPad Prism 8 (GraphPad 1
Software, USA). I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
RESULTS: All examined patients had amplitude peaks in the neurogenic, myogenic,
respiratory, and pulse ranges. There were no significant correlations between the BACKGROUND AND AIMS: According to population registries, the survival of
glomerular filtration rate and the amplitudes of myogenic and neurogenic flux motions diabetic patients with end-stage-renal disease (ESRD) remains low today. In this
(p>0.05) (Fig. 1). However, there was a significant positive correlation between the context, it is reasonable to develop new therapeutic strategies based on advances in
contribution of myogenic flux motions to the low-frequency range and glomerular science of the important role of magnesium (Mg) and L-carnitine deficiency (via
filtration rate (p<0.01), and a negative one – for the contribution of neurogenic flux inflammation and endothelial dysfunction) in mechanisms of cardiovascular
motions (p<0.01) (Fig. 2). In six observations there was a tendency to a decrease in the remodeling, high morbidity and mortality rates. Thus, the purpose of the present study
contribution of endothelial flux motions as the glomerular filtration rate decreased. was to evaluate the effect of Mg and L-carnitine supplementation on 3-year survival
and development of the cardiovascular complications in diabetic hemodialysis (HD)
patients.
METHOD: 48 type 2 diabetic ESRD patients were included in this prospective cohort
study (male/female, 29/19; age, 59.960.6 years; HD duration, 34.864.8 month;
diabetes mellitus duration, 174.767.1 month). The study was performed in accordance
with the provisions of the Declaration of Helsinki last revision. Depending on the
treatment programme, patients were divided into two groups: the 1st (main) group
(n=24) in addition to basic treatment (hypoglycemic, antihypertensive therapy,
according to indications - correction of anemia, hyperparathyroidism,
hyperphosphatemia) was treated by combination of magnesium aspartate (0.5 g/day
orally) and L-carnitine (1 g/day parenterally after each HD session (three times
weekly); the 2nd (comparison) group (n=24) was only on the basic therapy. Complex
treatment lasted 12-months; administration of L-carnitine was performed
continuously throughout the year, while magnesium aspartate – by three 2-months’
courses/year. The follow up period in both groups was 36 months. Quantitative data
are expressed as means6SEM, qualitative ones – as %. Kaplan-Meier method and Log-
rank test were used to estimate survival of HD patients, v2-test – to compare the
frequency values.
RESULTS: The cumulative proportion of survivors at the end of follow-up was 60.4%;
however, after 36 months, the survival rate of diabetic HD patients who received a
combination of magnesium aspartate and L-carnitine as part of their modified
treatment was significantly higher (75 vs. 45.8%; Log-rank=2.07, p=0.038) compared to
patients who were on basic therapy (Figure). Survival time in main and comparison
groups was 31.961.7 and 26.462.2 months respectively. It is noteworthy, that
throughout the year (from 10 to 22 months), no completed events were recorded in
subjects who underwent Mg and L-carnitine supplementation.
CONCLUSION: (1) The combined use of magnesium aspartate and L-carnitine in
addition to the basic 12-month treatment provides an effective reduction of
cardiovascular complications and promotes 3-year survival of diabetic HD patients. (2)
The results obtained substantiate the advisability of using repeated courses of Mg and
L-carnitine administration 1 years after the end of the primary modified treatment to
improve the prognosis in these ESRD patients.

CONCLUSION: The results of this study showed that laser Doppler flowmetry has the
potential to diagnosis the nature of the dysfunction of individual microcirculation
modulation mechanisms. In patients with chronic kidney disease of the C3-C4 stage
decreasing the glomerular filtration rate correlated with decreasing the contribution of
myogenic flux motions and increasing the contribution of neurogenic flux motions to
the total power of the low-frequency part of the LDF signal amplitude-frequency
spectrum. These changes can be explained within the framework of the existing MO641 Figure: 3-year survival in diabetic HD patients with different treatment
understanding of the pathogenesis of diabetic microangiopathy, namely, damage to the programs.
smooth muscle layer of the wall of arterioles and venules with damage to myocyte

i374 | Abstracts
Nephrology Dialysis Transplantation Abstracts
The results of a 3-year prospective follow-up determined a significant decrease the (57%) patients were on dialysis and 12 (13%) had a functioning transplant. Reasons for
incidence of adverse cardiovascular events, in particular myocardial infarction (4.2 vs. admission included infection (n=21), to undergo a procedure eg arteriovenous fistula
29.2%; v2=5.40, p=0.020), stroke (4.2 vs. 33.3%; v2=5.98, p=0.014), or progression of creation (n=21), AKI (n=10) and fluid overload (n=8).
heart failure (15 vs. 50%; v2=7.85, p=0.005), in diabetic ESRD patients receiving
complex pathogenetic treatment with the inclusion of magnesium aspartate and L-
carnitine.
MO643 Table 1: Type of diabetes and insulin regimen of patients admitted under
nephrology care

MO642 DAPAGLIFLOZIN HAS NO IMPACT ON SHORT-TERM BLOOD Insulin regime Type of diabetes
PRESSURE VARIABILITY IN PATIENTS WITH TYPE-2
DIABETES MELLITUS Type 1 Type 2 Drug induced/
(n=33) (n=52) post transplant
Eirini Papadopoulou1,2, Marieta Theodorakopoulou1, Charalampos Loutradis1,
(n=5)
Georgios Tzanis1, Glyceria Tzatzagou3, Kalliopi Kotsa4, Ioanna Zografou2,
Apostolos Tsapas5, Asterios Karagiannis2, Pantelis Sarafidis1 Once daily 0 6 1
1
Aristotle University of Thessaloniki, Department of Nephrology, Hippokration Hospital, Twice daily 5 31 2
Thessaloniki, Greece, 2Aristotle University of Thessaloniki, Second Propaedeutic Basal bolus 27 15 2
Department of Internal Medicine, Hippokration Hospital, Thessaloniki, Greece,
3
Papageorgiou Hospital, First Department of Internal Medicine, Thessaloniki, Greece, CSCI 1 0 0
4
Aristotle University of Thessaloniki, First Department of Internal Medicine, AHEPA
These 90 patients accounted for 113 admissions with a median LOS of 5 (2-9) days. In
Hospital, Thessaloniki, Greece and 5Aristotle University of Thessaloniki, Second
46 (41%) admissions, there was at least one episode of hypoglycaemia and in 95 (84%)
Department of Internal Medicine, Thessaloniki, Greece
at least one episode of hyperglycaemia. During 12 (13%) admissions, there were neither
hypo nor hyperglycaemic episodes.
BACKGROUND AND AIMS: Increased blood-pressure-variability (BPV) is Insulin self-prescribers were younger (56612.7 ‘v’ 6069.7 years, p=0.04) and more
associated with increased cardiovascular and all-cause mortality in patients with type 2 likely to experience hypoglycaemia than those who did not self-prescribe (p=0.03).
diabetes mellitus (T2DM). Sodium-glucose co-transporter-2 (SGLT-2) inhibitors There was no significant increase in hyperglycaemia nor in median LOS between the
decrease the incidence of cardiovascular events, renal events, and death in this groups. Episodes of hypoglycaemia were more likely with a lower mean fasting blood
population. This study aimed to evaluate the effect of dapagliflozin on short-term BPV sugar (fbs), regardless of self-prescription of insulin (1163.8 ‘v’ 1365.1mmol/L,
in patients with T2DM. p=0.02)
METHOD: This is a secondary analysis of a double-blind, randomized, placebo- CONCLUSION: Most patients with DM admitted under the care of nephrology, self-
controlled trial in 85 patients with T2DM (NCT02887677). Subjects were randomized prescribe insulin. These patients are more likely to have an episode of hypoglycaemia
to oral dapagliflozin 10mg once daily or placebo for 12 weeks. All participants and hypoglycaemia is more likely to occur if the fbs is <13mmol/L. It is unclear how
underwent 24-h ambulatory blood pressure (BP) monitoring with the Mobil-O-Graph our experience differs from that of other specialties. However, reducing renal function,
NG device at baseline and study-end. Standard deviation (SD), weighted SD (wSD), eg in the setting of dialysis or AKI, and uncertainties regarding the carbohydrate
coefficient of variation (CV), average real variability (ARV) and variation independent content of hospital food may play a role in predisposing to hypoglycaemia. In order to
of mean (VIM) were calculated with validated formulae for the 24-h and the daytime facilitate safe management of DM in the inpatient nephrology wards, whilst preserving
and nighttime periods. patients’ autonomy, attention should be paid to the fbs level and self-prescription of
RESULTS: Dapagliflozin reduced 24-h brachial BP compared to placebo. From insulin should be permitted within a narrow range of the patients’ regular dosing
baseline to study-end 24-h brachial BPV indexes did not change with dapagliflozin regimen.
(SBP-ARV: 11.5163.45 vs 11.0563.35; p=0.326, SBP-wSD: 13.5963.60 vs 13.4863.33;
p=0.811) or placebo (SBP-ARV: 11.4763.63 vs 11.0563.00; p=0.388, SBP-wSD:
13.8564.38 vs 13.9763.87; p=0.308). Similarly, no significant changes in BPV indexes
for daytime and nighttime were observed in any group. At study-end, no differences
MO644 :DIABETES AND DIALYSIS:PROPOSAL FOR A CONTAGION
between the groups were observed for any BPV index. Deltas (D) of all indexes during
PREVENTION PROTOCOL IN COVID-19 PANDEMIA
follow-up were minimal and not different between-groups (SBP-wSD: dapagliflozin: -
0.1163.05 vs placebo: 0.1264.20; p=0.227).
Ersilia Satta1, Carmine Romano2, Tersa Della Corte3, Ilaria Raiola4,
CONCLUSION: This study is the first to evaluate the effects of an SGLT-2 inhibitor on
Carmelo Alfarone5, Guido Gembillo6, Gianluca Latte5, Mario Polverino8,
short-term BPV in patients with T2DM, showing no effect on dapagliflozin on all BPV
Sandro Gentile9
indexes studied. 1
Nefrocenter research srl, and Nyx Sturtup, Via xxIV May Cava dei Tirreni, Napoles, Italy,
2
Nefrocenter research srl, and Nyx Sturtup, Via xxIV May Cava dei Tirreni, Salerno, Italy,
3
Nefrocenter research srl, and Nyx Sturtup, Via xxIV May Cava dei Tirreni, 4Nefrocenter
research srl, and Nyx Sturtup, Via xxIV May Cava dei Tirreni, Naples, , 5Nefrocenter
MO643 EFFECTS OF SELF-PRESCRIPTION OF INSULIN ON
research srl, and Nyx Sturtup, Via xxIV May Cava dei Tirreni, Naples, Italy, 6Unit of
GLYCAEMIC CONTROL IN PATIENTS UNDER NEPHROLOGY
Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University
CARE
of Messina, Messina, Italy, 8Nefrocenter research srl, and Nyx Sturtup, Naples, Italy and
9
Department of Internal Medicine, University Campania L Vanvitelli, Naples, Italy
Ailsa Doak1, Karen Stevenson1, Colin C. Geddes1, Kate Stevens1
1
The Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital,
BACKGROUND AND AIMS: After the official coronavirus (SARS-CoV-2) pandemic
Glasgow, United Kingdom
declaration by the WHO, Italy had the second-largest number of confirmed cases, after
China. The Italian government introduced progressive infection-mitigation
BACKGROUND AND AIMS: Co-existence of diabetes mellitus (DM) and kidney measurements, thus dramatically reducing social interactions and preventing virus
disease is common. In-patient hypo- and hyperglycaemia are associated with adverse spread. During the summer, infection containment measures progressively loosened
outcomes and, for hypoglycaemia, an increased length of inpatient stay (LOS). NICE until, due to an unjustified interpretation of some permissions and the excessive
and the National Patient Safety Agency recommend in-patients with DM previously utilization of public transportation at school reopening, the contagion rate
established on insulin be allowed to self-prescribe to reduce hypo and hyperglycaemia. progressively increased until causing a severe challenge for our NHS again. Aim of the
It is unclear how this occurs in clinical practice in patients under nephrology care. study: to assess the efficiency of our previously described protocol in 18 Campania
We sought to describe glycaemic control and diabetes management in patients region-located Nefrocenter Consortium DCs as further adapted to new knowledge
admitted to our nephrology service. under the new ubiquitous contagion conditions and to identify SARS-CoV-2-infection
METHOD: All patients admitted to the Glasgow Renal and Transplant Unit between mortality rate and risk factors.
June and August 2020 were identified. In those with a previous diagnosis of DM, METHOD: Dialysis patients did so too during that period according to the expected
demographic data were collected including reason for admission and use of insulin. shifting prevalence over time (mean 6 SD: 853 6 30 per month; range 825 to 873) 6
Self-prescription of insulin, blood sugar levels and episodes of hypo (BM <4mmol/L) (11.8% in April, and 14.8% in November vs. a pre-COVID-19 12.0% rate in January).
and hyperglycaemia (BM >14mmol/L) were identified. Analysis was undertaken in RESULTS: More patients got infected in November (10.19%) than in April (0,24%),
SPSS v 27.0.1.0. and 22 patients of the 89 from the SARS-CoV-2 November positive subjects required
RESULTS: One hundred and sixty-seven patients with a diagnosis of DM were hospitalization for moderate-severe symptoms (24.72%), with death unavoidably
admitted over the three month period. coming in 19 (86.36% of hospitalized and 21.35% of infected patients) compared to the
The remaining results refer only to the 90(54%) patients established on insulin before only one recorded in April (0.12%). The pandemic’s two periods showed a strong
the index admission. Mean age was 5867.1 years, 56% (n=50) were male and 77% association between mortality rate and often co-existing comorbidities, primarily
(n=69) self-prescribed insulin throughout admission. Table 1 shows type of DM and represented by arterial hypertension, type 2 diabetes mellitus (T2DM), and chronic
regular insulin regimen. Mean HbA1C pre-admission was 6866.4mmol/mol. Fifty-one kidney disease (CKD).

10.1093/ndt/gfab094 | i375
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: The prevously efficient contagion containment measures adopted by


our DCs were not enough in November to fight the global infection risk pending on the
whole Italian social community around. The Authors discuss possible reasons and put
forward further suggestions for the best handling of any future infection waves

MO644 Table 1. General features of subjects on chronic dialysis as of April 23,


2020, and co-morbidities observed according to diabetes status. *IHD/AF/HF=
composite outcome: Ischemic Heart Disease/ Atrial Fibrillation/ Heart Failure. Data
expressed as MeanþSD, range, or n; (%). In no case were HIV Infection, Autoimmune
Disease, and Obesity present.

SARS-CoV-2 SARS-CoV-2 Total


positive negative n.
patients patients
(n. 89) (n. 784)
N (%) N (%) p
Comorbidities
IHD/AF/HF * 12 69.16 386 49.23 <.0001 398
Stroke 7 7.87 176 22.45 <.001 183
Arterial Hypertension 76 85.39 509 64.92 <.01 585
Type 2 Diabetes Mellitus 79 88.76 253 32.40 <’0001 332
Chronic Obstructive Pulmonary 31 34.83 178 22.70 <.01 209
Disease
Active Cancer in the past 5 years 2 2.25 0- - 2
Dementia 9 10.11 27 3.44 <.05 36
Chronic Liver Disease 19 21.35 156 19.90 n.s. 175
Respiratory Failure 14 15.73 134 17.59 n.s. 148
MO644 Figure 1 : Identification and management flowchart of SARS-CoV-2
positive dialysis patients. *asymptomatic, pre-symptomatic or mild symptomatic
Number of Comorbities
infection (fever, cough, dysgeusia, disosmia, headache, myalgia, in the absence of
0 0- 5 0.64 - 5 dyspnea and X-ray abnormalities (stage 1 and 2 according to NIH classification [64]); 
1 0- 105 13.39 - 105 moderate, severe or critical illness according to the same classification.
2 0- 189 24.11 - 189
3 at least 89 100.00 485 61.86 <’0001 574

MO645 BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN


WITH TYPE 2 DIABETES MELLITUS WITH AND WITHOUT
DIABETIC NEPHROPATHY
MO644 Table 2. Most common co-morbidities observed in SARS-CoV-2
positive patients compared to negative ones in the second pandemic period (1st august Daniela Valentinova Monova1, Russka Shumnalieva2, Simeon Monov2
th
- 13 November). In no case were HIV Infection, Autoimmune Disease, and Obesity 1
Medical Institute, Medical University - Sofia, Department of Internal Medivine,
present. *IHD/AF/HF = composite outcome = Ischemic Heart Disease/ Atrial Nephrology and Rheumatology, Sofia, Bulgaria and 2Medical University - Sofia,
Fibrillation/ Heart Failure. Department of Rheumatology, Sofia, Bulgaria

BACKGROUND AND AIMS: Diabetes mellitus and osteoporosis are both common
human diseases. Diabetic nephropathy is characterized by the presence of pathological
quantities of urine albumin excretion, diabetic glomerular lesions, and loss of
glomerular filtration rate in diabetics. Little evidence has been reported on
relationships between BMD and albuminuria.
The aim of this study is to compare the bone mineral density (BMD) in
postmenopausal women with type 2 diabetes mellitus (T2DM) with and without
diabetic nephropathy.
METHOD: We retrospectively analyze the BMD of the lumbar spine and femur using
dual-energy X-ray absorptiometry in 84 postmenopausal women with T2DM with (39)
and without (45) diabetic nephropathy. The serum levels of calcium, phosphorus, total
alkaline phosphatase, and urine albumin excretion were measured in all participants.
Diagnosis of albuminuria was based on albumin-creatinine ratio (ACR).
RESULTS: Age, body mass index (BMI) and time since menopause were not
significantly different between the two groups. The T-scores of basal BMD at L4 were
significantly lower in patients with diabetic nephropathy (-0,94 6 0,40) compared to
patients without nephropathy. No significant differences in serum creatinine were
detected between two groups of patients. Our data suggest that ACR was negatively
associated with lumbar spine and femoral neck BMD.
CONCLUSION: Our results suggest that postmenopausal women with diabetic
nephropathy have a lower BMD and are at increased risk of osteoporosis in the lumbar
spine compared with postmenopausal women without diabetic nephropathy. ACR was
negatively associated with lumbar spine and femur neck BMD. One of the explanations
that has been proposed for the association between albuminuria and osteoporosis is
that albuminuria is associated with reduced bone blood flow, resulting in a decreased
rate of bone remodeling and the development of osteoporosis.

i376 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO646 PATHOLOGICAL PROGNOSTIC FACTORS IN DIABETIC MO647 RENOPROTECTIVE EFFECT OF SGLT2 INHIBITORS AFTER
NEPHROPATHY: A RETROSPECTIVE STUDY FIVE YEARS OF TREATMENT: AN OBSERVATIONAL STUDY

Aurélie Sannier1, Valentin Maisons2, Mickael Bobot3, Francois Vrtovsnik1, Catarina Almeida1, Leonor Silva2, Tiago Costa2, Daniela Lopes1, Victoria Faria1,
Noemie Jourde-Chiche3, Christophe Barba1, Laurent Daniel4, Nathalie Rioux- Elena Suarez2, Rafaela Verıssimo2, Rute Caçola2, Pedro Gil2, Luıs Andrade2
Leclercq5, Cécile Vigneau5, Jean-Michel Halimi2, Jonathan Chemouny5,6,7 1
Centro Hospitalar Vila Nova Gaia Espinho, Nephrology, Vila Nova de Gaia, Portugal
1
Bichat-Claude Bernard Hospital, Paris, France, 2Chru Hôpitaux De Tours, Tours, France, and 2Centro Hospitalar Vila Nova Gaia Espinho, Internal Medicine, Vila Nova de Gaia,
3
hopital de la conception, Marseille, France, 4Hospital Timone, Marseille, France, 5CHU Portugal
Rennes - Pontchaillou Hospital, Rennes, France, 6IRSET, Rennes, France and 7University
Rennes 1 - Ufr Médecine, Rennes, France BACKGROUND AND AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors,
the most recent glucose lowering oral agents, prevent glucose and sodium reabsorption
BACKGROUND AND AIMS: Kidney Biopsies (KB) performed in patients with at proximal tubules. These drugs have the potential of nephroprotection by their
Type-2 diabetes (T2D) usually aim at differentiating diabetic nephropathy (DN) from glucose lowering effects, but also through direct renal effects, such as reducing
other kidney diseases. However, KB could also help refining patients’ prognosis, both intraglomerular pressure and suppressing the production of pro-inflammatory and
in terms of renal survival, and in terms of patient survival. In 2010, the Renal Pathology pro-fibrotic factors. Several randomized control trials have demonstrated these effects
Society developed a pathological classification of DN, but the prognostic value of the with slowing chronic kidney disease progression. The aim of our study was to evaluate
described items , is still imperfectly documented. We aimed to assess the prognostic the effect of SGLT2 inhibitors on estimated glomerular filtration rate throughout five
performances of these items to predict renal and patient survival. years of treatment.
METHOD: Native KBs with diabetic and/or hypertensive nephropathy (DN/HN) METHOD: This was a retrospective observational and longitudinal study that included
performed in patients with T2D in four French centers were analyzed and scored patients diagnosed with DM2 and treated with an iSGLT2 in a Diabetic Clinic.
according to the classification developed by the Renal Pathology Society. Clinical and Demographic and clinical variables were collected, including HbA1c, disease duration
biological data was collected from the patients’ records. Survival analyses were and cardiovascular risk factors (CVRF). Patient glucose-control therapy as well as
performed for renal survival (time to first dialysis or preemptive transplantation) and RAAS inhibitor drugs were gathered. The estimated Glomerular Filtration Rate (eGFR)
death after dichotomization of continuous data). For each of the analyses, we first by the formula CKD-EPI and albuminuria, using the urinary albumin-to-creatinine
established a model comprising clinical data only. We then assessed the benefit of ratio, were evaluated at the iSGLT2 introduction date and at 6, 12, 24, 36, 48 and 60
adding each of the pathological item to the clinical model. Finally, we performed a months of treatment. Categorical variables are presented as frequencies and
backward stepwise analysis to identify items predictive of renal and/or patient survival. percentages, and continuous variables as means or medians for variables with skewed
RESULTS: We analyzed 165 biopsies with DN/HN from patients with T2D and with at distributions. All reported p values are two-tailed, with a p value of 0.05 indicating
least 12 months of follow-up (unless they reached an endpoint during the first year). statistical significance. A paired Student’s t-test or paired-sample test were performed
Among them, 73 (44%) were male, 155 (94%) had hypertension, 53 (34%) hematuria, for continuous variables and a chi-squared test was performed for categorical variables.
22 (15%) had proliferative diabetic retinopathy (DR), 33 (23%) had non-proliferative RESULTS: A total of 205 patients, 54,6 % male, mean age 65,4 years, median baseline
DR, 90 (62%) had no DR (20 had missing data). Mean (SD) age was 63 (11), median HbA1c 8,4% and median duration of DM2 14 years were studied. Of all patients, 94,1%
[IQR] eGFRCKD-EPI was 29 [18;45] ml/min/1.73m2, urinary protein-to-creatinine ratio had at least 1 CVRF, 71,2% hypertensive, 83,4% dyslipidemia, 48,8% obese, and 25,4%
was 0.38 [0.14;0.83] g/mmol, HbA1c was 7 [6.2;8.2] % and diabetes duration before KB had past/current smoking habits. Regarding glucose-control therapy 17,1% were
was 10 [5;19] years. The median [IQR] follow-up was 33 months[18;57]. During the treated with one drug class and the remaining patients were treated with 2 or more
follow-up, 43 (26%) patients died and 69 (42%) required renal replacement therapy classes. Among the patients 82,0% of them were taking metformin and 51,2% were on
(RRT). The percentage of ischemic glomeruli, and presence of more than one area of insulin therapy. Also, 56,6 % were on a RAAS inhibitor. Overall, 129 (62,9 %) patients
arteriolar hyalinosis (ah=2), were predictive of renal survival and improved the received dapaglifozin therapy (5 or 10mg) and 76 (37,1%) empaglifozin (10 or 25mg).
predictive value of the model when added to clinical parameters. Presence of at least Regarding albuminuria at baseline, 37 patients had normal albuminuria (<30mg/g), 18
one convincing Kimmelstiel–Wilson lesion (nodular glomerulosclerosis or Class III patients had moderate albuminuria (30-300mg/g) and 6 patients had severe
DN) was predictive of death and similarly improved the predictive model (See figure). albuminuria (>300mg/g). As for eGFR, 15,6 % patients had an eGFR between 30 and
CONCLUSION: Pathological findings on KB, as classified by the Renal Pathology 60 and 84,4% patients had an eGFR greater than 60 ml/min/1,73m2. These clinical
Society, carry significant prognostic value in patients with T2D and DN/HN. Vascular features were similar between the patients that received either SGLT2 inhibitor, with
lesions (presence of arteriolar hyalinosis and less than 7% of ischemic glomeruli) the exception of obesity being more prevalent in the dapaglifozin group (55,8 % vs
predicted the need for RRT, while nodular glomerulosclerosis was predictive of 36,8%, p=0,009). Assessing the eGFR during the 5 years of treatment, a significant
death. decrease was noticed in the first 6 months from an 82,3 to 78,6 ml/min/1,73m2
(p=0,002), followed by a significant increase in the second semester to 82,9 ml/min/
1,73m2 (p<0,001). Thereafter there is a slight increase in eGFR throughout the years,
to a maximum of 84,1 ml/min/1,73m2 at 24 months and after a slow reduction to
80,6ml/min/1,73m2 in the end of the 5 years of SGLT2 inhibitor use.
CONCLUSION: This observational study shows that after an initial reduction in eGFR
during the first 6 months of treatment, the use of iSGLT2 after five years slowed the
decrease in eGFR, similar to what randomized control trials have demonstrated,
promoting a renoprotective effect on type 2 diabetic patients.

MO646 Figure: Upper and middle panels: Survival free of dialysis or preemptive
transplantation according to (A) eGFRCKD-EPI below (red) or over (blue) 30 ml/min/ MO647 Figure: Kidney function throughout five years of treatment with SGLT2
1.73m2, (B) UPCR below (red) or over (blue) 0.2 mg/mmol, (C) Hematuria absent inhibitors
(red) or present (blue), (D) Arteriolar hyalinosis 0-1(red) or 2 (blue), (E) Proportion of
ischemic glomeruli below (red) or over (blue) 7%, (F) Adjusted Cox regression analysis
for survival without dialysis of preemptive transplantation.
Lower panel: Patient survival according to (G) eGFRCKD-EPI below (red) or over (blue)
30 ml/min/1.73m2, (H) Nodular glomerulosclerosis absent (red) or present (blue), (I)
Adjusted Cox regression analysis for patients’ survival.

10.1093/ndt/gfab094 | i377
Abstracts Nephrology Dialysis Transplantation

MO648 SERUM SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR viz, IL 18/cr. Cystatin/Cr and NGAL/Cr. were 0.65, 0.64 and 0.51 respectively.
RECEPTOR IN PATIENTS WITH DIABETIC KIDNEY DISEASE Angiotensinogen/Cr and IL18/Cr showed correlation with log albuminuria r-0.3 p 0.00
and r-0.28 p 0.00 respectively; NGAL with log e-GFR (r-0.28 p0.00).Multivariate
Gabriela Elena Lupusoru1,2, Ioana-Georgiana Ailincai2, Bogdan logistic analysis showed Odds of contracting nephropathy is 7.5 times having higher
Marian Sorohan1,2, Andreea Gabriella Andronesi1,2, Mircea Lupusoru3, values of Log Angio/Cr.
Danut Andronesi4, Dana Manda5, Andra Caragheorgheopol5, Gener Ismail1,2 CONCLUSION: Urinary Angiotensinogen has higher diagnostic value than ACR and
1
Carol Davila University of Medicine and Pharmacy, Nephrology Department, e-GFR followed by IL 18 and Cystatin to diagnose DN at the pre-albuminuric stages
Bucharest, Romania, 2Fundeni Clinical Institute, Nephrology Department, Bucharest, but not urinary NGAL.
Romania, 3Carol Davila University of Medicine and Pharmacy, Physiology Department,
Bucharest, Romania, 4Fundeni Clinical Institute, General Surgery and Liver Transplant
Department, Bucharest, Romania and 5“C.I.Parhon” National Institute of
Endocrinology, Research Department, Bucharest, Romania

BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is the leading cause of
end-stage renal disease worldwide, associated with significant cardiovascular morbidity
and mortality. Soluble urokinase plasminogen activator receptor (suPAR) is a novel
biomarker associated with inflammation, endothelial dysfunction and kidney disease.
There is a lack of studies that investigate the role of suPAR in patients with DKD. Our
aim was to assess the level of serum suPAR and to evaluate its association with kidney
function, proteinuria and histological lesions in patients with DKD.
METHOD: We performed a cross-sectional study on 75 patients with DKD evaluated
in our department between 2019 and 2020. Inclusion criteria were: age> 18 years,
diagnosis of type 1 or type 2 diabetes mellitus, DKD and absence of malignancy,
autoimmune disease, infectious disease and liver disease. Demographical, clinical and
laboratory parameters were collected at the time of admission. A subset analysis was
performed on 28 patients with biopsy- proven diabetic nephropathy (DN) to
investigate the association of serum suPAR with histological lesions. Kidney function
was evaluated based on serum creatinine and estimated with CKD-EPI formula,
proteinuria was reported as 24h proteinuria and albumin/creatinine ratio (ACR) and
serum suPAR levels were measured with a solid-phase ELISA kit. The detection range
of the kit was 12 -360 pg/ml (7.8- 500).
RESULTS: Among the 75 patients, mean age was 57.9612.2 years, male was the
dominant gender (65.3%), mean BMI was 30.765.5 kg/m2, most patients had
hypertension (97.3%) and 22.7% were active smokers. Sixty six out of 75 patients (88%)
had type 2 diabetes and the median duration of diabetes was 180 months (120- 240).
Median values of estimated glomerular filtration rate (eGFR), 24h proteinuria and MO649 Figure 1: (a, b, c & d): - Box plots Showing median values, range and
ACR were 24.3 ml/min (15- 36), 4.8 g/24h (1.9- 7.1) and 2000 mg/g, respectively. significance of various biomarkers such as Urine Cystatin-C/urine Creatinine,
Median serum level of suPAR at the time of evaluation was 2857.2 pg/ml (1916.4- Angiotensinogen/Urine Creatinine, IL-18/Urine Creatinine, & NGAL/Urine
3700.1). Its level was positively correlated with duration of diabetes (r= 0.278, p= 0.01), Creatinine levels between Controls (ACR<30 & e-GFR<120) & Cases Groups (i).
eGFR (r= 0.634, p< 0.001), 24h proteinuria (r= 0.490, p< 0.001), ACR (r= 0.524, p< Hyper filtration: ACR<30 & e-GFR120, (ii). Normoalbuminuria: ACR<30 & e-
0.001) and negatively correlated with urine specific gravity (r= -0.284, p= 0.01). In the GFR<120 and (iii). Microalbuminuria: ACR30 & e-GFR>120
subset analysis on 28 patients with biopsy-proven DN, median suPAR level was 2474
pg/ml (1782-3745) and was positively correlated with DN class (r= 0.493, p=0.008) and
interstitial fibrosis and tubular atrophy (IFTA) score (r= 506, p=0.006), but not with
interstitial inflammation, arteriolar hyalinosis or arteriolosclerosis.
CONCLUSION: Our study showed a high serum level of suPAR in patients with DKD
and its association with duration of diabetes, urinary specific gravity, kidney function
and proteinuria. We also found a positive correlation with severity of glomerular
lesions and IFTA.

MO649 DIAGNOSTIC TESTS OF NOVEL URINARY BIOMARKERS TO


IDENTIFY EARLY STAGES OF NEPHROPATHY IN NON
HYPERTENSIVE TYPE 2 DIABETIC MELLITUS

Himansu Mahapatra1, Bindu Kulshreshtha2, Dr. Parul Goyal3, Anubhuti Chirkara4,


Tripti Khanna5, Anamika Singh1, Arpita Arora1, Yadunandan Prasad Gupta1,
Venkatesan Sekhar1
1
ABVIMS, DR. RML Hospital, Nephrology, New Delhi, India, 2ABVIMS, DR. RML Hospital,
Endocrinology, New Delhi, India, 3ABVIMS, DR. RML Hospital, Biochemistry, New Delhi,
India, 4MAMC, Biochemistry, New Delhi, India and 5Institute Council of Medical
Research, Ansari Nagar, ICMR, New Delhi, India

BACKGROUND AND AIMS: Activation of RAS and tubulointerstitial damage might


be seen in pre-albuminuria stage of diabetic nephropathy. Here, diagnostic tests of
urinary Angiotensinogen, Cystatin C, Neutrophil gelatinase associated lipocalin and IL
18 have been studied in pre-microalbuminuria diabetic patients.
METHOD: Total 952 Diabetic screened for Nephropathy (e-GFR 120&ACR30), MO649 Figure 2: Receiver Operating Curves (ROC) of all four biomarkers/urine
among them 120 cases were followed up for one year. At one year they were classified creatinine considering control reference (ACR<30 &e-GFR<120) to determine the
in to Hyperfiltration43, Normoalbuminuria29 and Microalbuminuria48 groups. discriminatory power of biomarkers for the diagnosis of Diabetic with Nephropathy.
Another 63 Diabetes without nephropathy were included as controls. Hypertension, on Fig3a; Angiotensinogen/ur., 3b; Cystatin-c/ur.cr, 3c; IL-18/ur.cr & 3d; NGAL/ur.cr.
ACEI/ARB, e-GFR<60ml/min/1.73m2 and all Macroalbuminuria conditions were
excluded. All were subjected to urine protein, ACR, HbA1c,e-GFR, along with urinary
bio markers(IL-18, Cystatin-C, NGAL and Angiotensinogen). Comparative analysis of
all groups, Diagnostic tests, correlation and logistic regression were analysed.
RESULTS: Urinary IL18/Cr, Cystatin /Cr. and Angiotensiogen /Cr. levels were higher
in groups of hyper filtration (13.47, 12.11 & 8.43mg/g), Normoalbuminuria
(9.24,11.74&9.15mg/g) and microalbuminuria(11.59,14.48&10.24mg/g) than
controls(7.38,8.39&1.26mg/g) but not NGAL/Cr. in all groups. High levels were
significant in all except Cystatin/Cr. & IL18/Cr. in normoalbuminuria group. The
AUC, sensitivity and specificity of Angiotensinogen (0.9, 90% and 80%) ACR (0.69,
40% and 100%) and e-GFR (0.6,37 and 100%)respectively. AUC of other biomarkers

i378 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO650 EMPHYSEMATOUS PYELONEPHRITIS IN TYPE 2 DIABETES – MO652 EFFECT OF ESTIMATED GLOMERULAR FILTRATION RATE
CLINICAL PROFILE AND MANAGEMENT (EGFR) ON HEMOGLOBIN CHANGE INDUCED BY SODIUM-
GLUCOSE COTRANSPORTER 2 INHIBITORS (SGLT2I)
Dr Sanjay Bhat1, Anupma Kaul2, Priyanka Rai1, Rohit Srivastav1
1
Ram Manohar Lohia Institute of Medical Sciences, Surgery, Lucknow, India and Alba Maroto1, Ester Domenech1, Maria Marques Vidas1, Paula Lo pez1, Jose’
2
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Nephrology, Lucknow, India M. Portoles1
1
Puerta de Hierro Majadahonda University Hospital, Majadahonda, Spain
BACKGROUND AND AIMS: Emphysematous pyelonephritis (EPN) is a rare but
life-threatening acute suppurative infection of the kidney among diabetics. There is no BACKGROUND AND AIMS: The use of sodium-glucose cotransporter 2 inhibitors
current consensus on management of EPN. (SGLT2i) is associated with increase of hemoglobin (Hb) levels and this effect has been
METHOD: A prospective observational study was conducted at Department of related to improvement of tubulointerstitial hypoxia and increase on EPO production.
General Surgery at RML institute of Medical sciences , Lucknow as well as at Eras Chronic kidney disease (CKD) associated anemia is mainly due to decreased EPO
Lucknow medical college, Lucknow from 2015-2018 to look for clinical, microbial synthesis. The aim of this study was to assess if the degree of Hb increase induced by
profile and treatment outcome of diabetic patients with emphysematous SGLT2i is higher on T2DM patients with decreased estimated glomerular filtration rate
pyelonephritis. (eGFR).
RESULTS: A total of 76 Diabetic patients diagnosed with pyelonephritis were METHOD: We analyzed the changes on Hb after 12 months of SGLT2i treatment in
identified, of which 15 patients were diagnosed with EPN (26.3%). The mean age of the T2DM patients with different degrees of eGFR. All patients were on maximum
patients was 58.466.5 years. Mean duration of diabetes was 5.3 6 3.3 years. 12 (82%) tolerated RAA system blockade, and none was on erythropoiesis or iron therapy.
of the 15 patients with DM had a glycosylated hemoglobin A1C level higher than 7.5. RESULTS: 62 patients were include, age 67,6 6 12,3 years, 72.6% males, eGFR CKD
Renal dysfunction at presentation was seen in 11 (73.3%) patients. Among the EPI 62,9 6 21 (21-108) ml/min/1.73m2. Type of SGLT2i was dapagliflozin (46.8%),
unilateral involvement, left kidney was more affected. Escherichia coli in 11 (73.3%), canagliflozin (30,5%) and empagliflozin (22,6%). 7 patients discontinued SGLT2i
Klebsiella sp. in 1 (6.6%), Pseudomonas in 1 (6.6%), and 1 each with polymicrobial and therapy and 62 were finally include in the analysis. Treatment with SGLT2i induced
fungal UTI respectively. Of 15 EPN patients, 13 (86.6 %) survived and 1 (6.6 %) increase of Hb levels ( KHb 0,57 mg/dl SE 0,17 95% CI 0,25-0,93, p 0,001)
expired. 2 of them underwent nephrectomy both survived. All patients with Stage I, II independently of eGFR (aR2 0.02 p ns) In the multivariate analysis, initial eGFR, and
and IIIa EPN (n = 12) were managed with antibiotics with or without PCD. In EPN basal Hb were the main determinants of the Hb increase induced by SGLT2i treatment
Stage IIIb/IV (n = 3), all the 3 (20 %) patients were managed with antibiotics and PCD (aR2 0,29). eGFR (60 vs >60 ml/min/173) or type of SGLT2i did not modified KHb
and later 2 (13.3%) needed nephrectomy. Only time to diagnosis, altered sensorium, CONCLUSION: We conclude that SGLT2 inhibitors induce increase on Hb level
shock at presentation and thrombocytopenia were associated with poor outcome in independently of eGFR, in patients with preserved renal function, by mechanisms that
EPN patients (P < 0.05) Multiple logistic regression tests showed shock (P = .04) and are yet to be determined.
and disturbance of consciousness (P = .05) on hospital admission as being the
independent factors for poor outcome.
CONCLUSION: EPN in diabetics needs high index of suspicion, timely diagnosis and
MO653 RISK FACTORS FOR DIABETIC NEPHROPATHY AMONG
good multidisciplinary approach with adequate antibiotics and surgical management
NEWLY DIAGNOSED TYPE 2 DIABETIC PATIENTS WITH
for better patient outcomes.
NORMAL BLOOD PRESSURE

Muhammad Abdur Rahim1, Shahana Zaman2, Samira Humaira Habib3


MO651 DIABETES CARE IN HAEMODIALYSIS TREATMENT : 1
BIRDEM General Hospital, Nephrology, Dhaka, Bangladesh, 2NICVD, Cardiology,
ADVANCES IN 2020 Dhaka, Bangladesh and 3BADAS, Health Economics, Dhaka, Bangladesh

Clementine Dillmann1, Clemence Tollard1, Yoann-Francois Chantrel2,


BACKGROUND AND AIMS: Diabetes mellitus (DM) is the leading cause of chronic
Hanane Mountassir2, Sophie Brokhes-Lecalvez2, Fatema Fall-Mostaine1,
kidney disease; principally resulting from the increasing prevalence of type 2 DM
Zafer Takla2, Rocsana Fickl2, Daniela BABICI2, Liviu Serb3, Laurence Kessler1,
(T2DM). Patients with T2DM pass through pre-diabetic stages and at the time of
Francois Chantrel2
1
diagnosis, up to half of the T2DM patients may have different macro- and micro-
CHU Strasbourg, Endocrinologie-Diabete-Nutrition, Strasbourg, France, 2Mulhouse, vascular complications, including diabetic nephropathy. Hypertension has adverse
AURAL, Dialysis Unit, Mulhouse, France and 3GHRMSA, Endocrinologie-Diabete- impacts on diabetic nephropathy. This study was designed to evaluate the risk factors
Nutrition, Mulhouse, France for diabetic nephropathy among newly detected T2DM patients with normal blood
pressure.
BACKGROUND AND AIMS: Management of diabetes and follow-up of METHOD: This case-control study was done at out-patient department of a referral
haemodialysis patients are still poorly standardized. The objective of this study is to hospital in Dhaka, Bangladesh from January 2018 to June 2019. Newly detected (<3
establish a descriptive inventory of all routine parameters for monitoring diabetes and months), adult (18 years), T2DM patients of either sex, who underwent test for urine
glycemic control by Continuous Glucose Monitoring (CGM). albumin-to-creatinine ratio (UACR), at least twice (6 weeks apart), within a 6-month
METHOD: The study recruited 32 diabetic patients in a medical dialysis unit. period, were included in this study. Patients with hypertension (newly diagnosed or
Glycemic control was assessed using CGM (FreeStyle Free ProV R ) over at least 11 days known cases/on antihypertensive medications), known kidney disease, features of
with measurement of: mean blood glucose level, percentage of blood glucose level: < 70 glomerulonephritis, systemic diseases including systemic lupus erythematosus and
mg/dl (TBR), between 70 and 180 mg/dl (TIR), and > 180 mg/dl (TAR). The results vasculitis, history of recent fever and exercise, urinary tract infection and pregnancy
are expressed in average or median [25-75 percentiles]. SPSSV R statistical analyses were excluded. Patients with UACR 30 mg/g in at least two (of three, if done)
compared extra and per dialytic periods. samples were cases and those with UACR <30 mg/g were controls.
RESULTS: Patients’ mean age was 7168 years, diabetes duration was 2166.5 years RESULTS: Total patients were 135, including 27 cases [moderately increased
(87.5% T2DM), mean weight was 77613kg, HbA1c was 760.98%, 98% had a high risk proteinuria (previously, microalbuminuria) (UACR 30 – 299 mg/g) = 25 and severely
of foot injury (Grade 2 and 3) . Only 46.8% of the patients were followed by a diabetes increased proteinuria (previously, overt proteinuria) (UACR 300 mg/g) = 2] and 108
specialist and 84.3% were treated with insulin and 18.75% received oral medication controls. Mean age was 42.9 years and there was female (64.8%) predominance.
while only 50% performed self blood glucose-monitoring. The average blood glucose Thirteen percent patients were smokers, 12% had dyslipidaemia, 51% had family
level was 133613 mg/dl (1000 measurements). CGM results for 32 patients over the history of DM and 44.9% had family history of diabetic nephropathy. Besides diabetic
total period were: TIR at 70% [58-76], TAR at 15% [4.6-29], and TBR at 9.6% [3.7- nephropathy, other chronic complications of DM were diabetic retinopathy (6.7%),
20].Per-dialytic TIR (84%; [76-93]) was significantly higher (p=0.02) than extra- diabetic peripheral neuropathy (0.7%) and coronary artery disease (1.5%). Regarding
dialytic TIR (68%; [56-75]). Per-dialytic TAR (5.5%; [0.0-10.7]) was significantly lower risk factors for diabetic nephropathy, family history of DM [odds ratio (OR) = 2.31,
(p<0.01) than extra-dialytic TAR (14%; [3.6-29]). TBR did not vary significantly. 95% confidence interval (CI) = 0.923 – 5.415, p = 0.003) and diabetic nephropathy (OR
CONCLUSION: The majority of patients were treated with insulin but only 50% = 3.28, 95% CI = 1.523 – 9.297, p = 0.001), smoking (OR = 3.08, 95% CI = 1.066 –
performed self- of blood glucose. Hypoglycaemia was lower during dialysis period. 98% 0.934, p = 0.003), dyslipidaemia (OR = 2.11, 95% CI = 0.241 – 3.464, p = 0.004) and
of patients had a high risk of foot injury. CGM could be a usefull tool for the evaluation coexisting diabetic retinopathy (OR = 6.51, 95% CI = 1.46 – 11.79, p = 0.003) were
of glycemic profile of haemodialysis patients, and allows a better adjustment of their significant. On multivariate logistic regression, family history of DM (OR = 2.13, 95%
treatment. CI = 1.412 – 4.216, p = 0.003) and diabetic nephropathy (OR = 3.31, 95% CI = 2.145 –
5.249, p = 0.001), smoking (OR = 3.11, 95% CI = 2.234 – 4.123, p = 0.003),
dyslipidaemia (OR = 2.14, 95% CI = 1.363 – 3.324, p = 0.005) and diabetic retinopathy
(OR = 6.23, 95% CI = 4.197 – 9.464, p = 0.004) were significant.
CONCLUSION: Family history of DM and diabetic nephropathy, smoking,
dyslipidaemia and concomitant diabetic retinopathy were significant risk factors for
diabetic nephropathy among newly diagnosed T2DM patients with normal blood
pressure.

10.1093/ndt/gfab094 | i379
Abstracts Nephrology Dialysis Transplantation

MO654 REAL LIFE EXPERIENCE AFTER 20 MONTHS USING SGLT2 RESULTS: In table 1 the basal characteristics of this population are shown.
INHIBITORS Analysis of the complete population showed a significant decrease of proteinuria
(Initial mean proteinuria was 1636þ/-1513 mg/24h vs final mean proteinuria of
Renata Carvalho1, Ba rbara Ribeiro1, Joana Medeiros1, José M
ario Bastos1, 1320þ/-1480mg/24h, p=0.015).
Raquel Vaz1, Sofia Homem Melo Marques1, Anto nio Rmalheiro1
Furthermore, the analysis by groups depending on initial proteinuria revealed that
1
Hospital de Braga, Nephrology, Portugal both groups had a significant reduction of proteinuria after 6 months:
Group 1 ( proteinuria < 1g/24h) presented initial mean proteinuria of 689þ/-1050
BACKGROUND AND AIMS: Diabetic kidney disease (DKD) develops in almost half
mg/24h vs final proteinuria of 648þ/-957mg/24h. p=0.033
of diabetic patients and is the leading cause of chronic kidney disease (CKD). SGLT2
Group 2 ( proteinuria >1g/24h) presented initial mean proteinuria of 2917þ/-
inhibitors (SGLT2i) have consistently shown to confer kidney protection in patients
1046mg/24h vs final proteinuria of 2244þ/-1600mg/24h. p=0.015
with type 2 diabetes (T2D). The recent KDIGO guidelines suggest their use as a first
A second exam depending on initial GFR was carried out, proving that those with
line medication along with metformin. After the study CREDENCE was published, in
lower initial GFR maintained a significant decreased of proteinuria after 6 months of
mid-2019, DKD patients at the Nephrology outpatient department of the Hospital of
treatment.
Braga were started on SGLT2i. We aimed at assessing these patients’ clinical and
CONCLUSION: In our cohort, against our hypothesis, we didnt observe lower
laboratory data after the introduction of the new drug.
reduction of proteinuria when we started the treatment with proteinuria above 1 g/24h.
METHOD: We collected data on age, gender, weight, blood pressure (BP) values, the
We can consider that the effect of SGLT2i doesn’t decreased in patients with higher
use of renin-angiotension-aldosterone system inhibitors (RAASi), kidney function,
initial proteinuria. Therefore, we should always consider and offer this therapeutic
glycated hemoglobin (HbA1c), glycosuria, proteinuria and albuminuria at baseline and
option to our ND patients.
during the two next patient assessments. Data was analyzed using SPSSV R.

RESULTS: Twenty-nine DKD patients who started SGLT2i between May 2019 and
August 2020 were followed. Mean age was 71.2613.5 years, 22 patients were male and
their mean weight was 86.9613.9 kg. They had had T2D for a mean of 15.9610.3 years
and a significant percent had end organ damage: 34% had diabetic retinopathy, 24%
complaints suggestive of neuropathy, 51% had documented heart failure and 27% had
cerebral vascular disease. Most were hypertensive with a mean BP of 156619/
83611mmHg and 72.4% were taking RAASi. One third were treated with insulin.
Most patients were started on canagliflozin (n=28) and one patient started
empagliflozin. After starting the drug, patients were evaluated at a mean time of
141655 days and had a second reevaluation at a mean time of 254672 days. On the
first evaluation they showed a significant reduction in the mean systolic BP to
140615.1mmHg (p=0.001). Glycated hemoglobin decreased from a mean of 7.461.3%
to 7.161.1% although this difference was not significant (p=0.4). Protein-creatinine
urinary ratio was significantly reduced from a median value of 1.48 (IQR 0.24-1.85) to
0.93 (IQR 0.40-1.56). Mean serum creatinine increased significantly from baseline until
the first evaluation at 1.9660.49 to 2.2760.66mg/dL (p=0.00) but remained stable on
the second evaluation (2.2960.79mg/dL). Seventy percent of the patients developed
significant glycosuria (urinary concentration >500mg/dL) after starting SGLT2i.
When asked about adherence, most non-glycosuric patients admitted not having
started the drug.
CONCLUSION: Despite having a weak effect in the reduction of HbA1c, SGLT2i are
an exciting drug for kidney protection in DKD. Patient adherence is easy to assess
based on glycosuria. In our experience and based on this criterion drug compliance was
acceptable (at least 70%) and we were able to reinforce instructions among non-
compliant patients. Some of the benefits of SGLT2i were evident soon after they were
started such as the improvement in BP and proteinuria. The initial increase in plasma
creatinine was expected due to reduction in intraglomerular pressure and
hyperfiltration and was noticeable only on the first assessment. We expect to continue
SGLT2i use DKD patients.

MO655 PROTEINURIA DECREASE AFTER SGLT2I : WHAT CAN WE


EXPECT?

Candela Moliz1, Esther Casillas1, Vanessa Lopes Martın1, Irene Martin1,


Elizabeth Viera1, Milagros Fernandez Lucas1, Javier Villacorta1
1
Hospital Ramon y Cajal, Nephrology, Madrid, Spain

BACKGROUND AND AIMS: The effect of sodium-glucose cotransporter-2


inhibitors (SGLT2i) in reducing proteinuria secondary to type II diabetic nephropathy
is well known. However, in daily practice we might have the impression that those
patients who present with a higher proteinuria at the beginning of SGLT2i treatment
might not reach an equal decrease of proteinuria compared to those with lower initial
proteinuria (under 1g/24h). To verify this hypothesis we analysed the evolution of our
patients depending on the initial proteinuria.
METHOD: A retrospective analysis of 40 patients who had initiated treatment with
SGLT2i was carried out. At the beginning of treatment, 23 patients presented
proteinuria over 1 gram/24h and the other 17 presented less than 1g/24h. The decrease
of proteinuria after 6 months of follow-up was analysed in each group. The variations
in serum creatinine, haemoglobin and glycosylated haemoglobin were also examined.
A second analysis depending on initial glomerular filtration rate (Under and over 60
ml/min) was also performed.

i380 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i381–i391, 2021
10.1093/ndt/gfab099

MO657 RANDOMIZED CONTROL TRIAL OF INTERMITTENT


DIALYSIS. EXTRACORPOREAL DIALYSIS: TECHNIQUES HEMODIALYSIS WITH REGIONAL CITRATE VS PRIMING
HEPARIN WITH PREDILUTION IN PATIENTS AT RISK OF
AND ADEQUACY BLEEDING

Olivier Moranne1, Sylvain Cariou1, Ziyad Messikh1, Emilie Pambrun1,


MO656 CORRELATION BETWEEN CHANGES IN THE BODY FLUID Florian Garo1, Celine Schultz1, Julien Prouvot1, Sophie Renaud1, Pascal Reboul1
1
VOLUME CALCULATED BY THE URIC ACID KINETIC MODEL Nimes University Hospital, Nephrology Dialysis Apheresis, NIMES, France
AND CHANGES IN THE BODY WEIGHT*
BACKGROUND AND AIMS: Standard intermittent haemodialysis (SIHD) includes
Shigeru Nakai1, Kiyoshi Ozawa2, Kazuhiko Shibata3, Takahiro Shinzato4 anticoagulation to avoid clotting of the dialysis system. In patients at high risk for
1
Fujita Health University School of Health Sciences, Faculty of Clinical Engineering bleeding, alternativ methods have been developed to avoid systemic anticoagulation.
Technology, Toyoake, Aichi, Japan, 2Shinzinkai Yokosuka Clinic, Internal medicine, Regional citrate anticoagulation (RCA) is usually used with continuous renal
Yokosuka city, Kanagawa, Japan, 3Meishinkai Toshin Clinic, Internal medicine, replacement therapy and low blood flow but the PromotheusV R device (Freseinus

Yokohama city, Kanagawa, Japan and 4Daiko Biomedical Engineering Research Medical care-Germany) allow RCA for liver support therapy with dialysis system
Institute, Nagoya city, Aichi, Japan 4008HV R and blood flow over 200ml/min. The aim of this study was to compare the

IHD with RCA (IHD-RCA) to SIHD without systemic anticoagulation in patients at


BACKGROUND AND AIMS: Uric acid (UA) is a solute unable to cross the cell high risk for bleeding.
membranes in general tissues by any of simple diffusion, facilitated diffusion or active METHOD: We conducted a randomized control trial study evaluating the superiority
transport. These facts imply that UA distribution volume (UDiV) equals to the of IHD-RCA with PrometheusV R device compared to SIHD with 5008HV R dialysis

extracellular fluid volume (ECFV). We have developed a method for calculating UDiV monitor using priming heparin (5000UI unfractionated heparin) with predilution (25
from serum uric acid levels before and after hemodialysis based on a uric acid kinetic ml/min) in a 4 hour IHD strategy in patients with high risk for bleeding.
model (Shinzato T, Int J Artif Organs 2020). Urea is evenly distributed throughout the Randomization was stratified on vascular access. Sixty adult patients were randomly
body fluids. Therefore, the total body fluid volume (TBFV) can be calculated by using allocated to one IHD-RCA session or SIHD in a one ICU unit university center from
the same method as the calculation of UDiV for the serum urea level. The remaining 2019 to 2020. Bleeding risk was defined by nephrologist and inclusion need well-
body fluid volume, which is TBFV minus UDiV, is considered to reflect the functioning fistula or double-lumen catheters with a protocol blood flow higher than
intracellular fluid volume (ICFV). In this study, we clarified the relationship between 200 ml/min. The primary end point was the percentage of successful study period,
the amount of change over time in UDiV and ICFV calculated by the uric acid kinetic defined as no premature interruption of a 4 hour hemodialysis session. Secondary end
model and the amount of change over time in the actual body weight of hemodialysis points included dialysis adequacy (KT/V), dialysis circuit bubble trap status and
patients. dialyzer membrane status by visual inspection. The study was declared in ClinicalTrial
METHOD: Subjects were 1,101 patients with chronic maintenance hemodialysis. NCT03562754.
UDiV and ICFV before and after dialysis were calculated for two time points, RESULTS: Two patients from IHD-RCA were excluded of analysis because of early
December 2019 and June 2020. vascular access failure. Causes of bleeding risk were activ bleeding in 25(43%), recent
RESULTS: The amount of change in UDiV per body during the dialysis session surgery or organ biopsy in 31(53%) and Stroke in 2 sessions. 10(17%) patients were
showed a very good correlation with the amount of body weight change during the treated by IHD for AKI3 and other for chronic hemodialysis. 24(41%) patients have
same dialysis (UDiV change = 0.950 x body weight change - 0.158, R-square 0.90, p < fistula, and the mean blood flow was significantly higher in SIDH group vs IHD-RCA
0.0001). The amount of change in ICFV during the 6 months from December 2019 to (294 vs 263 ml/min, p<0.001). All sessions were performed with FX800 dialyzer
June 2020 showed a good correlation with the amount of change in post-dialysis body (Polysulfone, hollow-filter 1.8M2, FMC).
weight during the same period (ICFV change = 0.270 x post-dialysis body weight No statistically significant difference was observed for primary end point between
change þ 0. 240, R-square 0.21, p <0.0001). group with 96% (27/28) of success for IHD-RCA and 83% (23/28) for SIHD (p=0.09).
CONCLUSION: These results suggest that the body fluid volume calculated by the uric For secondary end point, no statistically significant difference was observed for KT/V
acid kinetic model has high accuracy. delivery between group (1.69 vs 1.61, p=0.27) but score was statistically significant
different between groups for visual inspection of fiber bundles (p<0.01) and dialysis
circuit bubble traps aspect ( p<0.01 ) with higher score for SIHD.
CONCLUSION: No statitically significant difference was observed between 2 groups
for 4-hour heparin-free hemodialysis sessions but we observed lower session failure
with IHD-RCA. We confirm efficacy of Prometheus device for IHD-RCA in this
population. Moreover, we report a low risk of 4-hour heparin-free session failure with
SIHD without systemic anticoagulation using double lumen access, priming heparin,
high blood flow, predilution and Polysulfone High-flux dialyser in comparison with
other studies.

MO658 POLYVINYLPYRROLIDONE IN HEMODIALYSIS MEMBRANES:


IMPACT ON PLATELET LOSS DURING HEMODIALYSIS

Adam Zawada1, Pascal Melchior1, Ansgar Erlenkötter2, Dirk Delinski1,


Manuela Stauss-Grabo3, James Kennedy1
1
Fresenius Medical Care Deutschland GmbH, Global Research and Development,
Product Engineering Center Dialyzers & Membranes, Product Development, St. Wendel,
Germany, 2Fresenius Medical Care Deutschland GmbH, Global Research and
Development, Product Engineering Center Dialyzers & Membranes, Biosciences –
Biotechnology, St. Wendel, Germany and 3Fresenius Medical Care Deutschland GmbH,
Global Medical Office, Clinical and Epidemiological Research, Bad Homburg, Germany

BACKGROUND AND AIMS: Hydrophilic modification with polyvinylpyrrolidone


(PVP) increases the biocompatibility profile of synthetic dialysis membranes. However,
MO656 Figure 1: The correlation between changes in UDiV and in body weight PVP may be eluted into patient’s blood, which has been discussed as a possible cause
during dialysis session for adverse reactions rarely occurring with synthetic membranes. We now investigated
the content of PVP and its elution from the blood-side surface from commercially
available dialyzers, including the novel FX CorAL with a-tocopherol-stabilized, PVP-
enriched membrane, and link the results to the level of platelet loss during dialysis as a
maker of biocompatibility.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

METHOD: Six synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax cardiovascular outcomes, induces acceleration of atherosclerosis and abnormal bone
[Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta metabolism [2,3]. Optical monitoring of the uremic marker molecules in the spent
[B. Braun]) were investigated in the present study. The content of PVP on blood-side dialysate has been proposed [4] to estimate on-line concentration and removal of
surface was determined with X-ray photoelectron spectroscopy (XPS). The amount of uremic toxins, allowing to assess total removed solute and removal rate of uremic
elutable PVP was measured photometrically after 5h recirculation. The level of platelet toxins. Although several studies have been published covering the on-line optical
loss was evaluated in an ex vivo recirculation model with human blood. monitoring of the spent dialysate, there is scarce knowledge about relation between
RESULTS: Highest PVP content on the blood-side surface was found for the spent dialysate and blood concentrations for protein-bound uremic solutes.
polysulfone-based FX CorAL (26.3%), while the polyethersulfone-based The aim of this study was to evaluate the relationship between protein bound uremic
THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for toxin IS concentration in blood and spent dialysate during hemodialysis (HD) and
the autoclave steam sterilized THERANOVA (9.1 mg/1.6m2 dialyzer) and Polyflux (9.0 hemodiafiltration (HDF) with different treatment settings, with the potential of
mg/1.6m2 dialyzer), while the lowest PVP elution was found for the INLINE steam evaluating uremic toxins’ levels in blood by assessing uremic toxins’ concentration in
sterilized FX CorAL and FX CorDiax (< 0.5 mg/1.6m2 dialyzer, for both). Highest spent dialysate.
platelet loss was found for xevonta (þ164.4% compared to the reference) and the METHOD: 22 ESKD patients (16 male and 8 female, 55617 years) on chronic HDF
lowest for the FX CorAL (-225.2%) among the polysulfone-based dialyzers; among the were enrolled into the study (fistula N=15, graft N=7). For each patient 4 midweek
polyethersulfone-based dialyzers, THERANOVA (þ95.5%) had the highest and dialysis sessions (length 240min, HD: N=1, Qb=200ml/min, Qd=300ml/min, 1,5m2;
ELISIO (-52.1%) the lowest platelet loss. HDF: N=3, median (interquartile range) Qb = 298 (296-356) ml/min, Qd= 795 (500-
CONCLUSION: PVP content and elution differs between commercially available 800) ml/min, Vsubst = 21.8 (15-24.5) L, 1,8m2 and 2,2m2) were included. During each
dialyzers and was found to be linked to the membrane material and sterilization dialysis session, blood samples were taken at 0 min (start) and 240 min from the
method. The amount of non-eluted PVP on the blood-side surface may be an arterial blood line, and dialysate samples were taken at 7 min and 240 min from the
important determinant for the hemocompatibility of dialyzers. outlet of the dialysis machine. After sample processing, serum total, serum free and
spent dialysate IS concentrations were determined by HPLC. Regression analysis was
carried out.
RESULTS: Median (interquartile range) IS concentrations in blood were 10.02 (6.68 -
14.68) mmol/L for free IS, 101.33 (56.99- 125.66) mmol/L for total IS, and 3.74 (2.35-
MO659 INITIAL EXPERIENCE OF PERCUTANEOUS 5.93) mmol/L in dialysate at the beginning of dialysis, and 6.07 (3.58- 9.00) mmol/L,
ARTERIOVENOUS FISTULA CREATION 56.70 (28.91-80.67) mmol/L, 1.94 (1.15-2.98) mmol/L at the end of dialysis, respectively.
There was a strong correlation between IS concentration in blood and dialysate at the
Lamprini Balta1, Panos Kitrou2, Georgia Andriana Georgopoulou1, beginning and at the end of dialysis even without data normalization by treatment
Marios Papasotiriou1, Evangelos Papachristou1, Dimitrios Karnabatidis2 settings (Fig. 1), with the strongest correlation between free IS concentration and IS in
1
University Hospital of Patras, Department of Nephrology, Patra, Greece and 2University dialysate at 240 min (R2 = 0,976) and at the beginning of dialysis (R2 = 0,962).
Hospital of Patras, Department of Interventional Radiology, Patra, Greece

BACKGROUND: Arteriovenous fistulas (AVFs) for hemodialysis are inconstantly


used primarily due to problems with maturation and early thrombosis. An
endovascular approach -without open surgery- for fistula creation offers another
option for establishing a reliable vascular access. By this procedure, a arteriovenous
fistula is created in the area of the cubital fossa in the deep vascular system, either
between the ulnar artery and the accompanying vein or the radial artery and radial vein
and uses the perforating vein at the level of the elbow to transfer blood to the
superficial network of the arm.
AIM: To evaluate the safety, success and maturation rates of percutaneous MO660 Figure 1: Correlation between free a) and total b) IS concentration in blood
arteriovenous fistula creation. (B) and dialysate (D) at different timepoints during dialysis.
MATERIALS AND METHODS: From February 2018 to June 2020 (28 months), 30
percutaneous arteriovenous fistulas (pAVF) using the WavelinQ device were created in The reason for the higher correlation between free IS in blood and IS in dialysate is that
30 patients (male: 100%) with end stage kidney disease. Outcome measures were safety, only protein non-bound fraction of IS is available for removal by dialysis from blood
defined as adverse events occurring within the first month of creation, success, defined into dialysate.
as the ability to create an anastomosis between the vessels of interest and maturation CONCLUSION: There is a strong correlation between IS concentrations in blood and
rates, defined as the ability to perform at least one successful dialysis with the AVF. dialysate with different treatment settings during whole dialysis. Assessment of protein
Secondary outcome measures included procedural complications, secondary bound uremic toxins’ concentration in the spent dialysate by optical sensor could thus
procedures, time to cannulation, and AVF survival. also provide information about the concentration of uremic toxins in blood.
RESULTS: All cases were performed as day procedures. 23 out of 30 patients (70%) [1] Vanholder et al 2018; [2] Yamamoto et al 2020; [3] Barreto et al 2009; [4] Lauri et al
were already on hemodialysis carrying a permanent central venous catheter. Main 2019;
comorbidities were hypertension (21/30; 70%), diabetes (15/30; 50%) while 11/30
(30.5%) were smokers. Success was 100% (30/30). Mean follow-up was 547 days
(range: 14-1071 days). In one case a pseudoaneurysm of the brachial artery was created
immediately after sheath removal and in another case, an aneurysm of the AVF
anastomosis was observed 17 days post-procedure and AVF was legated with a covered MO661 COMPARISON OF CLINICAL EFFICACY OF CENTRIFUGAL-
stent placed in the arterial part. In all, 26/30 AVFs (86.6%) were successfully MEMBRANOUS DOUBLE FILTRATION PLASMAPHERESIS
cannulated. Mean time to cannulation was 61.3 days. Another one failed after AND MEMBRANOUS DOUBLE FILTRATION
maturation during the follow-up period. In total, 15 interventions were needed to PLASMAPHERESIS ON SEVERE LUPUS NEPHRITIS
achieve maturation (15/26; 0.58 procedures per AVF). 5 maintenance endovascular
interventions were performed during the follow-up period (5/26; 19.2%). Mean time Jianhua Dong1, Li Huang1, Chuan Li1, Ling Kong1, Lixuan Huang1, Wenjing Fan1,
from cannulation to the end of follow up was 566.2 days (range: 135-1041 days). Bian Wu1, Weixin Hu1, Yongchun Ge1
CONCLUSION: Current analysis suggests that percutaneous AVF creation is safe, 1
National Clinical Research Center of kidney Diseases, JinLing Hospital, nanjing, P.R.
successfully performed with high maturation rates. Large scale prospective studies are
China
needed to validate results.

BACKGROUND AND AIMS: The Study delves into the clinical efficacy and
advantages of centrifugal double filtration plasmapheresis on severe lupus nephritis
(LN) by comparing it with membranous double filtration plasmapheresis (DFPP).
MO660 INTERRELATIONSHIP BETWEEN PROTEIN BOUND UREMIC METHOD: A retrospective analysis was performed on 56 patients who were diagnosed
TOXIN INDOXYL SULFATE CONCENTRATION IN BLOOD AND with severe LN and had received DFPP treatment from May 2016 and January 2020. Of
SPENT DIALYSATE DURING HEMODIALYSIS TREATMENT them, 38 were given centrifugal DFPP and had their plasma centrifuged in a blood cell
separator, and 18 were given membranous DFPP and had their plasma centrifuged in
Joosep Paats1, Annika Adoberg2, Jürgen Arund1, Ivo Fridolin1, Kai Lauri1,3, an MPS07 plasma separator. An EC20W plasma component separator was used as the
Liisi Leis2, Kristjan Pilt1, Risto Tanner1, Merike Luman1,2 secondary filter to reprocess the separated plasma of all of them. The two DFPPs were
1 compared for differences in clinical efficacy, vascular access, dosage of anticoagulant,
Tallinn University of Technology, Department of Health Technologies, Tallinn, Estonia,
2 treatment cost and adverse events in patients with severe LN.
North Estonia Medical Centre, Centre of Nephrology, Tallinn, Estonia and 3SYNLAB
€ Tallinn, Estonia RESULTS: Of the 56 severe LN patients (including 43 females and 13 males), the
Eesti OU,
median of age of onset was 29 years old, the SLEDAI (Systemic Lupus Erythematosus
Disease Activity Index) was 18.666.0 points and the serum creatinine was
BACKGROUND AND AIMS: Indoxyl sulfate (IS) is a representative of the protein- 402(294,553) umol/L, and all patients had acute kidney injury and 51 of them (91.1%)
bound uremic retention solutes [1]. Among CKD patients, high serum levels of IS are required renal replacement therapy (RRT). A total of 142 DFPPs were performed,
associated with high cardiovascular and all-cause mortality – IS is linked to including 97 centrifugal DFPPs and 45 membranous DFPPs. After treatment and at

i382 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Month 3 of follow-up visit, patients in both the centrifugal DFPP group and the can be seen in both pre- and post-HD measurements of arms and whole body. The aim
membranous DFPP group had ANA, AdsDNA titer, quantitative urinary protein, of the study was to investigate whether this variation between access and non-access
urinary red blood cell count and serum creatinine significantly dropped and sides could affect single-side whole body measurements.
hemoglobin significantly increased over those before treatment, the differences in METHOD: Pre- and post-HD bioimpedance measurements with two 8-point devices
which between the two groups, however, were not statistically significant. The (InBody 770 and Seca mBCA 514) were performed in 11 HD patients with functioning
centrifugal DFPP group had a more significant drop in complements C3 and C4 after AV access in the arm (8 male, pre-HD 75.4 6 13.6 kg, post-HD 72.8 6 13.5 kg). Values
treatment. Comparison of the data before and after a single DFPP treatment showed of resistance at 5 kHz (R5) in the arm and whole body (R5 of arm þ trunk þ leg on the
that the membranous DFPP group had a more significantly longer prothrombin time, same side) were extracted. Whole-body extracellular water (ECW) was calculated using
but there were no differences in partial prothrombin time, fibrinogen and platelet whole-body R5 by the Xitron equation* to evaluate how measuring only one side of the
change between the two groups. At Month 3 of follow-up visit, 31 of the 51 RRT body can affect the fluid volume calculation.
patients (60.8%) (including 34 given centrifugal DFPP and 17 given membranous RESULTS: The R5 of the arm on the access side was lower compared with the non-
DFPP) were released from dialysis, including 23 given centrifugal DFPP and 8 given access side both pre- and post-HD (P < 0.01), measured by InBody. The same was seen
membranous DFPP. In the membranous DFPP group, all patients had the vascular with the Seca but did not reach statistical significance (Table 1). The estimated whole-
access built via the central venous catheter, while in the centrifugal DFPP group, 6 body ECW was higher on the access side for InBody (P < 0.01). With Seca, the same
patients (15.8%) had the vascular access built by puncturing into the artery or vein. The trend was seen but remained non-significant. While the difference in ECW between
dosage of the anticoagulant, the low molecular weight heparin, to the centrifugal DFPP both arms reported by InBody was small, the impact on calculated whole-body ECW
group was significantly lower than that to the membranous DFPP group (11746243 vs was much larger with a difference between sides of 0.50 6 0.82 L pre HD and 0.55 6
41066399IU, P<0.001), and in the centrifugal DFPP group, 29 patients (76.3%) were 0.81 L post HD.
given 4% citric acid alone for anti-coagulation. No blood coagulation occurred. In CONCLUSION: InBody appears to pick up the difference in fluid status between the
terms of treatment consumables, the membranous DFPP group had a significantly access and non-access side with greater precision than Seca. The large contribution of
higher cost than the centrifugal DFPP group (RMB4340.26237.0 vs 5677.060.0, the arm to whole-body resistance amplifies the impact of the presence of an AV access
P<0.001). Two patients (4.4%) in the membranous DFPP group developed skin on whole-body ECW estimations based on single-side wrist-to-ankle bioimpedance
ectasis, epistaxis or aggravated alveolar hemorrhage after treatment, and four patients measurements. Eight-point bioimpedance devices (like the tested InBody and Seca)
(4.1%) in the centrifugal DFPP group developed perioral numbness, numbness in distal measure both sides of the body, so, choice of measurement side does not enter the
extremities or tetany during treatment, which was alleviated after calcium picture.
supplementation.
CONCLUSION: Centrifugal DFPP differed little from membranous DFPP in clinical
efficacy in severe LN patients, but had lower anti-coagulation requirements, cost less
on treatment consumables, and caused no severe adverse events, so it can be used as an
important means to treat severe LN.

MO662 EFFECT OF ARTERIOVENOUS VASCULAR ACCESS ON


BIOIMPEDANCE MEASUREMENTS IN HEMODIALYSIS
PATIENTS

Lin-Chun Wang1, Fansan Zhu1, Ohnmar Thwin1, Priscila Preciado Rojas1,


Laura Rosales Merlo1, Xia Tao1, Stephan Thijssen1, Peter Kotanko1,2
1
Renal Research Institute, New York, United States of America and 2Icahn School of
Medicine at Mount Sinai, New York, United States of America

BACKGROUND AND AIMS: Fluid management remains a major problem in


hemodialysis (HD) patients, partly because of the lack of objective assessment
methods. Many methods have been proposed to estimate the fluid status in HD
patients and bioimpedance has established as one of the most popular clinical tools.
Resistance to alternate current was found to be lower in the arteriovenous (AV) access-
bearing side compared with the non-access side in post-HD bioimpedance
measurements. We hypothesized this difference between access and non-access sides

MO662 Table 1. Comparison of arm and whole-body resistance between access and non-access sides, measured with InBody and Seca in 12 hemodialysis
patients. Estimated extracellular water was calculated using Xitron equation.

Timepoint Pre-HD Post-HD


Device and Parameter Access side Non-access side P-value Access side Non-access side P-value
InBody
ECW of Arm [L] 0.99 6 0.17 0.92 6 0.17 < 0.01 0.90 60.16 0.82 6 0.17 < 0.01
R5 of Arm [X] 287.7 6 51.6 312.9 6 46.2 < 0.01 320.4 6 58.9 356.7 6 52.1 < 0.01
R5 of Whole Body [X] 562.4 6 88.3 589.2 6 93.3 < 0.05 639.3 6 96.2 676.2 6 101.5 < 0.01
Whole-body ECWXitron [L] 17.5 6 2.4 17.0 6 2.5 < 0.01 15.9 6 2.1 15.3 6 2.2 < 0.01
Seca
R5 of Arm [X] 308.3 6 54.0 332.1 6 49.8 0.09 346.9 6 59.9 378.9 6 56.7 0.06
R5 of Whole Body [X] 584.0 6 91.7 609.9 6 96.7 0.09 667.4 6 101.2 699.3 6 104.6 0.09
Whole-body ECWXitron [L] 17.1 6 2.4 16.6 6 2.5 0.08 15.4 6 2.1 15.0 6 2.2 0.07

Rx resistance at x kHz. Values are mean 6 standard deviation; groups were compared by paired t-test.
ECW: extracellular water, ECWXitron: extracellular water calculated by the Xitron equation*, which predicts the fluid volume by one-side wrist-to-ankle
measurement (Xitron technology,
 2 pffiffiffiffi Inc., San Diego,
 2CA,2 USA).

2
=3 KB qECW
*ECW ¼ kECW L R0W , where kECW ¼ 10001
DB . W is body weight [kg], L is height [cm], R0 is represented by the resistance value at 5kHz [X],
KB is a factor correcting relative proportions of the leg, arm, trunk and height, qECW is the resistivity of extracellular volume [X cm], DB is body density
[kg/L].

10.1093/ndt/gfab099 | i383
Abstracts Nephrology Dialysis Transplantation

MO663 THE UTILITY OF SMART SCALES TO MONITOR BODY RESULTS: Sixteen patients were included (13 males, mean age 72615 years). Four
COMPOSITION IN HEMODIALYSIS PATIENTS patients (25%) died. Factors associated to mortality were dialysis vintage (p=0.01), the
presence of infiltrates in chest X-ray (p=0.032), serum C-reactive protein (p=0.05) and
Lucia Cordero1, Marta Rivero Martınez1, Paula Jara Caro Espada1, lactate dehydrogenase (p=0.02) at one week, the requirement of oxygen therapy
Elena Gutiérrez1, Evangelina Mérida1, Lucia Aubert1, Justo Sandino Pérez1, (p=0.02) and the use of anticoagulation (p<0.01). At admission, post-dialysis
Claudia Yuste1 interleukin-6 levels were higher (p<0.01) in non-survivors and these patients differed
1
Hospital Universitario 12 de Octubre, Nephrology, Madrid, Spain from survivors in the reduction of interleukin-6 levels during the dialysis session
despite using a PMMA filter (survivors vs non survivors (25 [17-53]% vs -3 [-109-12]
BACKGROUND AND AIMS: Overhydration (OH) is an independent predictor of %, p=0.04).
mortality on hemodialysis (HD). The gold standard to assess OH is BCM monitor CONCLUSION: In hemodialysis COVID-19 patients, a positive balance of
from FreseniusV R , however BCM is a hospital hold device limiting its use. New smart interleukin-6 during the session was associated to higher mortality.
scales have emerged as household devices reporting daily body composition data.
OBJECTIVE: To determine if Renpho ES-CS20MV R could be useful on a 52 HD patient

to estimate body composition data.


METHOD: 72 body composition assessments (BCA) during mid-week HD session
were performed. Each BCA included: (1) Predialysis Renpho measurement, (2)
Predialysis BCM monitor measurement, (3) Postdialysis Renpho measurement. To
track the fluid balance during the HD session: (1) we recorded ultrafiltration, (2) food
or fluid intake was not allowed, and (3) none of the HD patients urinated during the
HD session. If any intravenous fluids were needed during the HD session, we
subtracted them off from UF.
RESULTS: Data from 52 HD patients were studied (age 58.8 6 16.8 years, 56.9 %
males, 14.7% diabetics), with a mean pre-HD weight of 70.0 6 13. 4 Kg, overhydration
of 1.7 6 1.5 L and urea distribution volume of 31.7 6 5.7 L. The mean ultrafiltration
during HD session was -1.8 6 0.9 L. Renpho estimated a Pre – HD hydration of 34.25
6 6.02 Kg vs 33.4 6 5.7 Kg by BCM, showing a good concordance between methods
(ICC 0.788 [0.67-0.86], B -0.58, p <0.01). Renpho poorly estimated pre – HD lean
tissue mass at 45.4 6 6.9 Kg compared with 33.8 6 8.0 Kg by BCM. Although Renpho
was able to provide a moderate concordant estimation of fat tissue mass (33.8 6 8.0 % MO664 Figure 1: Median reduction in serum interlekin-6 during the first
with Renpho vs 34.7 6 9.6%), the bias proportion was unacceptable. Post- HD hemodialysis session with a PMMA filter at admission was higher in surviving than in
hydration by Renpho was not able to reproduce the ultrafiltracion achieved during the non-surviving COVID-19 patients. A negative value means that serum interleukin-6
HD session (pre-HD 34.25 6 6.02 Kg vs post-HD 34.08 6 6.00 Kg). increased during dialysis.
CONCLUSION: Renpho has a proportional bias estimating predialysis hydration
compared with BCM monitor, but is not able to assess changes produced with
ultrafiltration or other parameters of body composition (as lean or fat tissue mass).
Although smart scales are unacurate to assess body composition on HD patients, they
could be useful on the follow up of them changing the accuracy for frequency.
MO665 THE BRAND-NEW NEEDLE CAP ELIMINATES ALL VISIBLE
MO663 Table 2. Hydration data from the study population and data obtained AIR BUBBLES DURING THE AUTOMATIC PRIMING PROCESS
from the body composition assessment (BCA). Data expressed as mean 6 standard OF HEMODIALYSIS MACHINES
deviation.
Kazuhiko Shibata1, Takahiro Shinzato2, Shigeki Toma3, Shigeru Nakai4,
Assessment Hydration status % Kg or L Koichi Tamura5
1
Toshin Clinic, Yokohama , Japan, 2Daiko Medical Engineering Institute, 3Heiseikai
Method
Toma Naika, 4Fujita Health University, Graduate School of Health Sciences and
Renpho Predialysis hydration 49.6 6 6.9 34.25 6 6.02 5
Yokohama City University Hospital, Department of Medical Science and Cardiorenal
Postdialysis hydration 51.3 6 6.6 34.08 6 6.00 Medicine, Japan

BACKGROUND AND AIMS: The air contamination from the dialysis circuit into the
BCM Total Body Water estimated 33.4 6 5.7 patient’s body is an unsolved serious problem. Recently, Automatic priming function
Predialysis Overhydration 1.7 6 1.5 of dialysis machines is widely used. There are rarely any air bubbles left in the
extracorporeal circuit after automatic priming of the dialysis machines. To use this
Ultrafiltration during HD session 1.8 6 0.9
method, the arterial and venous sides of the extracorporeal circuit are connected to
Urea distribution volume 31.7 6 5.7 create a closed circuit so that dialysate can circulate and overflowed through a line
Extracelular Water 9.12 6 11.8 from this closed circuit. However, air bubbles may enter when disconnecting the closed
extracorporeal circuit and attaching the needles. We tried to solve this problem by
Intracelular Water 17.1 63.4 simply connecting the arterial and venous needles to the extracorporeal closed circuit
before the process of automatic priming process. To prime the whole extracorporeal
circuit with needles, we had made a brand-new suitable cap of the needle, which is
tightly connected with a needle and has an open end. (Fig) This special cap allows the
needle to be incorporated into the closed circuit prior to the automatic priming
process, allowing the dialysis machine to completely remove the air during priming
MO664 DYNAMIC ASSESSMENT OF INTERLEUKIN-6 DURING process. The purpose of this study is to present the details of this new method and
HEMODIALYSIS AND MORTALITY IN COVID 19 compare its effectiveness in preventing air bubble contamination between the
traditional method and this new method.
Patricia Mun~oz Ramos1, Martin Giorgi1, Yohana Gil Giraldo1, Antonio De Santos1,
METHOD: A prospective, non-randomized, comparative study was conducted to
Almudena Nu n~ez1, Guillermina Barril1, Borja Quiroga1
verify whether air remained grossly visible after the needle was connected to the
1
Hospital Universitario de La Princesa, Nephrology, Madrid, Spain extracorporeal circuit.
The traditional method: DCS-100NX (Nikkiso Co Ltd, Tokyo Japan) was used for
BACKGROUND AND AIMS: The impact of the newly discovered severe acute extracorporeal circuit priming. After the automatic priming was finished. Nurses
respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease-19 disconnect the arterial and venous side of the extracorporeal circuit and connect both
(COVID-19) in hemodialysis patients remains poorly characterized. Some ends to the needles by hands. The nurse operates the dialysis machine to blow the small
hemodialysis techniques reduce systemic inflammation but their impact on COVID-19 amount of dialysate out of the needle and tried to remove the air. It takes nearly
has not been addressed. The aim of this prospective study was to evaluate factors 2minutes in each case. We examined the extracorporeal circuits consecutively.
associated to mortality in COVID-19 hemodialysis patients, including the impact of New cap-based method: The needles were connected to the closed circuit with the new
reducing interleukin-6 using a cytokine adsorbent filter. cap and auto-primed by the dialysis machine N100. Automatic priming, including the
METHOD: This is a prospective single-center study including 16 hemodialysis needle were performed consecutively.
patients with COVID-19. All were dialyzed using a polymethyl methacrylate (PMMA) In each method, we thoroughly checked for any remaining macro bubbles with the
filter. Interleukin-6 levels were obtained before and after the first admission naked eye. Since bubbles in the extracorporeal circuit on the arterial side are likely to be
hemodialysis session and at one week. Also we collected serum samples from 8 patients supplemented by the air trap chamber, only bubbles on the venous side were
of our unit as controls: 4 in online hemodiafiltration (OLHDF) and 4 in high-flux compared.
hemodialysis Baseline comorbidities, laboratory values, chest X-ray and treatments RESULTS: The study was conducted in October 15th to 24th 2020 at the Yokohama
were recorded and compared between survivors and non-survivors. Minami Clinic.

i384 | Abstracts
Nephrology Dialysis Transplantation Abstracts
The traditional method: We checked 50 extracorporeal circuits consecutively. There ferritin levels. Solute kinetics measurements showed higher myoglobin clearance
were bubbles in the venous side of the extracorporeal circuits 29 times out of 50 times. during SDHDF (45.95611.0 mL/min) compared to SDHD1 (20.1165.2 mL/min,
New cap-based method: 10 consecutive automatic priming, including the needle was p<0.01) or to SDHD2 (21.3963.55 mL/min, p<0.01). Likewise, there was a slight
performed. DCS-100NX was used as the dialysis machine. There were no bubbles increase in b2-microglobulin removal in SDHDF (64.92610.4 mL/min) compared to
visible to the naked eye in the arterial and venous side of the circuit. SDHD1 (59.78617.0 mL/min, p<0.01) or to SDHD1 (53.0167.71 mL/min, p<0.01),
STATISTICAL RESULTS: There was a statistically significant difference of the bubble whereas there were no significant differences in urea and creatinine clearances. On the
count between the traditional method and new cap-based method. (p=0.0001, other hand, predialysis osteometabolic (serum PTH, calcium, phosphate, alkaline
Pearson’s chi-square test) phosphatase, sodium, potassium, glucose and glycated hemoglobin), inflammatory
CONCLUSION: All visible bubbles were removed automatically by simply connecting (serum c-reactive protein and interleukin-6) or nutritional (serum albumin, total
the needles using this brand-new cap before a process of automatic priming. This easy- protein and lipid profile) parameters did not change significantly during the study. Left
to-use and highly effective cap could be considered an essential device for hemodialysis ventricular mass index, left atrial volume index and global longitudinal strain, assessed
treatment like seat belts in automobiles. by echocardiography at the end of all 3 periods, were similar, as well as brain
natriuretic peptide and homocysteine serum levels. Additionally, there were no
significant changes in any quality of life features evaluated by Kidney Disease Quality
of Life-Short Form, or symptoms assessed by Edmonton Symptom Assessment System
Revised Renal, throughout the full course of the study.
CONCLUSION: In spite of mild increase of predialysis mean arterial pressure and
hemoglobin levels along with greater removal of middle molecular weight solutes, no
others clinical, laboratory, echocardiographic or quality of life findings differed
significantly during the three periods. Together, these data do not provide evidence of
clinically meaningful benefit from on-line hemodiafiltration over high-flux
hemodialysis, both performed six times a week.

MO667 SWITCHING TO ONE-TIME USE OF DIALYZERS FOR


HEMODIALYSIS: A ONE-YEAR SURVIVAL ANALYSIS IN
TASHKENT

Olimkhon Sharapov1,2
1
Tashkent Pediatric Medical Institute, Internal Disease, Tashkent, Uzbekistan and
2
Republican Specialized Scientific Practical Medical Center of Nephrology and Kidney
transplantation, Nephrology, Tashkent, Uzbekistan

BACKGROUND AND AIMS: Until recently, for various reasons in Uzbekistan, it was
often necessary to reuse disposable dialyzers for hemodialysis procedures. On June 13,
2018, a Resolution of the President of the Republic of Uzbekistan was issued on
measures to improve the effectiveness of the provision of nephrological and dialysis
care to the population of our country. Thanks to this, funding and provision of all
nephrological and dialysis centers have sharply increased, as well as the country’s
transplant service has been re-established. Since the end of 2018, dialyzers are used
MO666 INVESTIGATIONS INTO DIFFERENCES AND SIMILARITIES exclusively once in all dialysis centers in our country. We were interested in
BETWEEN SHORT DAILY HIGH-FLUX HEMODIALYSIS AND comparatively studying the survival rate of dialysis patients during one year, before and
SHORT DAILY ON-LINE HEMODIAFILTRATION after the transition to the use of single dialyzers in our center.
METHOD: We conducted a prospective observation of 120 (63 men and 57 women)
Natalia Melo1, Lucio Isoni1, Rossana Simoes1, Ludimila Allemand1, patients with end-stage CKD and receiving programmed hemodialysis at our dialysis
Daniel Vasconcelos2, Juliane Lauar1, Istenio Pascoal1 center in Tashkent. Our observation took place for 2 years: from the beginning of 2018
1 to the end of 2019. The study took place in 2 stages, 1 year each: at the first stage,
alise - CBN&D, Brasilia, Brazil and 2University of
Centro Brasiliense de Nefrologia & Di within 1 year (from the beginning to the end of 2018), the survival rate of the observed
Brasılia, Brasilia, Brazil patients receiving hemodialysis with repeated use of disposable dialyzers was assessed.
At the second stage (after the transition to one-time use of dialyzers throughout the
BACKGROUND AND AIMS: Short daily hemodialysis (SDHD) has improved country), also for 1 year (from the beginning to the end of 2019), all the patients we
outcomes observed in conventional thrice-weekly hemodialysis (CHD). Analogously, observed received hemodialysis sessions with a single use of dialyzers. All patients were
short daily hemodiafiltration (SDHDF) has also improved outcomes observed in diagnosed with end-stage CKD. The average age of the patients was 49.7 6 14.1 years.
conventional thrice-weekly hemodiafiltration (CHDF). Furthermore, while high- The average duration of hemodialysis was 29.4 (6-252) months. All patients underwent
volume CHDF has been proclaimed to be superior to CHD, there have been no studies hemodialysis sessions with identical apparatus and dialyzers of the same manufacturer.
comparing SDHDF to SDHD. We performed a comparison of clinical, laboratory, The primary diseases in the patients were glomerulonephritis (n = 44, 36.7%), type 2
echocardiographic and quality of life features in dialysis patients treated by SDHD or diabetes (n = 38, 31.7%), urolithiasis (n = 13, 10.8%), polycystic kidney disease (n = 7,
SDHDF. 5.8%), lupus (n = 5, 4.2%) and others (n = 13, 10.8%). Survival was assessed using the
METHOD: Twelve patients (mean age 60.8615.4 years; 7 males; AVF 7, AVG 1, Kaplan-Meier method, the confidence interval was determined by Greenwood.
Catheter 4) on regular in-center SDHD program were studied in a longitudinal, RESULTS: During the entire period (24 months) of observation, out of 120 patients,
prospective, non-randomized, single-subject A-B-A design comparing high-flux 26.7% (n = 32) patients died, 73.3% (n = 88) survived (of which 10 patients underwent
SDHD to post-dilution on-line SDHDF. Patients had been for at least 6 months on kidney transplantation). We will assess the survival rate depending on the periods of
SDHD (105-150min, 6x/week; SDHD1) and were clinically stable before conversion to dialyzer use.
SDHDF (105-150min, 6x/week, mean total convective volume of 63.5765.44 L per During 1 year of follow-up (the period of repeated use of disposable dialyzers), 19.2%
week) for 6 months. Following that, all patients were switched back to SDHD for (n = 23) patients died, 80.8% (n = 97) survived and continued to receive hemodialysis,
another 6 months (SDHD2). Data were collected at the end of each period. Dialysis of which 2 (1.7%) patients underwent a kidney transplant and knocked out of
parameters throughout the study were matched and set as follows: high-flux observation. The main cause of death was cardiovascular complications (sudden
polysulfone dialyzers (BBraun Xevonta Hi 23V R ), blood flow 300–350 mL/min, dialysate
cardiac death, myocardial infarction, stroke, etc.), as a result of which 69.6% (n = 16) of
flow 500 mL/min and ultra-purified water (Aquaboss heat disinfection osmosis). The patients died. The survival rate for 1 year was S (t) = 0.815 [95% CI, 0.745-0.885].
results were expressed as mean 6 standard deviation. Each patient served as his/her Over the next 12 months (single use period), out of 95 patients continuing to receive
own control. Repeated measures analysis of variance (ANOVA) were used. hemodialysis, 9.5% (n = 9) patients died, 82.1% (n = 78) patients survived. 8.4% (n = 8)
RESULTS: Slightly higher predialysis mean arterial pressure (MAP) levels were of the observed patients underwent kidney transplantation. 55.6% (n = 5) of all
observed during SDHDF (102.51611.28 mmHg) compared to SDHD1 (MAP deceased patients died from cardiovascular complications. The survival rate at 1 year
95.569.82 mmHg, p<0.01) or to SDHD2 (97.61611.19 mmHg, p=0.03), without was S (t) = 0.901 [95% CI, 0.839-0.962].
significant differences in intradialytic blood pressure variability. Similarly, there was an CONCLUSION: Compliance with the standards for hemodialysis, in particular, the
increase in predialysis hemoglobin levels (Hb) during SDHDF (Hb 12.3961.2 g/dL), single use of disposable dialyzers for hemodialysis sessions leads to a decrease in the
compared to SDHD1 (Hb 11.3061.09 g/dL, p=0.02) or to SDHD2 (Hb 11.2361.84 g/ lethality of dialysis patients. The transition from multiple to single use of disposable
dL, p<0.01), although there were no significant differences in erythropoietin- dialyzers in one dialysis center in Uzbekistan showed a significant increase in survival
stimulating agent or iron supplementation weekly doses, transferrin saturation rates or by 10.6%.

10.1093/ndt/gfab099 | i385
Abstracts Nephrology Dialysis Transplantation

treatment options are needed, yet pharmacologic interventions remain limited. Several
extracorporeal treatments are currently explored concerning their potential to improve
the clinical course and outcome of critically ill patients with COVID-19. The SeraphV R

100 MicrobindV R Affinity adsorber (Exthera Medical, CA, USA) has recently been

introduced for the elimination of several pathogens from the blood and an emergency
authorization in patients with COVID-19 was granted by the FDA. Bacteria, viruses
(including the SARS-CoV-2 spike glycoprotein), fungi and toxins have been shown to
bind to the immobilized heparin on the ultra-high molecular weight polyethylene
beads of the device in a similar way to the interaction with heparan sulfate on the cell-
surface and are thereby removed from the bloodstream. Here we report the interim
analysis of the COVID-19 patients treated with the SeraphV R 100 MicrobindV R Affinity

filter (COSA) registry. The goal of the registry is to gather data regarding the safety and
efficacy of the SeraphV R 100 in the treatment of COVID-19 patients.

METHOD: Participating sites were advised to insert patient data of COVID-19


patients, treated with the SeraphV R 100, during their hospital stay into the COSA

registry (ClinicalTrials.gov Identifier: NCT04361500). A total of 66 items were asked in


a web-based platform.
RESULTS: Until January 2021, 33 patients with 39 treatment sessions form six
MO667 Figure 1: One-year survival analysis for single and multiple use of dialyzers different hospitals were reported to the register (seven female, median age 61 years,
Table 1). The patients were treated between March and December 2020. Eleven
patients with a hospital admission between March and August and 22 between
September and December 2020. The SeraphV R 100 treatment was initiated 9 days after

MO668 EXTRACORPOREAL REMOVAL OF MYOGLOBIN IN symptom onset, without any difference between survivors and non-survivors. Overall,
PATIENTS WITH RHABDOMYOLYSIS AND SEVERE ACUTE a mortality of 27% was reported. Serious comorbidities (as preadmission
KIDNEY INJURY: COMPARISON OF HIGH AND MEDIUM CUT- immunosuppressive therapy, lung fibrosis or CKD5T) were reported in all of the non-
OFF MEMBRANE AND AN ADSORBER CARTRIDGE survivors. Invasive ventilation was needed in 67% of these patients when Seraph
treatment was initiated. A non-significant trend towards higher Ferritin levels in non-
Alexander Jerman1, Milena Andonova1,2, Vanja Persi c1,2, Jakob Gubensek1,2 survivors (2000 (1963 – 8326) vs. 989 (644 – 2000), p=0.09) was reported. All
1 treatments were well tolerated, three clotting events were reported.
UMC Ljubljana, Dept. of nephrology, Ljubljana, Slovenia and 2Faculty of Medicine, CONCLUSION: Viral SARS-CoV-2 RNA is frequently (up to 78%) seen in the blood
University of Ljubljana, Ljubljana, Slovenia of critically ill COVID-19 patients and correlates with the severity of the disease. The
SeraphV R 100 can bind to viral spike protein, proinflammatory cytokines may be
BACKGROUND AND AIMS: Severe rhabdomyolysis often causes acute kidney reduced by the device and hemodynamic stabilization has been reported during the
injury (AKI). If severe, AKI significantly reduces myoglobin removal through the SeraphV R 100 treatment of COVID-19 patients. Platelets can be hyperactivated in
kidneys. Given molecular size of myoglobin, extracorporeal removal using newer association with SARS-CoV-2 proteins and thus presumably trigger the
hemodialysis membranes and adsorption techniques is possible, although its role on hypercoagulation and thrombosis. In this context, the removal of SARS-CoV-2
clinically significant outcomes is not yet fully established. We aimed to compare the proteins to prevent hyperactivated platelets appears to be a sensible approach.
efficacy of high cut-off (HCO) membrane, medium cut-off (MCO) membrane and All reported deaths were associated with serious preexisting comorbidities,
CytosorbV R adsorber on myoglobin removal.
immunosuppression, dialysis dependent renal failure, or a combination of these
METHOD: In this retrospective study we included 15 patients with AKI and factors. Hence, SeraphV R 100 treatment may be most beneficial in COVID-19 courses of
concomitant rhabdomyolysis with severely increased myoglobin (>20.000 mg/L), who patients without multi organ failure. More clinical data is needed to describe possible
underwent at least one extracorporeal procedure with the intention of extracorporeal benefits of the SeraphV R 100 in the treatment of COVID-19 patients.
myoglobin removal. There were 28 procedures performed: 13 HCO (TheraliteV R,

Gambro) dialysis, 9 MCO (TheranovaV R , Gambro) dialysis and 6 adsorber (CytosorbV


R,

Cytosorbents) procedures. Serum myoglobin and albumin levels were recorded from
the time frame of up to 12 hours prior to and up to 12 hours after the index procedure
and reduction rates (RR) for myoglobin were calculated. Albumin levels were
compared before and after procedure as a safety parameter.
RESULTS: Treatment duration differed significantly and was the longest for
CytosorbV R adsorber (median 11 h) and the shortest for MCO membrane (median 5 h).

Pre-treatment serum myoglobin levels were comparable across the groups. Reduction
in myoglobin during procedure was significant for HCO and MCO and borderline
significant in adsorber group, with respective median RR of 0.64, 0.54 and 0.50 (p =
0.83). Routine albumin substitution was implemented only in HCO group, but serum
albumin levels were stable in all subgroups.
CONCLUSION: In this preliminary observational study we found comparable
effectiveness of a novel MCO and ‘standard’ HCO dialysis membrane for serum
myoglobin removal in patients with severe AKI. Cytokine adsorber showed borderline
effectiveness, but the number of procedures in this group was small. MCO dialysis is
associated with lower costs and no need for albumin supplementation and therefore
might be the optimal mode of treatment of severe rhabdomyolysis-associated AKI. For
patients with multiorgan failure requiring cytokine removal and severe
myoglobinemia, hemoadsorption can reduce cytokine and myoglobin levels
simultaneously.

MO669 FIRST RESULTS OF THE COVID-19 PATIENTS TREATED


WITH THE SERAPHVR 100 MICROBINDVR AFFINITY FILTER

(COSA) REGISTRY

Julius J. Schmidt1, Mariet Vant Klooster2, Dan N. Borchina3, Stefan Büttner4,


Birgit Bader5, Larissa Herbst6, Thomas Fuehner2, Jan T Kielstein3 MO670 EXPANDED HEMODIALYSIS REDUCES THE
1 CONCENTRATION OF FREE LIGHT CHAINS IN PATIENTS
Hannover Medical School, Department of Nephrology and Hypertension, Hannover, WITH ACUTE KIDNEY INJURY IN MYELOMA CAST
Germany, 2KRH Klinikum Siloah, Department of Respiratory and Critical Care Medicine, NEPHROPATHY
Hanover, Germany, 3Academic Teaching Hospital Braunschweig, Medical Clinic V
Nephrology j Rheumatology j Blood Purification, Braunschweig, , 4Klinikum Konstantin Vishnevskii1, Olga Domashenko1
Aschaffenburg-Alzenau, Medizinische Klinik I, Alzenau, , 5St. Joseph Krankenhaus Berlin- 1
Tempelhof, Med. Abteilung II, Berlin, and 6University Hospital Erlangen, Medical Clinic 4 St. Petersburg State Healthcare Institution “City Hospital @ 15”, Dialysis department,
– Nephrology and Hypertension, Erlangen, St.-Petersburg, Russia

BACKGROUND AND AIMS: The COVID-19 pandemic has serious impact on health BACKGROUND AND AIMS: The myeloma cast nephropathy is largely associated
and economics worldwide. Despite the recent advent of SARS-Cov-2 vaccines, with the production of intact immunoglobulin and free light chains (FLC) by a plasma
cells monoclone. The use of high-flux hemodiafiltration (HDF) contributes to a

i386 | Abstracts
Nephrology Dialysis Transplantation Abstracts
decrease in the concentration of FLC. However, it is not always possible to achieve the MO671 COMPARASION OF EXPENDED HEMODIALYSIS USING A
required substitute volume with acute kidney injury (AKI) emergency treatment. An MEDIUM CUT-OFF DIALYZER VERSUS
alternative to HDF could be the usage of membranes with a medium cut-off (expanded HEMODIAFILTRATION: AN OBSERVATIONAL PROSPECTIVE
hemodialysis (HD), Expanded HD). The aim of this study was to compare the degree STUDY
of reduction in FLC concentration using conventional HD, HDF and Expanded HD.
METHOD: The study includes patients with newly diagnosed multiple myeloma who Tijana Azasevac1,2, Violeta Knezevic1,2, Gordana Strazmester Majstorovic1,2,
presented indications for HD therapy start. Procedures were performed on a daily basis Mira Markovic1, Vladimir Veselinov1, Nevena Eremic Kojic2,3, Dejan Celic1,2,
from the moment when indications for HD therapy were identified. The duration of Igor Mitic1,2
1
the first three procedures was 2 hours. Consistently for each patient the first procedure Clinical Centre of Vojvodina, Novi Sad, Clinic of Nephrology and Clinical Immunology,
was carried out using a standard low-flow filter, the second - using a high-flow dialyzer Novi Sad, Serbia, 2University of Novi Sad, Faculty of medicine Novi Sad, Novi Sad, Serbia
and HDF (substitute volume 9 liters for 2 hours), the third - using a Theranova 400 and 3Clinical Centre of Vojvodina, Novi Sad, Centre for Laboratory Medicine, Novi Sad,
filter (Baxter, Germany). The concentrations of FLC (kappa and lambda) and albumin Serbia
were determined every 30 minutes of each treatment. Chemotherapy was prescribed
according to the local clinical recommendations in combination with the ongoing renal BACKGROUND AND AIMS: Expended hemodialysis (HDx) with medium cut-off
replacement therapy. (MCO) membrane enables efficient depuration of middleweight uremic toxins, which
RESULTS: The study included 7 patients with cast nephropathy, mean age 6868 years. play significant roles in inflammation and cardiovascular morbidity. Hemodiafiltration
Average concentration before treatment: kappa FLC 8766727 lg/ml (norm 3.25-15.81 (HDF) is known for good removal of middle molecules but it requires more technical
lg/ml), lambda FLK 846112 lg/ml (norm 3.23-28.05 lg/ml), albumin 3461 g/l resources and well-functioning dialysis access.
(norm 40-50 g/l). After 2 hours of treatment, there was a decrease in kappa FLC The aim of this study is to evaluate the efficacy of depuration of uremic toxins with a
concentration with HDF (-34633%, p=0.01) and with Expanded HD (-31612%, high-flux dialyzer during HDF session and with a MCO membrane (TheranovaV R ) in
p<0.001), but not with conventional HD (-167, p=0.79, Fig 1). The lambda FLC HDx session and its impact on quality of life (QoL) in hemodialysis patients.
concentration also decreased with HDF (-41629%, p=0.01) and with Expanded HD (- METHOD: In an open, single-centre, prospective observational clinical study, 28 adult
28622%, p=0.01), but not with conventional HD (-3612, p=0.65, Fig 2). Albumin stable HD patients without residual renal function were assigned to be treated by on-
concentrations did not change significantly with any of the treatments. line HDF (HDF group) with the APS-21H dialyzer (polysulfone membrane, 2.1 m2,
RV
Asahi Kasei Medical Co., Japan) or by HDx (HDx group) with the Theranova 400 (1.7
m2) and Theranova 500 (2.0 m2) dialyzers (Baxter International Inc, USA). The study
RV

was conducted during 2019-2020 and completed after 12 months period. All patients
were receiving maintenance high-flux membrane HDF treatment at least six months
before they were enrolled in the study. Groups of patients were matched in age, sex,
BMI, dialysis length and underlying disease. Complete blood count (CBC), renal
function and inflammation, electrolytes, liver function tests, iron and nutritional status
were evaluated at the beginning of the study and after 3, 6, 9 and 12 months. Pre and
postdialysis levels for urea, creatinine, albumin, calcium, phosphorus, C-Reactive
Protein, kappa and lambda free light chains (FLC), vitamin B12, b2 microglobulin
levels were determined in each patient quarterly and reduction rate (RR) for uremic
toxins were calculated. Furthermore single-pool Kt/V, dose of erythropoietin therapy
(EPO) and vascular access were evaluated during the study, while bioimpedance
analysis using Body composition monitor (Fresenius Medical Care, Germany) and
QoL using SF-36 questionnaire (Kidney Disease Quality of Life Short Form-
KDQOLTM-36) were evaluated at the end of observation period. The values have been
reported as mean 6SD.
RESULTS: There were 28 patients (14 in each group) mean age of 54.24 years
(57.7169.65 in HDx group vs 59.8167.99 in HDF group). Median dialysis vintage was
4.77 years (5.33 in HDx group vs 6.46 in HDF group, p=0.55). Vascular access was
native arteriovenous fistula in 23 patients, arteriovenous graft in 2 patients and
tunnelled dialysis catheter in 3 patients (p=0.98). Kt/V was similar in both groups
(1.5760.31 vs 1.4560.24, p=0.9), as well as weekly dose of EPO (4533.361922.3 vs
MO670 Figure 1: Changes in the blood kappa-LC concentration during Expanded 4233.361971.8, p=0.67). Patients in HDF group had a significantly higher interdialysis
HD, HDF and Conventional HD treatments, % fluid overload (2,4861,37 in HDx group vs 3,6461,33 in HDF group, p=0.04), without
difference in relation to the systolic and diastolic blood pressure values, as well as
others BCM parameters. There were not significant differences in examined
parameters of CBC, renal function and inflammation, electrolytes, liver function tests,
iron and nutritional status at the beginning and at the end of the study. RR of small and
middle molecules are presented in Table 1. Serum albumin level has decreased from
37.8 g/dL to 36.4 g/dL in 12 months during HDx treatment with maximal change of
serum albumin level of -3.7% during that period (Figure 1). Evaluation of Kidney
Disease Quality of Life Short Form at the end of study period in both groups is shown
in Figure 2.

MO671 Figure 1: Serum albumin concentration and change of albumin levels


during 12 months HDx treatment

MO670 Figure 2: Changes in the blood lambda-LC concentration during Expanded


HD, HDF and Conventional HD treatments, %

CONCLUSION: Expanded HD, as well as high-flow HDF, helps to reduce the FLC
concentration in patients with cast nephropathy without loss of albumin, which may
have a positive effect on the multiple myeloma prognosis. Further studies are needed
regarding possibilities of using Expanded HD in the complex therapy for patients with
AKI in myeloma cast nephropathy.

10.1093/ndt/gfab099 | i387
Abstracts Nephrology Dialysis Transplantation

Low Low High High p


Flux flux flux flux
mean SD mean SD
Hemoglobin (mg/dl) 11.07 0.82 11.26 0.67 0.04
ESA dose (UI/week) 11620 2275 11860 2609 0.15
Ferritin (ng/ml) 416 184 476 215 0.03
Calcium (mmol/l) 2.27 0.11 2.29 0.126 0.049
Phosphorus (mmol/l) 1.55 0.3 1.48 0.31 0.008
PTH (pg/ml) 185.8 121 181.5 104.6 0.37
MO671 Figure 2: Evaluation of Kidney Disease Quality of Live Short From ALP (UI/l) 97.6 47 96.3 41.2 0.33
(KDQOLTM -36)
Ca based binder dose 1.88 1.2 1.77 1.3 0.26
(pill/day)
CONCLUSION: Compared to HDF, HDx with MCO membranes show greater RR for Non Ca based binder 3.08 1.99 2.8 1.9 0.12
large middle molecules such as lambda FLC (45kD), while RRs for middle molecules-
kappa FLC (23kD), b2 microglobulin (12kD) and small uremic toxins are similar. dose (pill/day)
During one year of treatment with MCO membranes serum albumin levels remain Urea reduction ratio (%) 73,14 5.07 74.5 6.6 0.001
stable. HDx treatment may improve quality of life, making an impact primarily in
Albumin (g/dl) 38 3.2 40.3 3.1 <0.001
energy status and emotional satisfaction.

Mean, SD for laboratory parameters during 6 months on low flux and 6


months on high flux hemodialysis.
MO672 HIGH FLUX VERSUS LOW FLUX HEMODIALYSIS: A PRE-
POST STUDY

Nadim Zaidan1, Nicole Nourie1, Serge Finianos1, Dania Nehme Chelala1,


Hiba Azar1
1
Hotel Dieu de France University Hospital, Nephrology department, Beirut, Lebanon
MO673 THE ASSOCIATION BETWEEN UREA KINETIC MODELING
BACKGROUND AND AIMS: High flux hemodialysis has largely replaced low flux WITH ANXIETY AND DEPRESSION AMONG PATIENTS ON
hemodialysis in developed countries. Clinical trials, in particular the Hemo and the MAINTENANCE HEMODIALYSIS AT UST HOSPITAL: A
MPO studies, conducted many years ago, showed that the survival benefit was mainly CROSS- SECTIONAL STUDY
for patients on long term hemodialysis for the first one and for high risk patients with
low albumin level (less than 40g/dl) for the latter. Moreover, the effect on Maureen Balmes - Garcia1, Dexter Clifton Pe1, Joseree Ann Catindig2,
hematopoiesis or mineral balance is not unequivocally established in the literature. In Gabriel Alejandro Baroque2
Lebanon, following the recommendations of the ministry of health, we switched 1
patients undergoing hemodialysis at our center from low to high flux starting April University of Santo Tomas, Internal Medicine, Manila, Philippines and 2University of
2019. We aimed in this study to assess the effect of this switch on hemoglobin level, Santo Tomas, Neurology, Manila, Philippines
dose of ESA used, mineral metabolism parameters and nutritional parameters.
METHOD: This is an observational pre-post study where each patient is his own BACKGROUND AND AIMS: Depression and anxiety are common psychiatric
control. Subjects included are adults on chronic hemodialysis for more than 6 months disorders that affect patients with chronic kidney disease on maintenance
at Hotel Dieu de France University Hospital. Patients who needed transfusion for hemodialysis. Possible explanation for the development of this mental disorders
bleeding, admission to the hospital or parathyroidectomy during the study period were includes physical and emotional stress, time restrictions, functional limitations, co-
excluded from the study. Demographic parameters, medical history and laboratory morbidities, adverse effects of medications and lack of adherence to dialysis treatment
values were extracted from the patients’ files. and its efficacy. Studies have shown that by improving hemodialysis adequacy, as
Paired t- test was used to compare values obtained in the 6 months on low flux measured by the urea kinetic remodelling (Kt/V), the clinical symptoms of the patient
compared to the 6 months on high flux hemodialysis. improve as well as their psychological condition. This study aimed to evaluate the
RESULTS: Seventy four patients received sequentially both techniques (45 males and relationship between psychological symptoms and hemodialysis adequacy.
29 females). Mean age was 66 years, mean dialysis vintage 65 months, diabetic and METHOD: This cross-sectional study was conducted on 87 hemodialysis patients at
vascular diseases were the most frequent causes of ESRD found in 27 and 15% of the the University of Santo Tomas Hospital. Anxiety and depression was assessed using the
cases. Hemoglobin level significantly increased from 11 þ/- 0.82 to 11.26 þ/- 0.67 mg/ validated Filipino version of Hospital Anxiety and Depression scale (HADS-P).
dl (p=0.04) with a non-significant trend towards a lower ESA dose: 11620 UI/week Anxiety and depression was defined as score of 8. Descriptive statistics were used to
(þ/-2275 UI) in the first period versus 10860 UI/week (þ/-2609 UI) during the second summarize the general and clinical characteristics of the participants. Frequency
period (p=0.15). Ferritin levels were higher in the second part of the study (416 v/s 476 counts and proportions were used as descriptors for nominal variables, median and
ng/ml) which may have contributed to the increase in hemoglobin. Phosphorus level range for ordinal variables, and mean and standard deviation for interval/ratio
decreased from 1.55 to 1.48 mmol/l (p=0.008) at the same doses of binders and variables. Chi square test was used to assess the association between age, sex, marital
practically stable levels of calcium and PTH. Most interestingly, albumin level status, duration of dialysis and Kt/V.
increased from 38 to 40.3 g/dl (p<0.001). Finally urea reduction ratio increased from RESULTS: The prevalence of anxiety and depression were 34.8% and 21.7%,
73.1% to 74.5% with a p value of 0.001. respectively (n=87). This study identified that younger patients, those belonging to age
CONCLUSION: Assuring quality ultrapure water is still a challenge in many 20-35 y/o were more depressed (33.3%) and anxious (66.7%). Similarly, females also
developing countries. Lack of firm evidence on beneficial effect in terms of mortality tend to be more anxious (42.5%) and depressed (22.5%). On the other hand, single
may delay sanitary authorities from imposing high flux hemodialysis. In our study, patients tend to be more anxious (41.7%) while married are more depressed (22.8%).
switching from low to high flux hemodialysis showed positive impact on phosphorus As to educational status, post graduate patients were more anxious (66.7%) and those
levels but most interestingly increased albumin levels a major predictor of mortality in with low educational attainment were more depressed (50%). Newly initiated patients
hemodialysis patients. (<1 year) were more anxious (57.1%) and those with longer years on hemodialysis (4-6
years) being more depressed (30.4%). As to laboratory parameters, anemic patients are
both anxious and depressed. Hypoalbuminemic patients were also anxious and
depressed. Patients with adequate hemodialysis were more anxious and depressed.
CONCLUSION: Anxiety and depression are common psychiatric disorder that are
associated with decrease quality of life. Addressing and including these conditions will
help to improve their psychological condition.

i388 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO674 SHORT DAILY HOME HEMODIALYSIS PROGRAM, IN
NEPHROCARE HEMODIALYSIS CENTER: REPORT STUDY
Percent Hadia Hebibi1, David Attaf2, Magali Ciroldi3, Laure Cornillac2, Charles Chazot4,
Anxiety score HADS-P >=8 34.8 Bernard Canaud5,6
1
Depression score HADS-P >=8 21.7 NephroCare Villejuif, Val de marne, Villejuif, France, 2Fresenius Medical Care FRANCE,
Fresnes, France, 3NephroCare Villejuif, Villejuif, France, 4Nephrocare Ile de France,
Fresnes, France, 5Université Montpellier, Montpellier, France and 6Fresenius Medical
Care, Bad Homburg vor der Höhe, Germany
MO673 Table. Frequency and Association of Anxiety and Depression to
Demographic Data
BACKGROUND AND AIMS: Several studies showed that DHHD improved survival
Anxiety Score HADS-P >=8 Test of Association and quality of life and allowed a lower cost for health system. The aim of this study was
Count Row N % p-value Remark to describe our first experience of DHHD in our dialysis center.
Age 20-35 2 66.7% 0.061 ns METHOD: We included 9 dialyzed patients trained on Nx StageV R machine (Fresenius

Medical Care) from February to December 2020. Data was retrospectively obtained
36-50 4 40.0% through review of our medical electronic records (EuclidV R ).

51-69 9 22.5% RESULTS: Among 9 patients trained, 8 were installed at home, with an average follow
up of 7 months. 6 patients were dialyzed in self hemodialysis facilities. The mean age
70 & above 9 56.3% was 45 years (28-71), 6 women, BMI: 24 kg/m2 (21-30), dialysis vintage: 5 years and 7
Sex Female 17 42.5% 0.132 ns patients are on transplant list. The Charlson score was: 5 (4-8), 5 patients had a
Male 7 24.1% residual diuresis> 500 ml/d. The average training duration was 5 weeks (4-8). Our
training program targeted the self-puncture of AVF and the self-assembly of the
Marital status Single 5 41.7% 0.740 ns machine by the patient. 100% of AVF were cannulated through Buttonhole technique.
Married 19 33.3% 6 patients were dialyzed 6 times a week and only one patient needed anticoagulants.
Educational Grade School 2 50.0% 0.208 ns The blood pressure improved on the first days of DHHD (# 50% of drugs for 50% of
patients). Hemoglobin level maintained between 10-12 g/dl with # EPO. The mineral
attainment High School 3 20.0% metabolism status was improved for all patients, with stopping of binders in one case.
College 15 34.1% DHHD reduced symptoms like fatigue, cramping and post-dialysis recovery for all
patients, and allowed for patients a better socio-professional integration. A medico-
Postgraduate 4 66.7% economic analysis is conducted.
Duration of <1 year 4 57.1% 0.027 sig CONCLUSION: DHHD improved blood pressure, anemia, mineral status and quality
treatment 1-3 yrs 3 13.6% of life. Through economy in medicaltransport and better socio-professional integration
DHD provides savings for the health system
4-6 yrs 12 52.2%
7 yrs or more 5 29.4%
Hemoglobin <100 7 36.8% 0.314 ns
MO675 HEMOADSORPTION WITH CYTOSORBV R CARTRIDGE IN
100-115 13 41.9% PEDIATRIC INTENSIVE CARE UNIT – A SERIES OF FOUR
>115 4 21.1% CASES
Albumin <3.4 6 40.0% 1.000 ns
Neva Bezeljak1,2, Vanja Persic 1,2, Darja Krevh Golubic 3, Igor Vidmar2,3,
3.4-5 10 37.0% Milena Andonova1,2, Alexander Jerman1, Barbara Vajdi c Trampuz1,2,
KT/V < 1.2 5 33.3% 1.000 ns Ana Zupunski Cede1,2, Vladimir Premru1,2, Jakob Gubensek1,2
1
>= 1.2 19 35.2% University Medical Centre, Centre for Acute and Complicated Dialysis, Department of
Nephrology, Ljubljana, Slovenia, 2University of Ljubljana, Faculty of Medicine, Ljubljana,
Depression score Slovenia and 3University Medical Centre, Department of Pediatric Surgery and Intensive
Age 20-35 1 33.3% 0.762 ns Care, Ljubljana, Slovenia
36-50 1 10.0%
51-69 9 22.5% BACKGROUND AND AIMS: Hemoadsorption with CytosorbV R cartridge is one of

extracorporeal blood purification therapies increasingly used in adult intensive care


70 & above 4 25.0% units in conditions with elevated inflammatory mediators. Many positive experiences
Sex Female 9 22.5% 1.000 ns of hemodynamic improvement of patients treated with hemoadsorption have resulted
in attempts of its application also in critically ill pediatric patients. Here we present a
Male 6 20.7% case series of four children treated with hemoadsorption in pediatric intensive care unit
Marital status Single 2 16.7% 1.000 ns (PICU) of University Medical Centre Ljubljana from September 2018 to January 2019.
Married 13 22.8% METHOD: All patients were mechanically ventilated and required vasopressor and
inotropic support. Hemoadsorption was used as a rescue therapy after all standard
Educational Grade School 2 50.0% 0.439 ns treatments for their underlying condition had been insufficient. CytoSorbV R cartridge

attainment High School 3 20.0% was coupled with continuous veno-venous hemodialysis (CVVHD, Prismaflex system,
College 8 18.2% Gambro) in pre-filter (ST60 set, Gambro) position. In children <10 kg body weight (2
infants), the extracorporeal circuit was prefilled with a 1:1 mixture of packed red blood
Postgraduate 2 33.3% cells and saline, with heparin added. Automated regional citrate anticoagulation was
Duration of <1 year 1 14.3% 0.546 ns used, blood flow was 30-100 ml/min and dialysate flow 500 ml/h.
RESULTS: The youngest child was 10 days old 1.9 kg premature female with acute
treatment 1-3 yrs 3 13.6% liver failure due to gestational alloimmune liver disease. CVVHD was started for
4-6 yrs 7 30.4% hyperammonemia and concomitant CytoSorbV R for severe hyperbilirubinemia (335

7 yrs or more 4 23.5% umol/l). Procedure was discontinued after 6 hours due to uncontrollable sepsis and
hemodynamic collapse. We managed to normalize ammonia values and reduce
Hemoglobin <100 5 26.3% 0.842 ns bilirubin concentration (116 umol/l). Further treatment was withdrawn as a result of
100-115 6 19.4% irreversible multiorgan failure.
>115 4 21.1% One month old 2.5 kg female patient was treated in PICU due to necrotizing
enterocolitis and refractory septic shock with multiorgan failure. Oliguric acute kidney
Albumin <3.4 4 26.7% 1.000 ns injury (AKI) required CVVHD and later on Cytosorb V R was added as an attempt to

3.4-5 6 22.2% limit severe hyperinflammatory condition. During 19 hours of treatment the need for
vasopressor support was increasing and metabolic acidosis was deepening. The patient
KT/V < 1.2 3 20.0% 1.000 ns required a short resuscitation a couple of hours into the procedure due to bradycardia
>= 1.2 12 22.2%

10.1093/ndt/gfab099 | i389
Abstracts Nephrology Dialysis Transplantation

which resulted in catheter and CVVHD circuit thrombosis. Dialysis was discontinued METHOD: From March till December 2020. Department for hemodialysis in Novi
as urgent surgery was necessary. The patient later died of uncontrolled septic shock. Sad did 184 renal replacement therapy (RRT) procedures (proc) on 65 Covid 19
Three years old 17 kg male was admitted with meningococcal septic shock, requiring positive pts.
initiation of veno-arterial ECMO. CytosorbV R with CVVHD was started and attached RESULTS: There were 73,85% men and 26,15% women (p < 0,01), with average (avs.)
to the ECMO circuit. A significant decline of interleukine-6 (IL-6) was achieved age of 65,8 years (SD 9,20). Most of them were admitted directly to the Intensive care
without any procedure-related side effect and treatment was discontinued after 68 unit, 64,62% (p < 0,01). The length of stay in hospital ranged from 2 - 61 days (avs.
hours as patient’s clinical status notably improved. The patient survived. 15,86; SD 11,19). The most common comorbidities were hypertension (86,1%),
Five years old 20 kg female patient, actively treated for acute lymphoblastic leukemia, diabetes (33,8%), coronary disease (30,8%) and chronic obstructive pulmonary disease
was admitted with E. coli sepsis. Septic shock was unresponsive to conventional (21,5%). Most common indication for RRT was acutisation of chronic kidney disease
treatment therefore she was started on CytosorbV R with CVVHD as oliguric AKI also (CKD) 43,08% (p < 0,01) followed by pre-existing end stage renal disease (ESRD)
developed. Two consecutive procedures were preformed, the first for 31 and the second 29,23% and AKI 27,69%. RRT was started 1 - 31 days after the admittance (avs. 8,51;
for 37 hours. Level of IL-6 decreased (from > 5000 ng/L to 1000 ng/L) and lactate level SD 7,33). 57 intermittent hemodialysis proc (30,98%) were done on 13 pts (14,06%)
normalized. We achieved reduction in vasopressors and oxygen need during both who were hemodynamicly and respiratory stable. The decision to initiate CRRT was
procedures and patient’s overall status greatly improved. made upon the renal indications, the presence of ARDS or significant volume load. A
CONCLUSION: Although significantly increasing the volume of extracorporeal total of 127 CRRT proc (69,02%) were done on 57 pts (87,5%). The most of them were
circuit, the use of CytosorbV R cartridge within CVVHD circuit is technically feasible CVVHDF (74,02%) and the rest CVVHD (25,98%). Most commonly used membrane
even in critically ill children with low body weight, if principles of pediatric renal was oXiris 47,24% (p < 0,001) followed by EMIC2 25,98%, Kit 8 17,32% and ST-150
replacement therapy are considered. More efficacy and safety data on CytosorbV R 9,45%. Most CRRT proc (89,76%) were done with heparin as an anticoagulant and 10
utilization are necessary before inclusion in routine clinical practice. Treatment proc (7,87%) in 5 pts using citrate. 3 proc (2,36%) in 2 pts were done without using
outcome is highly dependent on primary disease and severity of patient condition. anticoagulant. The procedurès duration had to depend on the number of devices, the
number of pts requiring CRRT and the number of available trained medical workers.
The average achieved length of proc was 712 min. (11 h and 52 min.) (SD 435,07).
Most patients had 1 (49,12%; p< 0,001) or 2 (30,69%) CRRT proc, up to 9 (avs. 2,23;
MO676 COMPLEMENT ACTIVATION BY DIALYSIS MEMBRANES AND SD 1,95). The average achieved ultrafiltration was 2716,41 ml (SD 1016,82). In 23 pts
ITS ASSOCIATION WITH SECONDARY MEMBRANE (40,35%) 26 CRRT proc (20,47%) had to be stopped earlier, because of circuit clotting
FORMATION AND SURFACE CHARGE (9,45%; p < 0,001), deterioration of hemodynamic instability/respiratory insufficiency
(7,09%), device malfunction (2.36%) and RRT need for another pts (1,58%). ARDS has
Pascal Melchior1, Ansgar Erlenkötter2, Adam Zawada1, Dirk Delinski1, developed 42 pts (64,61%). The need for vasoactive support had 41 pts (63,08%). 51 pts
Christian Schall3, Manuela Stauss-Grabo4, James Kennedy1 (78,46%) requiring RRT died.
1 CONCLUSION: Comparing group of pts who survived with group of those who died,
Fresenius Medical Care Deutschland GmbH, Global Research and Development,
greater number of pts with ESRD was in the first group. In survivor group, RRT was
Product Engineering Center Dialyzers & Membranes, Product Development, St. Wendel,
started earlier with greater number and shorter duration of proc. In the group of pts
Germany, 2Fresenius Medical Care Deutschland GmbH, Global Research and
who died, there were more ARDS and vasoactive support need. They had a higher
Development, Product Engineering Center Dialyzers & Membranes, Biosciences –
levels of CRP, leukocyte count and the neutrophil to lymphocyte ratio.
Biotechnology, St. Wendel, Germany, 3Fresenius Medical Care Deutschland GmbH,
Process Technology, Filter Production, St. Wendel, Germany and 4Fresenius Medical
Care Deutschland GmbH, Global Medical Office, Clinical and Epidemiological Research, MO677 Table 1. Characteristic of groups of pts who survived and the group of
Bad Homburg, Germany pts who died

BACKGROUND AND AIMS: Activation of the complement system may occur survived (No 14) died (No 51) p
during blood-membrane interactions in hemodialysis and contribute to chronic 64,14(SD 11,77) 66,27(SD 8,45)
Age 0,45
inflammation of patients with end-stage renal disease (ESRD). Hydrophilic
modification with polyvinylpyrrolidone (PVP) has been suggested to increase the sex M 10 (71,43%) 38 (74,51%) 0,91
biocompatibility profile of dialysis membranes. In the present study we compared fF 4 (28,57%) 13 (25,49%)
complement activation of synthetic and cellulose-based membranes, including the
polysulfone membrane with a-tocopherol-stabilized, PVP-enriched inner surface of No of comorbidities 2,86 (SD 0,86) 2,43 (SD 1,06) 0,84
the novel FX CorAL dialyzer, and linked the results to their physical characteristics. Indication AKI 0 (0%) 18 (35,29%) 0,00
METHOD: Eight synthetic and cellulose-based dialyzers (FX CorAL, FX CorDiax CKD ac 2 (14,29%) 26 (50,98%)
[Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO, SUREFLUX
[Nipro]; xevonta [B. Braun]; FDX [Nikkisio Medical]) were investigated in the present ESRD 12 (85,71%) 7 (13,73%)
study. Complement activation (C3a, C5a, sC5b-9) was evaluated in a 3h ex vivo Los in hospital (days) 16,83(SD 9,29) 15,63(SD 11,66) 0,37
recirculation model with human blood. Albumin sieving coefficients were determined 2,43(SD 1,95) 10,18(SD 7,39)
Los before RRT (days) 0,00
over a 4h ex vivo recirculation model with human plasma as a surrogate of secondary
membrane formation. Zeta potential was measured as an indicator for the surface Los before RRT (only 3(SD 2,27) 10,43(SD 7,42) 0,007
charge of the membranes. CRRT) (days)
RESULTS: The FX CorAL dialyzer induced the lowest activation of the three 4,38(SD 3,38) 1,88(SD 1,36)
complement factors (C3a: -39.4%; C5a: -57.5%; sC5b-9: -58.9% compared to the No of proc 0,008
reference). Highest complement activation was found for the cellulose-based Duration of proc(min.) 464,17(SD 27,36) 744,46(SD 456,48) 0,03
SUREFLUX (C3a: þ154.0%) and the FDX (C5a: þ335.0%; sC5b-9: þ287.9%) membranes oXiris1EMIC2 15 (42,86%) 78 (84,78%) 0,00
dialyzers. Moreover, the FX CorAL dialyzer had the nearest-to-neutral zeta potential (-
2.38 mV) and the lowest albumin sieving coefficient decrease over time. Albumin Kit81ST-150 20 (57,14%) 14 (15,22%)
sieving coefficient decrease was associated with complement activation by the UF/proc (ml) 2799,06(SD 457,88) 2702,91(SD 1111,24) 0,14
investigated dialyzers.
Anuria Y 8 (57,14%) 20 (39,22%) 0,37
CONCLUSION: Our present results indicate that the surface modification
implemented in the FX CorAL dialyzer reduces secondary membrane formation and N 6 (42,56%) 31 (60,78%)
improves the biocompatibility profile. Further clinical studies are needed to investigate vasoactive support Y 0 (0%) 41 (80,39%) 0,00
whether these observations will result in a lower inflammatory burden of hemodialysis
patients. N 14 (100%) 10 (19,71%)
ARDS Y 1 (7,14%) 44 (86,27%) 0,00
N 13 (92,86%) 7 (13,73%)
MO677 RRT DURING COVID 19 EPIDEMIC. EXPIRIENCE OF ONE
WBC (* 10¹9/l) 6,91 (SD 2,63) 11,82 (SD 8,63)
0,02
CENTER NLR 7,48(SD 3,92) 17,78(SD 14,25)
0,017
PLR 266,41(SD 162,52) 334,60(SD 322,35) 0,48
Gordana Strazmester Majstorovic1,2, Violeta Knezevic1,2, Tijana Azasevac1,2, 114,68(SD 141,80) 192,34(SD 107,23) 0,039
Mira Markovic1, Vladimir Veselinov1, Igor Mitic1,2 CRP (mg/l)
1 PCT (ng/ml) 3,81(SD 4,98) 12,67(SD 26,58) 0,28
Clinical center of Vojvodina, Clinic for nephrology and clinical immunology, Novi Sad,
Serbia and 2University of Novi Sad, Medical faculty Novi Sad, Novi Sad, Serbia

BACKGROUND AND AIMS: The incidence of Acute kidney injuri AKI during Covid
19 infection is 3 – 15%, up to 50% for patients (pts) with Acute respiratory distress
syndrome ARDS.

i390 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO678 DISTRIBUTION OF PERIPHERAL BLOOD T CELL RESULTS: Proportions of helper T (CD3þCD4þ), cytotoxic T (CD3þCD8þ), and
SUBTYPES IN HEMODIALYSIS PATIENTS TREATED WITH follicular helper T (CD3þCD4þ CXCR3-CXCR5þ) cells were similar in both
MEDIUM CUT-OFF MEMBRANES AND HIGH- membranes. The use of MCO decreased the ratios of peripheral CD3þT (p=0.07) and
FLUX MEMBRANES Th1 (CD3þCD4þCXCR3þCCR6þ) (p<0.0001) cells while increasing the ratio of NK
cells (p=0.03). In addition, the shift of the immune balance towards an increase in
Nuri Baris Hasbal1, Mustafa Sevinç2, Vuslat Yilmaz3, Taner Basturk4, Elbis Ahbap Th17 (CD3þCD4þCXCR3-CCR6þ) (p=0.005) and Th2 (CD3þCD4þCXCR3-
Dal5, Tamer Sakaci2, Perin Nazif Ozcafer2, Bengt Lindholm6, Abdulkadir Unsal7 CCR6-) (p <0.0001) cell ratios with HF.
1
Basaksehir Cam and Sakura City Hospital, Nephrology, Istanbul, Turkey, 2Sisli Hamidiye CONCLUSION: : The results can be interpreted as the prevention of a Th1 dominant
Etfal Training and Research Hospital, Nephrology, Istanbul, Turkey, 3Istanbul University, inflammation seen with HF. Therefore, it suggests that the use of MCO may reduce T
Aziz Sancar Institute of Experimental Medicine, Neuroscience, Istanbul, Turkey, 4Health cell based inflammation in peripheral blood.
Sciences University, Faculty of Medicine, Department of Internal Medicine, Sisli
Hamidiye Etfal Training and Research Hospital, Nephrology, Istanbul, Turkey, 5Sisli
Hamidiye Etfal Training and Research Hospital, Nephrology, Turkey, 6Intervention and
Technology, Karolinska Institutet, Division of Renal Medicine and Baxter Novum,
Department of Clinical Science, Stockholm, Sweden and 7Health Science University,
Faculty of Medicine, Nephrology, Istanbul, Turkey

BACKGROUND AND AIMS: Mortality in end stage renal disease is higher than in
the general population. In addition, there is also an increase in mortality that cannot be
explained by known risk factors. In this context, researchers have been determining on
these additional risk factors for years. Although inflammation is a proven risk factor,
further studies are still needed. In this study, we aimed to investigate the effect of
membranes on the distribution of T cell subgroups in peripheral blood mononuclear
cells (PBMC) that play an important role in inflammation. MO678 Figure 1: Distribution of T cells and subtype of T cells (TH1 and TH2) in
METHOD: Twenty-five patients were enrolled in the study, and patients received peripheral blood.
hemodialysis treatment first with MCO membrane (MCO) for 3 months and then with
high-flux membrane (HF) for another 3 months. Peripheral blood samples were taken
from the patients just before the hemodialysis procedure at 0 (starting with MCO), 3rd
(switching to HF) and 6th (end of study) months. PBMC’s were separated by ficoll
density gradient centrifugation and stored in liquid nitrogen. Frozen cells were stained
with fluorescently labeled monoclonal antibodies and were utilized with flow
cytometry device. Data were analyzed using FlowJo7.6.5 programs.

10.1093/ndt/gfab099 | i391
Nephrology Dialysis Transplantation 36 (Supplement 1): i392–i408, 2019
10.1093/ndt/gfab101

DIALYSIS. PERITONEAL DIALYSIS (fast peritoneal solute transfer rate, PSTR), without the need for excessive use of high
glucose. Randomized trials have demonstrated these benefits but are insufficiently
powered to investigate a clear impact on survival. We aimed to establish international
prescription practices and their relationship to clinical outcomes.
MO679 EFFECTS OF ALANYL-GLUTAMINE SUPPLEMENTED PD METHOD: The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)
FLUID ON THE PLASMA METABOLOME AND GUT is an international prospective cohort study in collaboration with the International
MICROBIOME IN EXPERIMENTAL PD* Society for Peritoneal Dialysis. The current analysis was drawn from A/NZ, Canada,
Japan, UK, and US in PDOPPS phases 1-2 (2014-2019). Patient demographics,
Jitka Lachova1,2, Rebecca Herzog1,2, Florian Wiesenhofer2, Klaus Kratochwill1,2 comorbidities, lab measurements, clinic blood pressure, membrane function (both
1
Zytoprotec GmbH, Vienna, Austria and 2Medical University of Vienna, Vienna, Austria solute transport rate and ultrafiltration capacity), dialysis prescription details, urine
and 24-hour ultrafiltration volumes were captured at study enrollment. Mortality and
permanent transfer to HD (HDT) events were collected during study follow-up
BACKGROUND AND AIMS: Peritoneal dialysis (PD) is associated with [median (IQR) = 1.1 yrs (0.6, 1.7)]. Linear and logistic models were used to analyze the
morphological and also functional changes to the peritoneum limiting the long-term association between icodextrin and blood pressure. Cox regression, stratified by
use. PD and CKD lead to vasculopathy, disrupt the endothelial and peritoneal barrier, country, was used to analyze the association of icodextrin with time from study
but also influence the gut microbiome. Microbial dysbiosis in return is speculated to enrollment to (a) death and (b) HDT, and adjusted for demographics, 13
drive inflammation as an additional risk factor for cardiovascular disease. New PD- comorbidities, transplant waitlisting, serum albumin, urine volume, facility size and %
fluids that could slow or prevent these processes are needed. Alanyl-glutamine APD use, study phase, while accounting for facility clustering.
(AlaGln) has immunomodulatory and cytoprotective properties and has been shown to RESULTS: Icodextrin was prescribed in 1,929 (35%) of 5,432 patients studied, but this
also improve endothelial barrier functions. Our aim is to investigate the effects of proportion differed by country, being >44% in all except the US, where it was 17%,
AlaGln-supplementation to PD-fluid on the gut microbiome and plasma and effluent and by facility within countries. Patients on icodextrin were more likely to have
metabolome and their interplay. coronary artery disease and diabetes, have lower residual 24-hour urine volume and
METHOD: Mice (C57/BI6N) underwent a subtotal nephrectomy (5/6 nephrectomy) function, use less high glucose, have faster PSTR and reduced ultrafiltration capacity,
to induce uraemia. Chronic exposure to PD-fluid was performed for 9 weeks via and have been on PD longer (PD vintage: median 1.19, IQR 0.50-2.76). Despite this,
subcutaneously implanted peritoneal catheters. Mice were exposed daily to 2 ml of patients using icodextrin achieved equivalent ultrafiltration to those using glucose at
commercially available glucose-based PD-fluid (3.86% glucose) without or with the every level of residual urine volume (see figure). The low use of icodextrin in the US
addition of 8 mM AlaGln. Uremic and healthy mice, kept in parallel were used as was more than compensated for by much greater use of high glucose and overall higher
controls. All mice were fed standard chow and tap water ad libitum. On the last day, ultrafiltration volumes at each level of urine volume. Icodextrin use was not associated
blood and an effluent (after a 30 minute dwell) were collected and faecal matter was with blood pressure (effects: 0.90 mmHg, 95% CI: -0.68, 2.47), mortality (Hazard ratio
collected from 3 different sites of the gut (ileum, caecum and colon). The plasma and [HR] 1.01, 95% CI: 0.83, 1.23) and HDT (HR 1.05, 95% CI: 0.90, 1.23).
effluent metabolome were analysed using a targeted approach. 180 metabolites were CONCLUSION: There are important national and facility differences in the
analysed with a mass spectrometry based kit (Biocrates) in both samples types. prescription of icodextrin, with the US a clear outlier, with less icodextrin and more
Following microbial DNA isolation, the microbiome has been analysed by 16S rRNA high glucose use, resulting in higher ultrafiltration volumes. These practices and the
sequencing. The experiment was approved by the local animal ethics committee. targeting of patients with less efficient membranes for fluid removal may mask any
RESULTS: Significantly elevated creatinine values in mice following 5/6 nephrectomy potential survival advantage associated with icodextrin.
confirmed their uremic status. Significantly different plasma and effluent levels of alanine
and glutamine were found in mice exposed to AlaGln supplemented PD-fluid. A
correlation analysis of the plasma revealed the uremic status of the mice as main driver of
differences whereas the effluent metabolome was mainly changed by PD fluid exposure.
Plasma of uremic mice also showed significantly increased levels of a toxic non-
proteinogenic amino acid symmetric dimethyl arginine (SDMA) and citrulline.
Microbiome analysis yielded over 2800 amplicon sequence variants. Microbiome
composition was location specific and influenced by the different treatments. The
microbiome data were also correlated with over 130 metabolites in both plasma and PD
effluent. Our data showed increased abundance in bacterial family Pseudomonadacea in
caecum of uremic mice and positive correlation with the plasma level of trans-tetra-
hydroxyproline. Mice exposed to conventional PD fluid had higher abundance of the
bacterial class Clostridia in the colon compared to mice with no PD exposition.
CONCLUSION: CKD itself and PD-fluid exposure both affect the gut microbiome and
the AlaGln-supplementation effects are likely reflected at the level of microbial
diversity and functional interaction with metabolites. As next step specific cellular and
molecular mechanisms of these effects are analysed. Preservation of mesothelial and
also endothelial cellular barrier function could be a clinically important benefit for
patients treated with PD, by preventing increased PD-associated pathomechanisms.

MO680 INTERNATIONAL COMPARISONS OF ICODEXTRIN


PRESCRIPTION PRACTICE AND ITS ASSOCIATION WITH
FLUID REMOVAL, BLOOD PRESSURE, PATIENT AND
TECHNIQUE SURVIVAL*

Simon Davies1, Junhui Zhao2, KP McCullough2, Yong-Lim Kim3, Ronald Pisoni2,


Angela Yee-Moon Wang4, Rajnish Mehrotra5, Talerngsak Kanjanabuch6,
Hideki Kawanishi7, Bruce Robinson2, Jeffrey Perl8
1
Keele University, Stoke-on-Trent, United Kingdom, 2Arbor Research Collaborative for
Health, Ann Arbor, MI, United States of America, 3Kyungpook National University
Hospital, School of Medicine, Daegu, Korea, Rep. of South, 4University of Hong Kong,
Hong Kong, Hong Kong, P.R. China, 5University of Washington, Department of
Medicine, Seattle, WA, United States of America, 6Chulalongkorn University, Bangkok,
Thailand, 7Tsuchiya General Hospital, Hiroshima, Japan and 8St. Michael’s Hospital,
Toronto, ON, Canada

BACKGROUND AND AIMS: Icodextrin is designed to maintain ultrafiltration


during the long dwell, especially when there is a risk of increased fluid reabsorption

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
MO681 PERITONEAL DIALYSIS TIME ON THERAPY AND REGIONAL
DIFFERENCES IN DEATH, TRANSFER TO HEMODIALYSIS
AND KIDNEY TRANSPLANTATION: RESULTS FROM THE
PDOPPS

Mark Lambie1, Junhui Zhao2, KP McCullough2, Simon Davies3,


Hideki Kawanishi4, David W Johnson5, James Sloand6, Mauricio Sanabria7,
Talerngsak Kanjanabuch8, Yong-Lim Kim9, Jenny I Shen10, Ronald Pisoni2,
Bruce Robinson2, Jeffrey Perl11
1
Royal Stoke University Hospital, Renal Unit, Stoke-on-Trent, United Kingdom, 2Arbor
Research Collaborative for Health, Ann Arbor, MI, United States of America, 3Keele
University, Stoke-on-Trent, United Kingdom, 4Tsuchiya General Hospital, Hiroshima,
Japan, 5Princess Alexandra Hospital, Brisbane, QLD, Australia, 6AstraZeneca
Pharmaceuticals, Gaithersburg, MD, United States of America, 7RTS Baxter, Bogota,
Colombia, 8Chulalongkorn University, Bangkok, Thailand, 9Kyungpook National
University Hospital, School of Medicine, Daegu, Korea, Rep. of South, 10University of
California, Los Angeles, LaBiomed at Harbor, Torrance, CA, United States of America
and 11St. Michael’s Hospital, Toronto, ON, Canada

BACKGROUND AND AIMS: Comparing and interpreting regional differences in


peritoneal dialysis (PD) time on therapy needs to consider differences in the rates of
permanent transfer to hemodialysis (HDT), death or kidney transplantation. Here we
describe these outcomes among countries in the Peritoneal Dialysis Outcomes and
Practice Patterns Study (PDOPPS), as well as reasons for PD discontinuation.
METHOD: PDOPPS is a prospective cohort study of randomly selected patients across
national samples of PD facilities from Australia/New Zealand (A/NZ), Canada, Japan,
Thailand, the UK, and the US. Fine and Gray models were used on a population of
7115 patients, of varying PD vintages at study entry [median (IQR) vintage = 0.82 yrs
(0.21, 2.03)], to analyse the cumulative incidence from PD start of transplantation,
HDT, or death (on PD or within 7 days of transfer to HD). This allows for the
determination of the % of patients remaining on PD at each PD vintage referred to as
Time on Therapy (ToT). Models were left truncated to account for PD vintage at time
of study enrollment. HDT was defined as no return from HD therapy within 12 weeks
of transferring to HD. Cox models were used to calculate hazard ratios (HR) for death
accounting for facility clustering and adjusted for patient age, sex, US black race, heart
disease, diabetes, psychiatric disorder, prior HD experience, urine volume, and
transplant waitlist referral.
RESULTS: Mean patient age ranged from 56 yrs in Thailand to 64 yrs in Japan
(Figure). Overall, 1261 patients transferred to HD, 76 patients transferred to HD/PD
hybrid therapy, 900 patients died and 506 were transplanted during follow-up. By 3
years, the % of patients remaining on PD ranged from 25% in UK, 34-40% in A/NZ,
Canada and US, to 47% in Thailand, and 54% in Japan (Figure). The much lower % of
patients on PD at 3 yrs in the UK vs Japan was largely due to the high % of patients
transplanted in the UK vs Japan: % transplanted ranged from 2% in Japan and
Thailand to 32% in the UK at 3 yrs. When defining a ‘poor outcome’ as either death or
HDT: (1) the % of patients still on PD or having been transplanted were quite similar
across all 6 countries, and (2) death was a much larger proportion of this ‘poor MO682 TAILORING AI-BASED REFERRAL TO INTENSIFIED
outcome’ in Thailand vs other countries. INTERVENTION PROGRAMS FOR PERITONITIS PREVENTION
Similar risks of HDT were seen across all countries except Thailand which displayed WITH COST-EFFECTIVENESS SIMULATION
much lower risks of HDT. This finding changed little with covariate adjustment (not
shown). Infection, reported as primary HDT cause, varied from 30% (Canada) to 66% Francesco Bellocchio1, Luca Neri1, Jasmine Ion Titapiccolo1, Mario Garbelli2,
(Thailand) of cases, and insufficient solute or water clearance as primary HDT cause Stefano Stuard3
1
ranged from 6% (Thailand) to 44% (Japan) of cases (not shown). Fresenius Medical Care, Clinical & Data Intelligence Systems - Advanced Analytics,
In Cox models, the adjusted HR of death, compared to the US, was higher in Thailand Italy, 2Fresenius Medical Care, Clinical & Data Intelligence Systems - Advanced Analytics
[1.55 (1.17-2.06)], lower in Canada [0.75 (0.61-0.92)], A/NZ [0.60 (0.47-0.78)], and and 3Fresenius Medical Care, Global Medical Office - EMEA, Bad Homburg vor der
Japan [0.36 (0.27-0.48)], and close to 1 in UK [0.98 (0.75-1.28)]. Höhe, Germany
CONCLUSION: Time on PD therapy differed considerably across countries. This was
mainly due to large country differences in proportion transplanted, so that BACKGROUND AND AIMS: Peritonitis is a common and potentially severe
transplantation has a greater impact on country variability in ToT than HDT and complication for peritoneal dialysis (PD) patients. It is associated with mortality and
death. Risk of death varied greatly across countries, particularly when accounting for technique failure risk and contributes significantly to their healthcare cost. Despite
case-mix. With the exception of Thailand, differences between countries in risk of several peritonitis prevention programs based on education and training have been
HDT were modest. Marked differences in recorded reasons for HDT merit additional implemented worldwide, it has been reported a large variability of efficacy across
study. patients groups and healthcare settings. In order to avoid unnecessary treatment of low
risk patients, healthcare prevention programs should be personalized based on accurate
patients’ risk profiling, so that high risk patients may be addressed with intensified
prevention programs.
However, referral strategy (i.e. defining when risk is too much and deserves special
attention) depends the availability, efficacy and cost of medical interventions.
In this study, we demonstrate through a program implementation simulator, how
different referral strategies to inform peritonitis prevention program among PD
patients informed by AI-based risk stratification tools, produce different healthcare
and health economics outcomes. In particular, the simulation considers a prevention
program characterized by standard of care, which affects all patients as well as an
intensive intervention for a subset of high-risk patients (e.g. special training or medical
treatment).
METHOD: The Peritonitis Risk Score model was trained and validated among 9325
PD patients treated in FMC network (Model accuracy, AUC=0.86). The pharmaco-
economic model simulation was performed considering a cohort of 22,900 adult PD
patients, treated in Fresenius Medical Care dialysis network between January 1, 2011
and December 31, 2018, for which the Peritonitis Risk Score was computed at a given
date. The occurrence of an acute peritonitis in the month after prediction has been
registered. We simulated the program outcomes in terms of proportion of referrals to

10.1093/ndt/gfab101 | i393
Abstracts Nephrology Dialysis Transplantation

the intensified prevention program, false omission rate, peritonitis risk reduction, MO683 EXPRESSION OF PARACELLULAR JUNCTION COMPONENTS
overall cost-savings, number needed to treat. AND TRANSCELLULAR TRANSPORTERS IN HEALTH, CKD5
We considered the following scenario based on previous cost-effectiveness analysis on AND PERITONEAL DIALYSIS
peritonitis risk prevention:
Iva Marinovic1, Maria Bartosova1, Eszter Lévai1,2,3, David Ridinger4,
Number of patients involved in the program: 22,900 Betti Schaefer1, Conghui Zhang1, Rebecca Herzog5,6, Peter Sallay3,
Cost saving for any prevented peritonitis: 250 US $ Karel Vondrak7, Felix Bestvater8, Michael Hausmann4, Klaus Kratochwill5,6,
Monthly cost of organizational intervention: 25500 US $ Sotirios G. Zarogiannis1,9, Claus Schmitt1
Effect size of the organizational intervention: 1.3 1
Center for Pediatric and Adolescent Medicine, University of Heidelberg, Pediatric
Cost for intensive care prevention for each patient: 35 $ Nephrology, Heidelberg, Germany, 2MTA-SE, Pediatrics and Nephrology Research
Risk threshold for selecting patients for intensive care prevention: 18% Group, Budapest, Hungary, 3Semmelweis University, 1st Dept. of Pediatrics, Budapest,
Hungary, 4Kirchhoff Institute for Physics, Heidelberg University, Heidelberg, Germany,
5
RESULTS: Given the action threshold selected, 5.3% of patients entered the intensified Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis,
intervention program (PPV=9.5%); the false omission rate was 2.2%. Cost savings for Medical University of Vienna, Department of Pediatrics and Adolescent Medicine,
the intensified healthcare where generated when the effect size of the intensified Vienna, Austria, 6Division of Pediatric Nephrology and Gastroenterology,
intervention exceeded 1.4 (figure 1A). For that effect size the number needed to treat Comprehensive Center for Pediatrics, Medical University of Vienna, Department of
for each prevented peritonitis was NNT=23.4. Overall, 162 peritonitis/month could be Pediatrics and Adolescent Medicine, Vienna, Austria, 7Motol University Hospital,
prevented in the whole network (peritonitis with no intervention=592; Peritonitis after Department of Pediatrics, Prague, Czech Republic, 8German Cancer Research Center
intervention=430). When a less conservative threshold was selected, 12.2% of patients (DKFZ), Light Microscopy, Heidelberg, Germany and 9Faculty of Medicine, University of
entered the intensified prevention program (PPV=7.3%), generating a false omission Thessaly, Department of Physiology, Larissa, Greece
rate=1.9%. Cost savings were never generated (i.e. the intensified program needed
investment to be sustained) but with the same effect size of 1.4 additional 24 BACKGROUND AND AIMS: Tight junction (TJ) proteins have been suggested as
peritonitis/months could be saved in the whole network (peritonitis with no molecular correlates for peritoneal semi-permeability and dialytic transport function in
intervention=592; Peritonitis after intervention=406). The number needed to treat for patients on peritoneal dialysis. Junction abundance in healthy individuals, in those
the intensified program was NTT=30.4 (figure 1B). with CKD5 and in patients on PD has not been described yet, the relation with
peritoneal solute transport is unknown.
METHOD: Junction and transporter expression was analysed in multi-omics data sets
from microdissected omental arterioles in children with normal renal function, CKD5
and on PD with low and high glucose degradation product (GDP) content (n=6/
group). Parietal peritoneal tight junction proteins CLDN-1,-2,-3,-4,-5,-15, the adapter
protein of claudins to actin cytoskeleton protein, zonula occludens-1 (ZO-1), the
tricellular junction protein tricellulin (TriC), and transcellular transporters for sodium
(ENaC), glucose (SGLT-1) and phosphate (PIT-1) were quantified in 40 non-CKD
individuals, 20 children with CKD5 and 20 and 15 children on low- and high-GDP PD
by quantitative, digital immunohistochemistry. Findings were correlated to 2-hour
peritoneal equilibration test data obtained within 6 months of biopsy sampling (n=23).
Primary human umbilical vein endothelial cells (HUVEC) were used to study the
effects of single PD compounds on transepithelial electrical resistance (TER) and
molecular size-dependent paracellular transport capacity. Co-stained monolayers were
visualized by confocal microscopy. Single junction molecule localization and clustering
were analysed by super resolution microscopy.
RESULTS: Transcriptome and proteome pathway enrichment analysis of arteriolar
junction and membrane protein demonstrated regulation in CKD5 versus health, and
differential regulation by low- and high-GDP PD versus CKD5. In the parietal
peritoneum all junctions and cellular transporters were expressed in endothelial and
mesothelial cells. Pore forming CLDN-2, -4 and -15 were localized also in
submesothelial immune cells. Parietal peritoneal junction abundance was age-
dependent and also modified by CKD5 and PD. Mesothelial and endothelial
abundance of the selective cation/water channel CLDN-2 increased in patients on low-
and high-GDP PD fluids. Adaptor protein ZO-1 was upregulated in low GDP-PD
versus CKD5, while sealing proteins CLDN -3 and -5 were downregulated. D/P
creatinine, D/P phosphate, D/D0 glucose were similar in CKD5 and PD groups. D/P
creatinine correlated with mesothelial CLDN-15, with arteriolar CLDN-2 and TriC and
with endothelial ENaC. D/P phosphate correlated with endothelial CLDN-15, D/D0
glucose with mesothelial CLDN-4 and arteriolar CLDN-2. Capillary ZO-1 correlated
with 24-h ultrafiltration standardized to body surface area and dialytic glucose
exposure. In vitro, TER was decreased by low pH, glucose and 0.5mM methylglyoxal
after 5h. Alanyl-glutamine (AlaGln) dose-dependently increased TER, and reduced
10kDa and 70kDa solute at 24mM, increased the abundance of ZO-1 and CLDN5 at
cell-cell contacts, and on nanoscale clustering of the pore-forming CLDN2 and
CLDN5.
CONCLUSION: Abundance of parietal peritoneal sealing and pore forming junctions
CONCLUSION: Cost-effectiveness simulating tool provides a rational evaluation
and transcellular solute transporters varies with cell type and age and is differentially
framework for AI-based referral to peritonitis preventive programs. This tool can be
regulated by PD and associated with dialytic transport function. Our preliminary
easily adapted for any healthcare program based on patient risk score.
analyses illustrate the role of junctions and cellular transporters for solute transport
across the peritoneal mesothelial and endothelial cell barrier. In-depth understanding
of specific molecular functions should provide targets for modulation to improve
efficacy of PD.

MO684 A CO-CULTURE MODEL FOR TESTING EFFECTS OF


CYTOPROTECTIVE ADDITIVES IN PD FLUIDS ON THE
SECRETOME OF MESOTHELIAL AND ENDOTHELIAL CELLS

Juan Manuel Sacnun1,2, Rebecca Herzog1,2, Klaus Kratochwill1,2


1
Medical University of Vienna, Austria and 2Zytoprotec GmbH, Vienna, Austria

BACKGROUND AND AIMS: The composition of all currently available peritoneal


dialysis fluids (PDF) triggers morphological and functional changes in the peritoneal
membrane. Periodic exposure leads to vasculopathy, hypervascularization, and

i394 | Abstracts
Nephrology Dialysis Transplantation Abstracts
diabetes-like damage of vessels of the peritoneal membrane, eventually leading to RESULTS: Normalized anti-SARS-CoV-2 IgG titer in the four groups is illustrated in
technique failure. Patients undergoing dialysis generally, have a high risk of Figure 1A. The mean IgG/protein levels in Group 3 and Group 4 are 86-fold (p=0.023)
cardiovascular events. It is currently unclear if there is a mechanistic link between and 220-fold (p=0.0003), respectively, above the mean IgG/protein levels in COVID
peritoneal membrane failure and cardiovascular risk. In vitro and in vivo studies have negative patients (Group 1 and 2 combined). The discrimination between patients with
shown that cytoprotective additives (e.g. dipeptide alanyl-glutamine (AlaGln) or kinase and without COVID-19 is excellent (AUC 0.938). At a threshold of 0.0024%, the
inhibitor lithium chloride (LiCl)) to PDF reduce peritoneal damage. Here, we sensitivity and specificity are 89.6% and 97.9%, respectively (Figure 1B). Using same
developed an experimental model for investigating effects of such additives on threshold as Figure 1B, in Group 3, 9 out of 11 patients had a positive IgG response in
secretome-mediated signalling between cell-types of the peritoneal membrane which all samples. In 5 patients, IgG levels decreased over time. The mean normalized total
are relevant in the cardiovascular context. antibody/protein levels in Group 3 and Group 4 are 7.3-fold and 24-fold above those in
METHOD: For modelling the peritoneal membrane in vitro, mesothelial (MC) and COVID negative patients (combined Group 1 and 2; both p<0.001). Distribution
endothelial cells (EC) were co-cultured in transwell plates. MC were grown in the pattern, ROC analysis, and dynamic change over time of total SARS-CoV-2 antibodies
upper compartment and primary microvascular cells were grown in the lower are like those of IgG (Figure 1D-F).
compartment. MC were exposed to PDF with or without cytoprotective compounds (8
mM AlaGln in glucose-based PDF 3.86% or 10 mM LiCl in icodextrin-based PDF),
while EC below were kept in medium. Cell damage was assessed by quantification of
lactate-dehydrogenase (LDH) release, neutral red uptake and cell morphology.
Proteome and secretome profiles were analysed for both cell-types in co-culture or
separately with an isobaric-tag labelling approach with a multiplexed liquid
chromatography/mass spectrometry (LC-MS) approach. Prior to analysis of the
secretome a bead-based equalizer approach based on a combinatorial peptide ligand
library (CPLL) was performed to enrich low abundant proteins.
RESULTS: EC injury after PD-fluid exposure of MC was decreased with the addition
of AlaGln or LiCl, showing a link between the individual cell outcomes. Proteome
analysis revealed perturbation of major cellular processes including regulation of cell
death and cytoskeleton re-organization, which characterize PDF cytotoxicity. Selected
markers of angiogenesis, oxidative stress, cell junctions and transdifferentiation were
counter-regulated by the additives. Co-cultured cells yielded differently regulated
pathways following PDF exposure compared to separate culture. We were able to
identify and quantify 334 secreted proteins in the co-culture system. The secretome
analysis showed variation in several clinically relevant proteins and important
extracellular processes such as extracellular matrix reorganization, vesicle transport or
collagen deposition. Comparison to previously published abundance profiles of
omental arteriolar proteins from paediatric PD patient and age-matched controls
confirmed overlapping protein regulation between endothelial cells in vitro and in vivo.
CONCLUSION: This study shows that harmful effects of PDF-stressed MC also affect
EC and elucidates potential mechanisms by which cytoprotective additives may
counteract the signalling axis between local peritoneal damage and systemic CONCLUSION: Covid-19 serology tests can provide much information including
vasculopathy. An in vitro co-culture system may be an attractive approach to simulate diagnosis, immune response, local seroprevalence, et al. Currently, most of serology
the close proximity of different cell types in the peritoneal membrane for testing direct tests are done using blood-related specimens. To our knowledge, this is the first study
and indirect effects of cytoprotective additives. Characterisation of PD-induced reporting SARS-CoV-2 antibodies in spent PD dialysate. Presence of SARS-CoV-2
perturbations may allow identifying molecular mechanisms linking the peritoneal and antibodies in spent PD dialysate of peritoneal dialysis patients potentially provides a
cardiovascular context, offering therapeutic targets to reduce current limitations of PD new way to perform frequent serology tests for this high-risk group. As USA is moving
and ultimately decreasing cardiovascular risk of dialysis patients. fast on national vaccination at this moment, using test strip developed for PD effluent
to quickly and frequently check SARS-CoV-2 antibody in PD effluent could be used to
monitor the vaccination efficiency while avoiding clinic visit.

MO685 PRESENCE OF SARS-COV-2 ANTIBODIES IN SPENT


PERITONEAL DIALYSATE
MO686 THE EFFECT OF A CONTINUOUS TRAINING PROGRAM ON
Xiaoling Wang1, Nadja Grobe1, Amrish Patel1, Jaime Uribarri2, Peter Kotanko1,2 PERITONEAL DIALYSIS PATIENTS’ SURVIVAL
1
Renal Research Institute, 315 E 62nd st third floor, new york, United States of America Marios Theodoridis1, Stamatia Bezirgianidou2, Humeyra Serif-Damadoglou2,
and 2Icahn School of Medicine at Mount Sinai Konstantia Kantartzi2, Ploumis Passadakis2, Elias Thodis2,
Stylianos Panagoutsos1
BACKGROUND AND AIMS: Infection with severe acute respiratory syndrome 1
University Hospital of Alexandroupolis, NEPHROLOGY, ALEXANDROUPOLIS, Greece
coronavirus 2 (SARS-CoV-2) elicits cellular and humoral immune responses. In
patients with coronavirus disease 2019 (COVID-19), IgM, IgA, and IgG antibodies
against SARS-CoV-2 emerge within a few days and can be detected in several body BACKGROUND AND AIMS: Peritoneal Dialysis (PD) is a well-established method
fluids, such as serum and oral fluids. End Stage Kidney Disease patients are especially for dialysis of end stage kidney disease patients. Peritoneal membrane alters with time
vulnerable in this pandemic as they are immunocompromised, putting them at higher from several causes such as bioincompatible PD solutions, uremia, and the cumulative
risks of infection and impaired response to vaccines. While repeated blood draws in effect of peritonitis episodes. Each center follows a specific training program to prevent
hemodialysis patients pose no substantial medical or logistic problems, the situation is the appearance of peritonitis episodes. The aim of this study was to retrospectively
different in those treated by peritoneal dialysis. To overcome that limitation, we evaluate the influence of proper and continuous training on the mortality of peritoneal
explored the presence or absence of SARS-CoV-2 antibodies in spent peritoneal dialysis patients.
dialysate in patients treated with acute and chronic peritoneal dialysis, respectively. METHOD: This is a single center retrospective study of 133 PD patients conducted for
METHOD: We analyzed spent PD dialysate samples from four distinct patient groups, the time period 2009 – 2019 (10 years). The training course was taught one-on-one,
namely Pre-Covid-19 controls (Group 1; 15 samples collected between May 2019 and nurse-to-patient at the initiation of dialysis and then once every 6 months at their
Feb 2020), Covid-19 negative controls during ongoing pandemic (Group 2; 33 samples regular visit or sooner if there was a peritonitis episode. The program included a rated
collected between March and September 2020); chronic PD patients with confirmed questioner based on the Canadian Association of Nephrology Nurses for Nursing
Covid-19 (Group 3; 30 samples collected between March and September 2020,); and Standards and Practice Recommendations published on August 2008. The patients
patients with confirmed Covid-19 and acute kidney injury treated with acute PD were divided into two groups according to the mean value (34) of their questioner sum
(Group 4; 18 samples collected in April 2020). (QS). Group A included 69 patients with mean age of 66 6 15 years (36 M, 33 F) with
SARS-CoV-2 IgG titer in spent PD dialysate was measured by enzyme-linked mean PD duration of 45 6 30 months and they achieved a score less than 34. Group B
immunosorbent assay (ELISA) targeting Nucleocapsid (N) protein of SARS-CoV-2 included 64 patients with mean age of 61 6 18 years (42 M, 22 F) with mean PD
virus (MPBIO cat#: 08440100). Total SARS-CoV-2 antibodies (IgG, IgM, and IgA) duration of 626 32 months and they achieved a score greater than 34. The cumulative
were measured using ELISA targeting recombinant N Protein and Spike protein (S all-cause survival of the PD patients was calculated by Kaplan Meier, was compared
Protein) (AFFYPRO Cat#: EA821). Absolute IgG concentration was calculated using using Long Rang analysis and was also adjusted for their age, gender, the modality of
IgG standard provided by the MPBIO ELISA kit. The total antibody titer was PD applied, the presence of Diabetes and their level of education. Using Cox
calculated as a relative value to the mean of antibody levels of COVID-19 negative Regression, we tried to find independent risk factors such as the score they achieved in
patients. To account for different dialysate and ultrafiltration volumes, antibody titers the questioner. The two groups were compared also for their overhydration and their
were also normalized to total protein concentrations in the spent dialysate samples. frequency appearance of peritonitis or exit site infection.
The ratio of IgG or total antibody to total protein reflects the normalized titer. RESULTS: The cumulative survival using Kaplan-Meier analysis revealed statistically

10.1093/ndt/gfab101 | i395
Abstracts Nephrology Dialysis Transplantation

significant deference between the two groups (Log Rank p<0.001) with Group B creatinine ratio was used to classify PET categories. The study endpoint was five years
(QS>34) achieving better survival. When the survival was adjusted for age, sex, for stable transporters, and at the time of two category rise in the PET test for increased
Diabetes, PD modality the result remains the same. Trying to find among the total of transporters.
our patients the possible risk factors for mortality, using Cox Regression analysis, their RESULTS: Baseline demographics, diabetes frequency, residual renal function (RRF),
QS score (representing their training level for PD) was statistically significant (HR non-phosphate baseline laboratory, parathormone levels, and PD modalities were
0,931 {0.892, 0.971}, p=0.001) independent risk factor, as well as age and PD modality, similar between the increased transporters (n=48) and the stable transporters (n=93).
for our patient survival. Additionally, Group B (QS>34) had statistically significant a Significantly more patients were using renin-angiotensin-aldosterone system (RAAS)
smaller number of peritonitis episodes (p<0.001) and presence of peripheral edema blockers in stable transporters and high-glucose dialysates in increased transporters
(p<0.001). (p=0.03 and p<0.01). Icodextrin, calcitriol, calcium-based phosphate binder use, and
CONCLUSION: In our study we concluded that continuous and monitored training of the number of peritonitis episodes were similar between the groups. Increased
peritoneal dialysis patients has a significant effect on their survival and the frequency of transporters reached the endpoint in 3.9(60.7) years. Increased transporters had a
peritonitis appearance. higher baseline phosphate than stable transporters (p=0.02). The frequency of patients
with an RRF and groups’ mean RRF in ml were similar at the endpoint (p=0.37,
p=0.13). Increased transporters had a significantly higher baseline and endpoint CaXP
than stable transporters (p<0.01 and p=0.02). Baseline weekly peritoneal Kt/V and
MO687 FREE WATER TRANSPORT AND ABSOLUTE DIP OF peritoneal creatinine clearance (PCrCl) were similar at baseline. Increased transporters
DIALYSATE SODIUM CONCENTRATION: EARLY CLINICAL had significantly lower endpoint peritoneal Kt/V and insignificantly lower endpoint
PARAMETERS FOR PERITONEAL FIBROSIS IN PD PCrCl than stable transporters (p<0.01 and p=0.05). DUF was negative for increased
PATIENTS? transporters and positive for stable transporters. Age, diabetes, peritonitis episodes,
RAAS blocker use, and PD modality were insignificant in Cox regression analysis. A
Marisa Rold~ao1, Rachele Escoli1, Hern^ ani Gonçalves1, Francisco Ferrer1, CaXP of >55 was related to 2.51-fold, and high-glucose dialysates were associated with
Karina Lopes1 a 2.93-fold increased risk for a rise in transport status (p=0.01 and p<0.01). Mean
1
Centro Hospitalar Médio Tejo, Nephrology, Torres Novas, follow-up was 7.0 (63.9) years for stable transporters and 5.6 (62.0) years for
increased transporters. Technical survival was significantly higher in stable
BACKGROUND AND AIMS: Reduction of peritoneal salt and water removal is an transporters (p=0.03).
important cause of shortened patient and technique survival in peritoneal dialysis CONCLUSION: Our study revealed a CaXP of >55 is a risk factor for a significant
(PD). The aim of this study was to longitudinally analyze changes in fluid and solute increase in transport status, presumably due to peritoneal calcification.
transport parameters in PD patients during the first year of treatment, using peritoneal The peritoneal Kt/V, PCrCl, and UF rates declined accordingly. The high-glucose
equilibration test (PET). dialysates are associated with a high risk in analyses. However, it is not possible to
METHOD: Retrospective observational study of incident PD patients who underwent determine whether these solutions are the cause or the result of Type I membrane
4-hour 3.86% glucose PET with additional measurement of ultrafiltration at 1 hour, 1 failure.
month after PD initiation and 12 months later. Parameters of peritoneal transport such
as dialysate-to-plasma ratio of creatinine (D/Pcreat), ultrafiltration at 1 and 4 hours,
small-pore ultrafiltration (SPUF), free water transport (FWT), sodium removal and
absolute dip of dialysate sodium concentration (DDNa) at 1 hour (as an expression of
sodium sieving), were calculated. Serum cancer antigen 125 (CA-125) was also
assessed. Clinical, analytical and demographic data were analyzed. Statistical analysis
was performed using SPSS (Version 23 for Mac OSX).
RESULTS: The average age of 16 incident PD patients was 58.69 6 8.51 years, 10
(62.5%) were male and 5 (31.8%) were diabetic. Ten patients (62.5%) were on
automated peritoneal dialysis (APD). One month after PD initiation, membrane
characteristics were: D/P = 0.684 6 0.589, total UF at 4h = 0.696 6 0.283L, UF at 1h =
0.487 6 0.162L, SPUF = 0.303 6 0.359L, FWT = 0.207 6 0.738L, %FWT = 51.855 6
11.828%, sodium removal = 38.048 6 16.087mmol/L and DDNa = 11.125 6
3.34mmol/L. Average serum CA-125 was 51.206 6 22.6U/mL. A paired sample t-test
was performed to compare these parameters 1 and 12 months after PD initiation and
revealed a statistically significant increase of 0.116 0.196L (p=0.042) on SPUF and
18.607 6 7.1mmol/L (p=0.019) on sodium removal. DDNa showed a decrease of 2.5 6
0.743mmol/L (p=0.005) and % FWT of 11.782 6 12.831% (p=0.002). FWT also
showed a decrease of 0.168 6 0.019L, total UF at 4h of 0.206 6 0.142L and UF at 1h of
0.114 6 0.243L, however did not reach statistical significance. D/Pcreat remained
stable. CA-125 showed a mild decrease of 3.644 6 22.364U/mL although not
statistically significant. Pearson correlation revealed a positive correlation between the
variation of total UF at 4h and the variation of FWT (r=0.553, p=0.026) and DDNa
(r=0.503, p=0.047), but not with SPUF, sodium removal, D/Pcreat or CA-125, during
the study follow-up period.
MO688 Figure 1: Study Groups’ Calcium Phosphate Product, Peritoneal Creatinine
CONCLUSION: The reduction of FWT through aquaporins and, particularly, the
Clearance, Peritoneal Kt/V, Delta Ultrafiltration, and Technical Survival
reduction of DDNa as a sodium sieving measure, appear to be the first functional
Ca: Calcium, P: Phosphate, CrCl: Creatinine Clearance, DUF: Delta Ultrafiltration
changes in peritoneal membrane, suggesting that fibrosis may begin soon after PD
Stable Transporters: No significant change in the peritoneal equilibration test category
initiation. Our results indicate that FWT and DDNa can be used to access fibrotic
in five years
peritoneal alterations earlier than other conventional parameters such as D/Pcreat.
Stable Transporter Endpoint: At the end of five years
Increased Transporters: At least two categorical increases in the peritoneal
equilibration test within five years
Increased Transporter Endpoint: At the time of two categorical increases in the
peritoneal equilibration test
DUF= Mean Endpoint UF – Mean Baseline UF
MO688 CALCIUM PHOSPHATE PRODUCT IN PERITONEAL
DIALYSIS: A RISK FACTOR FOR TYPE I MEMBRANE
FAILURE?

Berfu Korucu1, Omer Faruk Akcay1, Galip Guz1


1
Gazi University Faculty of Medicine, Nephrology, Ankara, Turkey
MO689 PITTSBURGH SLEEP QUALITY INDEX SCORE PREDICTS
ALL-CAUSE MORTALITY INDEPENDENTLY IN CHINESE
BACKGROUND AND AIMS: Type I membrane failure (T1MF), increased transport
DIALYSIS PATIENTS
status with ultrafiltration, and solute removal inadequacy are among the most
challenging issues in peritoneal dialysis (PD) continuity. Although quite common, the
Qianqian Han1, Bo Liu1, Shumin Lin1, Jiajia Li1, Peifen Liang1, Sha Fu2,
causes of T1MF are not fully understood. This study aims to identify risk factors
Suqiong Yang2, Guiqiong Zheng2, Bin Li3, Qiongqiong Yang2
associated with T1MF. 1
METHOD: This is a retrospective, single site, cohort study of incident adult peritoneal Sun Yat-sen Memorial Hospital, Nephrology, Guangzhou, P.R. China, 2Sun Yat-sen
dialysis patients sampled between January 2000 and January 2020. Patients were Memorial Hospital, Nephrology and 3The First Affiliated hospital, Sun Yat-sen University
classified as “increased transporters” who had two or more categories of a rise in
peritoneal equilibration test (PET), and “stable transporters” who had had a rise of 1 or BACKGROUND AND AIMS: The relationship between Pittsburgh Sleep Quality
no categories from their baseline during follow-up. The four-hour dialysate/plasma Index (PSQI) score and survival of dialysis patients has not been well studied. The aim

i396 | Abstracts
Nephrology Dialysis Transplantation Abstracts
of this study was to explore the association between PSQI score and all-cause mortality
in dialysis patients.
METHOD: Fifty-one hemodialysis and 58 peritoneal dialysis patients were enrolled in
this study. PSQI score >5 and 5 indicated "poor sleepers" and "good sleepers",
respectively. The primary outcome was all-cause mortality. Kaplan-Meier survival
curve, restricted cubic splines (RCS) regression analysis and Cox proportional hazards
regression analysis were performed.
RESULTS: The median PSQI score was 7.0 (4.0-10.0). Sixty-seven (61.5%) patients had
poor SQ. Compared with good sleepers, poor sleepers had significantly lower levels of
hemoglobin [74.0 (61.0, 85.0) vs. 78.0 (68.0, 97.0), P = 0.03] and serum bicarbonate
(18.0 6 4.5 vs. 20.0 6 3.7, P = 0.022). The follow-up time was 69.1 6 29.9 months. The
survival curve showed no difference in patients with PSQI >5 and those with PSQI 5
(P=0.292, Figure 1). RCS analysis showed that 7 was the cutoff value at which the effect
of PSQI score on mortality changed. A PSQI score of more than 7 increased the risk of
all-cause mortality (Figure 2). Compared to patients with PSQI 7, survival was
significantly worse in those with PSQI >7 (P=0.009, Figure 3). By multivariate Cox
proportional hazards analysis, PSQI total score was the independent risk factor of all-
cause mortality (hazard ratio [HR] = 1.20, 95% confidence interval [CI]= 1.05-1.36, P =
0.007). Patients with a PSQI score > 7 had a 2.96-fold increased risk of all-cause
mortality (HR = 2.96, 95% CI=1.15- 7.61, P = 0.025).

MO689 Figure 3: Kaplan–Meier analysis of dialysis patients with PSQI 7 and >7.
The patients with PSQI >7 had significantly worse survival rate than those with
PSQI 7.

CONCLUSION: PSQI score can be used as a predictor of all-cause mortality in dialysis


patients, those with PSQI >7 were associated with increased odds of mortality.

MO690 HIGHER EXPRESSION OF TOLL LIKE RECEPTOR AND CELL


ADHESION MOLECULES ARE ASSOCIATED WITH
RECURRENT/RELAPSE PERITONITIS AND MORTALITY IN
PATIENT ON CAPD

Narayan Prasad1, Nida Fatima1, Mantabya Singh1, Chinmoy Sahu2


1
SANJAY GANDHI POST GRADUATE INSTITUTE OF MEDICAL SCIENCES (SGPGIMS),
NEPHROLOGY, Lucknow, India and 2SANJAY GANDHI POST GRADUATE INSTITUTE OF
MEDICAL SCIENCES (SGPGIMS), PATHOLOGY, Lucknow, India
MO689 Figure 1: Kaplan–Meier analysis of dialysis PSQI 5 group and >5 group.
There was no significant difference in survival between the two groups.
BACKGROUND AND AIMS: CAPD is an established modality of treatment for
patients with end stage renal disease (ESRD). Peritonitis is a leading cause of technique
failure and death in patients on CAPD. Studies on expressions of host genetic factors
like TLRs, CAMs, Pro and Anti-inflammatory cytokines and their link to peritonitis
and other co-morbidity and functional status are lacking throughout the world. Hence
the present study was done to determine the expressions of TLR2 and TLR4, CAMs
and inflammatory cytokines in patients on CAPD.
METHOD: A total of 110 ESRD patients categorized into 3 groups: 1- CAPD patients
(n=45), group 2- CAPD with peritonitis patients (n=35), and group 3- CAPD patients
with recurrent/relapsing peritonitis. (n=30) from department of Nephrology, Sanjay
Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Raebareli Road,
Lucknow were included in the study.
Blood sample was collected for analysis of cytokines and Cell adhesion molecules level
and RNA extraction. Dialysate (only from patients undergoing PD with or without
peritonitis)- whole drained bag; 50-100 ml for microscopy and culture for bacterial and
fungal pathogens using automated BACTEC culture system in patients with peritonitis
MO689 Figure 2: Restricted cubic spline (RCS) analysis showed that 7 was the cutoff and supernatant was collected for cytokine ELISA.
value at which the effect of PSQI score on mortality changed. PSQI score of more than Statistical analysis: One-way ANOVA (Two tailed) and non-parametric student t-test
7 increased the risk of all-cause mortality in univariate analysis (Figure 2.A) and used for statistical analysis of differences between the group.
multivariate analysis adjusted by age, eGFR, CVD, infection, diabetes nephritis, and RESULTS: mRNA expression of TLR 2 and TLR 4 expression was higher in peritonitis
hypertensive nephropathy (Figure 2.B). and recurrent/relapsing peritonitis group as compared to CAPD patient without
peritonitis group. mRNA expression of TNF-alpha, IL-1B and IFN-gamma was higher
in peritonitis group of patients compared to all other group of patients. mRNA
expression of IL-10 and IL-4 was also highest in Peritonitis group.
Level of IL-1b and TNF-alpha was observed to be elevated in peritonitis and recurrent/
relapse peritonitis patients compared to CAPD in sera and dialysate. IL-12 level in Sera
was also elevated in peritonitis patients but its level in dialysate was highest in CAPD
without peritonitis as compared to peritonitis and recurrent/relapse. IL-10 and IL-4
was observed to be elevated in peritonitis group followed by CAPD with recurrent/
relapse peritonitis in sera whereas in dialysate level of IL-4 was higher in both
peritonitis group and Recurrent groups of patients but IL-10 level was highest in
peritonitis group but less in recurrent/relapse.
mRNA Expression levels of adhesion molecule ICAM-1 and LFA-1 were observed to
be higher in Peritonitis and Recurrent groups as compared to the CAPD without
peritonitis; whereas, in sera the level of ICAM-1 was higher in peritonitis patients.
However, in dialysate its level was observed to be almost similar. Level of LFA-1 was
observed to be higher in peritonitis group in dialysate but in sera its level was higher in
Recurrent group with peritonitis.
CONCLUSION: It is likely that CAMs are also involved in the pathogenesis of CAPD
peritonitis, its morbidity and mortality. TLRs activation by bacterial molecules leads to
the induction of chemokines and cytokines through the activation of NF-ķB pathway

10.1093/ndt/gfab101 | i397
Abstracts Nephrology Dialysis Transplantation

and may be responsible for atherosclerosis, morbidity, and mortality in ESRD patients. transplantation. It is known that the ultrafiltration (UF) capacity of PD is much lower
Elevated level of ICAM-1, IL-1beta, TNF-a and IFN-G may be responsible for chronic than that of HD, which explains the higher incidence of overhydration in PD patients,
inflammation in PD patients. which increases morbidity and mortality in this group of patients, being the second
cause of change to HD. Due to this limitation, it is essential to know and fully exploit
all the factors that influence the UF in PD. The net UF in DP is the result of 4 forces: 1)
the osmotic force, the strongest and only one that is deliberately controlled; 2)
intraperitoneal pressure (IPP) modulated by intraperitoneal volume (IPV), UF volume
itself, posture, BMI, physical activity, etc.; 3) capillary hydrostatic pressure, modulated
by the degree of fluid overload, and 4) capillary oncotic pressure proportional to
hypoalbuminemia, in turn related to fluid overload. The IPP with typical values of 10-
16 cm H2O, should not exceed 18 cmH2O, this excess leads to the development of
mechanical, infectious and functional complications, among them, a decrease in UF.
Elevated IPP is a little known cause of UF failure and, due to its easy diagnosis and
application, it should be ruled out in cases of overhydration in PD. Another parameter
to consider when favoring UF in PD is the residence time of the dialysate solution in
the abdominal cavity through the APEX time calculation (functional test derived from
the classic peritoneal balance test). In the present study, we intend to define the role of
IPP and APEX time as diagnostic and adjunctive evaluation techniques to optimize UF
in PD patients. We determined the correlation of IPP and APEX time with
MO690 Figure 2: Cytokines level in Serum of patients with CAPD, CAPD ultrafiltration and biochemical variables in PD patients.
peritonitis and Recurrent/Relapae peritonitis by ELISA(values are in pg/ml and ng/ METHOD: Pilot, observational, cross-sectional, analytical study.
ml)(*P<0.05) RESULTS: Thirty patients were included, 10 (33%) patients on PD in the IPD modality
and 20 (66.7%) in the CAPD modality. Of which mostly men (53%). The mean residual
uresis of the general population was 534.33 ml. The average UF with a 1.5% solution is
238.1, for a 2.5% solution the average UF is 296.2 and for a 4.25% solution the average
UF is 535 ml. No statistically significant mean differences were found between both
groups. (p  0.05). The average IPP in the supine position was 13.1 cmH2O, the sitting
position was 22.8 cmH2O, and the vertical 25.4 cmH2O, the variability of the PIP in
the prone position at 15.8 cmH2O is striking. No statistically significant differences
were found between the averages of the analysis groups (p  0.05). The average
calculated APEX time was 42.4 minutes. When performing the correlation of UF with
IPP, APEX, Dif. Na, D/P and D/Do, as well as the correlation between APEX time and
time in DP. Being able to determine that there is no correlation between the different
variables. No statistically significant differences were found. (p  0.05).
CONCLUSION: It is the first study in Mexico that evaluates the usefulness of APEX
and IPP time in Adult patients on CAPD and IPD. It was determined that
Intraperitoneal Pressure does not influence Ultrafiltration levels. In our study we
demonstrated that the APEX time, an index of the optimal ultrafiltration residence
time, was not correlated with the UF volumes. Therefore, the adequacy of peritoneal
MO690 Figure 3: Cytokines level in Dialysate of patients with CAPD, CAPD dialysis must not only be based on functional tests, it must be personalized and be
peritonitis and Recurrent/Relapae peritonitis by ELISA(values are in pg/ml and ng/ based in conjunction with clinical, biochemical, nutritional parameters and functional
ml)(*P<0.05) tests.

MO690 Figure 4: mRNA expression (Fold change) of TLR-4, TLR-2, TNF-a IFN-
gamma IL-1beta, IL4 and IL-10 in patient’s subgroups

MO691 CORRELATION OF INTRAPERITONEAL PRESSURE AND


APEX TIME WITH ULTRAFILTRATION AND BIOCHEMICAL
MO692 COULD THE RESIDUAL RENAL FUNCTION REMAIN A KEY
VARIABLES IN PATIENTS IN PERITONEAL DIALYSIS
DETERMINANT OF PLASMA OXALIC ACID CONCENTRATION
IN PERITONEAL DIALYSIS PATIENTS?
Lionel Cristian Vargas Arispe1, Laura Gabriela Amador Reyes2, Rafael Valdez
Ortiz2, Lucia Monserrat Perez Navarro2, Carlos Mauricio Paredes Fern~ a¡ndez1
1
Natalia Stepanova1, Lesya Korol1, Lyudmyla Snisar1, Larysa Lebid1
Cochabamba, Cochabamba, Bolivia and 2Hospital General de Mexico, Nefrology, 1
State Institution “Institute of Nephrology of the National Academy of Medical Science
Ciudad de México, Mexico
of Ukraine”, Nephrology & Dialysis, Kyiv, Ukraine

BACKGROUND AND AIMS: Chronic Kidney Disease represents a growing and


BACKGROUND AND AIMS: Under physiological conditions, the bulk of circulating
serious public health problem, which progresses to terminal stage with glomerular
oxalate (90% to 95%) is ultimately excreted by the kidneys. Under uremic and/or
filtration rate <15 ml/min/1.73m2. It makes it necessary to implement substitute
anuric conditions, dialysis is considered to be the main method of oxalate removal.
therapies for renal function with hemodialysis (HD), peritoneal dialysis (PD) or kidney

i398 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO692 Table 1. Oxalate balance pattern according to anuria status in the PD patients.

Oxalate balance pattern All (n = 62) PD patients with preserved PD patients with P-value
diuresis (n = 41) anuria (n = 21)
POx, mg/L 3.8 [2.2-4.3] 3.9 [3.0-4.9] 3.8 [2.7-5.5] 0.69
UOx, mg/d 33.8 [16-47.2] 33.8 [16-47.2] - -
PDEOx, mg/d 13.2 [11.1-14.7] 13.5 [10.6-20.9] 12.0 [11.0-13.1] 0.02
Overall oxalate removal level, mg/d 31.4 [13.1-55.2] 53.1 [29.6-62.6] 14.1 [11.9-25.0] <0.0001
ROxCL, L/week/1.73m2 36.9 [4.8-72.1] 36.9 [4.8-72.1] - -
PerOxCL, L/week/1.73m2 29.6 [11.5-45.2] 40.6 [15.0-53.8] 20.1 [11.2-35.7] 0.009

ROxCL was correlated with residual diuresis (r=0.71, p<0.001) and, accordingly, UOx excretion and overall oxalate removal level (r=0.8, p<0.0001).
However, neither residual diuresis nor overall oxalate removal level was associated with POx concentration in the PD patients (r=-0.03, p=0.98 and
r=0.09, p=0.52, respectively). In the partial correlation test, only PerOxCL was found to be an explanatory factor for POx concentration in the PD patients
regardless of their age and gender (r=-0.47, p<0.0001).

Nevertheless, little evidence is available on oxalate balance in peritoneal dialysis (PD) each variable was studied using Kaplan-Meier analysis and the log-rank test. All tests
patients. The present study aimed to evaluate the separate contribution of residual were assessed at a statistical significance of p<0.05.
renal and peritoneal oxalate clearances to oxalate balance in PD patients. RESULTS: Thirty-seven patients were enrolled. Three patients refused to participate in
METHOD: We performed a cross-sectional observational study involving 62 PD the study, and one patient was excluded because they had a medical reason. Therefore,
patients with the average age of 50.5613.5 years and PD vintage of 37624 months. 33 patients (age: 74.8 6 5.9 years) were finally included in the present study. The
Plasma oxalate (POx) concentration, levels of daily urinary (UOx) and peritoneal median follow-up time was 39 months (interquartile range: 28–49 months), during
dialysis effluent oxalate (PDEOx) excretion were evaluated. POx concentration was which 19 (57.6%) deaths occurred.
measured spectrophotometrically using MAK315 kit (Sigma, Spain); UOx and PDEOx Death during follow-up was significantly associated with lower 6MWD (234.6.96115.8
concentrations were determined using an oxalate oxidase/peroxidase reagent vs. 351.96105.8 m), lower serum albumin (Alb, 2.760.6 vs. 3.260.4 mg/dL), and lower
(BioSystems, Spain). In addition, oxalate transport status (4-hour D/P oxalate ratio), Geriatric Nutritional Risk Index (GNRI, 79.769.9 vs. 88.567.1) than those who did
renal oxalate clearance (ROxCL) and peritoneal oxalate clearance (PerOxCL) were not die (died vs. not died group, respectively). No other variables were significantly
calculated. different between the groups. The cut-off value, discriminating those at high risk of
RESULTS: Among the examined PD patients were 41 (66%) patients with preserved mortality, for the 6MWD was 338m, Alb was 3.0 ml/dL, and GNRI was 83.7. In the
diuresis and 21 (34%) patients with anuria. The anuric PD patients had lower PerOxCL Kaplan-Meier survival analysis and log-rank test, 6MWD, Alb, and GNRI were
and, accordingly, peritoneal and overall oxalate removal levels compared with the significantly associated with all-cause mortality.
patients with preserved diuresis (Table 1). CONCLUSION: This is the first study, to our knowledge, to show that lower 6MWD
CONCLUSION: The results of our research demonstrated an important role of the scores were associated with all-cause mortality in older adults on PD, suggesting that
residual renal function in oxalate balance in PD patients. However, the decline in RRF objective exercise tolerance measures may be useful for the risk stratification of older
could partially (but not completely) contribute to the increase in POx in PD patients. adults undergoing PD. Although the results were obtained from a small sample size,
Thus, PerOxCL but not ROxCL could significantly affect oxalate balance in PD this study has clinical significance because older adults on PD are rare. The 6MWD is a
patients. useful measurement that reflects exercise tolerance, has good reliability, has low cost,
and is easily applicable. The results of this study support those of previous studies in
other groups showing that 6MWD and nutritional status significantly predicted
prognosis. Therefore, low exercise tolerance and malnutrition may represent an
important therapeutic target in this population.

MO693 EXERCISE TOLERANCE AND NUTRITIONAL STATUS


PREDICTS ALL-CAUSE MORTALITY IN OLDER ADULTS ON
PERITONEAL DIALYSIS: A SINGLE-CENTER PROSPECTIVE
OBSERVATIONAL COHORT STUDY
MO694 SWELLING OF PERITONEAL TISSUE DURING PERITONEAL
Hiroki Yabe1, Yuto Imoto2, Sayaka Ito2, Ayaka Onoyama2, Keiko Okada3, DIALYSIS: COMPUTATIONAL ASSESSMENT USING
Hirotake Kasuga3 POROELASTIC THEORY
1
School of Rehabilitation Sciences, Seirei Christopher University, Department of Physical
Therapy, Hmamatsu, Japan, 2Nagoya Kyoritsu Hospital, Department of Rehabilitation Jacek Waniewski1, Joanna Stachowska-Pietka1, Roman Cherniha2,
and 3Nagoya Kyoritsu Hospital, Department of Nephrology, Japan Bengt Lindholm3
1
Institute of Biocybernetics and Biomedical Engineering, Warszawa, Poland, 2Instytut
BACKGROUND AND AIMS: Peritoneal dialysis (PD) is beneficial for older adults Matematyky Nan Ukrayiny, Kyiv, Ukraine and 3Karolinska Institute, Sweden
with end-stage renal disease (ESRD) because it allows for dialysis treatment in their
own homes. The risk factors associated with specific prognoses in elderly PD patients BACKGROUND AND AIMS: Experimental studies and computational modeling
need to be explored to continue stably without adverse events. However, the risk of show increased hydration of peritoneal tissue close to peritoneal surface after
adverse events specific to older adults on PD has not been thoroughly investigated. The intraperitoneal (ip) administration of hypertonic dialysis fluid. This overhydration -
critical risk factor for ESRD and aging is decreased physical function. The purpose of due to fluid inflow from peritoneal cavity (driven by increased intraperitoneal
this study was to assess the association between physical function and outcomes in pressure) and from blood (due to high interstitial concentration of osmotic agent
older adults on PD. diffusing from the cavity) - may lead to tissue swelling, as observed in experiments and
METHODS: This was a single-center, prospective observational cohort study. Stable, in disturbed physiological conditions. We estimated the degree of swelling using linear
ambulatory patients undergoing PD between April 1, 2014, and September 31, 2016, poroelastic theory with fluid and solute transport parameters obtained from clinical
were enrolled. Six-minute walk distance (6MWD), short physical performance battery studies.
(SPPB), lower extremity muscle strength (LES), and 10-meter walk speed were METHOD: The spatially distributed model of peritoneal transport was extended by
measured for each patient. Laboratory data were also collected. All subjects were equations for tissue deformation and stress derived from linear poroelastic theory. The
followed up until death or the end of the follow-up period (December 31, 2019). This model describes also fluid and osmotic agent flows across tissue and capillary wall. We
ethical institution at the Seire Christopher University approved all procedures assumed that transport and deformation occur across a layer of tissue with initial intact
performed in this study. Informed consent was obtained from all the patients. width L0 and deformed width L; the deformation is described as the ratio L/L0.
Baseline patient characteristics and physical function were compared using an Transport parameters are assumed as average values estimated for intact tissue by
unpaired t-test or Mann-Whitney U test. Receiver operating characteristic curve Stachowska-Pietka (2019). As tissue stiffness (Lame coefficient) for muscle is not
analysis on mortality prediction was performed to calculate the area under the curve in known, we examined stiffness ranging from 110 mmHg (connective tissue;
the significant value of the unpaired t-test or Mann-Whitney U test. We used the interstitium) to 700 mmHg (solid tumor). We assumed that for initial periods of
Youden index to determine the optimal cut-off point, and patients were categorized peritoneal dialysis when osmotic pressure of dialysis fluid is high: 1) osmotic pressure
into 2 groups by each cut-off value. The relationship between all-cause mortality and gradient across the capillary wall prevails over the combined Starling forces, 2) spatial

10.1093/ndt/gfab101 | i399
Abstracts Nephrology Dialysis Transplantation

profile of osmotic agent concentration in tissue (interstitial fluid) can be approximated MO695 THE ASSOCIATION OF CIRCULATING CD14++CD16+
by exponential function with the penetration depth KS. The model yields an equation MONOCYTES, NATURAL KILLER CELLS AND REGULATORY
for L/L0 to be solved numerically, but an approximated closed formula also works well T CELLS SUBPOPULATIONS WITH CARDIOVASCULAR
for typical dialysis conditions. DISEASE IN A COHORT OF PERITONEAL DIALYSIS
RESULTS: The model predicts that swelling of peritoneal tissue depends on factors PATIENTS
such as tissue stiffness, tissue width, solute penetration depth, and transport
parameters for tissue and capillary wall, and on the forces that induce fluid transport: Anila Duni1, Olga Balafa2, George Vartholomatos3, Margarita Oikonomou2,
intraperitoneal pressure and the increment of osmolality of dialysis fluid over plasma Paraskevi Tseke5, Athanasios Kitsos6, Ioanna Theodorou2, Haralambos Pappas2,
osmolality. Examples of L/L0 yielded by the model - with use of glucose 1.36% dialysis Rigas Kalaitzidis7, Michael Mitsis8, Evangelia Ntounousi9
1
fluid and for two levels of ip hydrostatic pressure (Pip) - are shown. In Figure, left University Hospital of Ioannina, Department of Nephrology, Ioannina, Greece,
2
panel, for L0 = 1 cm representing human abdominal muscle, and solute diffusional University Hospital of Ioannina, Department of Nephrology, Ioannina, Greece,
3
penetration KS=KD=0.055 cm, or lower, as due to diffusion against fluid flow, University Hospital of Ioannina, Laboratory of Haematology - Unit of Molecular
KS=KD/2=0.027 cm, is plotted versus the tissue stiffness; the dialysis fluid with glucose Biology, Ioannina, Greece, 5Alexandra General Hospital, Renal Unit, Athina, Greece,
6
1.36% is applied (osmolality increment of 60 mmol/L at the beginning of peritoneal University Hospital of Ioannina, Department Of Nephrolgy, Ioannina, Greece,
7
dwell, Waniewski et al, 1996) and Pip is 15 mmHg. As stiffness of abdominal and University Hospital of Ioannina, Department of Nephrolgy, Ioannina, Greece,
8
bowel muscles may be expected around 300 mm Hg, swelling might be up to 15%; it University of Ioannina, Department of Surgery, School of Medicine, Ioannina, Greece
decreases with lower ip hydrostatic and osmotic pressures. Hypothetical dialysis at Pip and 9University of Ioannina, Department of Nephrology, School of Medicine, Ioannina,
= 0 (isobaric with interstitial fluid) would reduce swelling by factor 2, see Figure, right Greece
panel. The depth of osmotic agent penetration into the tissue impacts tissue hydration
and swelling, see Figure 1 for L/L0 with twice reduced KS. The model and its BACKGROUND AND AIMS: Advanced chronic kidney disease (CKD) is
approximation by the closed formula provide practically the same outcomes for clinical characterized by elevated expression of the proinflammatory and pro-atherogenic
peritoneal dialysis, see Figure 1, but some discrepancy between them may occur for CD14þþCD16þ monocytes subset. The role of lymphocyte subpopulations including
thin tissue, as rat abdominal wall. The approximate formula for L/L0 works well if KS natural killer (NK) cells and CD4þCD25þ regulatory T cells (Tregs) in the
is much shorter than L0. Nevertheless, for high degree of swelling a nonlinear theory modulation of inflammation and immunity and subsequent cardiovascular
should be constructed. implications have received increasing attention. The role of immune cell
subpopulations remains to be determined in peritoneal dialysis (PD) patients. The aim
of this pilot study was to investigate potential correlations between blood levels of
CD14þþCD16þ monocytes, NK cells and Tregs with phenotypes of established
cardiovascular disease (CVD), including coronary artery disease (CAD) and heart
failure (HF) in a cohort of PD patients.
METHOD: 29 stable PD patients (mean age 66.96 years 614.5, 62% males) were
enrolled. Exclusion criteria were a history of malignancy, autoimmune disease, active
or chronic infections and a recent (< 3 months) cardiovascular event. Demographic,
laboratory and bioimpedance measurements data (overhydration, extracellular and
total body water and their ratios) were collected. The analysis of peripheral blood
immune cell subsets was performed using flow cytometry (FC). Additionally, in 7 PD
patients the distribution of the immune cells was evaluated by FC at two time points:
T0 (before initiation of PD - CKD stage G5) and T1 (after PD start).
RESULTS: The median dialysis vintage was 34.5 (range 3.2-141) months. Overall, PD
patients had 527 6 199 monocytes and 1731 6 489 lymphocytes while mean
percentage of CD14þþCD16þ monocytes was 9.3 66.36% (normal range 2-8%), NK
cells 16.6610.3% (normal range 5-15%) and Tregs 2.161.76% (normal range 1-3%).
There was no correlation of either of these cell subpopulations with age, PD vintage,
inflammation markers (CRP, fibrinogen, albumin, hsTroponin-I), overhydration
markers or comorbidities. Only increased NK cells were associated with the presence of
HF in PD (24.87 vs 14.92%, p 0.047). In multiple regression analysis, NK cells levels
were strongly associated with the presence of edema (beta coef=13.7, p<0.001) and
CAD (beta coef=7.1, p=0.046). At T0 mean percentage of CD14þþCD16þ
monocytes, NK cells and Tregs were 9.7 64.5%, 17.1 63.84% and 2.386 1.26%
respectively whereas at T1 mean percentage of CD14þþCD16þ monocytes was 13.3%
68.4, NK cells 19.866.47% and Tregs 1.560.6%. Paired t-test of cell subpopulations
(T0 vs T1) showed that only the Tregs were significantly decreased (p =0.018), while
the other subpopulations did not differ and remained increased.
CONCLUSION: Our study is the first to evaluate the potential association between
specific immune cell subsets and cardiovascular disease in long-term PD patients.
Increased NK cells levels directly correlate both with the presence of HF and CAD in
PD patients. Longitudinal results suggest that CD14þþCD16þ and NK cells remain
increased after PD start, while Tregs decrease further. The state of pro-inflammation
and immune deregulation appear to persist after initiating PD. Future research is
required to evaluate the role of immune cells subsets as potential tools to identify
patients who are at the highest risk for complications and to guide interventions that
may improve clinical outcomes.

MO696 INCREMENTAL PERITONEAL DIALYSIS: BENEFICIAL


EFFECTS

Adriana Fernandes1, Joa ~o Carva~o2, Rita Verıssimo3, Patrıcia Branco3,


Patricia Matias3, Rita Calça3, Ana Rita Martins3
1
Hospital Beatriz Ângelo, Nephrology, Loures, Portugal, 2Hospital Central do Funchal,
CONCLUSION: In peritoneal dialysis, exposure of peritoneal tissue to hypertonic Nephrology, Funchal, Portugal and 3Hospital de Santa Cruz, Nephrology, Carnaxide,
dialysis fluid at increased hydrostatic pressure contributes to overhydration and Portugal
swelling (by 5-15% after fluid infusion) of the tissue. The extent by which this swelling
may contribute to changes in peritoneal tissue structure and function warrants further BACKGROUND AND AIMS: Incremental peritoneal dialysis (Incr_Dial) is a renal
studies. replacement therapy strategy based on lower dose prescription rather than the
standard “full dose” (Full_Dial). Individualized clearance goals were achieved
combining residual renal function (RRF) and peritoneal clearance. Maintaining RRF is
a crucial issue to peritoneal dialysis (PD) patients and the best PD strategy to preserve
it is subject to debate. The aim of this study is to compare Incr_Dial and Full_Dial in
terms of RRF preservation and other clinical outcomes.

i400 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: This was a single-center, retrospective descriptive study. We included a the patient fulfilled six out of eight criteria for diagnosis of HLH. The patient was
cohort of incident and prevalent adult PD patients in the PD Unit between January – managed with Anti Tubercular Treatment along with Dexamethasone and he showed a
December of 2020. Patients without a follow-up < six months and who started PD at gradual improvement in overall clinical and laboratory parameters.
another center were excluded. Patients were assigned according to their first PD CONCLUSION: Secondary HLH may occur after Tuberculous peritonitis in patient of
protocol in two groups – Group A: Incr_Dial protocol (continuous ambulatory PD: ESRD on CAPD. Refractory peritonitis with hyperferritenemia, cytopenias,
less than four dwells daily, less than 2 L dwell volumes, less than seven days a week hypertriglyceridemia should raise the suspicion for HLH. Timely identification and
treatment, or some combination of these; automated PD: without a long dwell, less treatment of HLH may improve patient outcomes.
than 10 L daily delivered by cycler and day dwells, treatment for less than 7 days a week
or some combination of these); Group B: Full_Dial protocol. Statistical analysis was
performed using SPSS 20.0. Statistical significance level p <0.05.
RESULTS: Among 84 PD patients, 68% underwent incremental PD (Group A) and
31% underwent conventional full-dose PD (Group B). The mean age was 55.9615.4
years, 60.7% were male and 32.5% diabetic. There were no statistically significant
differences between the two groups regarding: demographic characteristics,
comorbidities (diabetes, hypertension, cardiac insufficiency or ischemic heart disease)
and drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers
and/or loop diuretics). The median Incr_Dial duration to achieve PD full dose was 10.2
months (IQ 5.1-17).
At the beginning of PD, there was no statistically significant difference in diuresis
between both groups (A: 1.79L vs B: 1.2L, p=0.07), however after 6 months of PD there
was a superior urinary output in Group A (A: 1.67L vs B: 1.1L, p=0.037). Group A
(Incr_Dial) was also associated with a superior renal clearance of creatinine at the
beginning (A: 81 L/sem/1.73m2 vs B: 56.8L/sem/1.73m2, p=0.021) and after 12 months
(A: 70.7L/sem/1.73m2 vs B: 26.3 L/sem/1.73m2, p<0.01); and superior Kt/V renal/
week at the beginning (A: 1.48 vs B: 1.02, p=0.02) and after 12 months (A: 1.28 vs B:
0.49, p<0.001).
There are no differences between mortality (A: 1.9% vs B: 12%, p=0.094), peritonitis-
free time (A: 158 days vs B: 236 days, p=0.133) and the numbers of peritonitis per year
(A: 0.32 vs B: 0.5, p=0.940). However, the rate of hospital admissions per year was
lower in Group A (A: 0.22 vs B: 0.70, p=0.001).
CONCLUSION: Incremental PD is a safe strategy of renal replacement therapy to start
PD. In our PD population, it showed similar patient survival rates and a significantly
less hospital admissions. Incremental PD was also beneficial for preserving RRF when
compared to full-dose PD.

MO697 Figure 1: Bone Marrow showing Hemophagocytosis

MO697 TUBERCULOUS PERITONITIS WITH HEMOPHAGOCYTIC


LYMPHOHISTIOCYTOSIS IN A PATIENT ON CONTINUOUS
AMBULATORY PERITONEAL DIALYSIS: A CASE REPORT

Manisha Dassi1, Anil JhaJhria1, Neeru Aggarwal1, Lakshmikant Jha1


1 MO698 IS PERITONEAL DIALYSIS SUITABLE METHOD FOR OBESE
Max Super Specialty Hospital, Department of Nephrology and Renal Transplantation,
PATIENTS?
Ghaziabad, India
Tatjana Damjanovic1, Jelena Bjedov1, Vesna Maslarevic Radovic1, Bojan Stopic 1,
BACKGROUND AND AIMS: Tuberculosis is a leading cause of morbidity and Tatjana Rajcic2, Mirjana Manasic3, Radomir Naumovic1, Nada Dimkovic1
mortality worldwide. Tuberculous peritonitis in patients on Continuous Ambulatory 1
Zvezdara Clinical Center, Belgrade, Nephrology Department, Belgrade, Serbia,
Peritoneal Dialysis (CAPD), though uncommon, has been reported from different 2
Pozarevac General Hospital, Pozarevac and 3Pancevo General Hospital, Pancevo,
parts of the world. Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic
Serbia
inflammatory disorder characterized by uncontrolled proliferation of lymphocytes &
histiocytes and is reported to have high mortality. Secondary forms of HLH have been
described for various diseases. Here, we report a case of HLH secondary to BACKGROUND AND AIMS: In recent years, obesity has reached epidemic
Tuberculous peritonitis in a patient of End Stage Renal Disease (ESRD) on CAPD. proportions, and it’s a great challenge to choose an adequate treatment for obese ESRD
METHOD: A 49 years old male ESRD patient, on CAPD presented with peritonitis patients. The aim of the study was to analyze the outcome in patients with peritoneal
and was initially managed with antibiotics. He required catheter explantation in view dialysis with different degrees of nutrition expressed through body mass index at the
of refractory peritonitis and was switched to haemodialysis. The patient continued to beginning of treatment.
have low grade fever, yellowish discharge from infra-umbilical CAPD catheter METHOD: The prospective clinical study included 53 incidental patients, who started
explantation surgical wound along with lower abdominal pain & tenderness. He was peritoneal dialysis between June 2006 and August 2015. According to BMI on the
lost to follow up and presented again after 1 month with fever, weight loss, multiple beginning of treatment, patients were divided into three groups: normal weight: BMI of
cutaneous ecchymotic spots and copious amount of yellowish discharge from infra- 18.5 - 24.9 kg/m2, n=17, overweight: BMI of 25 - 29.9 kg/m2, n=25, obese: BMI> 30.0
umbilical surgical wound. On examination, he had fever, conjunctival pallor, kg/m2. n=11. Mechanical and infective complications, technique survival and patients
hepatosplenomegaly and a 5 cm infra-umbilical midline poorly healed discharging survival were analyzed over 48 - months period.
surgical scar with surrounding skin erythema and induration. Blood investigations RESULTS: In terms of mechanical complications, there was no difference between the
revealed Hb 5.1 gm/dl, TLC 1500/uL, Plts 32000/uL, Ferritin 1053 ng/ml, TG 350 mg/ groups- malposition of the catheter (p = 0.769), leakage of dialysate (p = 0.462), hernia
dl, LDH 650 U/l, Bil T/D 1.3/1.0 mg/dl, OT/PT 160/174 IU/l, ALP 219 U/l, GGT 238 (p = 0.381). Exit site infection were most prevalent in group 3 - 1 episode/22 patient
U/l, TP/Alb 5.2/2.5 gm/dl, APTT C/T 27.9/63.0, INR 1.27. NCCT abdomen revealed months vs 1 episode/30 patient months in groups 1 and 2, but without statistical
hepatosplenomegaly, loculated collection in right subphrenic region extending into the significance (p = 0.272). However, the lowest incidence of peritonitis was in the group 3
abdominal and pelvic cavity, anterior abdominal wall defect infero-right lateral to the - 1 episode/40 patient months vs 1 episode/30 patient months in group 2, and 1
umbilicus and generalised increased density in mesenteric fat. Diagnostic sub-phrenic episode/33 patient months in group 1, but even here the difference did not reach
fluid Aspirate analysis revealed a yellow turbid fluid with TLC 22300, ADA 106 U/L statistical significance (p = 0.624). Cardiovascular events – myocardial infarction,
and positive Real Time PCR for Mycobacterium tuberculosis complex. Aspirate stroke and peripheral vascular disease were rare in all groups, with no statistical
pyogenic and fungal cultures were sterile. Bone marrow evaluation revealed marked significance between groups. The incidence of hospitalizations was highest in the obese
degree of histiocytic hemophagocytosis. Patient fulfilled six out of eight criteria for group – 1 episode/22 patient months vs 1 episode/27 patient months in group 2, and 1
diagnosis of HLH. He was started on Anti Tubercular Treatment along with episode/25 patient months in group 1 (p = 0.735). Kaplan Meier’s analysis showed the
dexamethasone. He gradually became afebrile with resolution of infra-umbilical wound worst, but not significant, survival of the technique in a group of obese patients (group
discharge, improvement in clinical and laboratory parameters. 1 vs. group 2; p = 0.536; group 1 vs. group 3 - p= 0.662; group 2 vs. group 3 - p = 0.357).
RESULTS: We report a case of HLH secondary to Tuberculous peritonitis in a patient Also, overall patient survival was not differed between the groups (group 1 vs group 2 -
of ESRD. The patient was on CAPD and required catheter explantation in view of p = 0.387; group 1 vs group 3 - p= 0.885; group 2 vs group 3 - p = 0.375). According to
Refractory peritonitis. Despite explantation and adequate antibiotics, he continued to Cox’s analysis, only values of total cholesterol at the end of the follow-up period (p =
have fever, discharge from surgical wound, pain abdomen, weight loss and poor 0.027) and diastolic blood pressure (p = 0.013) were significantly associated with
appetite. Further evaluation revealed evidence of Tuberculous Peritonitis. In addition, overall survival obese patients.

10.1093/ndt/gfab101 | i401
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: In the present study the degree of nutrition at the beginning of CONCLUSION: In our study, APD and CAPD patients had similar technical survival
treatment had no significant effect on the outcome of peritoneal dialysis treatment. regardless of the peritoneal transport characteristics. However, CAPD was found to be
Therefore, patients should not be discouraged for peritoneal dialysis on the basis of a factor for peritonitis. Thus, it may be appropriate to initiate the PD treatment with
BMI. APD modality and evaluate patients to switch modalities with PET only in case of
peritoneal dialysis inadequacy.

MO699 PERITONITIS RISK OF PD MODALITIES AND TECHNICAL


SURVIVAL ACCORDING TO BASELINE PERITONEAL MO700 EPIDEMIOLOGICAL ADMISSIONS IN PERITONEAL DIALYSIS
TRANSPORT STATUS IN A SINGLE DIALYSIS CENTER

Hasan Haci Yeter1, Omer Faruk Akcay1, Galip Güz1 Vincenzo Antonio Panuccio1, Silvia Lucisano1, Rocco Tripepi2, Giovanni
1
Gazi University Faculty of Medicine, Nephrology, Ankara, Turkey Luigi Tripepi2, Francesca Mallamaci1,2
1
Grande Ospedale Metropolitano “Bianchi Melacrino Morelli”, Nephrology, Dialysis and
BACKGROUND AND AIMS: The PD modality is usually modulated according to the Transplantation Unit, Reggio Calabria, Italy and 2Institute of Clinical Psychology,
PET and dialysis adequacy during follow-up but, initial modality choice generally National Research Counsil, Reggio Calabria, Italy
depends on patient preferences and lifestyle regardless of patients’ baseline transport
status. However, the relationship between baseline transport status, the PD modality BACKGROUND AND AIMS: The knowledge of the impact of peritoneal dialysis
chosen, and technical survival is not well established. Peritonitis is one of the leading (PD) program in terms of hospitalization rate can provide solid guidance for
causes of technical failure, hospitalization, and death in PD. While obesity, low nephrologists for management purpose. In a historical cohort of adult PD patients, we
albumin levels, exit-site infections, and nasal staphylococcus carriage are well-defined examined the hospitalization rates and causes of hospital admissions.
risk factors for peritonitis, some suggest CAPD could be another risk factor due to METHOD: One hundred ninety-one consecutive PD patients between January 1st
increased daily connection to PD. Many studies indicated that CAPD and APD have 2000 to December 31st 2018 were enrolled. The maximum follow up was 194 months.
similar technical survival rates. In this study, we aimed to identify the impact of the Their mean age was 65615 years, 110 were males, 56 had co-morbidities and 67 were
baseline transport status on technical survival of CAPD and APD. We also investigated diabetics. The median PD vintage was 35 months (interquartile range 20-63 months).
peritonitis risk of modalities considering all defined risk factors. RESULTS: During the follow-up, 163 out of 191 patients (85%) underwent hospital
METHOD: This is a retrospective, single-center, cohort study of incident adult PD admission for a total of 356 hospitalizations [57 hospitalizations per 100-person-years].
patients followed-up between January 2010 and January 2020. One hundred and The most frequent cause of admission was infection (20 hospitalizations per 100-
thirty-six patients, followed-up for at least three years, were included. Patients with person-years) mainly due to peritonitis (12 hospitalizations per 100-person-years)
malignancy and who had less than 1.7 Kt/V per week were excluded. Peritonitis is followed by cardiovascular diseases (17 hospitalizations per 100-person-years).
defined according to the "International Society Peritoneal Dialysis" guideline. Hospitalizations due to miscellaneous causes were 21 per 100-person-years. In the
According to the baseline PET, patients were divided into two groups as follows; 1) whole group, high NYHA score [Incidence Rate Ratio (IRR): 1.52, 95%CI 1.21-1.89,
high or high average transporters and 2) low or low average transporters. Risk factors P<0.001], residual diuresis <500 ml/die (IRR: 1.43, 95%CI 1.13-1.82, P=0.002),
for peritonitis, five years, and overall technical survival of both modalities according to malnutrition (IRR: 1.47, 95%CI 1.08-1.99, P=0.01) and older age (>65 years) (IRR
baseline transport status were determined. 1.26, 95%CI 1.02-1.56, P=0.03) and were associated to all-cause hospitalizations. In an
RESULTS: The mean age was 35.5612 years, and the median follow-up time was 47 analysis by hospitalization type, the factors related to admission for infection diseases
(36-178) months. Sixty-six (48%) of the patients were female. Patients’ first-year Kt/V was malnutrition (IRR: 1.91, 95%CI 1.16-3.03, P=0.005) and high NYHA score (IRR:
per week was 2.1860.4, and the mean ultrafiltration was 0.960.4 liters. 26 (19%) of the 1.52, 95%CI 1.03-2.22, P=0.02). As expected, hospitalizations due to cardiovascular
patients had diabetes mellitus, 57(42%) patients had hypertension, and 27 (20%) of the causes were strongly related to older age (>65 years) (IRR 2.02, 95%CI 1.35-3.03,
patients had a history of hemodialysis of more than three months. 89 (65%) of the P<0.001), diabetes (IRR 2.13, 95%CI 1.43-3.18, P<0.001), high NYHA score (IR 2.14,
patients were performing CAPD, 59 (66%) of whom were low or low-average 95%CI 1.43-3.21, P=0.001], residual diuresis <500 ml/die (IRR: 1.65, 95%CI 1.06-2.55,
transporters. 47(35%) of patients were performing APD and 28(60%) of whom were P=0.02) and previous cardiovascular events (IRR: 1.50, 95%CI 0.98-2.25, P=0.05).
high or high-average transporters. During the follow-up, a total of 71 peritonitis CONCLUSION: Analyzing the causes and the rate of hospitalization in PD patients
episodes were observed, and the incidence of peritonitis was 0.13 episodes/year. allows more accurate management of these high risk category of patients and
Univariate logistic regression analysis showed that CAPD, low education level (being contributes to a more efficient organization of a renal department.
primary school graduate or illiterate), HD treatment before PD, and bathing less than
once per week were associated with peritonitis risk. However, multivariate analysis of
associated factors demonstrated that only CAPD was a significant risk factor for
peritonitis [odds ratio:2.360 (95% confidence interval:1.075-5.180), p=0.03]. Kaplan-
Meier survival analysis showed that low or low-average transporters and high or high-
average transporters had similar technical survival rates in both CAPD or APD at the
MO701 COMBINED PROCEDURE OF PRE- EXISTING ABDOMINAL
end of three years (figure 1). Similar rates were found in overall survival.
WALL HERNIA REPAIR AND PERITONEAL CATHETER
INSERTION. LONG TERM FOLLOW- UP IN PERITONEAL
DIALYSIS TREATMENT

Tatiana Tanasiychuk1, Daniel Kushnir1, Oleg Sura1, Husein Darawsha2,


Ariel Chami3, Arie Bitterman3, Victor Frajewicki1
1
Carmel Medical Center, Department of Nephrology and Hypertension, Haifa, Israel,
2
Carmel Medical Center, Department of Emergency Medicine, Haifa, Israel and 3Carmel
Medical Center, Department of General Surgery A, Haifa, Israel

BACKGROUND AND AIMS: Successful peritoneal dialysis (PD) program requires a


combination of optimal peritoneal access and low incidence of complications. Between
pitfalls of this modality are early mechanical complications such as leak, malfunction,
and new abdominal wall hernia formation in the long term of PD treatment. Pre-
existing abdominal wall hernia is a relative contraindication for PD. Hernias are also a
known and not uncommon complication over the course of PD and one of the causes
of technique failure. In our center, a physical examination and an ultrasound for
hernias detection are routine procedures before the start of PD. If a hernia is
discovered, combined hernia repair and catheter implantation are performed. The aim
of this study was to assess to long- term results of this approach.
METHOD: The current study presents the retrospective analysis of 10 years’
experience of our PD program (1.01.2009 – 31.12. 2018) including all incident PD
patients who underwent their first peritoneal catheter placement procedure during the
study period. The primary endpoints of the study were the rate of hernia formation in
the course of PD treatment, type of hernias, identification risk factors for hernia
formation and rate of hernia recurrence after previous repair. The secondary endpoint
MO699 Figure 1: Five years and overall survival analysis of patients with low or low- was the rate of procedure-related complications: infectious, leaks and primary catheter
average transporters and high or high-average transporters malfunction in patients who underwent surgical catheter insertion compared to
percutaneous technique. Patients were followed until the end of PD treatment or until
31.10.2019.

i402 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: A total of 211 patients were included in the analysis. Of these, 24.5% patients. In PD patients, the most common cause of all hospitalisations was peritonitis
underwent surgical procedures and 75.5% percutaneous insertion. Mean follow-up was (23%). In ICHD patients, the most common cause was access-related (33%).
23.3 6 25 months (2 to 96 months). About half (53.1%) of the patients were diabetic, CONCLUSION: PD was associated with a higher hospitalisation rate, a shorter time to
aged 64.2613 years. In 32 patients (15%) a preventive hernia repair with a first hospitalisation and more hospitalisations compared to ICHD. One explanation
simultaneous catheter implantation were performed. Patients who underwent a might be that the threshold for admission to hospital is lower for PD patients
preventive hernia repair were significantly older than other patients (69.4611.1 years compared to ICHD patients.
versus 63.2613.1 years, P=0.013).
During the study period, 203 of 211 patients were treated by PD. Thirty three (16.1%)
have developed 38 new hernias. Patients suffering from a new hernia during PD were
predominantly male, with longer dialysis vintage than patients without new hernia
formation (35.3622.8 months versus 23622.9, respectively. P=0.001). Five of 33
patients suffered multiple hernias, including recurrent hernias at the same site. Most
MO703 URINE VOLUME AS A MARKER OF RESIDUAL KIDNEY
common types were inguinal and umbilical (44.7% each other), while only few were
FUNCTION IN PERITONEAL DIALYSIS PATIENTS:
incisional or ventral. None of our patients suffered from a pericatheter one. The overall
QUANTITATIVE ASSESSMENT
rate of new hernias development was 0.09/patient/years. Neither age, comorbidities,
obesity nor polycystic kidney disease did not increase the rate of hernia formation
Joyce Pinto1, Malgorzata Debowska1, Rafael Gomez2, Jacek Waniewski1,
during the course of PD treatment. There was no significant association between type
Bengt Lindholm3
of catheter insertion procedure (surgical/percutaneous) and infections, leakages or 1
catheter function. Institute of Biocybernetics and Biomedical Engineering, Warszawa, Poland, 2RTS SAS,
Leak incidence in diabetic patients was significantly higher in comparison with Cali, Colombia and 3Karolinska Institute, Baxter Novum and Renal Medicine,
nondiabetic patients (8% versus 1%, P=0.021). Infectious complications were not Stockholm, Sweden
different between diabetic and not diabetics patients (5.4% among diabetic patients
versus 2% nondiabetic, P=0.29). BACKGROUND AND AIMS: In dialysis patients, urine volume is an easy-to-obtain
CONCLUSION: Our findings show that male gender and prolonged peritoneal marker of residual kidney function but information is lacking of its potential value as
dialysis duration are the main risk factors for the appearance of hernias in the course of an estimate of the renal contribution to total clearance of small solutes. We explored
PD therapy. Our data also confirm previous observations that the placement of PD whether correlations of urine volume with different estimations of the residual renal
catheter using a paramedian incision approach significantly reduces the incidences of function for urea, creatinine, and phosphorus, could be used to assess renal solute
exit site and incision hernias. We suggest that early diagnosis of latent asymptomatic clearances and renal mass removal for investigated solutes.
hernias and hernia repair prior to starting PD can improve technique survival. METHOD: In an observational study of 94 non-anuric (urine output  100 mL per 24
hours) patients (54% men, median age 59 [45 - 68] year, BMI 25.8 [21.4 - 27.7] kg/m2)
undergoing automated (n = 59) or continuous ambulatory (n = 35) peritoneal dialysis
(PD), we evaluated renal, peritoneal and total (renal plus peritoneal) solute removal (g/
week) and clearance (L/week) in relation to urine volume (L/day). Urine volume, renal
clearances, ratio of urine solute to serum solute concentration, removed mass of each
solute and the ratio of mass removed by urine (renal clearance) over total mass
MO702 DIFFERENCES IN HOSPITALISATION BETWEEN
removed by urine and dialysate (total clearance) for urea, creatinine and phosphorus
PERITONEAL DIALYSIS AND IN-CENTRE HAEMODIALYSIS
were estimated from 24 h collections of urine and dialysate and determination of solute
PATIENTS
concentrations in serum, urine and dialysate. Statistical dependence between variables
was tested using Spearman’s correlation coefficient (rho). Data are expressed as median
Anita Van Eck van der Sluijs1, Anna Bonenkamp2, Vera Van Wallene1,
with interquartile range.
Tiny Hoekstra2, Birgit Lissenberg3, Friedo W. Dekker4, Frans J. Van Ittersum2,
RESULTS: Median 24-hour urine output was 560 [323 – 938] mL. Renal mass removal
Brigit Van Jaarsveld2, Alferso C. Abrahams1
1
for urea, creatinine and phosphorus was 10.1 [4.5 – 17.1], 3.5 [1.8 – 5.6] and 1.0 [0.4 –
UMC Utrecht, Nephrology and Hypertension, Utrecht, The Netherlands, 2Amsterdam 1.7] g/week, respectively. The average contribution of residual renal removal to the
UMC, locatie VUmc, Nephrology, Amsterdam, The Netherlands, 3Amsterdam UMC, loca- total mass removed was 28% [17% - 41%] for urea, 56% [30% - 72%] for creatinine and
tie VUmc, Epidemiology and Data Science, Amsterdam, The Netherlands and 4Leiden 44% [24% - 58%] for phosphorus. Serum creatinine correlated weakly and negatively
University Medical Center (LUMC), Clinical Epidemiology, Leiden, The Netherlands with urine volume (rho = -0.26, p < 0.05), but no such relationship was observed for
urea and phosphorus. Only urine concentration of creatinine correlated weakly with
BACKGROUND AND AIMS: End stage kidney disease (ESKD) and dialysis urine volume with rho = -0.28 and p < 0.01. Urine concentration over plasma
treatment are associated with high morbidity, frequently resulting in hospitalisation. concentration did not correlate with urine volume for any solute. Renal urea clearance
However, studies comparing hospitalisation between different dialysis modalities (20.1 [11.4 - 35.7] L/week) correlated positively with creatinine renal clearance (43.0
report conflicting results. Some studies report an equal number and length of hospital [18.9 - 75.1] L/week), (rho = 0.92), and with phosphorus renal clearance (17.3 [7.6 -
admissions, while others conclude that peritoneal dialysis (PD) patients are more likely 32.9] L/week), (rho = 0.89, p < 0.001; Fig. 1A), while renal creatinine clearance
to be hospitalised. In addition, most studies only analyse data of patients that remain correlated positively with phosphorus renal clearance (rho = 0.86, p<0.001). Urine
on their initial dialysis modality. However, a transition from one dialysis modality to volume correlated positively with urea, creatinine and phosphorus clearances at rho
another, e.g. from PD to in-centre haemodialysis (ICHD), certainly occurs in current 0.78, 0.63 and 0.73, respectively (all p< 0.001), and with renal removal of mass of urea,
dialysis practice. Therefore, the aim of this study was to compare hospitalisations creatinine, and phosphorus with rho= 0.83, 0.68 and 0.74 (Fig. 1B), respectively; all
between PD and ICHD patients, taking into account transfers between dialysis p<0.001.
modalities.
METHOD: The retrospective Dutch nOcturnal and hoME dialysis Study To Improve
Clinical Outcomes (DOMESTICO) collected hospitalisation data of ESKD patients
who started dialysis treatment between 2012 and 2017. Eligible patients had a
minimum dialysis duration of 3 months. For baseline comparison, groups were defined
based on the dialysis modality (i.e. PD or ICHD) 3 months after dialysis initiation.
Primary outcome was hospitalisation rate, which was analysed with a multi-state
model that attributed each hospitalisation to the dialysis modality the patient was
treated with at that the time. Secondary outcomes were time to first hospitalisation,
number of hospitalisations and length of hospitalisation. Time to first hospitalisation
was analysed with Cox regression analysis, with dialysis modality as a time-varying
covariate. Number of hospitalisations was analysed with negative binomial regression,
and length of stay with Poisson regression. All analyses were adjusted for potential
confounders. MO703 Figure 1: Dependencies between renal clearances of phosphorus and urea
RESULTS: In total, 252 PD and 443 ICHD patients from 31 Dutch dialysis centres (panel A), and renal phosphorus removal and urine volume (panel B).
were included. Baseline characteristics of the groups were comparable, apart from a
lower dialysis vintage and a slightly lower comorbidity score in the PD group. Patients
transferred more often from PD to ICHD (33%), than from ICHD to PD (11%) during CONCLUSION: In PD patients, solute renal clearances and renal mass removal for
a median follow-up period of 22.0 months [IQR 11.1-36.4]. The crude hospitalisation urea, creatinine and phosphorus may be predicted from urine volume. Among renal
rate for PD was 2.3 (65.0) and for ICHD 1.4 (63.2) hospitalisations per patient-year. clearances for urea, creatinine, and phosphorus two of them may be assessed based on
Using a multistate model, the adjusted hazard ratio (HR) for hospitalisation rate was measurements of the third one.
1.1 (95%CI 1.02-1.3) for PD compared to ICHD patients. Cox regression analysis
showed a significant difference in time to first hospitalisation with an adjusted HR of
1.3 (95%CI 1.1 - 1.6) for PD compared to ICHD patients in the first year after dialysis
initiation. After the first year, the time to first hospitalisation had an adjusted HR of 1.9
(95%CI 1.4–2.5) for PD compared to ICHD patients. The number of hospitalisations
was significantly higher, while the length of stay was non-significantly higher for PD

10.1093/ndt/gfab101 | i403
Abstracts Nephrology Dialysis Transplantation

MO704 THE PROGNOSTIC IMPACT OF WEIGHT GAIN AFTER CONCLUSION: Sleep disturbances are common in PD patients and are associated
PERITONEAL DIALYSIS with decreased quality of life. Therefore, they must be taken into account in the
therapeutic measures recommended in order to improve the quality of life of these
Win Hlaing Than1,2, Jack KC Ng1, Gordon CK Chan1, Winston Fung1, Cheuk patients and reduce morbidity and mortality.
Chun Szeto1,2
1
Carol & Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine &
Therapeutics, Prince of Wales Hospital, Shatin, N.T., Hong Kong, P.R. China and 2Li Ka
Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of
Hong Kong, Shatin, N.T., Hong Kong, P.R. China
MO706 PATIENTS AND CENTER-RELATED FACTORS IN
BACKGROUND AND AIMS: The prevalence of obesity has increased over the past PERIOTONEAL CHOICE IN INCIDENT PATIENTS: A
decade in patients with End Stage Kidney Disease (ESKD). Obesity at the initiation of REGIONAL EXPERIENCE
peritoneal dialysis (PD) was reported to adversely affect clinical outcomes. However,
there are few studies on the prognostic relevance of weight gain after PD. Vincenzo Antonio Panuccio1, Giovanna Parlongo1, Rocco Tripepi2, Giovanni
METHOD: We reviewed the change in body weight of 954 consecutive PD patients Luigi Tripepi2, Paola Cianfrone3, Agata Mollica4
from the initiation of dialysis to 2 years after they remained on PD. Clinical outcomes 1
including patient survival, technique survival, and peritonitis rate in the subsequent Grande Ospedale Metropolitano, Nephrology, Dialysis and Transplantation Unit,
two years were reviewed. Reggio Calabria, Italy, 2Institute of Clinical Psychology, National Research Counsil,
RESULTS: The mean age was 60.3 6 12.2 years; 535 patients (56.1%) were men and Reggio Calabria, Italy, 3Azienda Ospedaliero-Universitaria “MATER DOMINI” - Policlinico
504 (52.8%) had diabetes. After the first 2 years on PD, the average change in body Universitario "Magna Grecia”, Nephrology and Dialysis Unit, Catanzaro, Italy and
4
weight was 1.26 5.1 kg; their body weight was 63.0 6 13.3 kg; body mass index (BMI) Azienda Ospedaliera di Cosenza - Ospedale dell’Annunziata, Nephrology, Dialysis and
24.4 6 4.4 kg/m2. The patient survival rates in the subsequent two years were 64.9%, Transplantation Unit, Cosenza, Italy
75.0%, and 78.9% (log rank test, p = 0.008) for patients with weight loss 3 kg during
the first 2 years of PD weight change between -3 and þ3 kg, and weight gain 3 kg, BACKGROUND AND AIMS: Effective outpatient organization is essential in the
respectively. The corresponding technique survival rates in the subsequent two years management of patients with chronic kidney disease. Although peritoneal dialysis (PD)
were 93.1%, 90.1%, 91.3%, respectively (p = 0.110), and the peritonitis rates were has many advantages it is still not popular.
0.761.5, 0.661.7, and 0.661.1 episodes per patient-year, respectively (p = 0.3). When METHOD: The aim of this study was to evaluate patient and center-related factors
the actual BMI after the first 2 years of PD was categorized into underweight, normal that affect the final choice of peritoneal dialysis (PD) versus hemodialysis (HD) in the
weight, marginal overweight, overweight, and obesity groups, the patient survival rates Calabrian region (Italy). We analyzed 2 annual regional surveys performed by
in the subsequent two years were 77.3%, 75.2%, 73.3%, 74.3%, and 75.9%, respectively nephrologists (2017 and 2018) in incident dialysis patients. Collected factors included:
(p= 0.005), and technique survival 98.0%, 91.9%, 88.0%, 92.8%, and 81.0%, respectively early and late referral to the dialysis program, pre-dialysis participation in outpatient
(p= 0.001). After adjusting for confounding clinical factors by multivariate Cox visits, first dialysis access [peritoneal catheter (PC), central venous catheter (CVC),
regression models, weight gain  3kg during the first 2 years of PD was an arteriovenous fistula (AVF)], final dialysis treatment (HD or PD) and the care giver.
independent protective factor for technique failure (adjusted hazard ratio [AHR] 0.049; RESULTS: The study sample included 296 incident patients (63% males) aged 66615
95% confidence interval [CI] 0.004-0.554, p = 0.015), but was an adverse predictor of years. Time to referral influenced the type of first dialysis access. Among patients with
patient survival (AHR 2.338, 95%CI 1.149-4.757, p = 0.019). In contrast, weight loss  early referral, 35% initiated dialysis by a PC, 34% by AVF and 31% by CVC, while
3kg during the first 2 years of PD did not predict subsequent patient or technique among those with late referral, only 5% started dialysis by a PC, 15% by AVF, and the
survival. majority (80%) by CVC (P<0.001). Time to referral was also associated with pre-
CONCLUSION: Weight gain during the first 2 years of PD confers a significant risk of dialysis visits (34%, 33% and 34% versus 5%, 22% and 73%, respectively, P<0.001).
subsequent mortality but appears to be associated with a lower risk of technique failure. When evaluating clinical suitability for treatment modality, 54% of early referrals and
The mechanism of this discordant risk prediction deserves further study. 45% of late referrals were eligible for PD. The choice of dialytic modality was again
related to time to referral: 38% with early referral chose PD compared to 15% of those
with late referral (P<0.001). Furthermore, in patients who participated in the pre-
dialysis program, 38% started PD versus 11% of patients that did not participate
(P<0.001). The role of the caregiver remains uncertain.
CONCLUSION: These data confirm that a more attentive and dedicated organization
of the pre-dialysis outpatient program would contribute to a greater expansion of the
MO705 SLEEP DISTRUBANCES IN PATIENTS ON PERITONEAL peritoneal dialysis program.
DIALYSIS

Dahmane Rihem1, Chaker Hanen1, Toumi Salma1, Zini Olfa1, Mseddi Fatma1,
Kammoun Khawla1, Yaich Soumaya1, Ben Hmida Mohamed1
1
Hedi chaker Hospital, nephrology, SFAX, Tunisia
MO707 MICROBIOLOGY, CLINICAL SPECTRUM AND OUTCOME OF
BACKGROUND AND AIMS: Sleep disturbances are more common in patients with INFECTIOUS PERITONITIS IN PATIENTS ON AUTOMATED
chronic renal failure and on dialysis than in the general population. They affect their PERITONEAL DIALYSIS
mental health and quality of life. The objective of this study was to evaluate the sleep
disorders of patients on peritoneal dialysis (PD). Nadia Cherni1, Samia Barbouch1, Meriem Hajji1, Nada Sallemi1,
METHOD: We report the results of a descriptive cross-sectional study in 27 patients Mondher Ounissi1, Hafedh Hedri1, Fathi Ben Hamida1
on PD in order to assess the quality of sleep in these patients and its relation with 1
Charles Nicolle Hospital, Medicine A, Tunis, Tunisia
mental health and quality of life. Sleep quality was performed using the Pittsburgh
Sleep Quality Index (PSQI) to assess origin and extent of sleep disorders. Anxiety-
BACKGROUND AND AIMS: Automated peritoneal dialysis (APD) is a renal
depressive disorders were assessed using the HAD (Hospital anxiety and depression)
replacement therapy that offers patients various advantages such autonomy and
scale. The quality of life (QOL) measurement was performed by the SF36 and KDQoL.
comfort. Peritoneal dialysis-related infectious peritonitis (IP) is the most common and
RESULTS: We included 15 men and 12 women with an average age of 45.74 years (21–
severe complication of APD. It is the main cause of technique failure and transfer to
77). Eleven patients were on automated peritoneal dialysis (APD) and 16 patients on
hemodialysis and can even be life-threatening. Given the seriousness of this
continuous ambulatory peritoneal dialysis (CAPD). The mean duration of dialysis was
complication, it is necessary to establish preventive strategies and adapt the therapeutic
45.77 6 25 months. Poor quality of sleep was reported in 14 patients. The mean PSQI
management.The aim of this study was to determine the microbiological and clinical
was 7.22 6 4.87. The most affected components were sleep duration and usual sleep
profile of IP, to specify its causes its rate and outcome in patients treated by DPA at the
efficiency. Depression was objectified in 22.22% of patients and 26% of patients had
unit of Charles Nicolle hospital in Tunis between January 2000 and December 2018.
anxiety.
METHOD: We conducted a single-center descriptive retrospective study in the
Impaired quality of sleep was associated with decreased quality of life. The components
peritoneal dialysis (PD) unit of Charles Nicolle Hospital in Tunis. We identified the
of the physical dimension of quality of life: limitation due to physical condition,
episodes of IP occurring in patients treated with APD during the period from January
physical pain were significantly lower in dialysis patients with good quality of sleep
2000 to December 2018. We studied the clinical, biological and evolutionary aspects of
(p=0.014, p= 0.033 respectively)
IP.
The mental dimension component of QOL of SF36: relationship to others, limitation
RESULTS: APD was used in 85% of patients treated at our PD unit during the study
due to mental condition was also lower in patients with sleep disturbances (p=0.039,
period. 322 episodes of IP occurred in 183 patients, that was an IP rate of 0.1 episodes/
p= 0.036 respectively).
patient-year. 58% of patients treated with DPA have not presented IP. The mean age of
Symptoms and problems, as well as the effects and the burden of kidney disease were
the patients who presented PI was 43 years þ/- 15(Extreme: 17-77) with a sex-ratio of
not associated with poor quality of sleep. Impaired sleep quality was also not
1.23. 74% of patients had a professional activity. 98% of patients had co-morbidities
significantly associated with depression or anxiety in our series.
dominated by hypertension (88%), dyslipidemia(73%) and diabetes(16%) with a
median Charlson score of 2[2-3] (Extremes: 2-9). Their average Body Mass Index was
24kg/m2þ/-5. 33% of the patients were smokers. The average training duration before

i404 | Abstracts
Nephrology Dialysis Transplantation Abstracts
starting APD was 13daysþ/-5. The IP were evenly distributed according to seasons the association between serum EDPs and abdominal aortic calcification (AAC) in PD
(27% occurred in autumn, 26% in spring, 25% in summer and 22% in winter). IP were: patients remain limited.
a 1st episode in 55% of cases, a new episode in 30% of cases, a relapse in 10% of cases, a METHOD: 126 eligible PD patients were included and first grouped by the presence of
recidivism in 3% of cases and a recurrence in 2% of cases. Fever was present in 34% of AAC by an abdominal computed tomography (CT) scan. Patients with AAC were then
patients, abdominal pain in 75% of them. The dialysate was cloudy in 98% of cases. The grouped into severer and non-severer group according to the annularity of
median number of leukocytes in the PD fluid was 380/mm3(Range: 15-8000)with a calcification. Logistic regression analysis was conducted to analyze the association
mean% of neutrophils of 73%þ/- 27. Dialysate culture was positive in 60% of cases, between EDPs and AAC or severer AAC. Nomograms were generated to evaluate
negative in 38% of cases and contaminated in 2% of cases. Among the positive cultures, individualized risk of AAC and severer AAC.
only one was fungal (Candida albicans). Bacterial IP were distributed as follows: 64% RESULTS: Serum EDPs were significantly elevated in PD patients compared with
Cocci Gramþ dominated by Staphylococcus aureus (48%), 34% Bacillus Gram- healthy controls (interquartile ranges: 37.65-55.02 versus 24.23-39.20 ng/mL;
(mainly Klebsiella pneumoniae (21%) and Pseudomonas (21%)), 2 cases of Bacillus p<0.001), and gradually increased as AAC worsens. Moreover, EDPs had the most
Gramþ (Corynebacterium afermentans and Lactobacillus) and 2 cases of excellent discriminatory power to differentiate AAC compared with other mineral
polymicrobial culture (Cocci Gramþ and Bacillus Gram-).IP was of unknown cause in metabolism markers. After adjustment for potential variables, higher EDPs were
48% of cases, related to an asepsis lack in 19% of cases, the orifice infection in 18% of associated with greater risk of developing AAC (Odds ratio: 1.056, 95%CI: 1.010-1.103)
cases and tunnelitis in 2% of cases. The other causes were essentially endogenous. and severer AAC (Odds ratio: 1.062, 95%CI: 1.004-1.123). Receiver operating curve
Probabilistic antibiotic therapy was effective in 34% of cases. An adaptation according analysis (ROC) revealed that a combination of EDPs substantially improved the
to the microbiological results was carried out in 19% of cases. Hospitalization was accuracy of diagnostic performance for AAC and severer AAC. Nomogram
required in 10% of patients. 20% of peritonitis was refractory. Catheter ablation was demonstrated exceptional ability in recognizing PD patients with susceptibility to AAC
performed in 14% of patients.IP caused the death of 8 patients and represented 37% of or severer AAC.
the causes of transfer to hemodialysis. CONCLUSION: Serum EDPs can predict the presence and severity of AAC in PD
CONCLUSION: IPs are a turning point for the survival of the patient and the patients, indicating the possible roles to recognize PD patients at risk for developing
technique. Knowing the microbiological profile of these infections will make AAC and severer AAC.
therapeutic interventions precocious and effective in order to preserve the prognosis of
patients in APD at the short and long term.

MO708 INCREASE IN PERITONEAL DIALYSIS-RELATED


HOSPITALIZATION RATES DURING COVID-19 PANDEMIC

Viviane Calice-Siva1, Helen Ferreira2, Gabriela Sevignani2, Marcos Vieira1,


Raıssa Vodianitskaia3, Fabiana Nerbass1
1
Fundaç~ao Pr o-Rim, Joinville, Brazil, 2Centro de Tratamento de Doenças Renais,
Joinville, Brazil and 3Univille, Brazil

BACKGROUND AND AIMS: In March 2020 to reduce the coronavirus spread in


Brazil professional regulatory agencies allowed the telemedicine for distance patients’
monitoring. All peritoneal dialysis (PD) patients from our center previously followed
monthly in face-to-face visits were monitored by telephone call appointments since
then. In this study, we aimed to investigate and compare the hospitalization rates
before and during the telehealth assistance.
METHOD: Patients aged 18 years and older in March 2020 were included. We
analysed total hospitalization rate and PD-related hospitalization rate (infectious, MO710 GALECTIN-3, IS IT A NEW PLAYER IN PERITONEAL
mechanical dysfunction and hypervolemia) 6-month before (first phase) and 6-month INFLAMMATION AMONG PATIENTS UNDERGOING
after (second phase) telehealth implementation. PERITONEAL DIALYSIS?
RESULTS: A total of 117 patients were included (male: 45%; age: 56.9 6 16.2 years old;
PD vintage: 15 (7–26) months; automated PD: 97%; diabetes: 45%). There were 15 Yael Einbinder1,2, Keren Cohen-Hagai1,2, Sydney Benchetrit1,2, Tali Zitman-Gal2
1
hospital admissions in 13 patients (2 patients were admitted twice) during the first Meir Medical Center, Kefar Sava, Israel and 2Tel Aviv University, Sackler Faculty of
phase, resulting in an incident rate (IR)=23 per 1000 patients-month. In the second Medicine, Tel Aviv-Yafo, Israel
phase, the numbers increased to 34 admissions (3 due to covid-19) in 30 patients (1
patient admitted twice and another four times), IR=56 per 1000 patients-month. The BACKGROUND AND AIMS: Peritoneal dialysis (PD) is a common used method for
total hospitalization incident rate ratio (IRR) was 2.43 (CI 95% 1.32 – 4.48). The total renal replacement therapy. Prolonged PD treatment causes structural and functional
PD-related hospitalization increased from 4 (3 hypervolemia, 1 mechanical) to 20 (12 changes in the peritoneal membrane which are attributed to local inflammatory
infectious, 3 mechanical; 5 hypervolemia) episodes during telehealth assistance, process in the peritoneal cavity. Galectin-3 (Gal-3) is a galactoside-binding lectin with
representing 26% to 59% of total hospitalizations. IRR for PD-related hospitalization pro-inflammatory and pro-fibrotic effects. The aim of this study was to assess
was 5.5 (CI 95% 1.8 – 16.4). correlation between Gal-3 serum and dialysate effluent levels with peritoneal
CONCLUSION: After telehealth implementation, the risk of hospitalization raised membrane transport characteristics.
significantly, mainly due to PD-relates causes that increased 5.5 times. Potential causes METHOD: Gal-3 levels in serum and dialysate effluent were measured simultaneously
of this finding are lack of proper training for distance monitoring to patients and in prevalent PD patients in morning visit or during peritoneal equilibration test (PET).
health care workers, life habits and routine of care modifications and social isolation. Gal-3 levels were correlated with clinical and laboratory parameters. Interlukin (IL) -6
More studies are needed to assess the independent impact of telehealth on PD patients levels were measured in dialysate effluent. Gal-3 mRNA and protein expression were
outcomes. evaluated after exposure of primary endothelial cell culture to several dialysate
solutions.
RESULTS: 37 PD patients were included in the study; mean age was 65.7613.1 years,
mean dialysis vintage was 17.5613 months. Gal-3 levels in dialysate effluent correlated
with peritoneal equilibration test (PET) results (0.663, p=0.005) and effluent IL-6 levels
(0.674, p=0.002) but not with serum Gal-3 levels or dialysis vintage. Patients with high
MO709 ASSOCIATION BETWEEN SERUM ELASTIN-DERIVED PET results had higher effluent Gal-3 levels as compared average low PET results. In
PEPTIDES AND ABDOMINAL AORTIC CALCIFICATION IN multivariate regression analysis effluent IL-6 level was the most dominant predictor of
PERITONEAL DIALYSIS PATIENTS: A CROSS-SECTIONAL effluent Gal-3 levels. Gal-3 mRNA and protein expression in primary endothelial cell
STUDY culture were not affected by stimulation with dialysate solutions.
CONCLUSION: Our study demonstrated presence of Gal-3 within the dialysate
Cao Jingyuan1, Zhao Shizhu2, Lu Guoyuan2 effluent in PD patients. Gal-3 levels correlated with peritoneal membrane transport
1
Department of Nephrology, Taizhou People’s hospital, Fifth Affiliated Hospital of characteristics and effluent IL-6 levels suggesting a role in the inflammatory process
Nantong University, Taizhou, P.R. China and 2Department of Nephrology, the First within the peritoneal cavity.
Affiliated Hospital of Soochow University, Suzhou, P.R. China

BACKGROUND AND AIMS: Peritoneal dialysis (PD) patients experience accelerated


arterial aging, which is characterized by elastin degradation. Although elastin-derived
peptides (EDPs) have been reported to be associated with vascular diseases, studies on

10.1093/ndt/gfab101 | i405
Abstracts Nephrology Dialysis Transplantation

MO711 COMPARISON OF PERITONEAL DIALYSIS EFFICACY residual diuresis, isquemic cardiopathy and left ventricle mass index, NT-proBNP >
MARKERS IN DIABETIC AND NON-DIABETIC PATIENTS 1600 pg/mL was associated with patient overhidratation (exp (B) 1,44, 95% CI 0,15-
2.73).
Jo~ao Carv~ao1, Adriana Paixa ~o Fernandes2, Rita Verıssimo3, Rita Calça3, Ana
No statistical difference was observed considering nutritional parameters, peritoneal
Rita Martins3, Patricia Matias3, Patricia Branco3 transport, dialysis efficacy and NT-proBNP.
1
Hospital Central do Funchal, Nephrology, Funchal, Portugal, 2Hospital Beatriz Ângelo, CONCLUSION: In this population, higher levels of NT-proBNP were associated with
Nephrology, Loures, Portugal and 3Hospital Santa Cruz, Centro Hospitalar Lisboa overhydration status and left ventricular dysfunction. Therefore, BIA and NT-proBNP
Ocidental, Nephrology, Carnaxide, Portugal may be complementary to clinical evaluation of PD patients. BIA results can be
affected by malnutrition with loss of cell mass according to some studies. In our
BACKGROUND AND AIMS: Diabetes mellitus (DM) is the leading cause of end- population NT-proBNP is not affected by nutritional status and therefore can also be
stage kidney disease. Peritoneal dialysis (PD) is an effective and convenient modality of used as a congestive marker in malnourished patients. Longitudinal application of BIA
renal replacement therapy, however in diabetic patients, higher technique failure is could be a useful clinical tool to evaluate adequacy in PD patients.
feared. This cross sectional study aimed to investigate if diabetic patients are good
candidates for peritoneal dialysis in terms of dialysis efficacy and volume overload
management when compared with non-diabetic patients.
METHOD: We conducted a cross-sectional study including 60 patients with end-stage
kidney disease currently in peritoneal dialysis. Echocardiography was performed using
HDI 5000, allowing M-mode, two-dimensional measurement. Peritoneal equilibration MO713 ENCAPSULATING PERITONEAL SCLEROSIS IN KIDNEY
test exam was used to evaluate transport rate and dialysis efficacy. A multifrequency TRANSPLANT RECIPIENTS
bioimpedance (BIA) analyzer was used. Overhydration (OH) was defined as an extra-
cellular water (ECW)/total body water (TBW) over 15%. Clinical and biochemical Imen Ouertani1, Azzabi Awatef1, Sahtout Wissal1, Ben Aicha Narjes1,
variables were also explored. Mrabet Sanda1, Ferdawes Sabri1, Zellema Dorsaf1, Guedri Yosra1,
RESULTS: A total of 60 patients completed evaluation. Overall, 60% (n=36) were Abdelatif Achour1
males with a mean age of 55,8 6 15,3 years, BMI 25.9 6 3.9 kg/m2, 31,7% (n=19) had 1
DM. Median PD vintage was 21 months, automated PD 30%, 8.3% (n=5) were anuric Sahloul Hospital, Nephrology department, Sousse, Tunisia
and 10% (n=6) were overhydrated. The median serum N-terminal pro b-type
natriuretic peptide (NT-proBNP) level was 1071 pg/mL. Left ventricule (LV) mass BACKGROUND AND AIMS: Encapsulating peritoneal sclerosis (EPS) is a life-
index and LV ejection fraction were 129.0 6 51.1 g/m2 and 62.8 6 13.0%, respectively. threatening complication of long-term peritoneal dialysis (PD). Causative factors are
The median excess volume overload was 0.9L. the chronic exposure to bioincompatible PD and peritonitis episodes. Pro-
Patients were divided in 2 groups (diabetic and non-diabetic). No differences were inflammatory state and oxidative stress associated with chronic uremia may further
found between the 2 groups in terms of time in PD, peritoneal transportation, dialysis accelerate these pathomechanisms. Clinical symptoms are, essentially, signs of
efficacy, diuresis, hemoglobin, albumin, normalized protein catabolic rate, hydration intestinal obstruction. Treatments commonly used are corticosteroids, tamoxifen,
status, weight, body mass index, arterial hypertension, chronic heart failure, LV immunosuppressants like azathioprine, mycophenolate mofetil (MMF), or mTOR
ejection fraction, LV mass index, CA-125 value, clinical signs of fluid overload, systolic inhibitors which has fibrinolytic properties and may help with reducing inflammation.
and diastolic blood pressure. However, diabetic patients were younger (51,6 versus In the last ten years, the incidence of SEP in kidney transplant recipients has increased,
58,0; p=0,02), more likely to have peripheral arterial disease (42,1 versus 7,3%, p=0,03), but few cases have been reported. Given the rare nature of this pathology, we decided
ischemic heart disease (52,6 versus 7,3%, p<0,001) and had higher levels of NT- to publish the cases of two EPS happening after kidney transplantation (KT).
proBNP (5932 versus 4216 pg/mL, p=0.04). CASE REPORT: We report the cases of two male patients aged 46 and 25 with a
However, when using a multivariable analysis, in a model adjusted to age, residual history of chronic renal failure, who benefited of continuous ambulatory peritoneal
dialysis, efficacy of dialysis, diabetic patients did not have a significant difference in dialysis (CAPD) for three years. The first patient was switched to haemodialysis (HD)
volume overload, dialysis efficacy and markers of cardiac dysfunction when compared for sub-dialysis, with one episode of peritonitis and one episode of catheter infection.
with non-diabetic patients. The second patient had three episodes of peritonitis complicated by asymptomatic
CONCLUSION: In this population, diabetes was associated with higher levels of NT- EPS, hence its transfer to HD. Our two patients presented, at 30 and 40 days post KT,
proBNP, however it did not translate in higher fluid overload, lower dialysis efficacy or an episode of acute intestinal obstruction with abdominal scans fitting with a
worst cardiac dysfunction, when compared with non-diabetic patients. We conclude mechanical bowel obstruction on an encapsulating peritonitis without signs of
that PD is able to control hydration status, dialysis efficacy and cardiac dysfunction in complication. Both patients were on corticosteroid therapy (15 and 17.5 mg/day)
diabetic patients with similar efficiency as in non-diabetic patients. combined with MMF and Calcineurin inhibitors (CNIs) (Tacrolimus). Medical
measures were not effecient. Surgical treatment was then considered. During the
operation, a classical picture of EPS was found characterized by a thin cocoon-like
sclerotic membrane encasing the small bowel. A complete resection of the
encapsulating sclerotic membrane and total adhesiolysis were performed, with an
immediate improvement on the clinical level. No recurrence was noted for both
patients at 5 and 24 months respectively.
MO712 EVALUATION OF VOLUME OVERLOAD STATUS MARKERS IN CONCLUSION: The specificities of our patients compared to the reported cases were
PERITONEAL DIALYSIS PATIENTS the short duration of the PD and the relatively young age. In fact, some studies
demonstrated an increased incidence of EPS in younger patients. In addition, this
Jo~ao Carv~ao1, Adriana Fernandes2, Rita Verıssimo3, Rita Calça3, complication has declared itself despite corticosteroid therapy. Some case reports have
Ana Rita Martins3, Patricia Matias3, Patricia Branco3 demonstrated an increase in the incidence of SEP in kidney transplant patients,
1
Hospital Central do Funchal, Nephrology, Funchal, Portugal, 2Hospital Beatriz Ângelo, suggesting the possible implication of CNIs which have a profibrotic effect and may
Nephrology, Loures, Portugal and 3Hospital Santa Cruz, Centro Hospitalar Lisboa promote peritoneal matrix accumulation.
Ocidental, Nephrology, Carnaxide, Portugal

BACKGROUND AND AIMS: N-terminal fragment of B-type natriuretic peptide


(NT-proBNP) can reflect changes in hydration status and may help the nephrologist to
estimate it. Fluid volume overload is a major concern in dialysis patients, and it is
associated with increased cardiovascular risk and death. This study evaluated the MO714 MEAN PLATELET VOLUME / PLATELET COUNT RATIO IN
relationship between serum NT-proBNP levels and left ventricular (LV) dysfunction PERITONEAL DIALYSIS: ASSOCIATION TO PERITONEAL
and extra-cellular excess water in peritoneal dialysis patients. TRANSPORT STATUS
METHOD: We conducted a cross-sectional study of 60 peritoneal dialysis (PD)
patients. Incident and prevalent patients were included. Echocardiography was Matthias Zeiler1, Antonio Federico1, Tania Monteburini1, Stefano Santarelli1
performed using HDI 5000, allowing M-mode, two-dimensional measurement. A 1
multifrequency bioimpedance (BIA) analyzer was used. Overhydration (OH) was “Carlo Urbani” Hospital, Nephrology and Dialysis Unit, Jesi, Italy
defined as an extra-cellular water (ECW)/total body water (TBW) over 15%. Clinical
and biochemical variables were also analysed. BACKGROUND AND AIMS: Mean platelet volume volume (MPV) is gaining
RESULTS: A total of 60 patients were evaluated (male 60% (n=36), mean age was 55,8 scientific interest with regard to cardiovascular risk stratification. The MPV/platelet
6 15,3 years, BMI 25.9 6 3.9 kg/m2 and 31.7% (n=19) had diabetes mellitus (DM). count ratio seems to be more specific than mean platelet volume alone as a surrogate
Median PD vintage was 21 months, automated PD 30%, 8.3% (n=5) were anuric and parameter for platelet activation. The MPV/platelet ratio might be of interest in
10% (n=6) were overhydrated. The median serum NT-proBNP level was 1071 pg/mL. peritoneal dialysis (PD) as the distribution and integrity of endothelial – platelet
LV mass index and LV ejection fraction were 129.0 6 51.1 g/m2 and 62.8 6 13.0%, interaction in the abdominal space determines its function. The aim of the study was to
respectively. The median excess volume overload was 0.9L. evaluate the associations between MPV/platelet ratio and peritoneal transport status.
Serum NT-proBNP levels correlated positively with, diabetes (r=0.27, p=0.04), METHOD: In 123 PD patients (median age 65 years) MPV and platelet count were
isquemic cardiopathy (r=0.37, p=0.01), LV mass index (r=0.48, p=0.001) and measured together with anthropometric patient data and peritoneal function at
extracellular water (r=0.31, p=0.02) and negatively with LV ejection fraction (r= -0.81, catheter placement and after 6 months during the first peritoneal equilibration test
p=0.01). In a multivariable analysis, in a model adjusted to time in DP, diabetes, (PET). MPV and platelet count were determined with a fully-automated hematological

i406 | Abstracts
Nephrology Dialysis Transplantation Abstracts
analyzer. Correlation analysis was performed. constituted the control group.
RESULTS: The MPV/platelet ratio decreased significantly from 3.99% at placement to RESULTS: In the HD group, 14 patients (46.6%) were PPD positive, and ın the PD
3.50% at the first PET (median values, Wilcoxon test p<0.001). Neither group 16 patients (53.3%) were PPD positive. In the PPD-positive HD patients 64.2%
anthropometric data, nor creatinine clearance, nor BUN clearance, nor Kt/V (renal, (9/14), and in the PPD-positive PD patients 62.4% (10/16) had an induration of 10 mm
peritoneal, total), nor erythrocyte sedimentation rate, nor C reactive protein were or greater. In the control group, 21 of 30 patients (70%) were PPD positive.
associated to MPV/platelet ratio. Only D/P urea and D/P creatinine were significantly Comparison of both HD and PD groups with the control group showed signifcant
correlated to MPV/platelet ratio (D/P urea r=0.223, p=0.01; D/P creatinine r=0.199, diferences in PPD reactivity (p<0.01). Albumin levels were signifcantly high in the
p=0.03). Slow transporters presented a significantly lower MPV/platelet ratio than control groups (p<0.01), and cholesterol levels were signifcantly high in the PD and
average transporters (median values, 3.49% versus 3.83%, Mann-Whitney test p=0.03). the control groups (p<0.05). Transferrin levels were signifcantly high in the PD
CONCLUSION: Peritoneal dialysis is reducing significantly the MPV/platelet ratio. (p<0.01). The lymphocyte counts were signifcantly high in the control group
Differences in MPV/platelet ratio are reflected in the peritoneal transport status at 6 compared to the HD patients (p<0.05). The lymphocyte subset percentages CD19
months after dialysis start. The reduction of the MPV/platelet ratio might respect a were high in the control groups (p<0.05), and CD16/56 was signifcantly high in the
reduced platelet and endothelial activation even in the abdominal space. PD groups (p<0.05). All the parameters were also similar between PPD-positive and -
negative same groups.
CONCLUSION: The prevalence of PPD positivity was lower in the PD and HD
groups. The PPD test responses were not related to the peripheral lymphocyte counts,
subsets and malnutrition parameters.

MO715 PROFILE OF INFECTIVE ENDOCARDITIS IN HEMODIALYSIS


PATIENTS

Samarra Badrouchi1, Hajji Mariem1, Samia Barbouch1, Fethi Ben Hmida1,


Harzallah Amel1, Taieb Ben abdallah1 MO717 EFFECT ON BLOOD PRESSURE OF UNCOMPENSATED 130
1
Charles Nicolle Hospital, Internal medecine A, Tunis, Tunisia MM SODIUM DIALYSATE IN CAPD PATIENT WITH
RESISTANT HYPERTENSION
BACKGROUND AND AIMS: Infectious complications are the second leading cause
Silvio Borrelli1, Mario Bonomini2, Arduino Arduini3, Roberto Palumbo4,
of death in hemodialysis patients. This population is particularly exposed to
Luigi Vecchi5
bacteremia, on the one hand, because of the vascular access necessary for hemodialysis, 1
which is a gateway to the various micro-organisms, and on the other hand, factors of University of Campania “Luigi Vanvitelli”, Nephrology Unit, Napoli, Italy, 2G.
susceptibility to infections. Infective endocarditis (IE) is the cardiac endothelium d’Annunzio University, Section of Nephrology and Dialysis, Chieti, Italy, 3Iperboreal
infection associated with bacteremia. It is a rare complication but its mortality remains Pharma, R&D Department, Pescara, Italy, 4Saint’Eugenio Hospital, Nephrology Unit,
high especially in patients on chronic hemodialysis. Roma, Italy and 5Terni Hospital, Nefrology Section, Terni, Italy
The aim of this study was to determine the microbiological profile, clinical and-
biological profile, characteristics in the ultrasound, therapeutic modalities, and BACKGROUND AND AIMS: In peritoneal dialysis (PD) blood pressure (BP) control
prognosis of IE in hemodialysis. is largely unsatisfied mainly due to sodium retention. Currently, sodium removal in PD
METHOD: This is a retrospective descriptive study of including chronic hemodialysis patients depends substantially on ultrafiltration. Lowering sodium in PD solution
patients, admitted in the Nephrology and Internal Medicine Department A of the might improve sodium removal by diffusion, though the real benefit of low PD
Charles Nicolle Hospital in Tunis for an IE during the period from 1973 to 2018. We solution remains still undetermined.
used the modified Duke criteria to confirm the diagnosis of IE. METHOD: In this case report, we used a novel uncompensated glucose-based PD
RESULTS: Nineteen patients were included, including 12 men and 7 women (gender solution (DextroCore LS, Iperboreal Pharma, Italy) containing 130 mM sodium to
ratio=1.7). The average age was 49.1 years [29-66 years]. Seven of them (37%) were treat resistant hypertension in 78-year-old female treated by CAPD (3 dwells glucose
known to have a valvular disease, two of them had a double mitro-aortic valve 1.5% a day, Na 132).
replacement. Six of them (32%) were diabetic and two patients (11%) were on RESULTS: At baseline, Ambulatory BP monitoring (ABPM) showed 24h-BP (152/81
immunosuppressive therapy. The vascular access initially used for HD were mmHg), diurnal BP (151/83 mmHg) and nocturnal BP (153/75 mmHg), with
arteriovenous fistula in 9 cases (47%), internal jugular catheter in 3 cases (16%), inversion of circadian rhythm in systolic BP (systolic night/day ratio: 1.02), despite the
subclavian catheter in 1 case (5%), Canaud catheter in 3 cases (16%), and 2 patients use of three anti-hypertensive (doxazosin 4mg, amlodipine 10 mg, telmisartan 80 mg)
were dialyzed by femoral catheter (11%). Clinically, all patients had an altered general and diuretic (furosemide 250 mg) at adequate doses. She had no signs of hypervolemia.
condition, fever was present in 14 cases (74%) and a heart murmur in 10 cases (53%). We switched from standard PD (132 mM/L) to low sodium PD solution using 1.5%
Blood cultures were positive in 14 cases (74%). The isolated germs were Staphylococcus glucose bags with sodium concentration of 130 mM. CAPD schedule was confirmed.
Aureus in 8 cases, Staphylococcus epidermidis in 4 cases, Pseudomonas aerogenosa in Second ABPM after six months reported a reduction 24h BP (131/73 mmHg), diurnal
3 cases, Enterobacterium in 1 case, enterococcus faecalis in 1 case, and Klebsielle (134/75 mmHg) and nocturnal BP (122/67 mmHg), with restoring of circadian BP
oxytoca in one patient. On cardiac ultrasound, mitral valve damage was found in 10 rhythm. No change in body weight, UF and residual diuresis was found. Diet and
patients, aortic sigmoid in 4 patients and tricuspid valve in 3 patients. The treatment therapy prescriptions were unmodified. No side effects were reported.
included appropriate antibiotic therapy in all cases and a valvuloplasty was indicated in CONCLUSION: Six-months PD treatment with uncompensated glucose-based PD
7 patients. Nine patients (47%) died during their hospitalization. solution containing 130 mM sodium in all daily dwells has allowed to reduce systolic
CONCLUSION: Hemodialysis patients are particularly exposed to IE. The most BP (-16 mmHg) in a CAPD patient affected by resistant hypertension, with no change
appropriate preventive method is the strict observance of asepsis when handling the in ultrafiltration and residual diuresis.
vascular access first and the rapid eradication of all infectious outbreaks.

MO718 ROLE OF CT-PERITONEOGRAPHY IN THE PATIENT WITH


MO716 THE RELATIONSHIP BETWEEN LYMPHOCYTE SUBSETS, GENITAL EDEMA AND PERITONEAL DIALYSIS
NUTRITIONAL STATUS AND TUBERCULIN REACTIVITY IN
CONTINUOUS AMBULATORY PERITONEL DIALYSIS AND Francisco Javier Centellas Pérez1, Agustin Ortega Cerrato1,
HEMODIALYSIS PATIENTS Juan Pérez Martınez1, Francisco Llamas Fuentes1
1
Hospital General Universitario de Albacete, Albacete, Spain
Mehmet Usta1, Alpaslan Ersoy2, Yavuz Ayar1, Ferrah Budak2
1
University of Health Scienses, Faculty of Medicine, Bursa City Hospital, Nephrology, BACKGROUND AND AIMS: Genital edema is a frequent complication in those
Bursa, Turkey and 2Uludag University, Faculty of Medicine, Nephrology, Bursa, Turkey patients who are on peritoneal dialysis, generally secondary to the increase in intra-
abdominal pressure that it entails. It occurs late after the implantation of the peritoneal
BACKGROUND AND AIMS: Skin test anergy is common in patients with uremia catheter (after 30 days of implantation).
and during maintenance hemodialysis treatment. However, up to date only one study The typical clinical manifestation of this condition is basically subcutaneous edema in
concerning skin test in peritoneal dialysis patients has focused on the issue. Our cross- the genital area, accompanied by pain and UF failure.
sectional controlled study was conducted to analyze the correlation of purifed protein The diagnosis must be made by using an imaging test, mainly CT-peritoneography.
derivative (PPD) test response with demographical features, nutritional parameters METHOD: A series of clinical cases of PD patients who consulted for genital edema is
and the distribution of peripheral blood lymphocyte subsets in peritoneal dialysis and reviewed, analyzing the role of peritoneography
hemodialysis patients. RESULTS: CASE 1
METHOD: Stable 30 hemodialysis (HD) patients (16 men, 14 women) and 30 A 76-year-old male, 15 days after the start of the technique, consulted for right scrotal
continuous ambulatory peritoneal dialysis (PD) patients (17 men, 13 women) were edema. It was decided to suspend CAPD and start hospital intermittent IPD with low
included. Thirty healthy cases (15 men, 15 women) with a mean age of 32.469.4 volumes. A CT-peritoneography was requested, which revealed a right peritoneal-

10.1093/ndt/gfab101 | i407
Abstracts Nephrology Dialysis Transplantation

vaginal duct and a left inguino-scrotal leak. Surgical correction of the anatomical defect coronary artery disease was observed in 58,8%, 29,4% and 15.7% of patients. In our
was performed without incident, with subsequent return of the patient to CAPD. study, 82.35% started on automated PD (APD) and 17,6% on continuous ambulatory
CASE 2 PD (CAPD). The rate of mortality was 53%.
A 78-year-old man, 15 days after the start of the technique, consulted for bilateral Switching modality from PD to hemodialysis occurred in 29,4% of cases. A univariate
scrotal edema. A CT-peritoneography was performed, which showed that the leak of logistic regression identified a coronary artery disease as significantly associated with
peritoneal fluid to the scrotum was due to bilateral inguinal hernia. Subsequently, increased mortality (HR=2,1 [1-2,1, IC 95%](p=0.035)).
inguinal hernioplasty of the surgical defect was performed without complications. CONCLUSION: Elderly patients on dialysis face many issues but can have continued
CONCLUSION: Genital edema, as a complication of patients with CAPD, appears in success with PD when they have adequate care and support. The control of the
approximately 4-10% of them. CT-peritoneography is the diagnostic technique of morbidities such as coronary artery disease is important to decrease the rate of
choice. mortality in patients using this modality of dialysis.
To do this, 150 ml of nonionic iodinated contrast, with a concentration of 300 mg/ml,
are diluted in approximately 2 liters of dialysis solution, which are introduced into the
peritoneal cavity of the patient 2 h before performing the CT.
Subsequently, a CT scan of the abdomen and pelvis including the perineum is
performed, in the supine position and craniocaudal direction.
MO720 SARS-COV2 INFECTION IN THE POPULATION ON
PERITONEAL DIALYSIS

Samarra Badrouchi1, Samia Barbouch1,2, Hajji Mariem1,2, Amira Sakay1,


Rawnak Houli1, Mondher Ounissi1, Imen Gorsane1,2, Fethi Ben Hmida1,2
1
Charles Nicolle Hospital, Departement of Nephrology, Tunis, Tunisia and 2Laboratory
of kidney pathology LR00SP01

BACKGROUND AND AIMS: The novel coronavirus disease 2019 (COVID-19) has
now spread to the entire world as a highly contagious pandemic. The disease has
proved to be more serious in populations with underlying diseases like kidney diseases,
diabetes, or cardiovascular diseases. People with end-stage renal disease are known for
their weakened immune systems and vulnerability to different types of infections.
Recent studies have shown high prevalence and poor prognosis of severe acute
MO718 Figure 1: 3D reconstruction of CT-peritoneography. respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hemodialysis patients,
but its effect on peritoneal dialysis (PD) patients is still unknown.
The aim of this study was to investigate the clinical, biological, and scannographic
particularities and the prognosis of SARS-CoV-2 infection in patients on PD.
METHOD: We conducted a monocentric descriptive study including all the confirmed
cases of SARS-CoV-2 infection in the PD unit of the Nephrology department in
Charles Nicolle Hospital. The first confirmed case was in March 2019 and our study
period ended in January 2021. We used Real-Time Reverse Transcriptase polymerase
chain reaction (RT- PCR) to confirm SARS-CoV-2 infection after nasopharyngeal
MO719 PERITONEAL DIALYSIS IN ELDERLY PATIENTS swabbing.
RESULTS: Eight patients were included: 7 men and 1 woman. The mean age was 40.25
years-old [22-60]. All the patients were hypertensive, 2 of them were diabetics and 3 of
Sonia Achouch1, Samia Barbouch2, Meriam Hajji1, Nadia Cherni1, them had cardiac pathologies: coronary heart disease in 2 patients and atrial fibrillation
Mondher Ounissi3, Imen Gorsane1, Hafedh Hedri4, Rim Goucha2, in the other patient. One patient had history deep vein thrombosis. All the patients
Taieb Ben Abdallah 5, Harzallah Amel 5, Fethi Ben Hmida6 were on automated PD with an average duration of PD of 40.56 months [1-84]. Two of
1
Tunisia, nephrology and research department, tunis, Tunisia, 2Tunisia, nephrology and them had history of peritonitis. Regarding the revealing symptoms of COVID-19, all
research department, Tunisia, 3Tunisian, nephrology and research department, tunis, the patients suffered from asthenia, a deterioration of general condition was observed
Tunisia, 4Tunisia, nephrology and research department, Tunis, Tunisia and 6Tunisia, in 7 patients, dry cough was also present in 7 patients, 4 patients described muscle and
nephrology and research department, tunisia, Tunisia body aches, 3 patients reported diarrhea and vomiting, dyspnea was observed in 2
patients, only one patient reported loss of taste and smell, and fever was present in only
BACKGROUND AND AIMS: Peritoneal Dialysis (PD) is now often being initiated in one case.Two patients had low peripheral oxygen saturation (70% and 88%). All the
older patients. The benefits of this modality of dialysis have been well demonstrated in patients had lymphopenia with an average of 557 [900-280]. C-reactive protein was
the literature. The aim of our study was to analyse the epidemiological and clinical high in 6 patients with an average of 84.7 mg/l. Chest computed tomography (CT) scan
profile of the elderly patients and to determine predictive factors of mortality was practiced in 3 patients, it was positive in all of them with average extent of damage
METHOD: It was a retrospective study including 51 case defined as patients 65-year- of 60%. Four patients were admitted in hospital and one of them in the intensive care
old, treated by PD in the Internal Medicine Department of the Charles Nicolle hospital unit (ICU) for high oxygen needs. All the patients received azithromycin, and vitamin
during the period between 1986 and 2020. C and D and zinc supplementation. A preventive dose of heparin was prescribed in 5
RESULTS: Fifty one patients were enrolled in the study. Their mean age was 71,6 6 patients. No patient required intubation. No patient had thromboembolic
5,4 years [65 - 86]. There were 32 men (62, 7%) and 19 women (37,2%) . The method complications. Six patients fully recovered since more than one month. Regarding the
of initiation was the PD in 53, 84%. Diabetic and vascular nephropathy was the first other two patients we have a follow-up of only one week since the beginning of
cause of End-Stage Renal Disease in 56% and 19,6%. The mean Charlson score was 5,5 symptoms, one of them is pauci-symptomatic and the other one is still admitted in the
6 1,4 [3-9]. The mean age when using PD was 70.8 6 6 years [54-86]. Autonomous ICU.
and active patients were detected in 29.4%. Diabetes mellitus, hypertension and CONCLUSION: According to our findings, patients on PD are not at increased risk
for severe illness from COVID-19 or other adverse outcomes.

i408 | Abstracts
Nephrology Dialysis Transplantation 36 (Supplement 1): i409–i429, 2021
10.1093/ndt/gfab097

MO722 PHOSPHATE-BINDER THERAPY WITH SUCROFERRIC


DIALYSIS. CARDIOVASCULAR COMPLICATIONS OXYHYDROXIDE REDUCES ENDOGENOUS CALCIPROTEIN
PARTICLE FORMATION AND CRYSTALLIZATION IN A POST-
HOC ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL IN
DIALYSIS PATIENTS
MO721 THROMBOTIC EVENTS AFTER COVID-19 INFECTION IN
HEMODIALYSIS PATIENTS*
Ursula Thiem1, Tim D. Hewitson2,3, Nigel D. Toussaint3,4, Maria C. Haller1,5,
1 1 1 Andreas Pasch6,7,8, Daniel Cejka1, Edward Smith3,4
Amir Shabaka , Enrique Gruss , Eugenia Landaluce-Triska , Eduardo Gallego- 1
Valcarce1, Clara Maria Cases Corona1, Javier Ocan ~a1, Ana Tato Ribera1, Ordensklinikum Linz - Elisabethinen Hospital, Department of Medicine III –
pez1, Karina R Furaz-Czerpak2, Gema Maria Fernandez Juarez1
Katia Lo Nephrology, Hypertension, Transplantation, Rheumatology, Geriatrics, Linz, Austria,
2
1 The Royal Melbourne Hospital, Department of Nephrology, Parkville, Victoria, Australia,
Hospital Universitario Fundacion Alcorc
on, Nephrology, Alcorcon, Madrid, Spain and 3
2 The University of Melbourne, Department of Medicine, Melbourne, Australia, 4The
Fundacion Renal I~nigo Alvarez de Toledo, Centro Los Llanos, M
ostoles, Madrid, Spain
Royal Melbourne Hospital, Department of Nephrology, Parkville, Australia, 5Medical
University Vienna, CeMSIIS - Center for Medical Statistics, Informatics, and Intelligent
BACKGROUND AND AIMS: There is an increased risk of thrombotic complications Systems, Vienna, Austria, 6Calciscon AG, Nidau, Switzerland, 7Lindenhofspital Bern,
in patients with COVID-19. Hemodialysis patients are already at an increased risk for Bern, Switzerland and 8Johannes Kepler University Linz, Department of Physiology and
thromboembolic events such as stroke and pulmonary embolism. The aim of our study Pathophysiology, Linz, Austria
was to determine the incidence of late thrombotic complications (deep vein
thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in
BACKGROUND AND AIMS: Calcification propensity of serum can be measured
maintenance hemodialysis patients after recovery from COVID-19.
with the so-called T50-test, which integrates the complex biological interplay of
METHOD: We performed a retrospective cohort study of 200 prevalent hemodialysis
promoters and inhibitors of calciprotein particle formation in blood into a single
patients in our center at the start of the pandemic. We excluded incident patients after
readout. Calcification propensity is associated with the risk for cardiovascular events
the cohort entry date and those who required hemodialysis for acute kidney injury, and
and death in dialysis patients. As we have recently demonstrated in a randomized,
excluded patients with less than 1 month follow-up due to kidney transplantation or
controlled, cross-over study in 39 chronic hemodialysis patients with
death from non-thrombotic causes.
hyperphosphatemia, lowering serum phosphate with high-dose phosphate-binder
RESULTS: 185 prevalent hemodialysis patients finally met the inclusion criteria; 37
therapy with 2000 mg/d of sucroferric oxyhydroxide (SO) over two weeks reduces
patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the
calcification propensity as determined by the T50-test compared to a two-week wash-
acute phase of disease without evidence of thrombotic events. There was an increased
out phase. Based on these results, we hypothesized that SO would influence
risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort
endogenous calciprotein particle (CPP) formation and crystallization, i.e. conversion
(18.5% vs 1.9%, p=0.002) after a median follow-up of 7 months. Stroke incidence was
from primary to secondary CPP.
38.9 episodes/1000 patient-years in patients infected with SARS-CoV-2, compared to
METHOD: To test this hypothesis, we conducted post-hoc analyses of the previously
an incidence of 2.8 episodes/1000 patient-years in non-infected patients during the
reported RCT (74% men, mean age 63627 years, median dialysis vintage 24, IQR 16-
follow-up period. The median time from diagnosis of SARS-CoV-2 to the first
36 months). Native serum CPP levels were measured by a fluorescent probe-based flow
thrombotic event was 62 days (interquartile range 5-118 days). Survival analysis with
cytometric assay. Moreover, hydrodynamic radii (Rh) of secondary CPP formed after
Kaplan-Meier curves revealed an increase in the rate of thrombotic events after SARS-
enrichment with exogenous calcium and phosphate was assessed by three-dimensional
CoV-2 compared to non-infected patients (see Figure 1). Mean survival from
cross-correlation dynamic light scattering.
thrombotic event was 6.160.4 months in the COVID-infected group, compared to
RESULTS: Phosphate-binder therapy with SO lead to a reduction in serum phosphate
6.9760.04 months in the non-infected group (p<0.001). Multivariate regression
levels from 2.2860.5 mmol/l to 1.6360.43 mmol/l (p<0.0001), accompanied by a
analysis showed that COVID-19 infection increased risk for late thrombotic events
significant reduction of endogenous calciprotein particle load and crystallization.
adjusted for age, sex, hypertension, diabetes, antithrombotic treatment and previous
Median (IQR) number of primary CPP decreased from 9.2x105 (7.7x105 - 12x105)
thrombotic events (OR 26.4, 95% CI 2.5-280.6, p=0.01). Clinical and laboratory
particles/ml to 3.8 x105 (2.7x105 - 4.4x105) particles/ml (p<0.0001) and secondary
markers did not predict thrombotic events.
CPP decreased from 5.4x104 (3.6x104 - 7.5x104) particles/ml to 3.2x104 (2.4x104 -
4.2x104) particles/ml (p<0.01, both by Wilcoxon matched-pairs test). Upon SO
therapy we also observed a significant reduction of secondary calciprotein particle size
as determined by Rh compared to phosphate-binder wash-out (214655 nm vs.
231652 nm, p<0.01 by paired t-test).
CONCLUSION: In chronic hemodialysis patients, lowering serum phosphate with SO
is associated with a reduction in the load of primary and secondary CPP and a smaller
size of secondary CPP.

MO723 EFFICACY AND SAFTY OF DAPAGLIFLOZIN FOR HEART


FAILURE: A SYSTEMIC REVIEW

Zhe Wang1
1
The Second Hospital of Tianjin Medical University, Blood purification, Tianjin,
P.R. China

BACKGROUND AND AIMS: Dapagliflozin is an inhibitor of sodium-dependent


glucose transporters 2, which is a new drug for diabetes mellitus. Recent researches
indicated that among patients with heart failure, the risk of worsening heart failure or
death from cardiovascular causes was lower among those who received dapagliflozin
than those who received placebo, regardless of the presence or absence of diabetes. This
systematic review aimed to evaluate efficacy and safety of dapagliflozin for heart failure.
MO721 Figure 1: Kaplan-Meier survival curves for freedom from thrombotic METHOD: According to the collaborative search strategy, MEDLINE(1966-2020.9),
events, stratified by COVID-19 infection status Embase(1974-2020.9), Chinese Wanfang database(1996-2020.9),CNKI(1979-2020.9),
the clinical control test database of Cochrane Library and were searched. Only
randomized controlled trials (RCT) were included in this research. Quality assessment
CONCLUSION: There is an increased risk of late thrombotic complications in and data extraction were conducted by two independent investigators. Meta-analysis
hemodialysis patients after infection with COVID-19. Further studies should evaluate was conducted by Stata 11.0.
the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after RESULTS: A total of 5 RCTs were identified which met the inclusion criteria,
recovery from COVID-19. including 5998 patients. Compared with control group, dapagliflozin was associated
with a lower risk of cardiovascular mortality/hospitalization for heart failure composite
events (HR=0.73, 95%CI 0.640.83, P<0.001), cardiovascular mortality (RR=0.80,
95%CI 0.680.93, P=0.005), hospitalization for heart failure (HR=0.68, 95%CI

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Abstracts Nephrology Dialysis Transplantation

0.580.80, P<0.001), and all-cause mortality (RR=0.80, 95%CI 0.700.92, P=0.002).


Dapagliflozin also increased the Kansas city cardiomyopathy questionnaire (KCCQ),
without increasing the risk of major hypoglycemia, volume depletion, renal adverse
event and amputation.
CONCLUSION: Dapagliflozin could effectively lower the risk of mortality and
hospitalization for heart failure, as well as improve the quality of life among patients
with heart failure.

MO723 Figure 4: Comparison of dapagliflozin versus controls on all-cause mortality

MO723 Figure 1: Comparison of dapagliflozin versus controls on hospitalization


for heart failure or cardiovascular death

MO723 Figure 5: Comparison of dapagliflozin versus controls on serious adverse


events

MO723 Figure 2: Comparison of dapagliflozin versus controls on cardiovascular


death

MO723 Figure 6: Comparison of dapagliflozin versus controls on major


hypoglycemic events
MO723 Figure 3: Comparison of dapagliflozin versus controls on hospitalization
for heart failure

MO723 Figure 7: Comparison of dapagliflozin versus controls on volume depletion

i410 | Abstracts
Nephrology Dialysis Transplantation Abstracts
kidney disease (CKD). However, effective treatment for CAC is lacked at present.
Previous studies have shown that endothelial cells (ECs) participated in vascular
calcification through endothelial-to-osteoblast transition. DAPT, N-[N-(3,5-
difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester, could inhibit the activity
of c-secretase and block the activation of the Notch1 pathway. In this study, we
investigated the function of DAPT in alleviating the CAC process by blocking
endothelial-to-osteoblast transition via inhibition of the Notch1 pathway.
METHOD: We administered 5/6 subtotal nephrectomy and a 10-week high-phosphate
diet (P, 2.0%) to construct a rat model of CKD. DAPT and AAV-129-5p was
administered orally and injected abdominally to rats respectively in the treatment
groups at the beginning of the high-phosphate diet. In vivo, it was performed to detect
the expression levels of EndMT and Notch1 pathway markers in the coronary arteries.
In vitro, the effect of high PTH levels on the endothelial-to-osteoblast transition and
the role of the miR-129-5p/Notch1 signaling pathway were studied in human coronary
artery endothelial cells (HCAECs).
RESULTS: In vivo, endothelial-to-osteoblast transition accompanied with the Notch1
pathway activation was found in HCAECs upon stimulation of PTH, characteristic
MO723 Figure 8: Comparison of dapagliflozin versus controls on acute kidney with up-regulated endothelial markers (CD31, CD34) and down-regulated
injury mesenchymal markers (CD44, CD10, a-SMA, FSP1) and ostoblast markers (Runx2,
Osterix). miR-129-5p was responsible for regulating Notch1; c-secretase was time-
dependently and concentration-dependently activated by PTH, which further affected
the transcription of downstream regulators (HES1, HEY1). DAPT arrested HCAECs
migration through decreasing c-secretase activity, thus inhibiting endothelial-to-
MO724 IS INDIVIDUALIZED DIALYSATE SODIUM REASON FOR osteoblast transition. In vivo data showed that serum c-secretase activity decreased in
BETTER SURVIVAL IN HEMODIALYSIS PATIENTS? rats intraperitoneally injected with DAPT (10mg/kg) once a week after 5/6
nephrectomy. DAPT intervention or overexpression of mir-129-5p inhibited coronary
Natasha Eftimovska-Otovikj1, Natasha Petkovikj2, Olivera Stojceva-Taneva3 endothelial-to-osteoblast transition by blocking the activation of the Notch1 pathway.
1 Notably, DAPT retarded CAC and MI without obvious negative effects on rats heart
General City Hospital 8th September, department of nephrology and dialysis, Skopje, function.
Republic Of North Macedonia, 2General City Hospital 8th September, department of CONCLUSION: DAPT is a promising agent for protecting against PTH-induced
cardiology, Skopje, Republic Of North Macedonia and 3Private dialysis center Diaverum, endothelial-to-osteoblast transition via inhibiting the Notch1 pathway in HCAECs,
dialysis center, Skopje, Republic Of North Macedonia thus alleviating CAC.

BACKGROUND AND AIMS: We are uncertain about whether dialysate sodium


improves overall health and well-being for people on haemodialysis, since there are a
mixture of probably good and bad effects. Dialysate sodium is one of the most easy
changeable parameter which can influence hemodynamic stability, echocardiography
and laboratory parameters. The aim of the study was to investigate whether dialysis
patients will have some beneficial effects of dialysate sodium set up according to serum
sodium.
METHOD: 77 nondiabetic subjects (41men; 36women) performed 12 months
hemodialysis (HD) sessions with dialysate sodium concentration setup at 138 mmol/L,
followed by additional 24 month ssessions wherein dialysate sodium was set up
according to pre-HD serum sodium concentration. Interdialytic weight gain (IDWG),
echocardiography, laboratory parameters and survival were analysed.
RESULTS: Sodium individualization resulted in significantly lower IDWG by using
individualized sodium according to pre HD serum sodium compared to standard
dialysate sodium (2.1760.79 vs 1.9360.64 kg, p<0,001). In all patients we confirmed
positive sodium gradient and univariate regression analysis showed that by increasing
the sodium gradient by 1 mmol/L, IDWG increased by an average of 0.189% and 7,1%
changes in IDWG can be explain by changing of the sodium gradient.
Echocardiography analysis showed an increase of 2.04 mm of left ventricular diastolic
diameter (LVDD) by increasing the sodium gradient for 1mmol/L and significantly
increased left ventricular mass (LVM) of 35.69 gr by 1kg increase of IDWG. Laboratory
analysis showed statistical significant increase in Kt/V, URR (urea reduction rate),
serum albumin and hemoglobin by using individualized dialysed sodium compared to
standard dialysate sodium, respectively (1.5060.24 vs 1.3660.22; 70.8065.24 vs MO726 EFFICACY OF OPHTHALMIC EXAMINATIONS FOR
67.0066.23%; 38.2363.80 vs 34.4662.53 g/L; 120.32610.14 vs 114.62610.34 g/L, PREDICTING VASCULAR CALCIFICATION IN MAINTENANCE
p<0.001). We confirmed significant decrease in serum potassium, with no change in HEMODIALYSIS PATIENTS
other electrolities (5.6260.60vs 5.1560.94). During the study, 7 patients died and
binary logistic regression univariate analysis showed that significant predictors of Woo Yeong Park1, Yaerim Kim1, Jin Hyuk Paek1, Seungyeup Han1, Kyung
mortality in patients dialyzed with individualized sodium dialysis according to pre-HD Tae Kang2, Ji Hye Jang2, Yu Cheol Kim2, Kyubok Jin1
plasma sodium concentrations were Kt/V, URR, and CRP (C reactive protein). 1
Keimyung University School of Medicine, Keimyung University Kidney Institute,
Analysis showed that patients with Kt/V lower than 1,2 have 8.8 times higher risk for
Department of Internal Medicine, Daegu, Korea, Rep. of South and 2Keimyung
death compared to patients with Kt/V>1,2, URR lower than 65% have 10,9 times
University School of Medicine, Department of Ophthalmology, Daegu, Korea, Rep. of
higher risk compared to URR>65% and CRP higher than 10 mg/L have 10.2 times
South
higher risk for death compared to patients with CRP lower than 10 mg/L
CONCLUSION: Individualization of dialysate sodium according to pre HD serum
sodium concentration result in better IDWG control, improvement of fluid overload BACKGROUND AND AIMS: Vascular calcification is a risk factor for cardiovascular
and regression of left ventricular hypertrophy, better dialysis adequacy and higher disease. In maintenance hemodialysis (MHD) patients, it has been reported that
survival compared to standard dialysate sodium. vascular calcification can be detected not only in coronary vessels, but also in ocular
areas. Ophthalmic examinations can be used to more easily measure the degree of
vascular calcification, but they are not sufficiently validated. Therefore, we aimed to
investigate the association between ophthalmic findings and vascular calcification, and
the prediction of the risk of cardiovascular disease in MHD patients.
MO725 DAPT ALLEVIATES CKD-RELATED CAC BY MODULATING
METHOD: Thirty two MHD patients were enrolled. Conjunctival and corneal
PTH-INDUCED ENDOTHELIAL-TO-OSTEOBLAST
calcification (CCC) score was calculated based on the Tokuyama method, and the
TRANSITION VIA NOTCH1 PATHWAY ACTIVATION
severity of CCC was graded between 0 and 5 by Porter and Crombie classification. The
extent of invasion in the corneal limbus and center was identified using anterior ocular
Liting Wang1, Yuxia Zhang1, Rining Tang1
1
CT. Coronary calcium deposit was scored using CT, and cardiac function was
Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine investigated by echocardiogram. We divided the study population into three groups:
mild (0-2 score), moderate (3-5 score) and severe (6-10 score) groups according to
BACKGROUND AND AIMS: Coronary artery calcification (CAC)-induced CCC scores.
myocardial infarction (MI) is an important cause of death in patients with chronic

10.1093/ndt/gfab097 | i411
Abstracts Nephrology Dialysis Transplantation

RESULTS: The mean coronary calcium scoring was 354.6 6 765.8 in the mild group,
768.2 6 594.0 in the moderate group, and 4034.9 6 2981.0 (P<0.001). The mean
extent of invasion in the corneal limbus and center was significantly higher in the
severe group than in the mild and moderate groups (P<0.001). Ejection fraction and
corrected calcium*phosphate were significantly higher in the severe group than in the
mild and moderate groups (P<0.001 and P=0.036). The CCC score was positively
associated with the coronary calcium scoring, the extent of invasion in the corneal
limbus and center, and parathyroid hormone level. The extent of invasion in the
corneal limbus and center was also positively associated with the coronary calcium
scoring. The CCC score was only negatively associated with ejection fraction.
CONCLUSION: Our study showed that CCC score and the extent of invasion in the
corneal limbus and center can predict the risk of cardiovascular disease in MHD
patients.

MO727 EFFECT OF SACUBITRIL/VALSARTAN ON SERUM


POTASSIUM AND BLOOD PRESSURE LEVELS OF DIALYSIS
PATIENTS WITH HEART FAILURE

Renee Mari Gula1, Marichel Coronel1, Russel Villanueva1,2,3


1
National Kidney and Transplant Institute, Adult Nephrology, Quezon City, Philippines,
The, 2Philippine General Hospital, Adult Nephrology, Manila, Philippines, The and
3
Manila Doctors Hospital, Manila

BACKGROUND AND AIMS: Heart failure is a frequent complication in patients


with chronic kidney disease (CKD). As the kidney function declines, the incidence of
heart failure and all-cause mortality increases. Heart failure is treated based on the
ejection fraction and most of the treatments are often dependent on the renal function.
The treatment guidelines of heart failure are not entirely applicable to those with CKD,
since this population is usually not included in the randomized control trials.
The introduction of neprilysin-inhibitor changed the paradigm of heart failure with
reduced ejection fraction (HFrEF) treatment but the effects on dialysis patients is still
under studied. Sacubitril/Valsartan is an ARNI that has been recommended as a
treatment for symptomatic HFrEF. Monitoring of renal function and potassium is
recommended for patients who will take Sacubitril/Valsartan and the two most
common side effects are hyperkalemia and hypotension.
This study evaluated the safety of Sacubitril/Valsartan by assessing the incidence of
hyperkalemia and hypotension on patients undergoing maintenance dialysis -
peritoneal or hemodialysis. The objective of the study was to compare the effect of
losartan against sacubitril/valsartan on the systolic blood pressure (SBP), diastolic
blood pressure (DBP), and serum potassium level across three time points (1st, 2nd,
and 3rd month follow-up).
METHOD: This retrospective, cohort, single-center study of dialysis patients with
HFrEF is designed to assess the safety of Sacubitril/Valsartan versus Losartan based on
the blood pressure and serum potassium level. A total of 96 patients on dialysis
diagnosed with HFrEF was included in the study. Half was prescribed with Sacubitril/
Valsartan while half was prescribed with Losartan. Serum potassium, systolic and
diastolic blood pressure were recorded at baseline and monthly on the first three
months of follow-up. Baseline 2d echocardiography was also reviewed.
RESULTS: There were 96 chronic kidney disease patients with HF; 48 were on
peritoneal dialysis and 48 on hemodialysis. Per group, 24 were given Losartan and 24
were given Sacubitril/Valsartan for 3 months. The mean age was 47.5 (15.5) years and
ranges from 19 to 78 years old. Sixty two percent were males. The most common
diagnosis were glomerulonephritis (36.5%), hypertensive nephrosclerosis (27.1%) and
diabetic nephropathy (26%).
In this retrospective study, we found that there were no episodes of hypotension and
hyperkalemia on both hemodialysis and peritoneal dialysis patients who were
prescribed with Sacubitril/Valsartan. All the hemodialysis patients included in this
study were maintained on thrice a week hemodialysis sessions and the peritoneal
dialysis patients had at least 3 exchanges per day.
There were no significant change at three points in time (1st, 2nd, and 3rd month
follow-up) in the levels of systolic blood pressure (p-value= 0.780, 0.609, 0.926),
diastolic blood pressure (p-value= 0.692, 0.206, 0.527), and serum potassium (p-value=
0.212, 0.084, 0.095) on patients maintained on Sacubitril/Valsartan compared to
Losartan. There was no evidence of hyperkalemia or hypotension on dialysis patients
taking both medications.
CONCLUSION: Sacubitril/Valsartan is recommended in the therapy for HFrEF
because of the documented benefits in the non-CKD and non-dialysis CKD patients. In
this study, Sacubitril/Valsartan is well tolerated and has same effect on the serum
potassium and blood pressure compared to Losartan. We concluded that there was no
episode of hyperkalemia and hypotension on dialysis patients taking both medications.
For the first time, this study demonstrated that Sacubitril/Valsartan is safe to be used in
dialysis patients.

i412 | Abstracts
Nephrology Dialysis Transplantation Abstracts

MO728 Figure 1: Schematic of optical coherence tomography angiography (OCTA)


metrics.

MO728 OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY (OCT-


A) METRICS PREDICT INTRADIALYTIC HYPOTENSION
EPISODES IN CHRONIC HEMODIALYSIS PATIENTS: A PILOT,
PROSPECTIVE STUDY

Giuseppe Coppolino1, Adriano Carnevali2, Valentina Gatti2, Caterina Battaglia2,


Giorgio Randazzo2, Irma Figlia1, Gemma Patella1, Giuseppe Giannaccare2,
Vincenzo Scorcia2, Michele Andreucci1, Davide Bolignano1
1
University Magna Graecia of Catanzaro, Renal Unit, Catanzaro, Italy and 2University
Magna Graecia of Catanzaro, Department of Ophtalmology, Catanzaro, Italy

BACKGROUND AND AIMS: In chronic hemodialysis (HD) patients, intradialytic


hypotension (IDH) is a complication that increases mortality risk. The pathogenesis of
this condition remains partly unexplained although dysfunctions of the nervous
autonomous system and various factors related to the hemodialytic procedure like
rapid or excessive ultrafiltration, excessive reduction in osmolality and reaction to the
dialyzer membrane or machine tubing, seem to play a key role. The observation of
ocular microcirculation gives us an exceptional chance to directly evaluate in vivo the
reactions of human circulation to stress stimuli. Indeed, the ocular microcirculation is
involved in systemic disease and early changes in vascular structures may predict the
development of systemic vascular disorders. We run a pilot study to analyzing possible
relationships between optical coherence tomography angiography (OCT-A) metrics CONCLUSION: In our study, we demonstrated that HD patients experiencing
and IDH and to evaluate whether OCT-A could represent a useful tool to stratify the frequent IDH episodes showed a different ocular pattern with respect to those not
hypotensive risk in dialysis patients. facing with this complication. Furthermore, a simple measurement of retinal and
METHOD: a total of 35 eyes (35 patients) being correctly analyzed. OCT-A was choroid parameters by OCT-A before a single dialysis session may help predicting the
performed before and after a single dialysis session. Patients were then followed up to risk of following IDH in the short-term. In HD patients, a single OCT-A measurement
30 days (10 HD sessions) and a total of 73 IDHs were recorded with 12 patients (60%) may represent a non-invasive, rapid tool to evaluate the compliance of vascular bed to
experiencing at least one IDH. HD stress and to stratify the risk of IDH in the short term.
RESULTS: Central choroid thickness (CCT), 6x6 mm whole vessel density (VD) of
superficial capillary plexus (SPC) and 6x6 mm foveal VD of deep capillary plexus
(DCP) were reduced after dialysis (Figure 1). At logistic regression analysis, IDH was
positively associated with baseline foveal VD of SCP and DCP, while an inverse
association was found with the choroid (Figure 2). In Kaplan-Meier analyses of
patients categorized according to the ROC-derived optimal thresholds, CCT, the 3x3
foveal VD of SCP, the 3x3 mm and 6x6 mm foveal VD of DCP and the 6x6 mm
foveal VD of SCP were strongly associated with a higher risk of IDH over the 30-days
follow-up.

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Abstracts Nephrology Dialysis Transplantation

MO729 LUNG ULTRASOUND GUIDED DRY-WEIGHT REDUCTION RESULTS: From 2 dialysis centres, a total of 46 HD patients were enrolled in the study
DECREASES CARDIAC CHAMBERS DIMENSIONS AND (65.2% male, mean age 71 6 12.6 years, mean dialysis vintage 4 6 3.9 years), which
IMPROVES VENTRICULAR DIASTOLIC FUNCTION IN resulted in 89 dialysis sessions to analyse. Mean systolic BP after start of dialysis was
HEMODIALYSIS PATIENTS: LONG-TERM ANALYSIS OF A 133.2 6 20.7 mmHg and mean UF volume was 1817.5 6 801.5 mL. 23 sessions showed
LUST SUB-STUDY a hypotensive gradient from the start till the end of dialysis, and 13 sessions progressed
with an increase of more than 10 mmHg. When the 8 kHz curve was plotted according
Charalampos Loutradis1, Christodoulos Papadopoulos2, Vassilios Sachpekidis3, to the 3 BP groups, a more plane increase in thoracic bioimpedance signal was
Robert Ekart4, Barbara Krunic5, Dorothea Papadopoulou6, Aikaterini Papagianni1, observed in the group with a normal tension course (Figure 1).
Francesca Mallamaci7, Carmine Zoccali7, Pantelis Sarafidis1
1
Hippokration Hospital, Aristotle University of Thessaloniki, Department of Nephrology,
Thessaloniki, Greece, 2Hippokration Hospital, Aristotle University of Thessaloniki, 3rd
Department of Cardiology, Thessaloniki, Greece, 3Papageorgiou Hospital, Department
of Cardiology, Thessaloniki, Greece, 4University Clinical Centre Maribor, Clinic for
Internal Medicine, Department of Dialysis, Maribor, Slovenia, 5University Clinical Centre
Maribor, Clinic for Internal Medicine, Department of Cardiology, Maribor, Slovenia,
6
Papageorgiou Hospital, Department of Nephrology, Thessaloniki, Greece and 7CNR-IFC
Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Calabria, Italy

BACKGROUND AND AIMS: Left ventricular hypertrophy (LVH) and dysfunction


are highly prevalent in hemodialysis patients and independently associated with
adverse outcomes. Few interventions were shown to effectively reduce LVH in
hemodialysis. This study examines the long-term effects of dry-weight reduction with a
standardized lung-ultrasound-guided strategy on echocardiographic indices of left and
right cardiac chambers in hemodialysis patients.
METHOD: This is the report of the 12-month trial phase of a randomized controlled
trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were MO730 Figure 1: 8 kHz curve for 3 blood pressure groups
randomized (1:1 ratio) in the active group (23 male and 12 female), following dry-
weight reduction guided by the total number of US-B lines prior to a mid-week dialysis There was a significant relationship between UFR and changes in relative
session and the control group (24 male and 12 female), following standard-of-care bioimpedance data, as well as thoracic (r = .49 at 8 kHz, r = .46 at 160 kHz, all ps <
treatment. Among several assessments, participants underwent two-dimensional and .001), as whole body bioimpedance (r = .58 at 5 kHz, r = .52 at 200 kHz, all ps < .001).
tissue-Doppler echocardiographic (TDI) at baseline and study-end. UFV correlated with changes in systolic BP (r = -.31, p < .01). Both bioimpedance
RESULTS: During follow-up dry-weight reduction took place in more patients in the techniques correlated with each other (r = .38, p = .001 for low frequencies; r = .29, p <
active compared with the control group (71.4% vs 22.2%; p<0.001). Left atrial (LA) .01 for high frequencies). Where the relative thoracic bioimpedance signal correlated
surface (-1.3764.50 vs 1.2865.00 cm2; P=0.006) and LA volume index (-3.22611.82 with changes in systolic BP (r = -.35 at 8kHz, -.32 at 160 kHz, all ps < .01) (Figure 2),
vs 4.76612.83 ml/m2; P=0.009) decreased in the active and increased in the usual-care whole body did not.
group. Left ventricle (LV) diastolic (-0.94611.45 vs 6.58613.92 ml/m2; P=0.015) and
systolic (-0.8967.11 vs 3.3867.89 ml/m2; P=0.018) volume index decreased only in the
active group. LV mass index slightly decreased in the active (134.21644.75 vs
133.57645.51; P=0.844) and was marginally increased in the control group
(134.21640.96 vs 143.77650.04 g/m2; P=0.089). Right ventricular (RV) systolic
pressure was stable in the active (23.74613.76 vs 24.35612.99; P= 0.795) and
significantly increased in the usual-care group (26.24612.95 vs 31.20616.13 mmHg;
P=0.028). Reductions in LV A wave were greater in the active compared to the usual-
care group (-4.98615.11 vs 2.23621.71 m/s; P=0.009). Changes in LV systolic and RV
diastolic function indices were not different between the two groups.
CONCLUSION: Over 12 months, a lung-ultrasound-guided strategy for dry-weight
reduction can effectively decrease cardiac chamber dimensions, prevent LVMi increase
and improve LV diastolic and RV systolic function.

MO730 THORACIC BIOIMPEDANCE AS AN INNOVATIVE TOOL TO


DETECT CHANGES IN BLOOD PRESSURE DURING MO730 Figure 2: Thoracic bioimpedance at 8 kHz and blood pressure data per time
HEMODIALYSIS frame of 10 minutes

Melanie Schoutteten1, Lucas Lindeboom2, Christophe Smeets 3, Bart De Moor4,


Jacques Peeters5, Chris Van Hoof6, Willemijn Groenendaal 7, Pieter Vandervoort8, CONCLUSION: Thoracic bioimpedance is associated with intradialytic BP changes,
Jeroen Kooman9 whereas whole body bioimpedance is not. Thoracic bioimpedance has the potential to
1
UHasselt, Faculty of Medicine and Life Sciences, LCRC, Diepenbeek, Belgium, 2imec The function as an important diagnostic and predictive tool in BP variability during HD.
Netherlands/Holst Centre, Connected Health Solutions Department, Eindhoven, The
Netherlands, 4Jessa Ziekenhuis, Nephrology, Hasselt, Belgium, 5Ziekenhuis Oost-
Limburg, Nephrology, Genk, Belgium, 6Imec Belgium, Leuven, Belgium, 8Ziekenhuis
Oost-Limburg, Cardiology, Genk, Belgium and 9Academic Hospital Maastricht, MO731 ASSOCIATION BETWEEN SKELETAL MUSCLE MASS AND
Nephrology, Maastricht, The Netherlands INTRADIALYTIC HYPOTENSION IN PATIENTS UNDERGOING
MAINTENANCE HEMODIALYSIS
BACKGROUND AND AIMS: Blood pressure (BP) variability is an important
cardiovascular risk factor that contributes to the high burden of cardiovascular Hyung Eun Son1, Eunji Baek1, Ji Young Ryu1, Sejoong Kim1, Ho Jun Chin1,
mortality in hemodialysis (HD) patients. Ultrafiltration rate (UFR) and plasma refill Ki Young Na1, Dong-Wan Chae1, Jong Chul Cheong1
rate modify the extracellular volume (ECV), which is a major determinant of the 1
Seoul National University Bundang Hospital, Nephrology, Seongnam-si, Korea, Rep. of
systolic BP. Segmental bioimpedance of the thoracic region addresses the central South
volume compartment of the body. We hypothesize that changes in bioimpedance
reflect changes in BP and that thoracic measurements are more accurately in detecting BACKGROUND AND AIMS: Patients undergoing hemodialysis showed higher
intradialytic BP changes compared to whole body bioimpedance. prevalence of sarcopenia than that of the healthy. As an intracellular water reservoir,
METHOD: During two consecutive short-term interval HD sessions, thoracic skeletal muscle mass would be important to predict intradialytic hypotension. This
bioimpedance signal was registered continuously from predialysis until the end of the study was designed to reveal the effect of skeletal muscle mass to intradialytic
session. Corresponding BP, whole body bioimpedance and ultrafiltration volume hypotension, which is also an indicator of volume status in patients under
(UFV) after the start and at the end of dialysis was registered. After outlier detection, hemodialysis.
valid raw bioimpedance data [Ohm] at 8 and 160 kHz for thoracic measurements, and METHOD: 150 patients from three hemodialysis centers in 2016 and 38 patients from
5 and 200 kHz for whole body measurements, were taken into further analysis. Dialysis one center under maintenance hemodialysis in 2020 were enrolled in this study, and
sessions were divided into 3 groups according to the development of the systolic BP: a total 177 patients were finally analyzed. We measured skeletal muscle mass,
drop  than 20 mmHg was defined as a hypotensive session, an increase  10 mmHg intracellular water, extracellular water, total body water and phase angle in 50 kHz by
was considered as a hypertensive session. Pearson correlation analysis was applied bio-impedance analysis just after a hemodialysis session. Information including
(r, p-value) to the relative data, calculated as a percentage from the start value. laboratory tests, chest x-ray, handgrip strength, mid-arm circumference and

i414 | Abstracts
Nephrology Dialysis Transplantation Abstracts
questionnaire to ask the patients’ general condition was collected. Intradialytic
hypotension over three months was observed. We analyzed several factors including
skeletal muscle mass which would have association with intradialytic hypotension over
three months by multivariate logistic regression model.
RESULTS: Tertile subgroups divided by the ratio of skeletal muscle to body weight
defined as skeletal muscle index were compared. Patients in low skeletal muscle index
had a higher rate of intradialytic hypotension (41%) while that of intermediate group
was 20% and high group was 5%. Patients in low skeletal muscle mass index group was
female-dominant, more obese, more diabetic and had lower handgrip strength than
higher skeletal muscle index group. In patients who had higher skeletal muscle mass to
body weight, the risk of Intradialytic hypotension was decreased (HR: 0.80 [95% CI
0.75-0.88], adjusted HR: 0.73 [95% CI 0.64–0.84]). Comparing tertile groups by skeletal
muscle index, patients in the group of higher skeletal muscle mass index showed lower
rate of intradialytic hypotension during hemodialysis, which was similar in inverse
probability of treatment weighted analysis. Confounders were age, gender, diabetes
mellitus, heart failure, ischemic heart disease, the ratio of ultrafiltration amount to
body weight and skeletal muscle index. Model including skeletal muscle index and
clinical parameters showed highest AUC area (0.877 [95% 0.823-0.930]) when the
model including clinical parameters only (AUC area: 0.807 [95% CI 0.735-0.879]) or
with each bioimpedance index (skeletal muscle mass to squared height, AUC area:
0.843 [95% CI 0.823-0.931]; the ratio of extracellular water to total water, AUC area:
0.809 [95% CI 0.736-0.883]; the ratio of intracellular water to total water, AUC area:
0.811 [95% CI 0.738-0.885] and phase angle, AUC area: 0.812 [95% CI 0.738-0.886]).
CONCLUSION: This study showed correlation between skeletal muscle mass by body MO731 Figure 3: Coefficient plot of variables including skeletal muscle to weight
weight and intradialytic hypotension. It especially suggested that skeletal muscle mass and clinical parameters in multivariate logistic regression model to explain intradialytic
to weight would be a good predictor of intradialytic hypotension and would be helpful hypotension
to decide appropriate dry body weight in hemodialysis.

MO732 HD-PATIENTS WITH ATRIAL FIBRILLATION TREATED


ADEQUATELY AND SAFE WITH DOAC BY INDIVIDUAL
DOSING USING ROUTINE ANTI-XA DRUG-EFFECT
MONITORING: LONG-TERM CLINICAL PRACTICE DATA

Karl August Brensing1, Peter Raab1, Peter Heidkamp1, Uwe Pöge1


1
Nierenzentrum Bonn, Dialysis Unit, Bonn, Germany

BACKGROUND AND AIMS: Hemodialysis (HD) patients (Pts) with nonvalvular


atrial fibrillation (AF) on anti-vitamin-K oral anticoagulation (VK-OAC) are at high
risk for cardio-vascular events, major bleeding and rapid vascular/valvular calcification.
Thus, current VK-OAC is debated since prospective studies are missing, but all direct
oral anticoagulation drugs (DOACs) are not labeled for ESRD. We studied the clinical
feasibility of long-term DOAC treatment in HD-pts using individual dosing by regular
anticoagulant drug-effect monitoring.
METHOD: We analysed 9 HD-patients with AF (median age 77 yrs; range=R: 59-86; 7
Male) on DOAC therapy for at least 6 months (n=1 rivaroxaban=Riva, n=8
apixaban=Apix) initiated by cardiologist with patients informed consent with lower
dose as in CKD-4 under regular (weekly) anti-Xa drug-effect monitoring (prior HD)
MO731 Figure 1: Study enrollment
using available routine laboratory test validated for low-molecular heparin: Target
trough range (12-24h after drug) was 0.1-1.0 U/ml (=prophylactic to therapeutic anti-
Xa levels; test range <0.1, >1.6 U/ml). Bleeding caused drug stop/reduction until anti-
Xa control.
RESULTS: Median study time was 14 months (R: 6-24). We analysed 310 anti-Xa
levels on Apix and 83 levels on Riva. After dose adjustment finally 2 Apix-Pts (22%)
received full CKD-4 dose (35 mg/week=wk) and 7 patients (78%) had median dose of
10 mg/wk (10-27 mg; 6x Apix) or 40 mg/wk Riva, i.e. 29% and 38% of usual CKD-4
dose. Two Pts with higher dose had clinical reasons: short-bowl-syndrome (less
resorption) or high grade (3-4) left atrial sludge (therapeutic goal). Overall, median
anti-Xa level was 0.47 U/ml (R: <0.1->1.6) and 80% were in center-accepted targets:
0.1-1.2 U/ml. Lower dose Pts had higher in-target-rate (83%) than the 2 high dose Pts
(70%) by more exceeding the upper limit.
During our study we saw no cerebral/systemic thrombo-embolic event or major
bleeding, but 2 pts had epistaxis (need out-patient intervention), 1x persistent
macrohematuria (need catheterization) and 3 pts. had multiple subcutaneous
hematoma, none needed event-related transfusion. We saw two non-cardiovascular
deaths (22%; 2/9): 1x pneumonic sepsis, 1x advanced cancer.
CONCLUSION: We provide new clinical feasibility data on long-term DOACs
therapy in HD-patients. Since DOACs are not labelled for ESRD we recommend strict
indication plus regular anti-Xa drug-effect monitoring for adequate individual dosing.
Our data support initial doses as for CKD-4 but applied only on HD-free days (4x/wk;
=57% of usual) and adjustment in steady-state (1-2 wks): final individual doses were
increased up to 100% in some patients, but mostly were reduced to 30-40% of usual
CKD-4 doses. Overall, this individual dosing approach for DOACs provided adequate
MO731 Figure 2: ROC curves of multivariate logistic models including clinical
anti-Xa levels to prevent thrombo-embolic as well as major bleeding events. This initial
indexes plus each parameter such as skeletal muscle to weight (Model 1), skeletal
data need to be confirmed in larger studies to improve evidence-based management of
muscle to height2 (Model 2), extracellular water to total body water (ECW/TBW)
HD-patients with nonvalvular AF.
(Model 3), intracellular water to total body water (ICW/TBW) (Model 4) or phase
angle (Model 5), and only clinical parameters* (Model 6).
*Clinical parameters: age, gender, cardiovascular comorbidities (congestive heart
failure and ischemic heart disease), diabetic neuropathy, cardiac index, and the amount
of Ultrafiltration per weight

10.1093/ndt/gfab097 | i415
Abstracts Nephrology Dialysis Transplantation

MO733 RISK FACTORS FOR INFECTIVE ENDOCARDITIS IN


PATIENTS RECEIVING HAEMODIALYSIS- A PROPENSITY MO733 Table 2: Logistic regression analysis to identify the risk factors predictive
MATCHED COHORT STUDY of infective endocarditis

Saif Al-Chalabi1, Tricia Tay1, Rajkumar Chinnadurai1, Philip A. Kalra1


1
Salford Royal NHS Foundation Trust, Department of Renal Medicine, Salford, United
Kingdom

BACKGROUND AND AIMS: Infective endocarditis (IE) is a serious infective


complication that usually results in prolonged hospitalisation and is associated with
high morbidity and mortality. It is sometimes difficult to promptly diagnose infective
endocarditis when a patient receiving hemodialysis presents with signs and symptoms
of bacteremia, a delay which can lead to worse outcomes. In this study, we aimed to
identify the risk factors that can predict infective endocarditis in haemodialysis patients
with bacteremia.
METHOD: This retrospective observational study was conducted on all patients
diagnosed with infective endocarditis (IE) and receiving maintenance hemodialysis
between 2005 and 2018 in Salford Royal Hospital and its satellite dialysis units
(catchment population of 1.5 million). The IE patients were propensity score matched
in a 1:2 ratio with similar hemodialysis patients without IE but with bacteremia
between 2011 and 2015. Propensity scores were generated by using binary logistic
regression analysis incorporating age, gender, diabetes status, and dialysis vintage as
variables. Logistic regression analysis was used to predict the risk factors associated
with developing IE. Statistics were performed using SPSS version-24.
RESULTS: We had a sample of 105 patients (35 IE vs 70 bacteremia). The median age
of the patients was 65 years with a predominance of males (60%). 43% were diabetic,
11.5% were receiving immunosuppression and 72% had a catheter for dialysis access.
IE patients had higher peak C-reactive protein (CRP) during admission compared to
patients with bacteremia and no IE (253 mg/l vs 152 mg/l, p=0.001). Patients who MRSA- Methicillin resistant Staph.Aureus status, OR-odds ratio, CI-confi-
developed IE had a longer duration of dialysis catheter use than the bacteremia group
(150 vs 19 days; p<0.001) (table 1). There was no significant difference between dence interval
causative microorganisms in both groups. Staphylococcus aureus caused most cases
(54% in IE and 47% in bacteremia). Our study showed clearly that patients who had IE
had longer hospital stay (45 vs 18 days, p=0.001) with a far higher 30-day mortality rate
(54.3% vs 17.1%, p<0.001). Logistic regression analysis showed previous valvular heart
diseases (OR: 20.1; p<0.001), a higher peak CRP (OR:1.01; p=0.001), and a longer
duration of catheter use (OR: 1.01; p=0.035) as significant predictors for infective MO734 CONTRIBUTION OF SOLUBLE ST2 TO THE EFFECT OF
endocarditis (table 2). RIGHT VENTRICULAR DYSFUNCTION ON MORTALITY IN
CONCLUSION: Bacteremia in patients receiving hemodialysis through a catheter as HEMODIALYSIS PATIENTS
access should be actively investigated with a high index of suspicion for IE particularly
those having valvular heart diseases, hypertension, higher peak CRP, and those with a Gregorio Romero-Gonza lez1,2, Susanna Ravassa2, Agnes Diaz-Dorronsoro3,
longer duration of dialysis catheter usage. Work up may need to include invasive Ana De la Fuente4, Nuria Garcia-Fernandez5, Miguel A. Rojas5, Ignacio Lorenzo5,
investigations such as transesophageal echocardiogram to confirm or reliably rule out Isabel Garcıa-Trigo5, Francisco M Mateo-De Castro5, Begon ~a Lopez2,
this devastating condition. Arantxa Gonza lez2, Javier Diez2,3,5
1
Complejo Hospitalario de Navarra, Nephrology, Pamplona, Spain, 2Centre for Applied
MO733 Table 1: Baseline characteristics and outcomes comparing bacteraemia Medical Research - University of Navarra, Program of Cardiovascular Disease,
and infective endocarditis Pamplona, Spain, 3Clinica Universidad de Navarra, Cardiology, Pamplona, Spain,
4
Clınica Universidad de Navarra, Cardiology, Madrid, Spain and 5Clinica Universidad de
Navarra, Nephrology, Pamplona, Spain

BACKGROUND AND AIMS: Right ventricular dysfunction (RVD) has been shown
to predict mortality in patients with kidney failure. It has been proposed that RVD in
these patients is mediated by inflammatory and fibrotic mechanisms, which may be
enhanced by hemodialysis (HD). The present study aimed to investigate the potential
associations between RVD and circulating biomarkers of myocardial inflammation and
fibrosis with all-cause mortality in HD patients.
METHOD: We performed a retrospective single-centre cohort study of prevalent
patients admitted in a chronic HD program for more than 3 months. Clinical
characteristics and echocardiographic parameters were assessed in all patients. Pre-
dialysis blood samples for measurement of inflammatory (e.g., C reactive protein,
interleukin-1, interleukin-18) and fibrotic (e.g., soluble suppression of tumorigenesis-2
[sST2], galectin-3, C-terminal pro-peptide of procollagen type I and N-terminal pro-
peptide of procollagen type III) biomarkers were collected. Right ventricular
dysfunction (RVD) was defined using tricuspid annular plane systolic excursion
(TAPSE) <1.7 cm or pulsed Doppler peak annular velocity (S) <9.5 cm/s. The ability
of sST2 to discriminate between mortality was assessed using AuROC curve.
RESULTS: We enrolled 48 patients (mean age 74 [64–79] years, 62.5% males) followed
over a period of 1.4 years. Mortality was higher 45.5% (log-rank, p=0.003) in patients
with RVD as diagnosed by S’ than in patients without RVD. No difference in mortality
was observed for RVD defined by TAPSE. There were no differences in the
morphology and function parameters of the left ventricle between patients with and
Continuous variables are presented as Median (Inter Quartile Range), p- without RVD. From all biomarkers measured only sST2 was associated with RVD.
Value by Mann-Whitney U test. Indeed, an age- and sex-adjusted analyses showed that doubling of sST2 was inversely
associated with a decreased in S(estimate=-2.03, 95% CI [-3.04 to -1.00] cm/s;
Categorical variables presented as number (Percentage), p-Value by P=0.002). Mortality was increased in patients with sST2 40.45 ng/mL compared to
Chi-Square test patients with sST2 <40.45 ng/mL (66.7% vs. 18.9%, log-rank; p=0.004). Crude analysis
MRSA- Methicillin resistant Staph.Aureus status, OR-odds ratio, CI-confi- showed that patients presenting with S’ <9.5 cm/s and sST2 40.45 ng/mL exhibited
higher mortality (log-rank; p=0.001) than patients with S’ >9.5 cm/s and sST2
dence interval <40.45pg/mL.

i416 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Albeit preliminary these findings suggest that an excess of sST2 may remains elusive. We sought to investigate the clinical utility of SudocanV R , a device that

be involved in RVD and on its effect on mortality in HD patients. The myocardial pro- quantify dysautonomia, in the prediction of IDH.
remodeling effect of sST2 among HD patients with RVD warrants further METHOD: We conducted a prospective monocentric study in adult HD patients from
investigation. July 2019 to February 2020. Dysautonomia was assessed by the measurements of hand
and foot Electrochemical Skin Conductance (ESC) by SudocanV R , before and after the

end of HD. A pathological hand ESC was defined by an ESC value < 40 ls in
Caucasian or < 30 ls in afro-American and Caribbean patients, and a pathological foot
MO735 INTERPLAY BETWEEN GDF-15 AND LEFT VENTRICULAR ESC by a value < 50 ls in Caucasian or < 30 ls in afro-American and Caribbean
HYPERTROPHY IN END-STAGE RENAL DISEASE PATIENTS patients.
ON DIALYSIS Arterial blood pressure (BP) was monitored before, every thirty minutes and after the
end of the HD session. The primary end point was the incidence of IDH, according to
Susana Coimbra1,2, Cristina Catarino2, Maria do Sameiro Faria2,3, the NKD/K-DOQI definition, during the 3 month-period study.
José Pedro Lopes Nunes4,5, Susana Rocha6, Maria Joa ~o Valente2, RESULTS: A total of 176 HD patients (64 614 years old) were enrolled. Mean pre-
Petronila Rocha-Pereira2,7, Elsa Bronze-da-Rocha2, Nuno Bettencourt3, dialysis hand and foot ESC were 45620 lS and 54622 lS, respectively. Thirty-five and
Ana Beco3, Sofia Homem Melo Marques3, José Gerardo Oliveira8,9, 40% of patients had a pathological ESC at the hand and foot, respectively. Forty-Six
José Madureira10, Vasco M.P. Miranda11, Luıs Belo2, Alice Santos-Silva2 IDH occurred during the study period. Logistic regression showed that a pathological
1 hand ESC was associated with an increased risk of IDH [OR=0.39, IC95% (0.15-0.97),
Instituto de Investigaç~
ao e Formaç~ao Avançada em Ci^encias e Tecnologias da Sa ude
p= 0.04]. The cumulative risk incidence of IHD during the study was 2.17 [IC95%
(IINFACTS), Cooperativa de Ensino Superior Politécnico e Universit ario (CESPU), Gandra,
2 (1.21-3.89), p= 0.01] and 1.89 [IC95% (1.06-2.38), p= 0.03], with a pathological hand
Paredes, Portugal, UCIBIO, REQUIMTE, Laborat orio de Bioquımica, Departamento de
and foot ESC, respectively.
Ci^encias Biol
ogicas, Faculdade de Farm acia da Universidade do Porto, Porto, Portugal,
3 CONCLUSION: A pathological hand ESC, as assessed by a simple, non-invasive test,
Clınica de Hemodi alise de Felgueiras, Felgueiras, Portugal, 4Departamento de
such as SudoscanV R , is associated with an increased risk of IDH.
Cardiologia, Centro Hospitalar Universit ario de S~
ao Jo~ao, Porto, Portugal,
5
Departamento de Medicina, Faculdade de Medicina da Universidade do Porto, Porto,
6
Portugal, LAQV, REQUIMTE, Laborat orio de Quımica Aplicada, Departamento de
Ci^encias Quımicas, Faculdade de Farm acia da Universidade do Porto, Porto, Portugal,
7
Centro de Investigaç~ao em Ci^encias da Sa ude, Universidade da Beira Interior, Covilh~
a, MO737 EVALUATION OF EXTRAVASCULAR FLUID IN
8
Portugal, Clınica de Hemodi alise do Porto, Porto, Portugal, 9CINTESIS, Faculdade de HEMODIALYSIS PATIENTS BY LUNG ULTRASOUND IN
10
Medicina da Universidade do Porto, Porto, Portugal, NefroServe, Clınica de COMPARISON WITH BIOIMPEDANCE
Hemodialise de Barcelos, Barcelos, Portugal and 11Clınica de Hemodi alise de
Gondomar, Gondomar, Portugal Anastasiia Putintceva1, Irina Zdanova1, Ekaterina Tsukanova2, Julia Fadeeva3,
Ashot Esayan4
1
BACKGROUND AND AIMS: Cardiovascular disease (CVD) is the major cause of Federal State Public Enterprise Nikiforov’s All-Russian Center for Emergency and
mortality and morbidity in chronic kidney disease (CKD), especially in end-stage renal Radiation Medicine of the Emergencies Ministry of Russia, Dialysis, Saint-Petersburg,
disease (ESRD) patients. Left ventricular hypertrophy (LVH) is a common Russia, 2Federal State Public Enterprise Nikiforov’s All-Russian Center for Emergency and
cardiovascular complication in CKD. Growth differentiation factor (GDF)-15 increases Radiation Medicine of the Emergencies Ministry of Russia, Functional diagnostics,
in tissue injury and inflammatory states associated with cardiometabolic risk. GDF-15 Saint-Petersburg, Russia, 3Limited Liability Company “Helix Severny”, Functional diag-
and N-terminal pro B-type natriuretic peptide (NT-proBNP) are both synthesized by nostics, Saint-Petersburg, Russia and 4Faculty of Postgraduate Education, First Pavlov
cardiomyocytes and may be associated with cardiorenal dysfunction. Our aim was to State Medical University of St. Petersburg, Nephrology and Dialysis, Saint-Petersburg,
study the association of GDF-15 with LVH in ESRD patients on dialysis. Russia
METHOD: This study included 196 ESRD patients on dialysis (hemodiafiltration and
high-flux hemodialysis). Left ventricular mass (LVM) was evaluated through BACKGROUND AND AIMS: The aim of study was to compare the lung ultrasound
echocardiographic studies, corrected for body surface area and the values are presented (LUS) and bioimpedance analysis (BIA) as methods to assess the hydration (fluid)
as LVM index (LVMI). LVH was defined by a value of LVMI > 115 g/m2 in men and status in maintenance hemodialysis (MHD) patients.
> 95 g/m2 in women. Patients were divided into two groups - LVH (n=131) and non- METHOD: The comparative analysis was performed in 87 MHD patients aged 24 to
LVH (n=65). LVMI, clinical and analytical variables (age, body mass index, dialysis 82 years (43 women, and 44 men). Patients with cardiac pacemakers and permanent
vintage, dialysis adequacy, GDF-15, NT-proBNP and pentraxin (PTX) 3 were catheters as vascular access were excluded from the study. Extravascular lung water
evaluated. (EVLW) in MHD patients was assessed simultaneously by LUS (Acuson X150
RESULTS: ESRD patients with LVH presented significantly higher levels of NT- ultrasound system with a CH5-2 curvilinear transducer, Siemens) and by the
proBNP and GDF-15, and a trend towards higher PTX3 values. In LVH patients, GDF- bioimpedance spectroscopy (BIS) (Bodystat Multiscan 5000) with frequency range of
15 correlated positively and significantly with NT-proBNP and PTX3; LVMI correlated 5-1000K Hz. Both LUS and BIS were performed before and 30 minutes after the
positively and significantly with pro-BNP and PTX3 levels; pro-BNP correlated hemodialysis (HD) session in the second and third sessions of the week. Ultrasonic
significantly and positively with PTX3. measurements were performed by summing LUS comets or B-lines along four
CONCLUSION: Our data show that in ESRD patients on dialysis with LVH, GDF-15 anatomical lines (parasternal, mid-clavicular, anterior, middle, and posterior axillary
is raised and shows a strong association with NT-proBNP, PTX3 and LVMI. Further lines) from II to V intercostal spaces on the right and from the II to IV intercostal
studies are needed to clarify if the rise in GDF-15 is a cause or a consequence of LVH spaces on the left. The quantitative assessment of B-lines (B-lines score, BLS) was
development. performed according to Picano E. et al. [2006]: normohydration – zero degree (<4 B
ACKNOWLEDGMENTS: This work was supported by Applied Molecular Biosciences lines) with the absence of EVLW, overhydration (OH) – 1st degree (5-14 BLS), 2nd
Unit-UCIBIO, financed by national funds from FCT/MCTES (UIDB/04378/2020), by degree OH (15-30 BLS), and 3d degree OH – >30 BLS with an insignificant, moderate
North Portugal Regional Coordination and Development Commission (CCDR-N)/ and severe amount of EVLW, respectively. The body hydration status assessment
NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE- technique by BIS was based on the overhydration (OH) index, the total body water
Rede de Quımica e Tecnologia-Associaç~ao in the form of a researcher (S. Rocha) – volume, extra- and intracellular water, and the body composition.
project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and Patient’s fluid status classified as normohydration (1.0-1.0 L), moderate OH (>1.0-
FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322). <2.5 L), and severeOH (>2.5 L), and dehydration (<1.0 L) [Henry C. Lukaski et al.,
2019]. The LUS do not allow assessing the state of dehydration, therefore, the
normohydration by LUS was the sum of normo- and dehydration by BIS. We used
SPSS Statistics 21.0 software for statistical processing of the data. To assess the
MO736 ELECTROCHEMICAL SKIN CONDUCTANCE BY SUDOSCAN: correlation between BLS and OH indicators, we used Spearman’s rank correlation
A NEW TOOL TO PREDICT INTRA-DIALYTIC HYPOTENSION coefficient. The statistical significance level was assumed to be 0.05.
RESULTS: Data of the body fluid status using LUS and BIS before and after HD-
Pauline Reach1, Maxime Touzot2, Yannis Lombardi2, Catherine Maheas2, session fully coincided in 33 of 87 MHD patients, partially coincided in 20 patients
Emmanuelle Sacco3, Audrey Fels3, Hélène Beaussier3, Pablo Antonio Urena before and in 25 patients after HD-session. LUS and BIS didn’t coincide completely in
Torres4, Gilles Chatelier5, Christophe Ridel2, Mathieu Zuber1 only 9 patients. Statistically significant correlation was revealed between BLS and OH
1 before (Rs=0.336; p<0.01), and after (Rs=0,317, p<0,01) HD session. A positive
Groupe Hospitalier Paris Saint-Joseph, Neurologie, Paris, France, 2Aura Paris Plaisance,
correlation between BLS and OH data was revealed in 53 patients, whose results were
Dialyse et Aphérèse thérapeutique, Paris, France, 3Groupe Hospitalier Paris Saint-
almost identical before (Rs=0,488, p<0.01), and in 58 patients after (Rs=0,658, p<0.01)
Joseph, Centre de recherche Clinique, Paris, France, 4Aura Saint-Ouen, Dialyse, Saint-
HD session.
Ouen, France and 5Hôpital Européen Georges Pompidou, CIC 1418, Paris, France
CONCLUSION: BIS remains the gold standard for the assessment of over-, normo-
and dehydration in MHD patients. LUS is a simple and adequate technique for
BACKGROUND AND AIMS: Intradialytic hypotension (IDH) is a common assessing the hydration status in MHD patients, and it is comparable to BIS in
complication in hemodialysis (HD) patients. It is associated with multiple risk factors assessing over-, as well as normohydration. However, the LUS doesn’t allow diagnosing
including cardiac dysfunction and alterations of the peripheral autonomic nervous the body dehydration.
system. To which extent, dysautonomia may contributed to the occurrence of IHD

10.1093/ndt/gfab097 | i417
Abstracts Nephrology Dialysis Transplantation

MO738 CLINICAL IMPACT OF ORAL ANTICOAGULATION THERAPY figure 1) with a significant correlation for platelet count and platelet function (r=0.42,
ON MORTALITY, EMBOLIC AND HEMORRHAGIC EVENTS IN p=0.001).
CHRONIC HEMODIALYSIS PATIENTS WITH ATRIAL
FIBRILLATION

Zorica Dimitrijevic1, Sonja Salinger2, Danijela Tasic1, Miomir Stojanovic1,


Karolina Paunovic1, Branka Mitic1
1
Clinical Center Nis, Nephrology Clinic, Nis, Serbia and 2Clinical Center Nis, Clinic for
Cardiovascular Disease, Nis, Serbia

BACKGROUND AND AIMS: A balance between embolic and bleeding risk is


challenging in patients on chronic hemodialysis (HD). Embolic prevention with oral
anticoagulation is the cornerstone for managing patients with atrial fibrillation (AF).
However, there is a lack of specific recommendations for the use of antithrombotic
therapy in HD patients with AF, and data about the efficacy and safety of oral
anticoagulation in those patients are limited. Anticoagulation may exacerbate the
hemorrhagic tendency; therefore, its potential benefits must be carefully weighed
against hemorrhagic complications. We aimed to analyze the impact of oral
anticoagulation on mortality, embolic and hemorrhagic events in chronic hemodialysis
patients with AF.
METHOD: We used data from 106 hemodialysis patients [median age of 72 years
(IQR 59–79) and 74.8% of the male gender] diagnosed with AF between 2016 and
2019. An analysis was performed to match the baseline characteristics of patients
treated or not with oral vitamin K antagonists (OAK). The impact of oral
anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk
analysis, with death being the competitive event. For embolic risk, we have considered MO739 Figure 1: Thrombocyte function in hemodialysis (HD) patients compared
a stroke, pulmonary or peripheral embolism, including arteriovenous fistula to healthy controls. HD patients, (n=60) showed significant altered thrombocyte
thrombosis. For bleeding risk, we have considered major bleeding according to the function as determined by area under the curve [AU*min] in Multiplate analyzer after
ISTH definition. induction of platelet aggregation with adenosine diphosphate compared to healthy
RESULTS: More than half of HD patients with AF were anticoagulated (65.1%; n=69). controls (n=67), calculated using independent t-test. Columns show median with
During a median follow-up of 27.6 months (IQR 11.8-42.9 months), 33 patients died interquartile range. ***, p<0.001.
(31.1%), 21 presented embolic events (19.8%), and 19 had a major bleeding event
(17.9%). In total, we recorded eight cerebral bleedings, ten gastrointestinal bleedings, Platelet function also correlated with the inflammatory state as seen by systemic CRP
and one urogenital bleeding. Of those, eleven (57.9%) were observed in orally levels (r=0.28, p=0.033). Regarding the clinical outcome, platelet function correlated
anticoagulated patients (p=0.066). Patients with bleeding events had a higher with hospitalization rates for infectious disease (r=0.27; p=0.040) and cardiovascular
prevalence of arterial hypertension (p=0.012), diabetes mellitus (p=0.002), advanced events (r=0.30; p=0.022). In case of hospitalization rates for infectious disease this
age (p=0.03) lower platelets count (p<0.001) and lower hemoglobin (p=0.04). After correlation remained stable irrespective of adjustment for thrombocyte counts (r=0.27,
propensity-score matching, anticoagulation therapy was associated with lower p=0.036).
mortality rate (HR 0.86, 95% CI 0.71-0.92; p=0.004) and embolic events (HR 0.78, 95% CONCLUSION: Lower platelet counts and altered function in HD patients was
CI 0.69-0.88; p=0.003), but more bleeding events (HR 1.83, 95% CI 1.34-2.91; associated with risk of hospitalization and markers of inflammation in this cohort. The
p=0.002). Multiplate analyzer appeared to be a valid and easily accessible method to assess
CONCLUSION: Among HD patients with AF, oral anticoagulation was associated thrombocyte function. Further studies are needed to determine whether assessment of
with lower all-cause mortality. Although survival free of embolic events was thrombocyte function in clinical routine should be used to stratify risk in the
significantly higher in patients with anticoagulation, the risk of major bleeding was vulnerable population of HD patients.
almost twice than in non-anticoagulated patients. Patients who experienced bleeding
events did not show worse outcomes. This study strengthens the role of low
hemoglobin and platelet counts as well as comorbidities on increased bleeding risk.
MO740 EFFECT OF DIPHOSPHONATES FOR VASCULAR
CALCIFICATION IN CHRONIC KIDNEY DISEASE: A META-
ANALYSIS
MO739 EX VIVO THROMBOCYTE FUNCTION IN HEMODIALYSIS
PATIENTS Canlin Yang1, Xiaotong Xie1, Jie Xing1, Xin Yang1, Xiao liang Zhang1
1
Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing, P.R. China
Vera Bonell1, Georg Lorenz1, Thorsten Kessler2, Uwe Heemann1,
Christoph Schmaderer1, Stephan Kemmner3 BACKGROUND AND AIMS: Vascular calcification is an independent predict factor
1
Klinikum rechts der Isar, Technical University Munich, Nephrology, Munich, Germany, of cardiovascular mortality and all-cause mortality in chronic kidney disease (CKD)
2
German Heart Center Munich, Cardiology, Munich, Germany and 3University Hospital patients. Animals experiments and clinical studies showed the inhibition effect of
Munich, Ludwig-Maximilians-University, Transplant Center, Munich, Germany diphosphonates in vascular calcification, but the results of the studies remains
controversial. This meta-analysis aims to evaluate the effects of diphosphonates on
BACKGROUND AND AIMS: Coagulation disorders with both risk for bleeding and vascular calcification in patients with CKD.
thrombotic events are common in hemodialysis (HD) patients. Altered thrombocyte METHOD: Randomized controlled trials (RCT) and non-RCTs of diphosphonates for
counts and function may account for that. Here, we sought to better characterize the treatment of vascular calcification in CKD patients until September 2020 were
thrombocyte function in hemodialysis patients. searched in the database of PubMed, Embase, Cochrane library, CNKI and Wanfang.
METHOD: Platelet function was investigated using the Multiplate analyzer (Roche) Literatures were screened according to the inclusion and exclusion criteria and quality
based on impedance aggregometry. Adenosine diphosphate (ADP) was used to induce was evaluated by two investigators independently. The standard deviation from mean
platelet aggregation and area under the curve (AUC) was used as primary endpoint. (SMD) and 95% confidence interval (CI) were used to representthe counting data. Data
Platelet counts and C-reactive protein (CRP) levels were measured. Hospitalization was extracted from the literatures were analyzed with Stata software (version 15.0).
the primary clinical outcome. Pearson regression was used to test for associations of RESULTS: A total of 6 RCTs and 1 non-RCT with 272 patients were included,
thrombocyte function and the primary endpoint. characteristics of the studies included are shown in Table 1. Meta-analysis indicated
RESULTS: In total 60 chronic HD patients undergoing dialysis 3 times per week, and that diphosphonates inhibit vascular calcification in CKD [SMD =-0.297, 95% CI = (-
67 healthy controls were included. In general, HD patients presented with significantly 0.591, -0.002), P = 0.049] (Figure 1). Etidronate is the most effective one in treating
lower thrombocyte numbers compared to healthy controls (Median: 221 vs. 245 G/l, with vascular calcification (P = 0.020) (Figure 2). But there isn’t significant difference in
p=0.029). Further, thrombocyte function as determined by AUC was significantly aortic artery calcification and coronary artery calcification compared with the control
altered in HD patients versus healthy controls (Median: 455 vs. 677 AU*min, p<0.001; group (P>0.05). There was no statistically significant difference in the change of blood
calcium, blood phosphate, and serum parathyroid hormone between two groups (all
P>0.05).

i418 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: Diphosphonates can inhibit the progression of vascular calcification
in CKD patients, and it hasn’t obvious effect on blood calcium, blood phosphate, and
serum parathyroid hormone. Etidronate is the most promising therapeutic agent.

MO740 Figure 1: Forest plot of effect of diphosphonates on vascular calcification in


CKD.

MO740 Figure 2: Subgroup analysis forest plot of effect of etidronate on vascular


calcification in CKD.

MO740 Table 1 Characteristics of the studies included in the meta-analysis

Author Year Country Population Number Age (x6s, yr) Treatment group Comparison Duration of Outcome Study
(Treatment group/ group follow-up (m) evaluated design
Comparison group)
Hashiba 2004 Japan Hemodialysis 18 (8/10) 63.962.76 Etidronate 200mg on No treatment 12 ACA by CT RCT
patients the days of dialysis for
6 months
Nitta 2004 Japan Hemodialysis 56 (35/21) 62.568.29 Etidronate 200mg No treatment 12 CACs by CT Non-RCT
patients daily for 14 days every
3months for 6 months
Hashiba 2006 Japan Hemodialysis 21 (12/9) 64.962.43 Etidronate 200mg on No treatment 23 ACA by CT RCT
patients the days of dialysis for
23 months
Ariyoshi 2006 Japan Hemodialysis 14 (8/6) 66.667.9 Etidronate 400mg No treatment 12 CACs by CT RCT
patients daily for 6 months ACS by CT
Toussaint 2010 Australia CKD stages 3- 50 (25/25) 62.6611.8 Alendronate70mg/ Placebo 18 AVC by CT RCT
4 weekfor 18 months
Torregrosa 2010 Spain Kidney trans- 101 (52/49) 48.9614.8 Risedronate 35mg/ Vitamin D and 12 VCS by X-ray RCT
plant week & Vitamin D and Calcium
recipients Calcium
Okamoto 2014 Japan Kidney trans- 12 (5/7) 52.969.3 Alendronate 35mg/ No treatment 24 ACI by CT RCT
plant week for 24 months
recipients

Abbreviations: ACA, aortic calcification area; CT, computed tomography; CACs, coronary artery calcification score; ACS, aortic calcification score; AVC,
aortic vascular calcification; VCS, vascular calcification score; ACI, aortic calcification index.

10.1093/ndt/gfab097 | i419
Abstracts Nephrology Dialysis Transplantation

MO741 TUMOR NECROSIS FACTOR ALPHA AND MAGNESIUM ARE MO743 FACTORS AFFECTING CEREBRAL OXYGENATION IN
LINKED TO CARDIAC VALVE CALCIFICATION IN DIABETIC HEMODIALYSIS PATIENTS: ARTERIAL STIFFNESS, MENTAL
HEMODIALYSIS PATIENTS ACTIVITIES, SMOKING

Oleksandr Susla1, Zoriana Litovkina1, Ihor Mysula1, Anatoliy Gozhenko2 Olczyk Piotr1, Mariusz Kusztal1, Tomasz Gołe R biowski1, Letachowicz Krzysztof1,
1
I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine and 2Ukrainian Katarzyna Madziarska1, Anna Szymczak1, Krajewska Magdalena1
1
Scientific Research Institute of Transport Medicine, Odesa, Ukraine Wroclaw Medical University, Nephrology and Transplantation Medicine, Wrocław,
Poland
BACKGROUND AND AIMS: The processes of cardiac valve calcification (CVC) in
diabetic hemodialysis (HD) patients are not fully understood. In this context, it is BACKGROUND AND AIMS: A significant deterioration of cognitive function in
reasonable to complex and comprehensively research the activity of chronic hemodialysis patients is observed in elderly and non-elderly patients. One of possible
inflammation and magnesium (Mg) imbalance as cardiovascular risk factors in end- explantation is significant changes in the circulatory system caused by regular lower
stage renal disease (ESRD). The main purpose of the current study was to determine cerebral regional saturation of oxygen (rSO2) during dialysis. We aimed to identify the
the relationship of tumor necrosis factor alpha (TNF-a) and Mg levels with the factors affecting the cerebral rSO2 in HD patients during session.
presence and severity of CVC in diabetic patients with ESRD. METHOD: 27 patients out of 80 hemodialysed in center patients were recruited for the
METHOD: We enrolled 136 patients undergoing HD (male/female, 78/58;age, study (exclusion criteria: significant vision defect, fistula in the dominant hand,
53.961.0 years; HD duration, 47.664.2 month) in this observational cross-sectional previous stroke, other neurological diseases impaired cognitive functions). The mean
study. The study was performed in accordance with the provisions of the Declaration age of the patients was 51 618 y, BMI 25.565, dialysis vintage was 2.3 y; 6 with DM
of Helsinki last revision. Depending on the presence of type 2 diabetes mellitus and 22 with HT. During the study, each patient completed battery of cognitive function
(T2DM) all subjects were divided into two groups: the 1st one – non-diabetic patients tests (MOCA, Beck’s Scale) including computer based assessment validated for elderly
(n=88); the 2nd one – diabetic patients (n=48). Presence of CVC was detected by (Cognifit), arterial stiffness surrogates (PWV, Aix75 using IEM Mobil-O-Graph) and
ultrasound. The mitral (MVC) and aortic (AVC) valve calcification degree were scored the saturation (rSO2) of frontal lobes were measured (INVOS 5100c system). Patient
as follows: 1, no calcification; 2, valve thickening without calcification; 3, valve annulus regular passive or active (reading, crosswords solving, electronic games) behaviour
or cusps calcification. Serum content of TNF-a as one of the key proinflammatory during sessions was noticed.
cytokine was determined by enzyme-linked immunosorbent assay. Serum Mg RESULTS: Factors showed correlations with rSO2 are displayed in table. Lack of
concentration was estimated by biochemical method. Data are expressed as correlations between rSO2 and HD vintage, diabetes or BMI was observed. Patients
means6SEM. Used nonparametric statistics methods: Mann-Whitney U-test, v2-test, mentally active during dialysis showed significant (p<0.05) higher rSO2 (60 vs 53%
Spearman’s rank R correlations. left, 58 vs 49% right), Cognifit score (368 vs 233) and PWV (6,3 vs 9,3 m/s) when
RESULTS: In diabetic HD patients TNF-a content was higher (13.8661.34 vs. compared to passive patient behavior (sleeping, watching TV).
8.7360.60 ng/L; Z=3.04, p=0.002) whereas Mg concentration (0.8760.02 vs. CONCLUSION: Significant differences in cerebral oxygenation in hemodialysis
1.0060.02 mmol/L; Z=4.91, p<0.001) – lower compared to non-diabetic ones, and in patients correlated with cognitive functions. In HD patients, cerebral rSO2 was affected
2nd group indices of TNF-a and Mg were related (Rs=-0.68, p<0.001). CVC was by multiple factors, including non modifiable factors: arterial stiffness, age and
detected in 66.6% of T2DM patients with predominance of calcification of both valves modifiable factors – active mental activity during session and smoking. Furthermore,
(35.4%) over isolated MVC (20.8%) and AVC (10.4%). Combined MVC and AVC in this is the first report describing lower levels of rSO2 in HD patients with significant
the 2nd group was observed 2.6 times more often (v2=8.78, p=0.003) than in the 1st central arterial stiffness (Figure).
one. For the first time it was established that in diabetic patients with ESRD the
presence of CVC closely associated with indices of TNF-a (Rs=0.51, p<0.001) and Mg
(Rs=-0.57, p<0.001). The MVC as well as AVC degree were related with the content of
TNF-a (Rs=0.49, p<0.001; Rs=0.52, p<0.001) and Mg concentration (Rs=-0.47, Spearman MOCA Beck Cognifit PWV AiX75 smoking Mental
p<0.001; Rs=-0.50, p<0.001) respectively. significant Scale score activities
CONCLUSION: (1) T2DM in HD patients is characterized with an increase of serum
TNF-a activity and simultaneous decreased of Mg content. (2) In diabetic patients with correlations
ESRD, both MVC and AVC are closely linked with the TNF-a accumulation and Left lobe rSO2 0,45 Ns 0,54 -0,65 -0,55 -0,40 0,47
hypomagnesemia. (3) Chronic inflammation and Mg deficiency can be important Right lobe rSO2 0,44 Ns 0,48 -0,59 -0,49 -0,42 0,43
factors of CVC progression and very high cardiovascular risk in diabetic HD patients.

MO742 PRELOAD DEPENDENCE OF PULMONARY


HAEMODYNAMICS AND RIGHT VENTRICULAR
PERFORMANCE: AN ECHOCARDIOGRAPHIC STUDY IN
PATIENTS ON HAEMODIALYSIS

Francesc Gual-Capllonch1, Fredzzia Graterol2, Jordi Soler Majoral2,


Ioana Bancu2, Elena Ferrer-Sistach1, Albert Teis1, Evelyn Santiago-Vacas1,
Nuria Vallejo1, Gladys Junca 1, Antonio Bayes-Genis1
1
University Hospital Germans Trias i Pujol, Heart Institute, Badalona, Spain and
2
University Hospital Germans Trias i Pujol, Nephrology, Badalona, Spain

BACKGROUND AND AIMS: Haemodynamic cardiac changes in haemodialysis are


associated with adverse cardiovascular outcomes and and they are difficult to measure.
Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to
pre-existing preload are often disregarded. To determine volume-related changes in the
pulmonary-right ventricle (RV) unit and the preload-dependence of its components,
we analysed pulmonary haemodynamics and right ventricular performance, taking
advantage of the plasma volume removal associated to haemodialysis (HD).
METHODS AND RESULTS: Fifty-three stable patients on chronic HD with LVEF
>50% and without heart failure were recruited (mean age 63.0612.4 years; 31.2%
women; hypertension in 89% and diabetes in 53%) and evaluated just before and after
HD (mean ultrafiltration volume 2.460.7l). SPAP from both times were available in 39
patients. After HD, SPAP decreased (42.2612.6 to 33.7611.6 mmHg, p<0.001)
without modification of non-invasive pulmonary vascular resistance (1.7560.44 to
1.7560.40 eWU, p=0.94). Age and drop in the E/e’ ratio were the variables associated
with greater reduction in PASP (p=0.022 and p=0.049, respectively). A significant
reduction of right chamber sizes was observed, along with a diminution in measures of
RV contractility, excluding RV longitudinal strain. Functional tricuspid regurgitation
(FTR) diminution was observed in 26% of patients, occurring in every case with more
than mild FTR. On multivariate analyses, left atrial size was the only predictor of
pulmonary hypertension (defined as SPAP >40 mmHg) (OR 1.29 (1.07–1.56),
p=0.006).
CONCLUSION: Rapid volemic changes determined by rapid fluid removal during
hemodialysis; may affect FTR grading, RV size and contractility, with RV longitudinal
strain being less variable than conventional parameters. SPAP decreases after HD, and
this reduction is related to age and greater diminution of the E/e0 ratio.

i420 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO744 HIGH SENSIVITY CARDIAC TROPONIN I, A POSSIBLE MO745 CARDIOVASCULAR EFFECTS OF HIGH FLOW ARTERIO-
BIOMARKER OF DIASTOLIC DYSFUNCTION IN VENOUSE FISTULA CLOSURE IN POST-KIDNEY
ASYMPTOMATIC PATIENTS IN HEMODIALYSIS TRANSPLANTATION PATIENTS

Maria Paz Castro Ferna ndez1, Luis Guillermo Piccone Saponara1, Rustam Iskhakov1, Natalya Belavina2, Ekaterina Ivanova3, Nataliya Klochkova2,
Esperanza Moral Berrio1, Guillermo Ferrer Garcıa1, Gloria Garcıa Conejo1, Eugene Zeltyn-Abramov2
~o Parrilla1, Eliana Olazo Gutierrez1, Marina Ugarte Camara1,
Agustın Carren 1
Moscow City Clinical Hospital 52, ICU, Moscow Russia, Russia, 2Moscow City Clinical
Patricia Sanchez Escudero1, Carmen Vozmediano Poyatos1 Hospital 52, Laboratory of Cardionephrology, Moscow Russia, Russia and 3Moscow City
1
Ciudad Real University General Hospital, Nephrology, Ciudad Real, Spain Clinical Hospital 52, Nephrology, Moscow Russia, Russia

BACKGROUND AND AIMS: Impairment in the diastolic function is strongly BACKGROUND AND AIMS: Presently, the dilemma of what to do with a
associated with heart failure and cardiovascular disease in patients with end-stage renal functioning arterio-venous fistula (AVF) in post-kidney transplantation patients is a
disease (ESRD), with a high prevalence of 50-65% and unobvious early symptoms. subject of debate. One of the arguments in favor of AVF closure is symptomatic
Hence, it is of great importance to explore serum biomarkers for early assessment of congestive heart failure (CHF) due to AVF-induced cardiomyopathy. The subject of
diastolic disfunction in patients with ESRD, providing evidence for performing an early the study was the evaluation of the dynamics of some morpho-functional cardiac
intervention. When myocardial cell membrane integrity becomes damaged, cardiac parameters in post-kidney transplantation patients with AVF-induced CHF before and
troponin is released into the circulation, inducing an elevation of serum cardiac after AVF closure.
troponin in asymptomatic patients on dialysis. We analyzed the relationship between METHOD: The results of prospective single center study are presented. 13 post
high-sensitivity cardiac troponin I biomarker (hs-cTnI) and left ventricular diastolic transplantation patients with severe AVF-induced CHF (III-IV f.c. NYHA) were
dysfunction (LVDD) in a cohort of asymptomatic patients on haemodialysis at our enrolled. Echocardiography (Echo), Doppler evaluation of AVF flow (Qa) and
center. calculation of cardiopulmonary recirculation (Qa/CO) were performed simultaneously
METHOD: Cross-sectional study. We include patients on haemodialysis in our center. (split-protocol) at baseline together with estimation of creatinine plasma level. All
Demographic variables (age, sex), associated comorbidity, hs-cTnI levels, and patients underwent surgical closure of AVF. In 8 weeks after the closure, an assessment
echocardiographic parameters were collected. Statistical analysis was performed with of CHF, Echo and creatinine plasma level were carried out in all enrolled patients.
SPSS 25.0. Categorical variables are expressed as percentages and compared using Chi2 Statistical analysis was performed using the STATISTICA 13 software (T-test).
test. Quantitative variables are expressed as mean 6 standard deviation, and T-student, RESULTS: The average age – 44 613 y, males 54%. All patients bore an upper arm
Anova or U-mann Whitney was used to compare them. Logistic regression analysis proximal AVF. The average flow of AVF (Qa) – 3.4 61.4 L/min, average Qa/CO – 49
was performed to determine independent predictors of LVDD. Statistical significance 615%, Qa/CO was more than 30% in 92% of patients. The median of AVF vintage was
for a value of p <0.05. 5 y (IR 3;10). In 8 weeks after AVF closure, complete clinical resolution of CHF,
RESULTS: 80 patients, with an average age of 67.44 6 13 years. 57.5% were men. reduction of volumetric heart parameters, decrease of sPAP, improvement of diastolic
86.3% had high blood pressure (HBP), 52.5% were diabetic, 75% dyslipidemic, and function were observed. There was no significant difference in the serum creatinine
51.2% had overweight/obese body mass index. 32.5% had previous history of ischemic value (1.85 60.66 mg/dL vs 1.97 60.95 mg/dL, p >0.05). The results of Echo data
heart disease, 41.3% had moderate/severe left ventricle hypertrophy (LVH), 8.8% left before and after AVF closure are presented in Table 1.
ventricular ejection fraction (LVEF) <55% and 37.5% LVDD. Mean hs-cTnI was 31.27 CONCLUSION: The surgical closure oh high flow AVF in post-kidney transplantation
6 59.37 ng/L. LVDD was related to age (71 6 10 years vs 65 6 14 years p = 0.049), patients with AVF-induced CHF was resulted in significant improvement of morpho-
HBP (96.7% vs 3.3% p = 0.036), moderate/severe LVH (63.3% vs 36.7% p = 0.002), functional cardiac parameters. The CHF due to AVF-induced cardiomyopathy should
heart rate (HR) (66.96 6 8.6 vs 77.28 6 43.63 p = 0.036) and hs-cTnI (47.48 6 81.97 be considered as one of the indications to AVF closure in post-kidney transplantation
ng/L vs 21.54 6 38.06 ng/L p = 0.005). We divide the hs-cTnI into quartiles, with mean patients.
hs-cTnI levels 4.83 6 1.92 ng/L in Q1, 9.86 6 1.68 ng/L in Q2, 20.67 6 4.26 ng L in Q3 CO, cardiac output; CI, cardiac index; LV EDVi, left ventricular end-diastolic volume
and 89.73 6 98.49 ng/L in Q4. We observed statistical significance for age (Q3 71 6 10 index; LV ESVi, left ventricular end-systolic volume index; LAVi, left atrial volume
ng/L vs 60 6 17 ng/L p = 0.040), HBP (Q4 141.60 6 16.68 ng/L vs Q1 123.90 6 25, 98 index; RAVi, right atrial volume index; TAPSE, tricuspid annular plane systolic
ng/L p = 0.025), overweight/obesity (p = 0.001) and LVEF <55% (p = 0.015). The excursion LVMi, left ventricular mass index; sPAP, systolic pulmonary arterial
logistic regression showed that HR (OR 0.94 95% CI 0.89-0.99 p = 0.025), LVH severity pressure; LVEF, left ventricular ejection fraction; ð/A ratio, E - peak early mitral inflow
(OR 5.16 95% CI 1.74-15.25 p = 0.003), and hs-cTnI > 20 (OR 4.11 95% CI 1.38-12.18 wave velocity, A - peak late mitral inflow wave velocity.
p = 0.011) are independent risk factors for LVDD.
CONCLUSION: hs-cTnI levels could be a biomarker of LVDD in asymptomatic
patients on haemodialysis. New studies with a greater number of patients would
increase the evidence for this claim, in order to carry out early intervention and
treatment.

MO745 Table 1 Results of Echo monitoring before and after AVF closure

Parameters Before AVF After AVF P value change (%) Mean Confidence
closure M (6SD) closure M (6SD) Difference (MD) Interval 95%
CI
CO, l/min 6.90 62.28 5.02 61.42 p = 0.0003 -27.2 -1.88 -3.030 to -0.730
CI, l/min/m2 3.7061.04 2.72 60.72 h = 0.0003 -26.5 -0.98 -1.704 to -0.256
LV EDVi, ml/m2 95 613 73 612 p = 0.00007 -23.1 -22.0 -32.13 to -11.87
LV ESVi, ml/m2 42 614 34 610 p = 0.0390 -19.0 -8.0 -17.85 to 1.85
LAVi, ml/m2 56 615 37 66 p = 0.0004 -33.9 -19.0 -28.25 to -9.75
RAVi, ml/m2 43 613 24 69 p = 0.0009 -44.2 -19.0 -28.05 to -9.95
TAPSE, sm 1.8 60.2 1.9 60.1 p = 0.0835 þ5.5 þ0.1 -0.03 to 0.23
LVMi, g/ m2 165 637 148 632 p = 0.0302 -10.3 -17.0 -45.00 to 11.00
sPAP, mmHg 56 615 29 64 p = 0.000031 -48.2 -27.0 -35.89 to -18.11
LVEF, % 55 615 54 69 p = 0.7652 -1.8 -1.0 -11.01 to 9.01
ð/A ratio 1.9 60.3 0.8 60.4 p = 0.00002 -57.9 -1.1 -1.39 to -0.81

10.1093/ndt/gfab097 | i421
Abstracts Nephrology Dialysis Transplantation

MO746 CARDIAC REMODELING AND PULMONARY HYPERTENSION


IN HEMODIALYSIS PATIENTS

Ekaterina Borodulina1, Alexander M. Shutov2


1
Kirov Branch of Medical Private Institution of additional professional education
«Nefrosovet», Department of Nephrology and Hemodialysis, Kirov, Russia and
2
Ulyanovsk State University, Department of Internal Medicine, Ulyanovsk, Russia

BACKGROUND AND AIMS: An important predictor of cardiovascular mortality


and morbidity in hemodialysis patients is left ventricular hypertrophy. Also,
pulmonary hypertension is a risk factor for mortality and cardiovascular events in
hemodialysis patients. The aim of this study was to investigate cardiac remodeling and
the dynamics of pulmonary arterial pressure during a year-long hemodialysis
treatment and to evaluate relationship between pulmonary arterial pressure and blood
flow in arteriovenous fistula.
METHOD: Hemodialysis patients (n=88; 42 males, 46 females, mean age was
51.7613.0 years) were studied. Echocardiography and Doppler echocardiography were
performed in the beginning of hemodialysis treatment and after a year.
Echocardiographic evaluation was carried out on the day after dialysis. Left ventricular
mass index (LVMI) was calculated. Left ventricular ejection fraction (LVEF) was
measured by the echocardiographic Simpson method. Arteriovenous fistula flow was
determined by Doppler echocardiography. Pulmonary hypertension was diagnosed
according to criteria of Guidelines for the diagnosis and treatment of pulmonary
hypertension of the European Society of Cardiology.
RESULTS: Pulmonary hypertension was diagnosed in 47 (53.4%) patients. Left
ventricular hypertrophy was revealed in 71 (80.7%) patients. Only 2 (2.3%) patients
had LVEF<50%. At the beginning of hemodialysis correlation was detected between
systolic pulmonary arterial pressure and LVMI (r=0.52; P<0.001). Systolic pulmonary
arterial pressure negatively correlated with left ventricular ejection fraction (r=-0.20;
P=0.04). After a year of hemodialysis treatment LVMI decreased from 140.49642.95 to
MO747 AN ASSESSMENT OF COMPLEXITY OF CARDIOVASCULAR
123.25639.27 g/m2 (h=0.006) mainly due to a decrease in left ventricular end-diastolic
SIGNALS USING ENTROPY IN HEMODIALYSIS SESSION AND
dimension (from 50.2366.48 to 45.1365.24 mm, p=0.04) and systolic pulmonary
GLUCOSE INJECTION DURING HEMODIALYSIS IN END
arterial pressure decreased from 44.83614.53 to 39.14610.29 mmHg (h=0.002).
STAGE RENAL DISEASE PATIENTS WITH AND WITHOUT
Correlation wasn’t found between systolic pulmonary arterial pressure and
DIABETES MELLITUS TYPE 2
arteriovenous fistula flow (r=0.17; p=0.4).
CONCLUSION: Pulmonary hypertension was diagnosed in half of patients at the
Longin Niemczyk1, Daniel Schneditz2, Katarzyna Buszko3, Anna Wojtecka4,
beginning of hemodialysis treatment. Pulmonary hypertension in hemodialysis
Marek Saracyn5, Stanisław Niemczyk4
patients was associated with left ventricular hypertrophy, systolic left ventricular 1
dysfunction. After a year-long hemodialysis treatment, a regress in left ventricular Medical University of Warsaw, Department of Nephrology, Dialysis and Internal
hypertrophy and a partial decrease in pulmonary arterial pressure were observed. Medicine, Warsaw, Poland, 2Medical University of Graz, Otto Loewi Research Center,
There wasn’t correlation between arteriovenous fistula flow and systolic pulmonary Graz, Austria, 3Nicolaus Copernicus University, Department of Theoretical Fundament
arterial pressure. of Biomedical Sciences and Medical Informatics, Toru n, Poland, 4Military Institute of
Medicine, Department of Internal Diseases, Nephrology and Dialysis, Warsaw, Poland
and 5Military Institute of Medicine, Department of Endocrinology and Isotope Therapy,
Warsaw, Poland

BACKGROUND AND AIMS: Few studies have focused on the imbalance of the
autonomic nervous system during hemodialysis (HD), although it seems to be an
important factor for the maintenance of blood pressure.
The aim of this work was to assess the impact of hemodialysis (HD) and glucose
injection upon entropy of heart rate and blood pressure during HD session in end stage
renal disease (ESRD) patients with and without diabetes mellitus (DM) type 2.
METHOD: 21 patients without DM (NDO), in age 54,95 þ/-13,08 y.o., and 10 DM
patients, in age 69,70 þ/- 8,27 y.o., were studied during HD. 30 minutes after dialysis
begins, 40% glucose solution was administered in the amount of 0.5g/kg body dry-
weight (constant rate of 1 mL/s). The cardiovascular signals were extracted from the
recordings using PortapresV R system. The analysis was performed using Amplitude

Aware Permutation Entropy (AAPE). The parameters of AAPE were set as d=7, A=0.5.
All statistical analysis were performed on significance level a=0.05. The comparisons
between groups were conducted with Mann-Whitney test with Holm corrections. The
comparisons in time points were performed using Friedman test with post-hoc
(Wilcoxon test with Holm corrections). The calculations of AAPE and all statistical
analysis were performed with Matlab R2020a and R.
RESULTS: The results are presented in table.

i422 | Abstracts
Nephrology Dialysis Transplantation Abstracts

BEFORE HD BEFORE GLUCOSE AFTER GLUCOSE END OF TEST p*


(t=-30) INJECTION (t=0) INJECTION (t=5) (t=60)
AAPE(HR) NS** NS** NS** NS**
DM 5.25þ/-0.66 5.00þ/-0.59 5.56þ/-0.28 5.51þ/-0.92 (t0/t5) p=0.019
NDO 5.10þ/-1.17 4.66þ/-1.42 5.08þ/-1.22 4.97þ/-1.40
AAPE(˚SYS) NS** NS** NS** NS**
DM 3.55þ/-0.36 3.07þ/-0.38 3.55þ/-0.50 3.23þ/-0.42 (t-30/t0) p<0.001
NDO 3.60þ/-0.28 3.14þ/-0.33 3.53þ/-0.36 3.42þ/-0.54 (t-30/t0) & (t0/t5) p<0.001
AAPE(˚DIA) NS** NS** NS** NS**
DM 5.02þ/-0.65 4.64þ/-0.73 4.96þ/-0.52 4.70þ/-0.79
NDO 4.69þ/-0.67 4.10þ/-0.68 4.63þ/-0.64 4.42þ/-0.83 (t-30/t0) & (t0/t5) p<0.01
AAPE(˚MAP) NS** NS** NS** NS**
DM 4.43þ/-0.59 3.92þ/-0.57 4.29þ/-0.68 4.16þ/-0.66
NDO 4.40þ/-0.52 3.84þ/0.52 4.24þ/-0.59 4.04þ/-0.79 (t-30/t0) p<0.01
(t0/t5) & (t-30/t60) p<0.05
AAPE(˚TPR) p=0.022 ** NS** NS** NS** NS**
DM 7.07þ/-0.25 2.11þ/-0.39 2.40þ/-0.36 2.26þ/-0.20 (t-30/t0), (t-30/t5) &
(t-30/t60) p<0.0001
(t0/t60) & (t5/t60) p<0.05
NDO 7.34þ/-0.69 2.27þ/-1.50 2.64þ/-1.27 2.26þ/-0.25 (t-30/t0), (t-30/t5) &
(t-30/t60) p<0.0001
(t0/t5) p<0.05

*- p value for difference in group; ** - p value for DM vs NDO

patients underwent multislice computed tomography to identify coronary artery


It was found that AAPE(HR) tends to decrease during dialysis (NS) and increases only
calcifications according to the standard procedure. CACS was calculated by the
in the DM group after glucose injection (p=0.019); without difference between groups.
Agatston method individually for the left main, left circumflex, left anterior
There were no differences in AAPE of blood pressure between the groups, but
descending, and right coronary arteries and then summed to calculate the total CACS
hemodialysis reduces AAPE(fiSYS) in both groups (p<0.001 in both DM and NDO
for each patient. Patients were distributed based on CACS: group 1 with CACS = 0,
groups) and AAPE(fiDIA) in NDO (p<0.01). AAPE(TPR) is high before dialysis, and
group 2 with CACS ranging from 1 to 400, and group 3 with CACS > 400.
decreases during HD in both groups (p<0.0001). There is no effect of glucose injection
RESULTS: Nine patients (89% men) had CACS = 0, 34 (47% men) had CACS 1-400,
on AAPE(HR) in both groups, but AAPE(fiSYS) and AAPE(fiDIA) increase in NDO
and 17 (76.5% men) had CACS > 400 (v2 = 7.467; p = 0.024). The mean age was
(p<0.001, p<0.01, p<0.05 respectively); without difference between groups.
5167, 61612 and 6468 years in groups 1, 2 and 3, respectively (p = 0.016). Patients in
AAPE(TPR) tends to increase after glucose injection (p<0.05 for NDO, NS for DM).
group 1 were significantly younger than patients in group 2 (p = 0.046) and group 3 (p
CONCLUSION: AAPE(HR)tends to decrease during HD, and glucose injections
= 0.012). The highest percentage of men was observed in group 1 (x2 = 7,668; p =
increase AAPE(HR) in DM patients. Hemodialysis reduce, and glucose injections
0.022). Other investigated demographic characteristics (dialysis vintage, body mass
increase AAPE of blood pressure especially in NDO. A weaker response to
index, smoking history, family CV history, systolic and diastolic blood pressure),
hemodialysis and glucose injection in diabetic patients may be caused by impairment
comorbidities (hypertension, diabetes, hyperparathyroidism, hyperlipidemia) and
of the autonomic system, and may have clinical impact – may leads to faint. Glucose
therapy (angiotensin converting enzyme inhibitors, angiotensin receptor blockers,
administration does not prevent autonomic system disorders in patients with DM.
statins, vitamin D, CaCO3, dialysate-magnesium concentration) did not differ
significantly between the investigated groups. CACS showed statistically significant
negative correlation with the serum iron (r = - 0.351; p = 0.007), while other laboratory
parameters (including calcium phosphate product) did not show statistically significant
MO748 CORONARY ARTERY CALCIUM SCORE IN ASYMPTOMATIC correlations.
PATIENTS RECEIVING CHRONIC HAEMODIALYSIS CONCLUSION: Older age and low serum iron are associated with higher CACS in
asymptomatic patients in the early years of HD. Therefore, these patients should be
Jovana Kusic Milicevic1, Radosav Vidakovic2,3, Marija Andjelkovic Apostolovic4,5, closely monitored for the early signs of CV disease.
Branislav Apostolovic1, Ana Ostojic1, Rodoljub Markovic1, Veselinka Djurkovic1,
Jasna Trbojevic  Stankovic 3,6, Tamara Jemcov1,3, Gordana Dragovic3,7
1
Clinical Hospital Centre Zemun, Department of Nephrology, Belgrade, Serbia, 2Clinical
Hospital Centre Zemun, Department of Cardiology, Belgrade, Serbia, 3Faculty of MO749 CATHETER ABLATION FOR ATRIAL FIBRILLATION IN
Medicine University of Belgrade, Belgrade, Serbia, 4Medical Faculty University of Nis, PATIENTS WITH CHRONIC KIDNEY DISEASE AND ON
Department of Medical statistics and Informatics, Nis, Serbia, 5Public Health Institute, DIALYSIS - A META-ANALYSIS
Nis, Serbia, 6Clinical Hospital Centre ”Dr Dragisa Misovic - Dedinje”, Department of
Dialysis, Belgrade, Serbia and 7Department of Pharmacology, Clinical Pharmacology Isaac Chung1, Yasir Khan1, Rao Kondapally2, Manav Sohal2,
and Toxicology, Belgrade, Serbia Debasish Banerjee1,2
1
St George’s University Hospitals NHS Foundation Trust, Renal and Transplantation
BACKGROUND AND AIMS: Vascular calcification has been reported to be an Unit, London, United Kingdom and 2Cardiology Clinical Academic Group, Molecular
independent predictor of all-cause mortality and cardiovascular (CV) events in and Clinical Sciences Sciences Research Institute, London, United Kingdom
patients with end-stage renal disease. Even in previously asymptomatic patients, early
years of haemodialysis (HD) are associated with high CV morbidity and mortality
BACKGROUND AND AIMS: Atrial fibrillation (AF) is common in chronic kidney
rates. Thus, it is important to precisely and timely identify individuals at risk of
disease (CKD) patients and is difficult to treat with antiarrhythmics and anticoagulants
coronary artery disease (CAD) who would benefit from further CV treatment.
due to abnormal metabolism and increased side effects. Catheter ablation if successful
Coronary artery calcium score (CACS) is an accurate tool for noninvasive assessment
may be a safer alternative. This review evaluates the efficacy of catheter ablation
of CAD. This study aimed to evaluate CACS in asymptomatic HD patients in early
therapy in CKD and haemodialysis (HD) patients.
years of treatment.
METHOD: MEDLINE and Embase databases were searched with the following search
METHOD: This multicentric observational study included 60 patients receiving
terms: “(atrial fibrillation AND (chronic kidney disease OR renal failure OR renal
chronic HD for less than 4 years, with neither signs nor symptoms of CV disease. All
function OR dialysis) AND ablation)” for journal articles of any language until

10.1093/ndt/gfab097 | i423
Abstracts Nephrology Dialysis Transplantation

December 2020. Two authors abstracted the data independently. Risk ratios were MO751 OXIDATIVE STRESS IN PATIENTS WITH CHRONIC RENAL
derived using random-effects meta-analysis. FAILURE AND CARDIOVASCULAR COMPLICATIONS
RESULTS: Of the initially identified 520 studies, 5 and 3 observational studies on CKD
and HD patients respectively were found reporting AF recurrence rates. During a mean Leila Azouaou toualbi1, Chahine Toualbi2, Khelfi Abderrezak3, Medina Arab4,
(SD) follow-up of 25.5 (9.8) months, CKD patients had a higher risk of AF recurrence Wafa Ballouti5, Henni Chader6, Abdelghani Benoui7, Atmane Seba8
1
compared to patients without CKD (RR 2.34, 95% CI 1.36-4.02, p<0.01). The university algiers 1, CHU nephrology hussein dey, medecine, nephrology, algiers alge-
heterogenicity test showed there were significant differences between individual studies ria, Algeria, 2Béjaı̈a, medecine ,surgy , Béjaı̈a, Algeria, 3university algiers 1, toxicology,
(I2 = 91%, 95% CI 82.2%-95.6%, p<0.01). In a mean (SD) follow-up of 40.3 (20.8) algiers algeria, Algeria, 4university algiers 1, CPMC, medecine, biochimy, algiers algeria,
months, HD patients may be at a higher risk of AF recurrence compared to healthy Algeria, 5university algiers 1, medecine , biochimy, algiers algeria, Algeria, 6university
non-dialysis AF patients (RR 1.21, 95% CI 0.64-2.30, p=0.55). Heterogeneity analysis algiers 1, Department of pharmacology, algiers algeria, Algeria, 7university algiers 1,
showed the studies were heterogeneous (I2 92.3%, 95% CI 80.8%-96.9%, p <0.01). medecine , nephrology, algiers algeria, Algeria and 8university algiers 1, medecine ,
CONCLUSION: Our meta-analysis suggests patients with CKD and patients on HD nephrology, algiers algeria, Algeria
are more likely to have AF recurrences after catheter ablation compared to AF patients
who are otherwise healthy. However, more robust evidence from randomized BACKGROUND AND AIMS: The atherosclerosis process is highly accelerated in
controlled trials comparing catheter ablation and pharmaceutical rhythm therapy are patients with chronic kidney disease (CKD). Oxidative stress is considered as one of
urgently needed to guide therapy in this difficult to treat population. the pro-atherogenic factors involved in accelerating the atherosclerosis process of the
carotid artery. The aim of the present study was to determine the relationship between
oxidative stress markers and the progression of carotid atherosclerosis in CKD
patients.
METHOD: The study was conducted on 220 patients with CKD and 40 controls, and
the disease stage was scored between 2 and 5D. Blood samples were taken and
myeloperoxidases, malondialdehyde, nitric oxide, glutathione, and oxidised low-
density lipoprotein were measured. Furthermore, we studied the correlations between
these biomarkers and clinical and para-clinical cardiovascular complications.
RESULTS: The average age of patients was 60.5 years. The oxidative stress markers
MO749 Figure 1: Risk ratio of AF recurrence after catheter ablation in CKD average 6 SD levels in CKD groups compared to the control were as follows:
patients. RR – Risk Ratio; eGFR – estimated Glomerular Filtration Rate myeloperoxidase (49.89 61.98 vs. 38.45 61.98 UI/ml), malondialdehyde (5.2 60.12 vs.
3.26 60.03 mmol/l), nitric oxide (56.82 61.06 vs. 42.19 62.1 mmol/l), glutathione
(42.21 61.3 vs. 79.4 62.6 IU/ml), and oxLDL (15.57 61.07 vs. 1.72 60.82 mmol/l).
While the glutathione level decreased significantly in advanced CKD stage (p < 0.05),
the concentrations of all the other biomarkers increased significantly in accordance
with CKD score (p < 0.05). Patients with high IMD (> 1 mm) had higher values of the
prooxidant markers (NO, oxLDL, MDA, MPO) but lower antioxidant marker values
(glutathione), compared to other patients with lower IMD
CONCLUSION: Cardiovascular diseases, mainly atherosclerosis, can be diagnosed
indirectly by measuring oxidative stress markers. Furthermore, theses markers can be
used to predict the progression of CKD, for better management of the disease.

MO749 Figure 2: Risk ratio of AF recurrence post-ablation in haemodialysis


patients compared to general population. RR – Risk Ratio; HD - Haemodialysis

MO750 THE COMBINED PROGNOSTIC SIGNIFICANCE OF ALKALINE


PHOSPHATASE AND INTRA-CRANIAL ARTERIAL
CALCIFICATIONS IN HEMODIALYSIS PATIENTS

Keren Cohen Hagai1,2, Daniel Erez3, Tali Zitman-Gal1,2, Feda Fanadka4,


Yael Einbinder1,2, Sydney Benchetrit1,2
1
Meir medical center, Nephrology and Hypertension, Israel, 2Tel Aviv University, Sackler MO751 Figure 1: Correlation of of oxidative stress markers and creatinine levels in
Faculty of Medicine, Tel Aviv-Yafo, Israel, 3Meir Medical Center, Department of Internal the studied population
Medicine D and 4Meir Medical Center, Radiology

BACKGROUND AND AIMS: Intra-cranial arterial calcification (ICAC) in


hemodialysis (HD) patients has a prevalence of about 90%, and its severity is correlated
with age, hemodialysis vintage and mineral bone disease. Elevated concentrations of MO752 EVALUATION AND ANALYSIS OF CHRONIC PAIN IN
calcium and phosphorus are not sufficient to induce medial calcification because of HEMODIALYSIS PATIENTS
inhibition by pyrophosphate. Alkaline Phosphatase (ALP) promotes vascular
calcification by hydrolyzing pyrophosphate. Epigenetic mechanisms regulation by Sanae Ezzaki1, Imane Failal1, Rania Elafifi1, Salma siham Elkhayat1,
Apabetalone downregulates pathways involved in vascular calcification. Ghizlane Medkouri1, Benyounes Ramdani1
1
This study assessed the combined impact of ICAC and elevated serum ALP on CHU ibnrochd, nephrology, CASABLANCA, Morocco
mortality among chronic HD patients.
METHOD: vascular calcifications represented by ICAC were measured simultaneous BACKGROUND AND AIMS: Despite progress these recent years in support the
with mineral bone disease parameters including serum ALP of chronic HD patients hemodialysis, chronic pain remains a problem concern that ultimately affect the
who underwent non-contrast brain computerized tomography (CT) from 2015 to 2018 quality of life and psycho-emotional state, even among dialysis patients already
in our institution. psychologically fragile. However, it is often overlooked and its characteristics in
RESULTS: This retrospective study included 153 hemodialysis patients (mean age chronic hemodialysis (HDC) are poorly understood. The purpose of this study was to
71.3612.1 years, 60.1% male). Of the total cohort, 12(7.8%) had no brain calcifications evaluate the prevalence, features, impact and treatment of pain in our population of
and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with chronic hemodialysis patients and to determine the factors associated with it.
normal ALP and no calcification as the reference group yielded adjusted odds ratios for METHOD: cross-sectional study conducted in January 2020 including 71 chronic
all-cause mortality of 4.6 (95%CI 1.7-12.7) among patients with brain calcifications and hemodialysis patients from the nephrology department of the CHU ibn rochd
normal ALP, p=0.003, and odds ratios for all-cause mortality of 6.1 (95%CI 2.1-17.7) CASABLANCA. They were subjected to a questionnaire on socio-demographic
among patients with brain calcifications and increased ALP. characteristics, the characteristics of the pain, its impact on daily life, the various
CONCLUSION: We founded an independent association between ICAC and the risk treatments performed. The pain is chronic if it persists for more than 3 months. The
of death among hemodialysis patients. The combined effect of ICAC and increased intensity was assessed using a visual analog scale.
ALP was significantly associated with higher odds-ratio for all-cause mortality in RESULTS: Of the 71 patients, 64.4% report chronic pain, the average age of our
chronic HD patients and may contribute to the risk stratification of these patients. patients was 46.5 years, ranging from 16 to 93 years, with a sex ratio M/F 1.1, seniority
hemodialysis was 17.3 years.
The pain is continuous, frequent, intermittent and rare in respectively 55.5%, 27.5%,
13.7%, 3.44% of cases, it is a weak, moderate, severe, very severe in respectively: 13.7%,
58.6%, 17.24%, 10.3%, causing musculoskeletal was predominant in 75.8% of cases, the
most common sites are: shoulders (47,23%), knees (34.5%), the head (41.2%) and the

i424 | Abstracts
Nephrology Dialysis Transplantation Abstracts
back (19.65%). It resounded on the patient’s daily activity in 55.17%, and sleep in
41.3%, the treatment was essentially based analgesics in 58.6% of cases, these analgesics
were level 1 in 47.1% cases and level 2 in 52.9% of cases. This is taken daily in 28.5% of
patients, common in 42.8% and 28.5% rare among of them, the disappearance of pain
was achieved in 65.51% of cases. In perdialyse, the intensity of the pain does not change
in 79.4% of patients.
Pain was favored by advanced age and age dialysis (advanced age (p = 0.043) and age
dialysis (p = 0.01).)
CONCLUSION: Chronic pain is a major problem in hemodialysis by its high
prevalence, its significant intensity and its impact on life daily patient. However its
management remains inadequate. Regular assessment of pain using a well-codified
questionnaire is necessary to improve the care of dialysis patients.

MO753 RELATIONSHIP BETWEEN MINERAL BONE DISEASE AND


ATHEROSCLEROSIS IN NON-DIABETIC PERITONEAL
DIALYSIS PATIENTS

Andreea Gabriella Andronesi1,2, Luminita Iliuta3, Cristina Cristache2,


Andreea-Florentina Burcea2, Gabriela Elena Lupusoru1,2, Bogdan Obrisca1,2,
Danut Andronesi4, Mircea Lupusoru5, Bogdan Marian Sorohan1,2, Gener Ismail1,2
1
Carol Davila University of Medicine and Pharmacy, Nephrology Department,
Bucharest, Romania, 2Fundeni Clinical Institute, Nephrology Department, Bucharest,
Romania, 3Carol Davila University of Medicine and Pharmacy, Department of
Biostatistics, Marketing and Medical Technology, Bucharest, Romania, 4Fundeni Clinical
Institute, General Surgery and Liver Transplant Department, Bucharest, Romania and
5
Carol Davila University of Medicine and Pharmacy, Physiology Department, Bucharest,
Romania

BACKGROUND AND AIMS: The term chronic kidney disease-mineral bone


disorder has the role of highlighting that the disturbed mineral and bone metabolism is
a major contributor to vascular calcification and finally cardiovascular disease in
chronic kidney disease (CKD), especially in hemodialysis. This relationship was less
studied in peritoneal dialysis (PD). The aim of the present study was to evaluate the
impact of metabolic bone disorder (MBD) on symptomatic atherosclerosis (stable
angina SA, acute coronary syndrome ACS, ischemic stroke, peripheral artery disease
PAD) in non-diabetic PD patients. We choose to exclude diabetic patients since they
are already at increased risk for atherosclerosis.
METHOD: We performed a prospective study in non-diabetic population of patients
in stable PD programme for at least 6 months. We analysed clinical and biological
parameters of calcium-phosphate metabolism (calcemia Ca, phosphatemia P, CaxP
product, intact parathormone iPTH), presence of atherosclerotic disease and we
performed carotid ultrasound for measurement of intima media thickness (IMT) as a
marker for subclinic atherosclerosis. Independent risk factors for atherosclerotic
disease were identified by multivariate analysis through logistic regression using IBM
SPSS ver. 20.0.
RESULTS: 246 consecutive non-diabetic PD patients (pts) were included (128M,
118F), mean age 56.3 þ 15.7 years (20-85), with a follow up of 6.561.1 years. 19 pts
(7.7%) had calcemia (Ca)>10.2 mg/dl, no patient had a Ca<8.2 mg/dl, 127 pts (51.6%)
had phosphatemia (P)>5.5 mg/dl, 45 pts (18.3%) had CaxtaP product>55 mg2/dl2, 68
pts (27.6%) had iPTH<150 pg/ml, 95 pts (38.6%) had iPTH>300 pg/ml. We found a
weak positive correlation between IMT and Ca (r=0.283, p=0.005); pts with iPTH<150
pg/ml and those with iPTH>300 pg/ml had a higher risk of increased IMT compared
to pts with iPTH 150-300 pg/ml (OR 4.1, p=0.009, for iPTH<150 pg/ml, respectively
OR 3.4, p=0.01 for iPTH>300 pg/ml). Pts with atherosclerotic disease had significantly
higher P and CaxP, without differences regarding Ca and iPTH (Table 1). An
iPTH<150 pg/ml was a risk factor for SA, ACS and PAD, while iPTH>300 pg/ml was
a risk factor for SA and ACS (Table 2). We perfomed multivariate analysis to identify
independent risk factors for SA, ACS, stroke and PAD by entering in the analysis the
factors identified in univariate analysis to be significantly associated with different
manifestations of atherosclerosis. Among independent risk factors identified for
atherosclerotic disease, iPTH<150 pg/ml was risk factor for SA (adjusted OR 11.5, MO754 THE INTERRELATIONSHIP BETWEEN FLUID OVERLOAD
p=0.007) and ACS (adjusted OR 221.4, p=0.01), iPTH>300 pg/ml was risk factor for AND VASCULAR STIFFNESS IN HEMODIALYSIS PATIENTS: A
ACS (adjusted OR 5.2, p=0.03), CaxP >55 mg2/dl2 was risk factor for ACS (adjusted SCOPING REVIEW
OR 33.5, p=0.02) and ischemic stroke (adjusted OR 4.4, p=0.01). No parameters of
calcium-phosphate metabolism were identified as independent risk factors for PAD. Aya Lafta1, Aminu Bello1, Sara Davison1, Stephanie Thompson1,
CONCLUSION: We found significant independent correlations between different Branko Braam1,2
parameters which characterize MBD and presence of symptomatic atherosclerosis in 1
University of Alberta, Medicine/Nephrology, Edmonton, Canada and 2University of
non-diabetic PD pts. The most important risk factors identified were abnormally low Alberta, Physiology , Edmonton, Canada
or high iPTH level, and elevated CaxP. The most striking result was the low iPTH
associated with SA and especially ACS, suggesting that an adynamic bone is incapable
BACKGROUND AND AIMS: Fluid overload and vascular stiffness are two
to buffer the serum calcium and phosphate, thus increasing the risk of vascular
independent predictors of cardiovascular events in hemodialysis (HD) patients. To
calcifications. Future studies may address the issue whether correction of these
date, observational and interventional studies that investigated the effect of inter- and
parameters may be associated with attenuation of atherosclerotic disease in this
intradialytic fluid overload changes on vascular stiffness in HD patients are very
population.
limited. We performed a scoping review to explore existing reports about effects of
fluid overload on vascular stiffness in adults receiving HD treatment and to identify
knowledge gaps for future research.
METHOD: We followed the framework originally developed by Arksey and O’Malley.
We searched Medline, Embase, CINAHL, and Cochrane Database of systematic
reviews from inception to October 29, 2019. References of review papers were screened
for relevant studies not identified from the initial search until saturation is achieved.

10.1093/ndt/gfab097 | i425
Abstracts Nephrology Dialysis Transplantation

RESULTS: Of 666 eligible studies, nineteen studies met the inclusion criteria. These fatal electrolyte disorder. New effective strategies for managing hyperkalaemia have
included clinical observational studies (n=16) and randomized controlled trials (n=3). recently become available. However, as yet, there is insufficient experience in routine
In general, most of the identified studies had small sample size and short term of follow clinical practice in HD.
up. Studies use different definitions of fluid overload and vascular stiffness. Measures of The aim of our study was to report the prevalence of chronic hyperkalaemia and
relative fluid overload like the ratio of extracellular fluid/intracellular fluid, fluid analyse the effects of different treatment strategies on potassium management, ratio of
overload/extracellular fluid, and/or extracellular fluid/total body fluid were used as a adherence and gastrointestinal symptoms in our HD population.
representative of fluid status. Pulse wave velocity and augmentation index were used METHOD: A 12-week, prospective, single-centre study in HD patients with chronic
interchangeably as vascular stiffness measures. The accumulated findings were hyperkalaemia (>5.5 mmol/l). Three study phases were established: Phase 1 — dietary
inconsistent and inconclusive. There was no consensus whether intradialytic fluid advice (DA); Phase 2 — calcium polystyrene sulfonate resins (CPSRs); and Phase 3 —
volume changes affected vascular stiffness. In the majority of the observational studies, patiromer. In each phase, we analysed sociodemographic data, related biochemical
a decrease in pulse wave velocity or augmentation index correlated with a decrease in data, treatment adherence and compliance (Simplified Medication Adherence
blood pressure after fluid correction by HD treatment. The randomized clinical trials Questionnaire [SMAQ]), gastrointestinal symptoms (Gastrointestinal Symptom Rating
used different methods and technologies for the correction of fluid overload, thereby, Scale [GSRS]), HD characteristics and usual medical treatment.
results were conflicting. RESULTS: 29.2% hyperkalaemia (46% mild); 13 patients (61.5% female); mean age
CONCLUSION: Current literature is insufficient to justify whether fluid overload 63.8 6 14.1 years and 46.4 6 41.6 months on HD. Serum K values decreased
changes have a direct effect on vascular stiffness in HD patients. The findings were significantly (*p <0.05) only in phase 3 (–0.75 mmol/l), with a higher percentage of
conflicting which limits the comparisons of studies and generalization of findings. patients reaching optimal K range. Compared with CPSRs, patiromer yielded
These knowledge gaps urge the need for further clinical studies to enhance the significantly better overall GSRS scores: abdominal pain (3.7 versus 2.5), constipation
understanding and to improve the quality of research in this topic. This includes (7.1 versus 5.3), indigestion (6.2 versus 5.6); and also better treatment compliance. No
standardized definitions and methodologies as well as longer term of follow up. significant changes were found in any other biocbhemical data, HD characteristics or
usual medication over the course of the study.
CONCLUSION: Chronic hyperkalaemia is a highly prevalent disorder on our HD
unit. Compared to dietary advice and traditional potassium binders; patiromer was
MO755 SPONTANEOUS SOFT TISSUE HEMATOMAS IN ESRD effective in managing chronic hyperkalaemia, leading to improvement in
PATIENTS WITH SYMPTOMATIC SARS-CO-V2 INFECTION – gastrointestinal symptoms and treatment adherence with no associated severe adverse
THE EXPERIENCE OF AN EMERGENCY NEPHROLOGY AND effects. Thus, considering our results, we shall consider patiromer a first-line treatment
DIALYSIS DEPARTMENT for chronic hyperkalaemia in our patients with HD.

Vacaroiu Ileana Adela1,2, Cristiana David1,2, Dragomirescu Razvan Ion Florin1,2,


Flavia Liliana Turcu1,2, Dumitraciuc Cristina3, Calinoiu Cristina3,
Radulescu Daniela1,2 MO757 COMPARISON OF ANTI-COAGULATION AND NO ANTI-
1
“Carol Davila” Medicine and Pharmacy University, Clinical Department no.3, COAGULATION IN DIALYSIS PATIENTS WITH ATRIAL
Nephrology, Bucharest, Romania, 2Clinical Emergency Hospital “Sf. Ioan”, Nephrology FIBRILLATION: A SINGLE CENTER RETROSPECTIVE STUDY
and Dialysis, Bucharest, Romania and 3Clinical Emergency Hospital “Sf. Ioan”, Vascular
Surgery, Bucharest, Romania Jun Young Lee1, Jae Won Yang1, Jae Seok Kim1, Seong Ok Choi1,
Byoung Geun Han1
1
BACKGROUND AND AIMS: While actual proofs plead for an increased thrombotic Yonsei University Wonju College of Medicine, Nephrology, Weonju, Korea, Rep. of
risk in SARS-Co-V2 infection and need for anticoagulant therapy in severe cases, we South
report suspicious occurrence of hemorrhagic events in a series of ESRD patients.
METHOD: 59 patients with stage 5 CKD were hospitalized in a two months interval, BACKGROUND AND AIMS: Atrial fibrillation (AF) is common arrhythmia in end
since our hospital was designated for the admission of mild-severe SARS-Co-V2 stage renal disease patients. Although, the need of anticoagulation to prevent stroke
patients exclusive. 8 patients were admitted for RRT initiation and 51 were and thromboembolism is increasing, the efficacy of anticoagulation is not proven in
maintenance dialysis patients admitted with SARS-Co-V2-associated complications. most of study. We retrospectively analyzed the risk and benefit of anticoagulation in
Beside hemodialysis and treatment of chronic complications of ESRD, all patients were dialysis patients with AF.
treated, according to the stage and gravity of SARS-Co-V2 infection and under METHOD: By using medical record, we retrospectively analyzed all data of 99 patients
continuous supervision of an infectious disease physician, with antivirals, antibiotics, who received dialysis therapy and diagnosed AF.
anticoagulants and IL-antagonists. Daily or at 2 days laboratory monitoring was RESULTS: Among 99 patients who diagnosed AF with dialysis 36 patients received
performed and consisted in evaluation of inflammatory markers, clotting tests, anticoagulation (17 coumadin, 19 apixaban 2.5mg bid), 63 patients received no
complete hemogram, D-dimer testing, IL-1 and IL-6 serum levels, serum urea, anticoagulation. There was no significant difference of baseline characteristics between
creatinine and albumin. anticoagulation, and no anticoagulation patients. Although no anticoagulation group
RESULTS: In 6 cases spontaneous soft tissue hematomas were noted, totalizing a experienced more all-cause (39.7% vs 32.4%, p=0.572) and cardiovascular mortality
number of 9 hematomas documented through ultrasound and CT-scan. In order of (17.6% vs 10.8%, p=0.197) than anticoagulation group it was not statistically
frequency, the locations were: 4 rectus abdominalis hematoma, 2 in the external significant. Compared to apixaban 2.5mg bid patients, coumadin anticoagulation
oblique, 2 in gluteus maximus muscle, and one in the right psoas muscle. The source of patients experienced more frequent mfig
the bleeding could not be identified in any patient. The occurrence of spontaneous ajor adverse cardiovascular events (35.3% vs 15.8%, p=0.109) but it was not statistically
hematomas was correlated with the D-dimer values (p=0.02), prolonged significant in multi variate Cox regression analysis (Hazard ratio 1.143, 95%
anticoagulation (over 7 days), albumin levels (p=0.01), platelets count (p=0.05). We Confidence Interval 0.503-2.597).
found no correlation with the serum urea, creatinine, hemoglobin, INR, or with the CONCLUSION: Apixaban 2.5mg bid was not inferior than coumadin considering risk
dialysis age. In all these cases cough was severe. A conservative approach was and benefit of anticoagulation in dialysis patients.
instituted, with daily US monitoring, withdrawal of anticoagulants and antiplatelet
medication, and blood transfusions. 2 patients necessitated surgical procedures and
two deaths were recorded.
CONCLUSION: In this brief report, we observed that in chronic hemodialysis patients
infected with SARS-Co-V2, risk of hemorrhagic manifestations may overcome the
benefits of anticoagulant routine therapy. There is a need to explore further this risk in
the future; until then, a careful individualized assessment of the safety and indications
for anticoagulant therapy regimens is mandatory for ESRD patients with symptomatic
new Coronavirus infection.

MO756 MANAGEMENT OF CHRONIC HIPERKALAEMIA IN CLINICAL


PRACTICE IN HAEMODIALYSIS

Vicent Esteve Simo 1, Irati Tapia Gonzalez1, Ursula Vadillo1, Claudia Guzman1,
Miquel Fulquet Nicola s1, Fatima Moreno Guzm an1, Vero
nica Duarte Gallego1,
Monica Pou Potau1, Anna Saurina Solé1, Diana Oleas1, Manel Ramırez de
Arellano Serna1
1
Consorci Sanitari Terrassa, Nephrology, Terrassa, Spain
MO757 Figure1: Comparison risk of cardiovascular mortality between
anticoagulation and no anticoagulation dialysis patients with atrial fibrillation
BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) on (p>0.05).
haemodialysis (HD) have an increased risk of hyperkalaemia, a serious and potentially

i426 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO758 DIAGNOSTIC ACCURACY OF ELECTROCARDIOGRAPHIC 24) of all patients with CVD in this group. The second place is occupied by angina, it
METHODS OF ESTIMATION OF LEFT VENTRICULAR was found in 18.5% (n=5) cases among patients with CVD. Combined CVS
HYPERTROPHY IN A HAEMODIALYSIS POPULATION pathologies were less common in the rural group. A total of 8 patients (29.6% of all
CVD cases) had several CVDs.
Sofia Skampardoni1, Philip A. Kalra2, Darren Green2 CONCLUSION: ardiovascular diseases in the urban population (62.5%) occur
1
The University of Manchester, United Kingdom and 2Salford Royal NHS Foundation almost one and a half times more often than in the rural population (44%). Combined
Trust (Formerly Hope Hospital), United Kingdom CVD pathology occupies a leading place in the structure of CVD in patients with CKD
5D, both urban and rural.
BACKGROUND AND AIMS: Left ventricular hypertrophy is common in end stage
renal disease (ESRD) and haemodialysis. Its association with cardiovascular outcomes
has been demonstrated. In this study we evaluated the diagnostic accuracy of
electrocardiographic methods of calculating LVH compared to Real Time 3-
Dimensional Echocardiogram (RT3DE) which we used as a surrogate gold standard
test.
METHOD: This study was performed as a post-hoc analysis of a sub-group of patients
enrolled into the Salford Kidney Study (SKS). Patients included into this analysis are
from the sub-group of SKS previously known as the CRISIS-HD cohort. All adult
haemodialysis patients at Salford Royal NHS Foundation Trust, UK or one of its
satellite units are considered for inclusion.
In this study we examined the sensitivity, specificity, positive predictive value and
negative predictive value of Sokolow – Lyon and Romhilt –Estes methods in
comparison to RT3DE.
RESULTS: The final sample comprised 44 patients. The vast majority were Caucasian
(39 patients). The mean age of the patients was 62 6 13 years and mean time on
dialysis 5.1 6 2.9 years. The sensitivity of both ECG methods for diagnosis of LVH was
very low. This was the case for the whole sample and also for individual groups.
Romhilt – Estes was marginally better than Sokolow – Lyon and that was especially the
case for male patients.
CONCLUSION: Our study shows that ECG methods for assessment of LVH that rely
on voltage criteria have very low sensitivity and unreliable specificity compared to
RT3DE and also conventional M –Mode echocardiography. As a result, they could not
be reliably used as a quick and inexpensive method of LVH estimation in clinical
practice in the case of haemodialysis patients.

MO759 COMPERATIVE STUDY OF THE CARDIOVASCULAR SYSTEM MO760 HEPARIN-INDUCED LDL PRECIPITATION IN A NON-
IN PATIENTS WITH CKD ON HEMODIALYSIS IN URBAN AND DIABETIC DIALYSIS PATIENT AS RESCUE THERAPY FOR
RURAL POPULATIONS OF UZBEKISTAN CRITICAL ISCHEMIC FOOT: A CASE REPORT

Olimkhon Sharapov1,2, Botir Daminov1,2 Gabriele Donati1, Angelodaniele Napoletano1, Anna Scrivo1, Lorenzo Gasperoni1,
1
Tashkent Pediatric Medical Institute, Internal Disease, Tashkent, Uzbekistan and Fulvia Zappulo1, Agnieszka Prygocka1, Vera Minerva1, Gaetano La Manna1
2
Republican Specialized Scientific Practical Medical Center of Nephrology and Kidney 1
IRCCS S.Orsola University Hospital, Nephrology Dialysis and Renal Transplantation
transplantation, Nephrology, Tashkent, Uzbekistan Unit, Bologna, Italy

BACKGROUND AND AIMS: According to recently published WHO data, kidney BACKGROUND AND AIMS: Dialysis per se represents an independent risk factor
disease has been the 10th leading cause of death in the world over the past 20 years. for peripheral arterial obliterating disease and in particular for critical ischemic limb.
The lethality of dialysis patients with cardiovascular pathology is 3 times higher than Conventional by-pass surgery or endovascular revascularization frequently did not
that of patients without CVD. This is especially pronounced in developing countries. avoid major limb amputation in dialysis patients or are excluded for wild calcificating
Uzbekistan is a country with a population of 34 million and has an equal urban and atherosclerosis. Extracorporeal LDL-apheresis by means of Heparin-induced LDL
rural population. In this regard, it is of interest to comparatively study the structure of Precipitation (H.E.L.P.) is proposed in some cases in combination to the traditional
CVD in patients with CKD stage 5D of the rural and urban population of Uzbekistan. clinical approach.
METHOD: We examined 165 (90 men and 75 women) patients with CKD stage 5 METHOD: Here we describe the case of a 83-year old patient who undergoes thrice
receiving dialysis in urban and rural areas of Uzbekistan. The patients were divided weekly hemodialysis from 1 year and who is affected by COPD, ischemic cardiopathy,
into 2 groups depending on their permanent place of residence and the medical center previous stroke and had a Charson score of 6. He was also affected by dry necrosis of
where they receive hemodialysis. 104 (51 men and 53 women) patients were included the second toe and parcel of the third toe of the right foot. The patient was not affected
in the Urban group and 61 (39 men and 22 women) patients were included in the Rural by diabetes. Lower limb arteriography showed right tibial artery obstruction anterior to
group. The average age of the urban population was 49.7 6 1.38 years, the rural the distal and dorsal third and severe stenosis with short sub-obstruction in
population was 45.5 6 1.83 years. All patients underwent programmed hemodialysis subarticular area of the left popliteal artery. The plan foot x-ray excluded osteomyelitis.
according to the standard scheme for 4 hours 3 times a day (12 hours/week). The The vascular surgery consultant found the arterial lesions not suitable for
average duration of hemodialysis in the Urban group was 37.0 6 4.77 months (M 6 revascularization advising monitoring and dressing of lesions. Nonetheless the patient
m) and 16.6 6 2.4 months in the Rural group. The main causes of CKD 5D in both complained of pain and opioid analgesics were administered. Cardioaspirin and
groups were glomerulonephritis (Urban-36.5%, Rural-62%) and type 2 diabetes atorvastatin were also administered. The patient was considered eligible for (H.E.L.P.)
(Urban-31.7%, Rural-18%). apheresis for the rescue of his limb. The patient underwent 8 sessions of H.E.L.P.
RESULTS: CVD comorbidity occurred in 55,8% (n=92) of all 165 examined patients, apheresis once a week for eight weeks in a non-dialysis day. His vascular access was a
of which 52 were men and 40 were women. The most common CVDs in all groups permanent cuffed hemodialysis catheter. H.E.L.P. consists firstly in plasma separation,
were hypertension (51%, n=84), coronary heart disease, presented as angina (28%, then apolipoprotein B-containing lipoproteins and fibrinogen are precipitated at a pH-
n=47), heart failure (14%, n=23) and various types of arrhythmias (5%, n=8). 77% value of 5.12 by the addition of a mixed acetate-heparin buffer to plasma. Before
(n=127) of patients had anemia due ESRD. In the group Urban(n=104), 62.5% (n=65) returning the plasma to the patient, the excess heparin is adsorbed and the pH
had CVD. The main CVD was Hypertension. It was found in 92% (n=60) of patients normalized by a bicarbonate dialysis. A total of 3 litres of plasma per session was
with CVD in this group. Less (65%, n=42) were patients with angina. Heart failure was treated. Each session lasted 3 hours and was carried out in the Dialysis ward. Blood
detected in 31% (n=20) of patients. Arrhythmia was diagnosed in only 5% (n=5). A samples were obtained directly before and immediately after each H.E.L.P. apheresis
large number of combined CVD have been identified. 69% (n=45) of all patients with for laboratory measurements.
CVD had a combined CVDs in different combinations. The most common RESULTS: A C-reactive protein of 4 mg/dL reflected systemic inflammation. At
combination was hypertension þ angina (n = 26). It accounted for almost 58% of all baseline (prior to H.E.L.P. apheresis), fibrinogen was 394 mg/dL, LDL cholesterol was
combined cases. Only 28% (n=17) of all cases with hypertension had "isolated" 122 mg/dL, lipoprotein(a) was 50.5 mg/dL. Total cholesterol was fairly normal even
hypertension. The main combination with hypertension was hypertension þ angina before H.E.L.P. apheresis with concentrations of 170 mg/dL. The pre vs post H.E.L.P.
(43%, n=26), 11% (n=11) of patients had hypertension þ angina þ heart failure, a values were significantly reduced for all the parameters considered (p<0.0001). The
combination in the form of hypertension þ angina þ arrhythmia had 3% (n=3) median reduction rate (RR) per session for fibrinogen was 63.8% (range 57.1-75.3%),
patients. Relatively fewer (n = 27, 44%) CVD were found in the Rural group. The most for lipoprotein(a) 66.1% (range 54.6-76.5), for LDL-cholesterol 50.8% (range 40-
frequent CVD was also a hypertension. Patients with hypertension made up 89% (n = 59.3%), for total cholesterol 40.7% (range 35.4-43.5%) (Figure 1). C reactive protein

10.1093/ndt/gfab097 | i427
Abstracts Nephrology Dialysis Transplantation

RRs was 61.2% (range 56.2-63.2%). Nonetheless, in the period between the H.E.L.P. METHOD: canine valvular interstitial cells (VICs), valvular endothelial cells (VECs)
apheresis a rebound was observed: for fibrinogen it was 64.9% (range 52.5-73.4%), for and human umbilical vein endothelial cells (HUVECs) were used in this study. CKD
total cholesterol 29.2% (range -4 – 54.3%), for LDL cholesterol 36.4% (range -20 – mice (C57b and Tek-EGFP-PolyA) was build by 0.2% adenine-diet for 6 weeks and HP
68.8%), for lipoprotein(a) 69.1% (range 44.1-73.9%). After the 8 sessions of H.E.L.P. diet/NP diet for 10 weeks.
apheresis, fibrinogen RR was 21%, LDL cholesterol RR was 75.4%, total cholesterol RR RESULTS: As for VICs, HP induced qVICs transfer into aVICs, not oVICs, which was
was 64%, lipoprotein(a) RR was 17%. After 6 months the patient underwent minor characterized with upregulated level of smoothelin and viemitin. There was no calcium
amputation of the second toe of the right foot, the third toe healed completely. The accumulation was observed, suggesting that VICs do not have the ability to synthesize
lesions of the foot before and after 1 year after HELP are showed in Figure 2. calcium crystals under pure HP intervention. As for VECs, aVICs activated by HP
induced VECs EndMT in a transwell-assay, which was characterized with decreasing
protein levels of endothelial markers (CD31, vWF, VE-cadherin) and increasing
protein levels of mesenchymal makers (a-SMA, FSP1, N-cadherin). Then, IL-8 was
found as the main factor releasing from VICs to induce VECs EndMT. In vitro, the
concentration of IL-8 in the lower chamber could reach 2-4ng/ml. Reparixin was used
to inhibit IL-8 receptor of VECs, which could relive aVICs-induced EndMT. In vivo,
the expression of valve CXCL-2 (the mouse IL8 functional homolog) was increased in
HP-diet compared with NP-diet, though the serum level of CXCL-2 was similar
between two groups. AAV9-sm22a-CXCL-2 and Reparixin could inhibit VECs EndMT
by inhibiting VICs relasing CXCL-2 and inhibiting VECs IL-8 receptor in CKD mice of
Tek-EGFP-PolyA respectively. Then, IL-8 was found to induced VECs EndMT by
miR-214-3p/PTEN/Akt pathway. Inhibiting EndMT by blocking IL-8/miR-214-3p
could alleviate ECM accumulation.
CONCLUSION: HP could induce qVICs transfer into aVICs, and aVICs could cause
VECs EndMT via IL-8/miR-214-3p/PTEN/Akt pathway. Both take part in ECM
accumulation in CKD-induced VC.

MO762 RELATIONSHIP BETWEEN INFLAMMATION AND


PERIPHERAL ARTERIAL DISEASE MEASURED BY ANKLE-
BRACHIAL INDEX IN CHRONIC HEMODIALYSIS PATIENTS

Yanet Parodis1, Tania Monzon1, Francisco Valga2,3, Gloria Anton-Perez1


MO760 Figure 1: Fibrinogen and Lipoproteins values pre and post HELP apheresis 1
sessions CENTRO DE DIALISIS AVERICUM NEGRIN LAS PALMAS, Las Palmas de Gran Canaria,
Spain, 2University Hospital of Gran Canaria Dr. Negrin, Nephrology, Las Palmas de
Gran Canaria, Spain and 3Universidad de las Palmas de Gran Canaria, Doctoral
School, Las Palmas de Gran Canaria, Spain

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is very common in


patients with chronic kidney disease. There are predisposing factors such as high blood
pressure, diabetes mellitus, and dyslipidemia that are highly prevalent in this
population. The ankle-brachial index (ABI) is a widely validated diagnostic method for
the diagnosis of PAD. A value below 0.9 is suggestive of this pathology. On the other
hand, inflammation is a phenomenon that favors development of atherosclerosis and
therefore could be another predisposing factor for PAD. There are emerging markers
of inflammation such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte
ratio (PLR) and systemic immune-inflammation index (SII) that have an excellent
correlation with classic markers such as C-reactive protein (CRP). The objective of our
study was to determine whether there is a relationship between ABI values and the
degree of inflammation in patients.
METHOD: A retrospective observational cross-sectional study was conducted in our
prevalent hemodialysis population between April-May 2019. ABI was measured
through the Microlife WatchBP Office ABITM device. The sample was divided into two
groups using 0.9 as a cut-off point: group 1 (ABI <0.9) and group 2 (ABI> 0.9).
MO760 Figure 2: Critical Ischemic Foot before HELP and after 1 year from 8 HELP
Inflammatory ratios (NLR, PLR and SII) and other parameters of bone kidney disease
sessions
such as serum calcium, bicarbonate, phosphorus, parathyroid hormone (PTH),
magnesium and vitamin D were determined.
RESULTS: 100 patients with chronic kidney disease on chronic hemodialysis
CONCLUSION: Drastic reductions of fibrinogen, LDL cholesterol and lipoprotein(a),
belonging to our Avericum Negrin center were analyzed. 42% (N = 42) of the sample
together with an adequate wound care, reduced the risk of major limb amputation in
were women and 42% (N = 42) were diabetic. The etiology of kidney disease was: 12%
this dialysis patient with critically ischemic foot that was not qualified for
(N = 12) renal nephroangiosclerosis, 35% (N = 35) diabetic nephropathy, 14% (N = 14)
revascularization.
chronic glomerulonephritis, 8% (N = 8) polycystic kidney disease, 17% (N = 17)
unknow and 14% (N = 14) others. 19% (N = 19) had a central venous catheter as
vascular access. The mean values of inflammatory and renal bone disease parameters
are described in Table 1. The values of PLR and SII index were significantly higher in
MO761 THE CONTRIBUTION OF HIGH-PHOSPHORUS IN patients with ABI <0.9. (Figures 1 and 2).
EXTRACELLULAR MATRIX ACCUMULATION OF VALVULAR
CALCIFICATION IN CHRONIC KIDNEY DISEASE

Liting Wang1,2, Yuxia Zhang1, Yujia Wang2, Rining Tang2


1
Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine
and 2Institute of Nephrology, Zhong Da Hospital, Southeast University, School of
Medicine, P.R. China

BACKGROUND AND AIMS: The characteristics of valvular calcification (VC) in


early stage are extracellular matrix (ECM) accumulation and muti-cells activation. In
our previous work, we found high-phosphorus (HP) diet aggravated ECM
accumulation in both aortic valve and mitral valve in rats with chronic kidney disease
(CKD). However, the underlying mechanism of HP contribution in ECM
accumulation of CKD-induced VC is still unknown.

i428 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO762 Table 1: Inflammatory and calcium phosphorus metabolism parameters
according to ABI values

Group 1: Group 2: P value


ABI <0.9 ABI>0.9
PCR (mg/L) mean6SD 17,93643.34 8.43611.32 0.283
Calcium (mg/dL) mean6SD 9.7963.65 9.9769.11 0.597
Bicarbonate (mmol/L) 21.0262.36 21.4462.5 0.463
mean6SD
Albumin (g/dL) mean6SD 3.6660.39 3.6360.44 0.876
Phosphate (mg/dL) 4.861.58 4.8261.62 0.749
mean6SD
PTHi (pg/ml) mean6SD 237.516164.83 522.066718.1 0.027
Magnesium (mg/dL) 2.8963.31 2.2260.31 0.974
mean6SD
Product CaxP mean6SD 41.71615.89 42.71615.89 0.899
25OH-vitamin D (ng/mL) 26.32615.28 25.68613.82 0.923
mean6SD
MO762 Figure 1: PLR values according to ABI Ferritin (ng/mL) mean6SD 624.466398.89 505.36652.03 0.054
NLR mean6SD 4.8265.66 3.6462.55 0.186
PLR mean6SD 181.49669.88 148.68667.03 0.019
SII mean6SD 999.3261047.77 769.26674.41 0.0001

MO762 Figure 2: SII values according to ABI

CONCLUSION: Patients with peripheral arterial disease (ABI <0.9) had higher PLR
and SII values

10.1093/ndt/gfab097 | i429
Nephrology Dialysis Transplantation 36 (Supplement 1): i430–i441, 2021
10.1093/ndt/gfab103

DIALYSIS. VASCULAR ACCESS

MO763 THE VON WILLEBRAND FACTOR IS A KEY PLAYER IN


ARTERIOVENOUS FISTULA MATURATION*

Suzanne Laboyrie1, Alwin De Jong2, Margreet De Vries2, Reshma Lalai1,


Laisel Martinez3, Roberto Vazquez-Padron3, Joris Rotmans1
1
LUMC, Nephrology, Leiden, Netherlands, 2LUMC, Surgery, Leiden, Netherlands and
3
University of Miami Leonard M. Miller School of Medicine, Vascular Surgery, Miami,
United States of America

BACKGROUND AND AIMS: Low arteriovenous fistula (AVF) maturation rate


remains a bottleneck in creating a long lasting lifeline to hemodialysis. AVF maturation
is determined by the intricate balance between outward remodeling (OR) and
formation of intimal hyperplasia (IH), during which vascular smooth muscle cell
(VSMC) proliferation is essential. Recently, the von Willebrand Factor (VWF) has
been shown to induce VSMC proliferation in vitro and in vivo. In this study we MO763 Figure 1: Blood flow (mL/s) in the common carotid artery (CCA) of the
investigate the role of VWF on VSMC proliferation and AVF functionality to gain a AVF was measured before AVF creation (baseline), immediately post-surgery (t=0), at
better understanding of the relationship between the two latter processes. t=7 and t=14.
METHOD: AVFs were created in wild-type (WT) and VWF (-/-) deficient (B6.129S2-
Vwf tm1Wgr) mice using the external jugular vein and the common carotid artery
(CCA). Mean velocity and diameter of the CCA was measured at baseline before
surgery, t=0 immediately post-surgery, t=7 and t=14 using ultrasonography to
determine flow volume (mL/s). The mice were sacrificed at t=14, AVFs were collected MO764 AVF VOLUME BLOOD FLOW REDUCTION AS THE FIRST
and OR and IH were analyzed using Weigert’s elastin and aSMA staining, using the STAGE OF TREATMENT OF CENTRAL VEIN STENOSIS IN HD
Mann-Whitney test. To study VSMC proliferation in vitro, VSMCs were isolated from PATIENTS
vena cava explants. VSMCs from VWF -/- mice were cultured with 10% VWF -/-
plasma with or without addition of VWF (Wilfactin). Proliferation was measured after Aleksei Zulkarnaev1, Vadim Stepanov1, Andrey Vatazin1, Ekaterina Parshina2,
40 hours. Humane patient-matched samples were obtained during two stage brachio- Mariya Novoseltseva1, Julia Chursinova1
basalic AVF surgery: the native veins at creation and venous AVF samples at 1
Moscow Regional Research and Clinical Institute, Surgical department of transplanta-
transposition. Maturation was defined as a luminal AVF diameter of > 6 mm. Samples
tion and dialysis, Moscow, Russia and 2Saint Petersburg State University Hospital,
were stained for VWF and aSMA. Positively stained tissue in the medial layer was
Department of outpatient dialysis, Saint-Petersburg, Russia
quantified using Histoquant and analyzed with the Wilcoxon signed-rank test.
RESULTS: WT mice showed better outcomes in AVF functionality. Whereas blood
flow did not increase in VWF deficient mice over two weeks after AVF-creation, WT BACKGROUND AND AIMS: It is well-known that central vein stenosis (CVS)
mice showed a steady increase in flow rate from t=0 to t=7 (1.97 fold) and t=14 (3.0 significantly reduces the time of AVF functioning. At the same time, according to
fold) . At 14 days, VWF -/- mice showed significantly reduced OR compared to WT current guidelines (KDIGO, European Vascular Surgery Society, European Best
mice, with a 1.46 fold smaller venous perimeter (p=0.008). Formation of IH was also Clinical Practice), only clinically significant CVS should be treated. Often, CVS
significantly reduced in VWF -/- mice (9.58 fold change, p = 0,0001), with a non- becomes clinically manifest due to a significant increase of AVF volume blood flow
significant 1.42 fold difference in luminal area. Lastly, an 8.05 fold decrease was (Qa) through the matured dialysis access. Aim: to assess the effect of Qa reduction on
observed in aSMAþ cells in the IH of VWF -/-mice (p = 0.0002). In vitro, addition of the CVS clinical course.
VWF caused an 1.5 fold increase in proliferation compared to VWF deficient VSMCs METHOD: We performed a retrospective study included 56 patients who underwent
cultured without VWF (p=0.016). Qa reduction as the first step of treatment, and 62 patients who received endovascular
As for chronic kidney disease (CKD) patients, our study showed significant wall interventions without Qa reduction (balloon angioplasty supplemented with stenting if
thickening and increase in aSMAþ tissue only in matured AVFs. There was significant necessary).
upregulation of VWFþ tissue in the media from native veins to venous AVF samples, Blood flow reduction was performed using banding under intraoperative ultrasound
with 183% in failed AVFs (p= 0.026) and 425% in matured AVFs (p= 0.013). Matured control.
AVFs had a 4.6 fold increase in VWFþ area in the medial layer compared to failed RESULTS: Surgical banding leads to a clinically obvious and statistically significant
AVFs (p= 0.033). decrease in Qa in all patients – fig. 1. In contrast, after endovascular intervention most
CONCLUSION: Our study demonstrates VWF as an inducer of VSMC proliferation of the patients show a modest but statistically significant increase in Qa - fig. 2. All
and thereby both OR and IH. Secondly, we show that VWF is essential for AVF surgeries were performed to reduce the severity of clinical manifestations of CVS. AVF
maturation and that enhanced expression in the media coincides with AVF maturation was better available for immediate cannulation after endovascular interventions than
in CKD patients. after banding: RR=4,537 [95%CI 1,416; 14,84], p=0,0116. However, the probability of
successful cannulation at the third postoperative HD session did not differ between
groups: RR=3.024 [95%CI 0.674; 13.67], p=0.2126. Taking in consideration these
findings, we can conclude that the short-term results of Qa reduction are satisfactory.

MO764 Figure 1: Qa before and after banding.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
MO765 CENTRAL VEIN STENOSES IN HD PATIENTS

Aleksei Zulkarnaev1, Andrey Vatazin1, Vadim Stepanov1, Ekaterina Parshina2,


Mariya Novoseltseva1
1
Moscow Regional Research and Clinical Institute, Surgical department of transplanta-
tion and dialysis, Moscow, Russia and 2Saint Petersburg State University Hospital,
Department of outpatient dialysis, Saint-Petersburg, Russia

BACKGROUND AND AIMS: The prevalence of central vein stenosis (CVS) in


patients on hemodialysis (HD) is difficult to be assessed directly. This is mainly caused
by the variety of clinical signs and the high frequency of asymptomatic CVS. Aim: to
assess the frequency of occurrence of various CVS forms in HD patients.
METHOD: The retrospective observational study is based on the results of treatment
of 1865 HD patients who underwent diagnostic and therapeutic procedures on
vascular access in our center. In case of vascular access dysfunction, patients were
MO764 Figure 2: Qa before and after endovascular intervention. examined according to a local protocol: ultrasound of the peripheral (to exclude lesion
of peripheral AVF segments) and central veins (over the available length), followed
After Qa reduction in case of recurrence of CVS symptoms or absence of their with CT-angiography or percutaneous angiography, if necessary.
complete resolving, we supplemented the treatment with endovascular interventions. RESULTS: AVF/AVG dysfunction was observed in 29.4% of patients (549 of 1865).
Both primary and secondary patency were significantly better than in the case of 211 patients were diagnosed with CVS. The prevalence of CVS was 11.3% (211 of 1865)
endovascular interventions without Qa reduction – fig. 3. among all HD patients and 38.4% (211 of 549) in patients with AVF dysfunction.
Among patients with CVS, 37% (78 of 211) had vein lesions without clinical symptoms
or with minimal manifestations (a tendency to decrease KT/V). The prevalence of
asymptomatic CVS was 4.2% (78 of 1865) in the general population of HD patients and
14.2% (78 of 549) in patients with AVF dysfunction. In case of asymptomatic CVS it
was detected by an ultrasound examination during CVC implantation (N=38), during
unsuccessful attempts to implant CVC (N=29), in the case of recurrent AVF
thrombosis without underlying peripheral segments lesion (N=9) or during
echocardiography (N=2).
The prevalence of asymptomatic CVS among patients without AVF dysfunction was
5.9% (78 of 1316). True prevalence of subclinical CVS among HD patients without
obvious signs of AVF dysfunction may vary widely.
A total of 48.8% (103 of 211) of all CVS cases were treated. At the same time, in 10.7%
(11 of 103) of cases, patients did not present symptoms of CVS, and surgery was
performed due to recurrent AVF thrombosis without damage of the peripheral parts of
MO764 Figure 3: Primary and secondary patency. AVF.
Patients with clinically manifest CVS who received endovascular interventions had a
Moreover, in patients who underwent endovascular interventions without Qa significantly higher risk of AVF loss compared to patients with asymptomatic CVS:
reduction, higher Qa values were associated with decrease of the primary and HR=2.566 [95% CI 1.706; 3.86], log rank p<0.0001. However, patients with an
secondary patency – fig. 4. So, increasing or maintaining large Qa values after asymptomatic CVS had a higher risk of AVF function loss compared to the general HD
endovascular intervention may be an important risk factor for CVS relapse and AVF population (HR=2,051 [95% CI 1,243; 3,384], log rank p= 0.0004) – fig. 1.
function loss.

MO765 Figure 1: Five-year functional secondary patency (the period from the
beginning of the AVF using to the complete loss of its function) in the general
population of HD patients.

The use of CVC is a known risk factor of CVS development. We analyzed the
relationship of CVS risk with multiply CVC placements and catheter dwell time using
the Cox proportional hazards regression model (fig. 2). In the univariate model, a
greater No of CVCs as well as longer time in place increased the risk of CVS. In the
multivariate model (v2=105.516, df=2, p<0.0001), catheter dwell time was no longer
associated with an increased risk of CVC, while the mean number of inserted catheters
remained an important risk factor.

MO764 Figure 4: Correlation of Qa with primary and secondary AVF patency in


patients who underwent endovascular interventions without Qa reduction.

CONCLUSION: Qa is an important factor of CVS clinical manifestation. When


determining treatment strategy, it is necessary to evaluate Qa first and reduce it, if
necessary. Manage of Qa allows to transfer manifest CVS into its subclinical course,
which itself leads to improved treatment results.
Endovascular interventions are the preferred treatment of CVS with clinical
manifestations in a case of underlying normal or suboptimal Qa.
MO765 Figure 2: Association of CVS risk with No of catheterizations and total time
of catheterization.

10.1093/ndt/gfab103 | i431
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: The prevalence of both symptomatic and asymptomatic forms of NPV value) – table 1. “Indirect dialysis signs” also have very low screening efficacy (Se
CVS in HD patients is high. Patients with vascular access dysfunction should be and Sp) and prognostic values – table 2.
carefully examined to identify the asymptomatic CVS. The mean No of
catheterizations is a more important risk factor of CVS than longer catheter dwell time.

MO767 Table 1. Clinical signs.

MO766 EARLY ARTERIOVENOUS FISTULA FAILURE Sign N RR PPV NPV Se Sp PLR h


PREDICTION WITH ARTIFICIAL INTELLIGENCE: A NEW Edema 459 12,05 0,555 0,954 0,917 0,699 3,051 <0,0001
APPROACH WITH CHALLENGING RESULTS
Dilated veins on the 442 5,56 0,75 0,87 0,66 0,91 7,12 <0,0001
Jose Ibeas1,2, Nu ria Monill-Raya1,2, Edwar Macias3, Carolina Rubiella1,2, skin of the chest
Joaquim Vallespin2,4, Jana Merino4, Eva Criado2,5, Josep Guitart5, Jose Vicario3, AVF aneurysm 460 0,54 0,17 0,68 0,13 0,75 0,51 0,0038
Antoni Morell3, Javier Serrano3
1 High thrombosis rate 456 3,19 0,62 0,81 0,42 0,9 4,3 <0,0001
Parc Taulı Hospital Universitary, Nephrology, Sabadell, Spain, 2Parc Taulı Hospital
Universitary, Clinical, Interventional and Computational Nephrology - CICN, Sabadell, Tension of the fistula 460 3,78 0,49 0,87 0,74 0,69 2,41 <0,0001
Spain, 3Universidad Aut onoma de Barcelona, Telecomunication and Systems vein
Engineering, Cerdanyola, Spain, 4Parc Taulı Hospital Universitary, Vascular Surgery,
Sabadell, Spain and 5Parc Taulı Hospital Universitary, Interventional Radiology,
Pain 460 1,36 0,37 0,73 0,1 0,93 1,52 0,2125
Sabadell, Spain Reduced sensitivity 445 1,85 0,46 0,75 0,22 0,9 2,23 0,0007
Difficulties of CVC 419 5,79 0,69 0,88 0,75 0,85 4,9 <0,0001
BACKGROUND AND AIMS: The native arteriovenous fistula is considered the implantation
vascular access of preference, since it is directly related to major survival, reduced
complications, mortality, and costs. Still, its proper maintenance remains a challenge Clinical picture in total 471 2,45 0,45 0,82 0,59 0,71 2,07 <0,0001
for nephrologists. A previous study from our group, which used the data of 117
arteriovenous fistulas, led to identify in the multivariable analysis age and vein
diameters as predictive factors for early failure. On the other hand, Artificial MO767 Table 2. “Indirect dialysis signs”.
Intelligence has been established as a tool to identify relationships between variables at
deep levels, which might be unseen with more conservative methods like classic
statistics. Therefore, through a Machine Learning technique known as Random Forest, Sign N RR PPV NPV Se Sp PLR h
the aim is to evaluate the same comorbidity, biological and Doppler ultrasound Kt/V decrease 459 1,91 0,42 0,78 0,47 0,75 1,84 <0,0001
variables data to identify those with a major relation with the early failure of the native
arteriovenous fistula. Bleeding from 449 1,67 0,4 0,76 0,4 0,76 1,66 0,0008
METHOD: Retrospective cohort study, gathering the same data of the previous study puncture
(from 2011 to 2015): survival, ultrasound mapping (morphology and hemodynamics), sites
comorbidities (blood pressure, severe arteriopathy, diabetes, Charlson’s Index), and
laboratory (haemoglobin, calcium, phosphorus, PTH, ferritin, PCR). Different Recycling 408 1,41 0,31 0,78 0,55 0,57 1,27 0,0385
Artificial Intelligence algorithms were tested, but the most suited one for the study’s Pressure in the 406 1,3 0,3 0,77 0,49 0,6 1,22 0,1137
aim turned out to be Random Forest. A model was trained, dividing the data in two
sets, training and validation, with an 80/20 ratio. The algorithm used 100 decision
"venous" line
trees, with a maximum individual depth of 3 levels. The training was made with the Ultrasound signs have low screening accuracy, but high prognostic values. In other
variables that represented the 100%, 95%, 90% and 85% of impact in the fistula’s words, in the presence of ultrasound signs, patient is likely to have CVS with high
maturation from a theresold according to Gini’s Index. probability – table 3.
RESULTS: Age 65.7 (32-88) years, male 59.8%. Hypertension 86.7%, diabetes 50.7%
and vascular disease 41.3%. The trained model obtained provided the following results
in the evaluation: accuracy 0.82, precision 0.86, AUROC 0.85, F1 0.86 (balance between
precision and predictive value). The most relevant variables by decision order were age, MO767 Table 3. Instrumental methods.
phosphorous, PTH, ferritin and calcium. Morphologic and hemodynamic variables
such as the vessels diameter, Peak Systolic Velocity, Charlson’s Index or PCR, were also
found to be relevant, but in a minor level. Sign N RR PPV NPV Se Sp PLR h
CONCLUSION: In comparison with classic statistics, Machine Learning techniques Ultrasound
might create a change of paradigm in predictive models for the patency of the vascular Stenosis visualization 446 5,63 0,93 0,84 0,51 0,98 32,65 <0,0001
access for Haemodialysis. Even though the Artificial Intelligence-based model provided
the same relevance for age in maturation failure as traditional models, other findings Dilated collateral veins 446 2,47 0,46 0,81 0,58 0,73 2,14 <0,0001
stand out, like the major participation of variables related with mineral metabolism or Monophase blood flow 446 4,06 0,9 0,78 0,29 0,99 23,23 <0,0001
inflammation, rather than ultrasound based ones.
spectrum
Ultrasound in total 446 5,8 0,89 0,85 0,56 0,97 19,82 <0,0001
CT angiography 63 12 1 0,92 0,95 1 – <0,0001
MO767 CENTRAL VEIN STENOSIS: FROM DIAGNOSTICS TO Percutaneous angiography 71 þ1 1 1 1 1 – <0,0001
TREATMENT STRATEGY When comparing the frequency of correct and incorrect classifications for different
types of lesion, ultrasound accuracy exceeds the clinical picture for types of lesion 1C
1 1 2
Aleksei Zulkarnaev , Vadim Stepanov , Ekaterina Parshina , and 1D (according to the types of lesion in Society of Interventional Radiology
Mariya Novoseltseva1, Aleksandr Fomin1, Julia Chursinova1, Andrey Vatazin1 Reporting Standards for Thoracic Central Vein Obstruction, doi: 10.1016/
1
Moscow Regional Research and Clinical Institute, Surgical department of transplanta- j.jvir.2017.12.013): RR= 3,433 [95% CI 2,074; 6,132], p<0.0001 and RR= 2,538 [95% CI
tion and dialysis, Moscow, Russia and 2Saint Petersburg State University Hospital, 1,592; 4,265], p<0.0001, respectively, but not for lesion types 2B and 3: RR=1.583 [95%
Department of outpatient dialysis, Saint-Petersburg, Russia CI 0.935; 2.779], p=0.0883 and RR=1 [95% CI 0.231; 4.325], p >0.9999, respectively. In
total, incorrect CVS type classifications is noted in 30.7% of cases when using
ultrasound imaging.
BACKGROUND AND AIMS: To analyze the screening and prognostic value of
CT angiography and percutaneous angiography are almost 100% effective in the
various diagnostic signs of central vein stenosis (CVS).
diagnosis of CVS. However, CT angiography is not always informative when AVF is
METHOD: The retrospective study included 549 patients with AVF/AVG
functioning and the volume blood flow is high. In turn, percutaneous angiography does
dysfunction. 211 patients were diagnosed with CVS, other patients had lesions of
not always allow to assess the condition of the veins of the contralateral side. At the
peripheral venous segments. In case of vascular access dysfunction, patients were
same time, correct detection of lesion type is pivotal to determine the future strategy of
examined according to the local protocol: ultrasound examination of peripheral (to
providing the patient with permanent vascular access. For example, the patient has
exclude damage of the peripheral AVF segments) and central veins (at an accessible
very little chance to get functional AVF in case of with two-sided subclavian vein
length) was performed, followed by CT angiography or percutaneous angiography, if
stenosis.
necessary.
CONCLUSION: The CVS diagnostics should be comprehensive, using different
RESULTS: Among various clinical signs only limb edema and dilated veins on the
methods for screening, confirming CVS and determining of it type.
chest demonstrated high sensitivity. Aneurysmal dilatation of an AVF was more
common in peripheral lesions (CVS RR<1). It should be considered that the clinical
signs itself are more likely to be associated with the peripheral lesion than CVS (high

i432 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO768 VASCULAR ACCESS FOR PEDIATRIC HEMODIALYSIS METHOD: In a retrospective review of a quality improvement project, we compared
PATIENTS IN CATALONIA: ANALYSIS OF DATA FROM THE cumulative 6-month CLABSI infection rates before and after transition from Tego
CATALAN RENAL REGISTRY (1997-2018) connectors to ClearGuardHD caps. CLABSI events, reported to National Healthcare
Safety Network (NHSN), were expressed as CLABSI events per 100 patient-months.
Ramon Roca-Tey1, Maria Gema Ariceta Iraola2, Héctor Rıos2, Jordi Comas3, All adult patients (age >18 years) receiving hemodialysis via a tunneled central
Jaume Tort3 catheter were included in the study from February 2018-August 2020. The study
1
Hospital de Mollet, Nephrology, Mollet del Vallès, Spain, 2Hospital Vall d’ Hebron, cohort was comprised of 13 outpatient dialysis units in a healthcare system with
Pediatric Nephrology, Barcelona, Spain and 3Health Department of Catalonia, Registre locations throughout the Northern Midwest and Southeastern United States. The date
de Malalts Renals de Catalunya (RMRC), Organitzaci o Catalana de Trasplantaments of change from Tego to ClearGuardHD was phased throughout the different units over
(OCATT), Barcelona, Spain the study period with events recorded 6 months pre- and post-intervention. Patients
receiving home dialysis therapies were excluded from the study.
BACKGROUND: The vascular access (VA) is the life-line for children with kidney RESULTS: The cumulative 6-month CLABSI event rate decreased by 75.7%; Tego
failure (KT) on hemodialysis (HD). The European Society for Paediatric Nephrology (0.465/100 patient-months) vs. ClearGuardHD caps (0.113/100 patient-months). A
Dialysis Working Group suggested that children requiring HD start with a functioning total of 17 CLABSI occurrences were reported within 3,654 patient-months with Tego
arteriovenous fistula (AVF) but a tunnelled catheter (TC) can be placed instead where use. However, only 4 CLABSI occurrences were reported within 3,527 patient-months
a short period on HD is anticipated before kidney transplantation (KT) (NDT 2019; 34: during ClearGuardHD use.
1746–1765). CONCLUSION: ClearGuardHD caps reduced the rate of CLABSI among
AIMS: To analyze the type of VA used by incident and prevalent KF pediatric patients hemodialysis patients and are superior to Tego connectors. These findings support
(pts) treated with HD in Catalonia prior studies. Implementation of ClearGuardHD caps may help eliminate CLABSI-
METHOD: Data from the Catalan Renal Registry of KF pts younger than 18 years of associated morbidity among individuals requiring maintenance hemodialysis therapy.
age undergoing kidney replacement therapy (KRT) were examined for a 22-year
period.
RESULTS: The modality of KRT used by incident KF pediatric pts has changed
significantly over time: the percentage of children who started KRT through HD
decreased progressively from 89.9% during the 1984-1989 period to 38.2% during the
2014-2018 period and, conversely, the percentage of children who started KRT by
using pre-emptive KT increased progressively from 5.1% to 42.6% between the same
periods (for both comparisons, p<0.001). During 2018, 18 children started KRT (rate:
12.8 per milion of population, pmp) by using pre-emptive KT (n=8, 44.4%), peritoneal
dialysis (n=5, 27.8%) or HD (n=5, 27.8%).
From 1997 to 2018, 112 KF pediatric pts started KRT by using HD (mean age 9.466,0
yr, male 58.9%, glomerular disease 36.8%). Most children started HD through an AVF
during the 1997-2001 period (56.5%) but this percentage decreased over time and no
children used an AVF for starting HD during the 2012-2018 period. On the contrary,
the percentage of children starting HD through a TC increased progressively from
8.7% to 72.2% between the same periods (for both comparisons, p<0.001). No
significant changes over time were recorded regarding untunnelled catheter (UC)
utilization from 34.8% (1997-2001 period) to 27.8% (2012-2018 period) (p=0.57).
Considering two age groups (0-6 vs 7-18 years), VA distribution was the following (%):
23.3 vs 76.7 for UC, 47.2 vs 52.8 for TC and 26.3 vs 73.7 for AVF (p=0.058). Regarding
KF presentation, UC was used mainly to initiate HD in crashlanders (53.3%) and AVF
was used mainly to start HD in children with steady kidney disease progression
(63.2%) (p=0.003).
The KRT modality of using prevalent KF pediatric pts has also changed significantly
over time: pts on HD decreased from 34.9% (n=15, mean age 13.5 yr) in 1997 to 4.7%
(n=5, mean age 11.6 yr) in 2018 and, conversely, pts with a kidney graft increased from
62.8% (n=27, mean age 13.7 yr) to 92.4% (n=98, mean age 11.2 yr) during the same
period (for both comparisons, p<0.001). The percentage of children dialyzed through MO770 BARE METAL STENTS IN HD PATIENTS WITH CENTRAL
an AVF decreased progressively from 1997 (100%) to 2018 (0%) (p<0.001). All VEIN STENOSES: TO STENT OR NOT TO STENT, THAT IS
prevalent HD pts were dialyzed through a catheter in 2018. THE QUESTION.
The KT rate increased significantly from 5.4 pmp (n=6) in 1997 to 17.1 pmp (n=24) in
2018 (p=0.007). The median time on HD (months) prior to the first KT decreased Aleksei Zulkarnaev1, Vadim Stepanov1, Ekaterina Parshina2,
progressively from 23.1 during the 1984-1989 period to 6.6 during the 2014-2018 Mariya Novoseltseva1
1
period (p<0.001). Moscow Regional Research and Clinical Institute, Surgical department of transplanta-
CONCLUSIONS: 1) The VA profile of pediatric population treated with HD in tion and dialysis, Moscow, Russia and 2Saint Petersburg State University Hospital,
Catalonia has radically changed over time. 2) Since 2012, AVF has practically Surgical department of transplantation and dialysis, Saint-Petersburg, Russia
disappeared as the VA in the incident and prevalent pediatric population on HD. 3)
Almost all children treated by HD since 2012 were dialyzed through a catheter due to BACKGROUND AND AIMS: According to the current KDIGO guidelines,
the short waiting time before receiving a kidney graft. 4) The high KT rate was a angioplasty should be preferred procedure for treatment of CVS instead of the bare
determining factor in choosing the AV type in the pediatric population treated with metal stents or self-expanding stent-grafts placement. However, bare stents are still
HD in Catalonia. significantly more affordable than stent grafts. Aim: comparative analysis of the results
of isolated balloon angioplasty (BA) and combined technique (BA with a stent
placement in HD patients with central vein stenosis (CVS).
METHOD: A retrospective study included 62 patients with functional AVF and
confirmed CVS: subclavian, brachiocephalic veins, vena cava inferior, or multiple
lesions. In 39 patients, stents were not used; isolated balloon angioplasty (BA) was
MO769 COMPARISON OF HEMODIALYSIS CONNECTORS CAPS VS performed. In 23 patients we used bare metal stents during the first endovascular
ANTIMICROIAL BARRIER CAPS IN CENTERAL LINE- treatment.
ASSOICATED BLOOSTREAM INFECTION RATES FOR RESULTS: The use of stents leads to increase of primary patency (the time interval
HEMODIALYSIS PATIENTS between the first and second endovascular interventions) – fig. 1A; HR (BA only vs.
stenting) 2.064 [95% CI 1.252; 3.404], p = 0.0017. The use of stents allows to increase
Connie Hemeyer1, Marshall Moreland1, Elsa Olson2, Peter Fitzpatrick1, secondary patency (the time interval between the first endovascular intervention and
Latonya Hickson1 the complete cessation of the use of AVF): HR=2.03 [95% CI 1.232; 3.347], p = 0.0021;
1 fig 1B.
Mayo Clinic Florida, Nephrology and Hypertension, Jacksonville, FL, United States of
America and 2Mayo Clinic Rochester, Nursing, Rochester, MN, United States of America

BACKGROUND AND AIMS: Central line-associated bloodstream infections


(CLABSI) lead to increased morbidity and mortality in hemodialysis-dependent
patients and are costly to treat. Devices such as hemodialysis connector caps (Tego)
and antimicrobial barrier caps (ClearGuardHD) represent promising interventions to
reduce CLABSIs. The aim of this study was to assess the efficacy of these devices in
reducing CLABSIs in hemodialysis patients who use tunneled dialysis catheters at
outpatient dialysis units in a healthcare system.

10.1093/ndt/gfab103 | i433
Abstracts Nephrology Dialysis Transplantation

only those procedures which fail to be completed being escalated to interventional


radiology. Access to real time imaging improves safety and quality of patient
experience by reducing the rate of procedural failure and can the rate of serious
complications.
The Sunderland Diagnostic and Interventional Nephrology (SDIN) service was
launched in 2018. Briefly, this is a ‘one stop shop’ for all of the above procedures with
pre-procedural assessment and post-procedural recovery provided in a dedicated renal
day-case area. Procedure lists run Monday to Friday, 52 weeks per year, and are
provided by four interventional nephrologists.
METHOD: Data was collected retrospectively on all activity under the Sunderland
Diagnostic and Interventional Nephrology service.
MO770 Figure 1: Primary patency and secondary patency after first endovascular RESULTS: The service has delivered the following benefits:
interventions.
• Reduction in bed pressures. Prior to SDIN, patients requiring urgent procedures
were admitted to hospital and this meant that 20% of renal beds were occupied
for vascular access procedures. This is similar regionally. SDIN has seen this fall
to virtually zero with almost all patients undergoing care on a day-case basis.
• Reduction in procedure cancellations. With no hospital admission necessary for
renal biopsies, the rate of procedures cancelled due to non-clinical grounds has
fallen from 60%in 2016 to 0% in 2020.
• Reduction in pressures in radiology for departmental ultrasound scan and elimi-
nation of waiting time. The vast majority of AVF/G scanning is performed at
point of care, and as the vascular access specialist nurses are present during scans,
the AVF can be ‘tattooed’ to mark most feasible points for cannulation.
• Increased capacity for AVF percutaneous intervention. With a national shortage
of interventional radiologists, expanding the workforce to provide this safe, lower-
MO770 Figure 2: Cumulative primary patency of 1-4 endovascular interventions. complexity venous work helps to reduce waiting times for renal patients
• Launch of vascular access flow surveillance.
Total need for surgical interventions did not differ: BA only 1.511 [95% CI 1.225;
1.843] and BAþstenting 1.277 [95% CI 0.997; 1.611] per 10 patient-months, incidence • Increased rates of definitive vascular access (AVF/AVG rather than TDC) – from
rate ratio 1.183 [95% CI 0.872; 1.612] p=0.2822. 62% in 2017 to 78% in 2020 in prevalent HD patients. This is due to a combina-
The second isolated BA allowed to increase patency compared to the first (HR of AVF tion of all the factors above.
function loss or relapse 0.512 [95% CI 0.32; 0.818], log rank p=0.001), and the third • Increase in patients receiving peritoneal dialysis and reduced pressure on surgery/
compared to the second isolated BA (HR=0.607 [95% CI 0.384; 0.959], log rank theatre capacity. 40% of PD catheters inserted under local anaesthetic by nephrol-
p=0.0157). The fourth isolated BA also showed a slight increase in AVF patency, but in ogists with a gold standard technique using ultrasound and fluoroscopy. This pro-
this case we observed no significant difference with the previous intervention (HR= vides flexibility to patients, allows patients who are unfit for general anaesthetic to
0.783 [95% CI 0.501; 1.225], log rank p=0.2433). choose PD, and facilitates an acute PD programme for AKI and late-presenting
In the case of BAþstenting, the second intervention, which was consisted of stent ESRD patients. This has contributed to a growth in Sunderland’s PD population
recanalization, allowed to increase patency of the AVF (HR= 0.433 [95% CI 0.231; from 18 patients in 2019 to 42 patients in 2020.
0.813], log rank p= 0.0014), but the third intervention was no longer accompanied by a
significant increase in patency (HR= 0.873 [95% CI 0.489; 1.558], log rank p= 0.629) CONCLUSION: A dedicated interventional Nephrology service leads to significant
and AVF function was completely lost. benefits for the providing unit and leads to efficiency savings. Most importantly,
CONCLUSION: The use of stents leads to a moderate increase in the median patency patients receive safe and efficient care leading to improved experience and in the long
of AVF and a significant increase in the proportion of patients with functional AVF in term improved clinical outcomes.
the long-term period. However, repeated surgeries are significantly less effective than
in a case of isolated BA. Therefore, we consider isolated BA to be the optimal treatment
strategy, and stenting should be used only if the isolated BA does not result in clinical
improvement.
Multiple endovascular interventions can extend the duration of AVF functioning, MO772 PRIMARY AND SECONDARY HYPEROXALURIA IN CHRONIC
however, in our study, AVF function was completely lost up to 52 months after the DIALYSIS PATIENTS: FOCUS ON VASCULAR ACCESS
clinical manifestation of CVS in all patients. Thus, isolated BA and BA combined with
a bare metal stent placement cannot be considered as a definitive treatment of CVS. Gabriele Donati1, Angelodaniele Napoletano1, Maria Mattiotti1, Fulvia Zappulo1,
Endovascular interventions provide only the necessary amount of time to create Anna Scrivo1, Lorenzo Gasperoni1, Daniela Giachino2, Irene Capelli1,
vascular access on the contralateral side or for shift of modality of renal replacement Raffaella Mauro3, Gaetano La Manna1
therapy. 1
IRCCS S. Orsola University Hospital, Nephrology Dialysis and Renal Transplantation
Unit, Bologna, Italy, 2S.Luigi Gonzaga University Hospital, Medical Genetic Unit,
Orbassano (TO), Italy and 3IRCCS S.Orsola University Hospital, Vascular Surgery Unit,
Bologna, Italy
MO771 A DEDICATED INTERVENTIONAL NEPHROLOGY SERVICE
LEADS TO BETTER RENAL SERVICE PROVISION BACKGROUND AND AIMS: Hyperoxaluria is a rare metabolic disorder chacterized
by widespread calcium oxalate deposition, if plasmatic oxalate level (pOx) overcomes
Rauri Clark1, Saeed Ahmed1, James Andrews1, Shalabh Srivastava1 saturation threshold. It could be primary (PH), a recessive disease associated with
1 mutation of the liver enzyme LDH, or secondary (SH), in 75% due to intestinal
Renal Medicine, Sunderland, United Kingdom malabsorption. Urolithiasis could be the first complication, and renal involvement
could progress until end-stage renal disease (ESRD). Mean pOx is higher in chronic
BACKGROUND AND AIMS: Interventional Nephrology is a renal procedural sub- dialysis patients than healthy individuals because of impaired renal clearance. Oxalate
speciality that provides procedures the following procedures necessary for the molecular weight (MW) is 88 Da and its clearance is that of low MW uremic toxins.
maintenance of dialysis access and renal diagnostics: Our aim is to assess an association between arteriovenous fistula (AVF) failures and
Hyperoxaluria.
• haemodialysis catheter insertion (TDC) and exchange with fluoroscopic guidance METHOD: In the period between 1/1/2004 and 12/31/2020, diagnosis of
• percutaneous peritoneal dialysis catheter insertion with fluoroscopic guidance Hyperoxaluria was carried out in 6 patients out of 1530 chronic dialysis patients
(0.39%). The median age of patients was 65.5 [26-72] years, the male/female ratio was
• biopsy of ‘native’ and transplanted kidneys 3:3 and the median dialysis vintage was 36 [1-181] months. Three patients come to
• Same day rapid access clinic, with point of care ultrasound assessment, for nephrological referral at stage 5 of CKD while 1 patient came to Italy when chronic HD
patients with AV fistula (AVF) or AV graft (AVG) symptoms was already started. At that time pOx was not considered. In these 4 patients the
presumptive diagnosis of ESRD was urolithiasis and diagnosis of Hyperoxaluria was
• AVF and AVG angiography, percutaneous angioplasty and percutaneous
carried out after the beginning of chronic dialysis, when pOx and genetic analysis were
thrombectomy performed. In 1 case biopsy on the kidney graft and in 1 case kidney biopsy after
• Central venous angioplasty nephrectomy were performed: oxalate deposition was detected. For 2/6 patients
In most centres regionally and nationally, these procedures are performed by a mix of diagnosis was carried out after biopsy of native kidneys before starting dialysis. All
nephrologists, radiologists and surgeons. In many centres haemodialysis catheter patients started medical therapy for hyperoxaluria. Five out of 6 patients were eligible
procedures are performed by nephrologists but without fluoroscopic guidance, with to HD, 1/6 to PD. AVF was judged the first choice vascular access.

i434 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: PH was diagnosed in 3/6 patients: mutations were detected on
chromosome 2. Malabsorption secondary to short bowel syndrome and chronic
pancreatitis could be assumed as causes of SH in 3 patients. Patient 1 underwent 2
combined liver-kidney transplantation: the first failed by arterial grafts thrombosis and
the second by renal primary non-function but the liver was still functioning, he died on
HD after 12 years. Patient 2 underwent liver and kidney transplantation and she is
nowadays dialysis-free. The median pOx pre-dialysis and before diagnosis was 165 [98-
259] umol/L (Table 1).
Patients on chronic HD underwent median of 3 [2-5] AVF interventions. Nine AVFs
were distal and 4 were proximal. The most frequent complication was AVF thrombosis
despite ASA treatment: half of the cases showed secondary AVF non-function, the
other half of AVFs failed to mature. Six tunneled cuffed permanent catheters (TCCs) as
definitive vascular access were successfully placed in the 5 patients on chronic HD.
Warfarin therapy was started to avoid TCCs thrombosis. The median survival of TCCs
was 9.5 [3-48] months. All the patients had a history of deep venous thrombosis
(DVT).
CONCLUSION: To our knowledge this is the first case series of multiple AVF failures
in patients with hyperoxaluria. In our experience TCCs show longer survival then AVF
in this group of patients, even if it could not be excluded the role of warfarin in
favoring this result. Even though a link between hyperoxaluria and thrombosis is well
established, the exact underlying mechanism is still uncleared. The role of PD as
dialysis technique of “first choice” should be enhanced also when residual renal
function is abolished. In ESRD patients with urolithiasis, diagnosis of Hyperoxaluria
should be ruled out before AVF placement.

Patients Proximal Distal AVF Primary Secondary DVT Median pOx Therapy
AVF AVF failure (n) failures (n) failures (n) (min-max) (umol/L)
1 1 2 3 1 1 2 78 [68-231] B6 vitamin
2 4 1 5 1 4 1 64 [37-259] B6 vitamin
3 2 0 2 2 0 2 78 [55-99] B6 vitamin, Bicarbonate, Calcium, Ossalactis
4 2 1 3 2 1 1 98 [98-98] B6 vitamin,
5 0 0 N.A. - - 0 50 [50-50] B6 vitamin, Calcium, Ossalactis
6 0 0 N.A. - - 0 N.A. B6 vitamin, Citrate

MO773 THE VASCULAR REALITY BEHIND ULTRASOUND VASCULAR Most patients were considered appropriate candidates for arteriovenous fistula creation
MAPPING: WHICH FACTORS PREDICT THE BEST (207, 82%), whereas 45 (18%) were assigned to PTFE graft. Obesity and male sex were
CANDIDATES FOR RADIOCEPHALIC ARTERIOVENOUS found to be predictors for being a good candidate for radiocephalic arteriovenous
FISTULA? fistula in a multivariate logistic regression model adjusted for age, hypertension, and
diabetes (OR 3.21, CI 95% 1.63-6.32, p-value 0.001 and OR 2.09, CI 95% 1.07-4.08, p-
Rui Barata1, Tiago Pereira1, Joana Marques1, Miguel Bigotte Vieira1, value 0.031, respectively). Figure 1 presents the arterial indicators analyzed during
Fernando Nolasco1 ultrasound mapping, including both upper limbs.
1
Hospital Curry Cabral, Nephrology, Lisboa, Portugal

BACKGROUND AND AIMS: Vascular accesses (VA) are key components for
efficient hemodialysis. Arteriovenous fistulas (AVF) are recommended over
arteriovenous graft (AVG), but deciding the type and location of a VA is challenging.
Preoperative vascular mapping before surgical creation of VA, especially trough
ultrasound (US), is helpful in this decision, contributing to improve AVF e AVG
outcomes.
Our study aims to identify patient factors associated with appropriate arterial US
parameters that predict feasibility for radiocephalic fistula creation.
METHOD: We analyzed a cohort of chronic kidney disease patients who underwent
US vascular mapping for preoperative planning of dialysis access from 2019 to 2020, in
a tertiary referral center. Patients were characterized based on its demographical
characteristics, and the presence of diabetes, hypertension, obesity, and smoking.
Arterial indicators were analyzed by ultrasound techniques in both upper arms, MO773 Figure 1: PWV - pulse wave velocity
including radial, ulnar and brachial arteries. Those indicators included arterial
diameter, calcification, doppler wave form, and pulse wave velocity.
Continuous variables were recorded as means (6SD) for normally distributed data and CONCLUSION: Our results show that obesity and male sex are predictors for
as medians (interquartile ranges) for nonnormally distributed data. Comparisons were radiocephalic arteriovenous fistula creation. While female sex has long been known to
made using t tests or Wilcoxon rank sum tests as appropriate. Categorical variables be a risk factor for VA failure, possibly because of worse arterial indicators, an
were examined by frequency distribution and recorded as proportions. Comparisons association between obesity and higher probability of distal AVF creation has not been
were made using the x2 test. Unadjusted and adjusted multivariate logistic regression established yet. Comparison between arterial indicators in obese and nonobese patients
models were fitted to identify predictors for a good candidate for radiocephalic shows that obese patients generally have better arterial indicators, especially higher
arteriovenous fistula. pulse wave velocities, and less arterial calcification.
RESULTS: A total of 252 patients were included. The mean age was 65616 years, 144 Given that some studies show an association between obesity and shorter fistula
(57%) were male, 211 (84%) where white, 40 (16%) were black, and 1 (0.4%) was asian. survival (due to higher secondary failure rate), our results may come as. A possible
Most had arterial hypertension (205, 81%), 98 (39%) had diabetes mellitus, 89 (35%) explanation for this difference is that obesity may exert a physical protective effect of
were smokers, and 72 (29%) were obese. The majority of patients were attending for the forearm vascular bed against iatrogenic damage (blood sampling and vessel
the first VA (186; 74%). cannulation). Besides that, factors other than vascular indicators may contribute to
ulterior VA failure, like the proinflammatory state in obese patients and its consequent
myointimal hyperplasia.

10.1093/ndt/gfab103 | i435
Abstracts Nephrology Dialysis Transplantation

However, our conclusions are based on preoperative findings, and not on VA CONCLUSION: Our study revealed that black race is an independent factor for PAV
outcomes, especially its patency and complications. Moreover, which further help to creation even after adjusting for classic risk factors as age, DM or HT. Long known
determine the better location for a VA creation, were not evaluated in this study. insidious factors, such as poor socioeconomic status or poor access to medical care,
have been pointed as justifiers to this disparity. However, facing the PAF-associated
risks, we believe that further work must be done to clarify potential involved
anatomical factors and potential reversible factors. Those patients have been described
throughout the literature as presenting with higher risk of VA failure and severe
MO774 PREDICTIVE FACTORS FOR PROSTHESIC ARTERIOVENOUS peripheral arterial disease. In parallel we found that radial and ulnar arteries diameters
FISTULA OPTION BY DUPLEX DOPPLER ULTRASOUND and radial pulse wave velocity (PWV) in DDU were significantly lower in PAV-
VASCULAR MAPPING submitted patients, suggesting distal arterial compromise and stiffness. Our work has
some limitations: neither vein parameters nor VA outcomes were analysed. However, it
Joana Marques1, Tiago Pereira1, Rui Barata1, Miguel Bigotte Vieira1, introduces a relationship between the black race and worse arterial indexes, and their
Fernando Nolasco1 impact on the choice of type of VA, as they seem not to be good candidates for AVF.
1
Hospital Curry Cabral - Centro Hospitalar Universit
ario de Lisboa Central, Nephrology
Department, Lisboa , Portugal

BACKGROUND AND AIMS: Vascular access (VA) remains the lifeline for
MO775 CONTROL OF BONE DISEASE ASSOCIATED WITH CHRONIC
hemodialysis (HD) patients. Arteriovenous fistulas (AVF) are recommended over
KIDNEY DISEASE AS A PREDICTOR OF PRIMARY
prosthesic arteriovenous fistula (PAF). However, the choice of the type of VA still
PERMEABILITY AFTER THE CREATION OF THE VASCULAR
reflects local practice differences and patient-specific demographic and clinical factors.
ACCESS
Duplex Doppler ultrasound (DDU) has been shown to be useful in evaluation of both
structural and functional aspects of the peripheral vessels, and is emerging as the
Luis Guillermo Piccone Saponara1, Maria Paz Castro Ferna ndez1, Nancy
preferred method for VA planning. Our aim was to find predictive factors for PAF
Giovanna Uribe Heredia2, Agustin Carreno1, Sara Anaya Fernandez1,
creation in our population, i.e. when AVF was not feasible.
Eliana Olazo Gutierrez1, Guillermo Ferrer Garcıa1, Patricia Sanchez Escudero1,
METHOD: We retrospectively analysed a cohort of chronic kidney disease patients
Gloria Garcıa Conejo1, Maria del Pilar Romero Barrag an1,
who underwent DDU vascular mapping for preoperative planning of HD access at a
Maria del Carmen Vozmediano Poyatos2
tertiary referral centre from 2019 to 2020. All the exams were performed by the same 1
DDU operator. Demographic, clinical and DDU characteristics were studied. Hospital General Universitario de Ciudad Real, Nephology, Ciudad Real, Spain and
2
Continuous variables were recorded as means (6SD) for normally distributed data or Hospital Universitario de Guadalajara, Cardiology, Guadalajara, Spain
as medians (interquartile ranges) for non-normally distributed data. Comparisons were
made using t tests or Wilcoxon rank sum tests as appropriate. Categorical variables BACKGROUND AND AIMS: Clinical practice guidelines recommend an
were evaluated by frequency distribution and recorded as proportions. Comparisons arteriovenous fistula (AVF) as the preferred vascular access for hemodialysis. Patency
were made using the x2 test. Unadjusted and adjusted multivariate logistic regression of the arteriovenous access is important for effective hemodialysis. However,
models were fitted to identify risk factors to PAF creation due to not being a good maintaining the patency of the AVF remains a challenge. We determined those
candidate for AVF. independent prognostic factors for the patency of the AVF at the time of its creation.
RESULTS: A total of 252 patients were included. The mean age was 65616 years, 144 METHOD: Cross-sectional study; We include all AVFs performed at the HGUCR in
(57%) were male, 211 (84%) where white, 40 (16%) were black and 1 (0.4%) was asian. the last 2 decades. Demographic variables (age, sex), etiology of CKD and associated
Two hundred and thirty seven (94%) patients were right-handed and 186 (74%) were comorbidity were collected. We determine the factors involved in the primary patency
being evaluated for the first vascular access. The majority had arterial hypertension of AVFs. Statistical analysis with SPSS 25.0. Categorical variables are expressed as
(HT) (205 (81%)); 98 (39%) had Diabetes Mellitus (DM), 89 (35%) were current or percentages and are compared using the Chi2 test. Quantitative variables are expressed
past smoker and 72 (29%) were obese. Most patients were considered appropriate as mean 6 standard deviation and the Mann Whitney Student-T/U was used to
candidates for AVF (207, 82%), whereas 45 (18%) were assigned to PAF. Figure 1 compare them. Statistical significance for a value of p <0.05.
compares the DDU’s arterial indexes of each group. In a multivariate logistic regression RESULTS: 622 AVFs performed in 482 patients were reviewed. 86.8% were
model adjusted for age, sex, HT, DM and obesity, black race was found to be a autologous. The mean age was 65.4614 years; 66.6% were male. The most frequent
predictor of being a candidate for PAV creation (OR 2.46; CI 95% 1.05-5.71; p-value etiologies of CKD were diabetic nephropathy (30.2%), unknown (18%), and
0.036). glomerulonephritis (16.6%). 91.2% had arterial hypertension (HBP) and diabetes
mellitus (DM) 47.9%. 48.7% received antiplatelet therapy and 15.6% anticoagulation
prior to the creation of the AVF. 27% presented primary failure. The univariate
analysis showed statistical significance for the qualitative variables HTA (p=0.002),
treatment with statins (p<0.01) and antiplatelet (p<0.01), and for the quantitative
variables fibrinogen (p=0.048), serum phosphorus (p=0.001), CRP (p=0.004),
triglycerides (p=0.05), ferritin (p=0.006) and age (p=0.05). When performing a
multivariate analysis using logistic regression, HTA (OR: 0.46 95% CI 0.22-0.95 p =
0.036), high phosphorus levels (OR: 1.22 95% CI 1.08-1, 49 p = 0.004) and statin
treatment (OR: 0.58 95% CI 0.36-0.96 p = 0.004) are predictors of primary VA failure.
CONCLUSION: In our study, HTA and antiplatelet therapy prior to the creation of
the VA behave as protective factors for primary failure, with high phosphorus levels
being an independent factor for primary failure of AVFs.

MO776 THE USE OF HAND GRIP DEVICE IN ELDERLY PATIENTS ON


ARTERIOVENOUS FISTULA MATURATION PROCESS

Irati Tapia Gonzalez1,2, Vicent Esteve1,2, Sara Iban ~ez1,3, Sandra Rubio1,
Fatima Moreno Guzman2, Miquel Fulquet Nicola s2, Veronica Duarte Gallego2,
Mo nica Pou Potau2, Anna Saurina Solé2, Manel Ramırez de Arellano Serna2
1
Hospital Terrassa. Consorci Sanitari Terrassa, Functional Unit Vascular Access, Terrassa
(Barcelona), Spain, 2Hospital Terrassa. Consorci Sanitari Terrassa, Nephrology, Terrassa
(Barcelona), Spain and 3Hospital Terrassa. Consorci Sanitari Terrassa, Vascular Surgery,
Terrassa (Barcelona), Spain

INTRODUCTION: The indication of creation arteriovenous fistula(AVF) may be


controversial in elderly population with advanced chronic kidney disease (CKD).
Postoperative exercises improve maturation. However, sometimes these exercises could
be difficult to perform in the elderly CKD patients. The hand grip device is easy to use,
inexpensive and able to increase the muscles of the hand and foream. Nevertheless,
scarce scientific evidence has been reported about the role of hand grip device on AVF
MO774 Figure 1: Comparison of arterial indexes of PAV-submitted patients and maturation process in elderly population.
AVF-submitted patients. OBJECTIVES: To evaluate the efficacy of a hand grip training program on AVF
maturation in our patients older than 75 years old with stages 5-5D CKD.

i436 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHODOLOGY: A 15 months prospective study. After surgery, all patients were MO778 ASSOCIATION OF ADVANCED GLYCATION END PRODUCTS
randomized to hand grip group (HG) or control group (CG). HG performed a training (AGE) AND INDOXYL SULPHATE WITH ARTERIO-VENOUS
program using a hand grip device. CO received usual care. Demographics data, upper FISTULA NON-MATURATION
limb muscle strength (ULMS), Doppler ultrasound (DUS), measurements (outflow
vein (OV) diameter and humeral artery blood flow rate (BFR), DUS and clinical AVF Mansi Singh1, Himansu Mahapatra1, Lokesh Sharma2, Lalit Pursnani1,
maturation as well as VA related complications (hematoma, stenosis, thrombosis, Muthukumar B1, Neeraj Inamdar1, Navjot Kaur1, Anamika Singh1,
pseudoaneurysm, aneurysm) were assessed at 4 and 8 weeks postoperatively. Chandra Krishnan1
1
RESULTS: 29 patients. 16 HG, 13 CO. 69% men. Mean age 80,562,9 years. 41,4% ABVIMS, DR. RML Hospital, Nephrology, New Delhi, India and 2ABVIMS, DR. RML
Radiocephalic AVF. Demographic data, ULMS and DUS measurement at baseline Hospital, Biochemistry, New Delhi, India
were similar. A significant increase was observed in ULMS only in HG at the end of
study (18,866,5 vs 21,367,1Kg, p=0,005). DUS measurements statistically increased BACKGROUND AND AIMS: The main hindrance in adequate utilization of
for both groups (OV diameter: CG 2,9 6 0,6 vs. 5,8 6 1,4mm; HG 2,9 6 0,8 vs. 7,2 6 Arteriovenous fistula (AVF) is its high rates of primary failure. Its etiology is multi
2,2 mm; humeral artery BFR: CG 132,96 30,3 vs. 1310,2 6 691,8ml/min; HG 128,16 factorial and several uremic toxins are under investigation. Here we explore the
28,9 vs. 1530,7 6 708,9 ml/min) at the end of study. HG group obtained highest potential influence of Advanced Glycation End Products (AGE) and Human Indoxyl
clinical (CG 21,4% vs HG 78,6%;p=0,018) and DUS maturation (CG 27,8% vs HG Sulphate (HIS) on AVF non maturation.
72,2%; p=0,011) at 4 weeks and highest clinical (CG 20% vs HG 80%;p=0,007) and METHOD: This one year prospective observational study included single stage AVF in
DUS maturation (CG 25% vs HG 75%; p=0,002) at 8 weeks, significantly. Despite no consecutive CKD 4 and 5 patients. At baseline, demographic, biochemical (including
significant differences, the number of complications was lower in the HG, mainly AGE and HIS levels) and doppler ultrasound of upper limb were done followed by
significant stenosis (CG 60% vs HG 40%; p=0,428). AVF construction. At 12 weeks, AVF was assessed for clinical maturation (usage of
CONCLUSIONS: The hand grip device is a useful, safety and easy to use training fistula with 2 needles for 75% of dialysis sessions during 15 day period); accordingly
device to improve the AVF maturation in elderly patients. This device results a novel divided in to matured or non-matured groups. Demographic and biochemical
therapeutic option for the AVF maturation in elderly patients. Further studies are parameters between both groups were compared; ROC and correlation of AGE and
required to support these outcomes in this population. HIS were analyzed.
RESULTS: Of 129 AVF, 67.4% were matured and 32.5% non-matured. Overall mean
age was 40.9 year, male predominance (77.5%) and more non-matured AVF among
diabetes. The mean value of AGE and IS was 0.18 mg/ml and 0.18mg/ml respectively;
but difference was non significant between two group. AGE levels were further
MO777 HISTOLOGICAL AND IMMUNOPHENOTYPICAL VESSEL showing positive correlation with CRP (p 0.01, r 0.21) and venous diameter (p 0.02, r -
CHANGES IN CHRONIC KIDNEY DISEASE 0.22). There were significant positive correlation between AGE and HIS (p<0.00, r 0.5)
but not with other parameters. AUC of AGE and HIS were 0.48 and 0.5 respectively
Aikaterini Lysitska1, Nikiforos Galanis2, Ioannis Skandalos3, and association could not be demonstrated between all studied parameters and AVF
Eustathios Mitsopoulos1, Nikolaos Antoniadis4, Aikaterini Papagianni5, outcome.
Maria Stangou5 CONCLUSION: Study cohort showed high incidence of primary failure without any
1
G.H. Papageorgiou, Nephrology , THESSALONIKI, Greece, 2Aristotle University, association of AGE and HIS with clinical AVF non maturation.
Thessaloniki, Greece, 3G.H. Agios Pavlos, Surgical, Thessaloniki, Greece, 4Aristotle
University, G.H. Hippokration , Transplant Surgery, THESSALONIKI, Greece and 5Aristotle
University, G.H. Hippokration, Nephrology , Thessaloniki, Greece

BACKGROUND AND AIMS: Recent studies suggest thw possibility of activating


immune mechanism in the onset and progression of atherosclerotic disease. The aim of
the present study was to evaluate the role of immune mechanisms in the vessel of
patients with Chronic Kidney Disease (CKD) and the association with clinical and
laboratory indicators of atherosclerosis.
METHOD: Patients with CKD stage V, in whom a radiocephalic arteriovenous fistula
(RC-AVF) was created, were included in the study. Patients were divided in two
groups, group A was consisted of patients who were on stage V, pre-dialysis, and being
prepared to start on hemodialysis (HD), and those who had already been on HD for at
least 3 years, and were having a new RC-AVF formation, due to previous failure,
group B.
Inclusion criteria were: age 25-80 years, gradual deterioration of renal function up to
stage V or under dialysis for more than 3 years. All patients should have been under
close follow up for at least 3 years prior to enrolment, with adequate control of
diabetes, hypertension, dyslipidemia, secondary hyperparathyroidism and anemia.
The control group included healthy volunteers of similar age, sex and ethnicity, who
agreed to have a radial artery biopsy during an orthopedic procedure because of a
fracture. All patients were informed and signed the consent form.
Patients’ history, primary disease and comorbid conditions, medication and clinical MO778 Figure 1: Box plot showing comparison of AGE & HIS levels between
examination were recorded based on hospital outpatients’ files. Prior to the scheduled subjects with and without AVF maturation.
day of RC-AVF creation, all patients underwent laboratory examination, included
hematological and serum biochemical analyses.
The histological characteristics, inflammatory activation and immunophenotypic
alterations of the radial artery wall were estimated and their association with the
severity of calcification and atherosclerosis were studied.
Presence and severity of atherosclerotic lesions in CKD patients was assessed based on MO779 DETECTION OF INTRADIALYTIC SLEEP APNEA IN
the measurement of common carotid intima – media thickness (IMT) of the common HEMODIALYSIS PATIENTS
and internal carotid on both sides.
RESULTS: Significant correlation was fount between inflammatory infiltration Paulo Paneque Galuzio1, Alhaji Cherif1, Xia Tao1, Ohnmar Thwin1,
[expression of CD3(þ), CD20(þ), CD68(þ) cells], cellular activation [CD34(þ), a- Priscila Preciado Rojas1, Matthew Cato1, Stephan Thijssen1, Peter Kotanko1,2
1
SMA(þ) cells] and calcification regulators (MPG, RANKL, OPG) with the degree of Renal Research Institute, Research Division, New York, United States of America and
2
vascular calcification, as this was estimated and classified based on Verhoff’s Elastic Mount Sinai Health System, Icahn School of Medicine, New York, United States of
and von Kossa staining America
Forty five patients with chronic kidney disease (CKD), stage V, either pre-dialysis
(p=25) (group A) or on hemodialysis (HD) (p=20) (group B) were included in the BACKGROUND AND AIMS: Sleep apnea syndrome (SAS) has emerged as an
study. There were no significant differences in age, sex, race, and also in the frequency important cardiovascular risk factor in hemodialysis (HD) patients. In patients with
of hypertension, diabetes mellitus or smoking habits between patients and controls. SAS, high-frequency oscillations of arterial oxygen saturation (SaO2) and arousal can
Presence and severity of atherosclerotic lesions in CKD patients was assessed based on be used to characterize repetitive respiratory cessation. Although these repetitive
the measurement of common carotid intima – media thickness (IMT) of the common patterns have been observed in SAS patients, it has not been studied during HD
and internal carotid on both sides. treatment. In this study, we aim to detect intradialytic SAS in HD patients to provide
CONCLUSION: Atherosclerotic disease in Chronic KidnEy Disease and its clinical novel prognosticators of adverse events related to SAS.
effects appear to be directly related to inflammatory ifiltration of blood vessels by T, B
lymphocytes, macrophages and myofibrolasts, as well as factors that affect calcification.

10.1093/ndt/gfab103 | i437
Abstracts Nephrology Dialysis Transplantation

METHOD: We use the Crit-LineV R monitor to record SaO2 at 1 Hz frequency, and analysis with SPSS 25.0. Categorical variables are expressed as percentages and are
video recording to capture periods of wakefulness for the entire treatment session compared using the Chi2 test. Quantitative variables are expressed as mean 6 standard
(3.560.5hr). We developed a recurrent-based time-series analysis to characterize the deviation and the Mann Whitney Student-T/U was used to compare them. We
desaturation and arousal in SaO2. For each patient, we compute four metrics, namely: performed a kaplan-Meier analysis determining primary, assisted and overall survival.
(i) the probability of recurrence for any given state (recurrent rate, RR), (ii) systemic Statistical significance for a value of p <0.05.
predictability (determinism, DET), (iii) occurrence of laminar state (LAM), and (iv) RESULTS: 622 AVFs performed in 482 patients were reviewed. 86.8% were
permutation entropy to quantify complexity. These four quantities were used to detect autologous. The mean age was 65.4614 years; 66.6% were male. The most frequent
episodes of SAS in patients while undergoing HD treatments. etiologies of CKD were diabetic nephropathy (30.2%), unknown (18%), and
RESULTS: We study 16 HD patients with arterio-venous vascular access. Their age glomerulonephritis (16.6%). 91.2% had arterial hypertension (HBP) and diabetes
was 54611 years, 63% were males and 69% were African Americans. SaO2 was mellitus (DM) 47.9%. 48.7% received antiplatelet therapy and 15.6% anticoagulation
measured during two HD sessions per patient. The mean SaO2 was 94.362.1%. We prior to the creation of the AVF. 27% presented primary failure. In the survival analysis
observe distinguishable patterns in which periods of awake and asleep are using the Kaplan Meier test, the mean time to perform angioplasty in dysfunctional
differentiated. Figure 1 shows a typical SaO2 annotated with the period of awake and AVFs was 14.661.37 months and to perform a thrombectomy 17.661.31 months. The
asleep (shaded area in Fig. 1A), during which the four metrics decrease during the overall survival of AVFs was 41.962 months. When assessing the type of AVF, we
corresponding period where the patient is asleep (Fig. 1B-C). Figure 1D-E shows the observed a longer survival for autologous (31.561.8) vs prosthetic (21.863.6) (p = 0.03
consistency of the metrics in all 16 patients, in which DET and entropy are analyzed log Rank 4.73).
around the onset of sleep. We observe monotonically decreasing trends around the CONCLUSION: In our study, autologous AVFs have better survival compared to
episode of sleep, suggesting that these results are sensitive to the sleep states, and prosthetic ones. Of the AVFs created, primary survival at one year (requiring
potentially to an episode of intradialytic SAS. angioplasty) was 64%, assisted primary survival (requiring thrombectomy) was 42%,
and overall survival 24%.

MO781 THE CATIONIC CELLULOSE BASED PAD REDUCE THE


HEMOSTATIC TIME AFTER HEMODIALYSIS

Kazuhiko Shibata1, Shigeru Nakai2, Yusuke Kobayashi3, Kiyoshi Ozawa4,


Koichi Tamura3
1
Toshin Clinic, Japan, 2Fujita Health University, Toyoake, Japan, 3Yokohama City
University , Yokohama, Japan and 4Yokosuka Clinic, Yokosuka, Japan

BACKGROUND AND AIMS: In case of prolonged bleeding at the vascular access site
after hemodialysis, a nurse must compress the bleeding site longer than usual. This
situation causes the risk of intravascular thrombosis and consumes valuable time of
both patients and staff. Therefore, effective hemostatic agents are desired. Nowadays,
chitosan is considered as one of the strongest hemostatic substance. Nipro Corporation
and Artisan-lab co., Ltd found the cationic cellulose could clot blood faster than
chitosan in the activated clotting time (Figure). After carefully examining its safety and
MO779 Figure 1: (A) Sa02 tor a representative patient, the shaded areas annotate efficacy, it was approved as medicine by the Japanese Ministry of Health, Labor and
the moments of sleep. (B) Recurrence quantification analysis (RQA, e.g.,RR, DET, and Welfare. Then, a trial to verify its clinical efficacy as a hemostat was conducted in the
LAM) and (C) permutation entropy calculated with rolling window procedure from Toshin Clinic. In our clinic, the timer is set on the hemodialysis machine after the
the time series (A). Normalzed entropy (D) and determinism (E) averaged around the needles are removed and pressure is started after hemodialysis. We examined how long
onset of sleep for all 16 patients. the timer should be set to be able to sufficiently stop bleeding in case cationic-cellulose
pads are used.
METHOD: Of the 150 hemodialysis patients treated at the Toshin clinic; patients who
CONCLUSION: Our preliminary analysis suggests that DET, LAM, RR, and entropy agreed to this trial were enrolled. We set a timer for 5 minutes initially using cationic-
may contain characteristic properties that could be used to detect the onset of cellulose pads for hemostasis, and was shortened in the next trial by 1 minute if the
intradialytic SAS, which are characterized by the high-frequency oscillatory patterns in bleeding had been stopped. If the patient did not consent, the timer was not shortened
SaO2. Further studies are needed to identify SAS-related desaturation and arousal further. from April 15th to December 31st in 2020. We checked the bleeding evidence
detected in the SaO2 measurement. The predictive power of these features and their of the puncture sites at the timing of immediately after relieving their compression. At
relationships to clinical outcomes warrants further investigation. their following hemodialysis session, we also checked the existence of adverse effects at
their puncture sites, such as contact dermatitis or infection.
RESULTS: Ten patients (9 men and 1 woman, Age 58.5y 613.1) agreed to participate
in this study. In the case of stable hemostasis, we continued to shorten the time by 1
minute each time, and added 1 minute in case of bleeding. After searching for the
MO780 SURVIVAL STUDY OF ARTERIOVENOUS FISTULAS CREATED shortest time to achieve stable hemostasis, we confirmed hemostasis an average of 14.2
IN A HIGH RESOLUTION HOSPITAL times in all cases. The average time to set for the timer was 3.0 6 0.94 minutes (2-5
minutes). Two patients refused to shorten the time set for the timer, the hemostasis
Luis Guillermo Piccone Saponara1, Maria Paz Castro Fern andez1, time were 5 and 4minutes respectively. The hemostasis time in all the other cases was
Nancy Giovanna Uribe Heredia2, Agustın Carren ~o Parrilla1, Sara Anaya equal or less than 3 minutes. In one case, the hemostasis time was reduced to 3 minutes
Fernandez1, Guillermo Ferrer Garcıa1, Gloria Garcıa Conejo1, Marina Ugarte with a cationic cellulose pad, compared to 30 minutes with The Neoplaster hemostatic
Camara1, Casimiro Valle Dominguez1, Maria del Pilar Romero Barraga n1, pad (Nipro Corporation) which is made with the carboxymethyl cellulose. Of the 142
Maria del Carmen Vozmediano Poyatos1 case compressions performed, 1 case resulted in bleeding and required 2 minutes of
1
Hospital General Universitario de Ciudad Real, Nephrology, Ciudad Real, Spain and additional compressions. All cases did not have any adverse effects such as redness,
2
Hospital Universitario de Guadalajara, Cardiology, Guadalajara, Spain itching or pain of their hemostatic pad attached sites.
DISCUSSION: This study showed that the average time to set for the timer, when
using cationic cellulose pad was 3 minutes on average, without any adverse effects.
BACKGROUND AND AIMS: Clinical practice guidelines recommend an
Cationic cellulose pads can stop bleeding safely, quickly and stably. At present,
arteriovenous fistula (AVF) as the ideal vascular access for hemodialysis. Autologous
clinically available strong hemostatic agents are too expensive to be applied for many
AVFs have higher primary, assisted primary and overall survival, associated with lower
patients. But the cost to get the cationic-cellulose to make hemostatic pads may be
morbidity and mortality compared to prosthetic AVFs. However, primary failure of
reduced enough to be distributed to many hemodialysis patients because this material
AVFs function is not uncommon, above all due to the vascular pathology of patients on
is mass-produced for hair conditioner, shampoo, and toothpaste.
hemodialysis (HD). We determined the survival rates in a series of vascular accesses
CONCLUSION: The average time set for the timer was estimated around 3 minutes
created in a high-resolution hospital.
using the cationic cellulose pad. The cationic cellulose pad can save precious time and
METHOD: Cross-sectional study; We include all AVFs performed during the last 20
efforts of both patients and staff through its quick hemostasis.
years. Demographic variables (age, sex), etiology of CKD and associated comorbidity
were collected. We determine the primary, assisted and global survival times. Statistical

i438 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO781 Table 1. The activated clotting time for various substances (Unit:
second) Total Arteriovenous Tunnelled p
fistula catheter
1st 2nd 3rd 4th 5th Average standard Value of Gender Male 29(36) 13(72) 16(62) ns
deviation t-test Age 84 (81-90) 83 (81-90) 84 (81-90) ns
Kaolin 102 103 99 105 98 101.4 2.88 Hypertension 44(100) 18(100) 26(100) ns
Chitosan 328 265 320 369 177 320.5 42.77 0.0019 Diabetes 25(56,8) 12(66,7) 13(50) ns
Cationic 56 44 58 59 68 57 8.6 0.0011 Peripheral 8(18,2) 6(33) 1(8) 0,03
cellulose arteriopathy
The same amount of each substance was measured and added in a Ischemic heart disease 18(41,9) 10(59) 8(31) 0,06
test tube. Ejection fraction 59 55 61 ns
Student t-test was conducted for the clotting time of kaolin. Follow-up time > 6m 34(42) 15(83) 19(73) ns
Vascular access unit 44(100) 13(72) 26(100) ns
monitoring
Vascular Access (%) ns
Arteriovenous ˚stula 26(61) ns
Tunnelled catheter 18(39) ns
MO782 VASCULAR ACCESS IN ELDERLY PATIENTS Vascular Access at the time ns
of beginningHemodialysis
(%)
Elena Burgos Garcıa1, Andres Villegas1, Fredzzia Graterol1, Jordi Soler Majoral1, Arteriovenous ˚stula 15(34) ns
Judit Cacho1, Lucia Martinez2, Manuela Lleida2, Jordi Bonal1 Tunnelled catheter 29(65,9) ns
1
Hospital Germans Trias i Pujol, Nephrology, Badalona, Spain and 2Hospital Germans Exitus 12(27) 8(47) 4(15) 0,037
Trias i Pujol, Angiology and endovascular surgery, Badalona, Spain
Survival 20 16 30 ns
BACKGROUND AND AIMS: The arteriovenous fistula (AVF) continues to be the
first-line vascular access (AV) in the hemodialysis population. However, it is disputed
whether the profitability and survival in the elderly patient are the same as in the CONCLUSION: In our population, male sex and catheter at the beginning of
younger patient. Thus, there are authors who propose the tunnelled catheter as the best hemodialysis have a significant association with exitus. AVF should be considered as
option in this group of patients. The objective of this study was to analyze the the first choice vascular access even in the subgroup of patients over 80 years old
characteristics of vascular access in incident patients over 80 years of age at our center.
METHOD: A retrospective analysis was performed included incident hemodialysis
patients >80 years between 2017-2020. Epidemiological and vascular access
complications related, as well as first permanent vascular access survival were analysed.
A Pearson’s correlation coefficients were employed to determine the correlation MO783 CENTRAL VEIN STENOSIS IN HEMODIALYSIS PATIENTS
between the exitus and other variables and Regression models of mixed effects of WITH PAST CENTRAL VEIN MANIPULATION
covariance (ANCOVAs) were created to determine the effect of these with the exitus.
RESULTS: Demographic characteristics of forty-four patients included are shown in Pedro Reis Pereira1, Cıria Sousa1, Natalia Silva1, Jose Francisco1,
Monica Fructuoso1, Teresa Morgado1
Table 1. Significant differences in sex and comorbidities (diabetes, ischemic heart
1
disease, peripheral vascular disease and hypertension) were found. A total of 26 Centro Hospitalar De Tr
as-Os-Montes E Alto Douro, E.P.E., Vila Real, Portugal
patients (62%) had a fistula at the time of beginning hemodialysis, all of them with pre-
surgical mapping and monitoring, only 15 (34%) of them being working. The most BACKGROUND AND AIMS: Central vein stenosis (CVS) is frequently observed in
prevalent type of vascular access (VA) was the left humerus-cephalic (21%). 12 (27%) hemodialysis patients. Risk factors for CVS include prior ipsilateral central venous
patients were exitus during the 36 months after the beginning of hemodialysis, with catheterization (CVC) and cardiac rhythm device (CRD) insertions. Though it may
significant differences between groups. The variables catheter, male, and type of VA have clinical manifestations, CVS is often asymptomatic and, therefore, not diagnosed.
showed a significant correlation with the exitus (-0.345, -0.347, -0.347 and -0.309 The aim of this work was to evaluate the prevalence of CVS in a population of
respectively). The multivariate analysis showed a significant association between hemodialysis patients, as well as underlying risk factors, clinical manifestations and
gender and catheter as vascular access at the beginning of hemodialysis with the exitus impact in patients’ vascular access.
(p<0.05) even after being adjusted for age and AVF. METHOD: We retrospectively evaluated all venous angiographies of prevalent
patients in our hemodialysis units from 2013 to 2018. In patients with proved CVS, we
evaluated history of prior short term and long term upper ipsilateral CVC and CRD
insertions. We also analyzed symptoms associated CVS as well as the rate of loss of
vascular access for hemodialysis related to the presence of CVS.
Total Arteriovenous Tunnelled p RESULTS: The prevalence of CVS in prevalent patients in hemodialysis during the
fistula catheter period of our study (n=209) was 14%. We identified 31 upper CVS in 29 patients
undergoing venous angiography. Left brachiocephalic vein was the most commonly
Gender Male 29(36) 13(72) 16(62) ns affected site (45.1% of cases), followed by the right brachiocephalic vein (19.3%), left
Age 84 (81-90) 83 (81-90) 84 (81-90) ns subclavian vein (16.1%), right subclavian vein (12.9%) and superior vena cava (6.4%).
Hypertension 44(100) 18(100) 26(100) ns The majority of patients with CVS (95%) had previous history of ipsilateral CVC
(previous short-term CVC in 40%, pervious short term and long-term CVC in 27%
Diabetes 25(56,8) 12(66,7) 13(50) ns and previous long-term CVC in 33%). Loss of vascular access for hemodialysis due do
Peripheral 8(18,2) 6(33) 1(8) 0,03 CVS was observed in 26% of patients with CVS.
CONCLUSION: A significant proportion of patients in hemodialysis presents CVS.
arteriopathy
The majority of patients with CVS had a previous history of ipsilateral central venous
Ischemic heart disease 18(41,9) 10(59) 8(31) 0,06 catherization. A significant proportion of patients with CVS had a previous history
Ejection fraction 59 55 61 ns central venous catherization uniquely with short term CVC, highlighting the
importance of the risk of vascular lesion, even during short periods of catherization.
Follow-up time > 6m 34(42) 15(83) 19(73) ns The presence of CVS is associated with a significant rate of loss hemodialysis vascular
Vascular access unit 44(100) 13(72) 26(100) ns access.
monitoring
Vascular Access (%) ns
Arteriovenous ˚stula 26(61) ns
Tunnelled catheter 18(39) ns

Continued

10.1093/ndt/gfab103 | i439
Abstracts Nephrology Dialysis Transplantation

MO784 ABDOMINAL AORTIC CALCIFICATIONS AND MO786 HEPARIN VERSUS SODIUM BICARBONATE CATHETER
ARTERIOVENOUS FISTULA CLINICAL OUTCOMES ON LOCK SOLUTION: AN ALTERNATIVE LOCK HEMODIALYSIS
HAEMODIALYSIS PATIENTS CATHETER?

Amira Saii1, Toumi Salma1, Beya Fendri1, Hanen Abid1, Rania Lahouimel1, Francesca Partipilo1, Francesco Detomaso1, Stefania Pietanza1,
Ikram Agerbi1, Najla Dammak1, Hanen Chaker1, Khaoula Kamoun1, Giuseppe Gernone1
Soumaya Yaich1, Mohamed Ben hmida1 1
ASL BA - Nephrology and Dialysis Unit - “S. Maria degli Angeli” and “S. Giacomo”
1
hospital hedi chaker sfax nephrology department, UR12ES14 renal pathology research Hospitals, Putignano-Monopoli, ASL BA, Putignano (BA), Italy
laboratory, Sfax Faculty of Medicine, sfax, Tunisia
BACKGROUND AND AIMS: Infections and thrombosis of central venous catheter
BACKGROUND AND AIMS: Vascular calcification has now been recognized as a (CVC) in hemodialysis patients are the major causes of catheter loss resulting in
major problem in dialysis patients because of its strong influence on the prognosis of hospitalization and increased costs. Interdyalitic catheter lock solutions, usually
this population. Several reports have shown the strong relationship between vascular heparin, avoid these complications. Among the many, sodium bicarbonate has been
calcification and clinical outcomes including cardiovascular events and arteriovenous proved as effective and safe catheter lock solution due to its antimicrobial and
fistula (AVF)survival. antithrombotic properties. The aim of this study was to compare the efficacy of two
The aim of this study is to evaluate the severity of vascular calcifications in our different CVC lock solution: sodium heparin versus sodium bicarbonate, to prevent
hemodialysis patients and to determine its impact on the AVF survival. catheter–related thrombosis and infection in hemodialysis patients
METHOD: It is a transversal descriptive and analytical study including chronic METHOD: They were enrolled, in a 12 months case-control study, 17 hemodialysis
haemodialysis patients in our unit of the nephrology department. patients with tunneled hig-flux CVC (femoral or internal jugular). Each patient was
A lateral lumbar spine radiograph was taken: the aortic arch calcification(ACC) score evaluated in its common treatment for CVC dysfunction (Qb, CVC that works in
(VCS) was calculated according to the score validated by Kauppila and Schousboe. The reverse branches during the hemodialysis session, use of urokinase or extra lock with
overall VCS ranged from 0 to 24. sodium heparin or 4% citrate) and infection (WBC count, C reactive protein -CRP,
RESULTS: Our study included 55 patients divided into 31 men and 24 women with a bloodstream culture, exit-site infection -ESI) during standard sodium heparin CVC
sex ratio of 1.29. The mean age was 49.54 6 12.66 years. The mean duration in HD was lock solution (hep-lock), for the first 6 months, and then, during sodium bicarbonate
96.166 73 months. 76.8% of the patients have hypertension, 26.8% are diabetic and lock solution (10 mEq/10 ml, bic-lock) for following 6 months. aPTT, PLT, Hct and
14.3% are smokers. AVF failure was noted in 34 patients (60.7%). albumin are also montly evaluated. Type and anticoagulant dose during hemodialysis
We divided our population in 3 groups: G1:23 patients with a low VCS (41.1%), G2: 15 sessions were unchanged over the study as well as any antiplatelet/anticogulant home
patients with a moderate VCS (26.8%) and G3: 17 patients with a severe VCS (30.4%). therapy.
Patients in G2 and G3 were more frequently diabetics (p=0.05): over 50% of patients in RESULTS: Fifteen patients on 17 completed the study and the main results are
G3 were diabetic and the mean duration in HD was longer: 133 months in G3, 102 reported in table 1. There were no significant differences between patients on
months in G2 and 74 months in G1 with a significant difference p=0.03. demographics and number of catheter days treatments for both study periods. The
We noted that AVF failure was more frequent in patients in G2 and G3 (65.7%) blood flow was similar in either study phases and stable during the hemodialysis
patients) versus patients in G1 (39.13%) with a significant difference (p=0.01) sessions (Qb 225613 ml/m’ at 2-hours vs 225615 ml/min at start of dialysis), even the
CONCLUSION: vascular access dysfunction is one of the leading causes of morbidity use of reverse branches was similar. Hep-lock showed a lower usage of extra lock drug
and mortality in haemodialysis patients We have demonstrated throw this study the in comparison with Bic-lock (0,4% vs 3,1%, p<0,05), data confirmed also for
relation between the presence of higher AAC grade and the poor survival of AVF in Urokinase (1,9% vs 3,4%, p=0,274). None bloodstream are registred while ESI and
our patients. WBC count show no significant differences between two study periods. No HD
So, an identification of these ACC by a simple lateral lumbar spine radiograph would catheter was loss during the study due to thrombosis or infection. Finally, Hct, CRP
allow the clinician to implement more rigorous and planned monitoring for such and Albumin was found slightly lower on Bic-lock phase.
AVFs. CONCLUSION: There is no CVC ideal lock solution and although sodium
bicarbonate is inexpensive and readily avalaible our data shows better CVC
performances with sodium heparin.

MO785 CAUSES OF THE DELAY IN CREATING PERMANENT


VASCULAR ACCESS IN HEMODIALYSIS PATIENTS

Abdulla Al-Sayyari1
1
King Saud Bin Abdulaziz University for Health Sciences, Riyadh

BACKGROUND AND AIMS: Many patients start HD with central venous catheter
(CVC) which has multiple complications This study aims at identifying the physicians’
perspectives regarding the reasons of delayed AVF creation
METHOD: This is a cross-sectional questionnaires-based survey designed at
discovering the physicians’ opinions and perception about the reasons for the delay in
the creation of permanent vascular access and patient’s factors, physicians factors, and
hospital factors leading to this delay,
RESULTS: There was a total of 212 participants, of whom 131 (61.8%) were of
consultant level.
The three most important factors associated with delay in AVF creation were “denial of
kidney disease or the need of AVF” (76.4%), “dialysis fears and practical concern”
(75.9%) and “the patient refusing to undergo AVF surgery” (73.1%). Significantly fewer MO787 USE OF THE PREVENTIVE HAEMOSTASIS IN SURGICAL
consultants (42.7%) than below consultants (45.7%) pointed out that “patient COMPLICATIONS OF VASCULAR ACCESS
noncompliance with nephrology appointments” was a significant factor (p=0.046).
The most important physicians & hospital factors was “insufficient conduction of pre- Simone Corciulo1, Bianca Covella1, Luigi Rossi1, Carlo Lomonte1
1
dialysis care and education about AVF initiation to the patient (63.7%) Miulli General Hospital, Nephrology, Acquaviva delle Fonti, Italy
The respondents were asked to choose one of four possible factors that they felt was the
main factor in delaying AVF creation. Over two thirds (68.4%) chose the patient factor BACKGROUND AND AIMS: Arteriovenous fistula (AVF) is currently the
as the main factor There was no significant difference in this response whether the recommended vascular access type and its preservation is required to ensure a safe
respondents were consultants or below consultants (p=0.8)) treatment for HD patients. Nevertheless, reinterventions are often needed to treat life
CONCLUSION: The most agreed on factors associated with AVF creation delay are threatening complications such as eschars, aneurysms, high flow.These surgical
the denial of the need for dialysis, fear of dialysis and practical concern, insufficient procedures are at high risk of bleeding, time-consuming and technically demanding.
conduction of pre-dialysis care and education about AVF initiation to the patient, and Here we describe our approach by using preventive hemostasis to treat different types
late referral to a nephrologist. a validated approach to patients’ selection and referral to of AVF complications, such as aneurysmectomy, high flow fistula correction,
vascular access creation that could be applied on different types of patient in different ulcerectomy.
regions is required . METHOD: The technique consists of a few steps. First, regional anesthesia is
performed by brachial plexus nerve block and intravenous antibiotic prophylactic

i440 | Abstracts
Nephrology Dialysis Transplantation Abstracts
therapy is administered. Then, an inflatable tourniquet is placed on the arm, applicable to surgical treatment of vascular access complication.
proximally to the elbow joint, after wrapping the site with a soft gauze to prevent
postoperative discomfort and bruising due to accidental pinch of the skin. The arm is
then elevated to allow passive exsanguination and a 5” Esmarch bandage is applied
from the hand to the tourniquet cuff. The methodical application of the Esmarch
bandage requires an assistant to hold the arm properly in the upright position. Once
the bandage is applied, the tourniquet is inflated to complete the exsanguination of the
extremity. The inflation pressure has to be adapted to patient systolic pressure,
generally a ’suitable’ pressure for an upper limb tourniquet is 250-300 mmHg. Lastly,
the Esmarch bandage is unwrapped and, after sterile surgical draping, it is possible to
proceed to skin incision.
RESULTS: From Jan 2019 to Dec 2020, we enrolled 9 patients with AVF complications
treated with the preventive emostasis. The mean age of the patients was 62 years
(range, 45-80 years). Table 1 shows types of AVFs and complications, performed
revisions, outcomes, short and long term complications. The tourniquet average time
of application was 29 þ 7,7 min. Preventive hemostasis ensures absence of blood loss,
even during high flow access revision. In one patient, a moderate subcutaneous
hemorrhage occurred 8 hours after the end of the surgical procedure, requiring further
revision. No vascular or soft tissue complications were reported except for temporary
dysesthesias.
CONCLUSION: Our experience shows that preventive haemostasis offers several
advantages for surgeons and patients, allowing a clear operative field and avoidance of
application of clamps, prevents blood loss, and reduce the need for blood transfusion.
Furthermore, reperfusion injury risk is minimized. The only complication occurred
suggests the recommendation to suture skin incision after removing the tourniquet to
reduce risk of postoperative bleeding. In conclusion, the technique is reliable and safely

10.1093/ndt/gfab103 | i441
Nephrology Dialysis Transplantation 36 (Supplement 1): i442–i443, 2021
10.1093/ndt/gfab095

MO789 SERUM SOLUBLE TRANSFERRIN RECEPTOR IS A


DIALYSIS. ANAEMIA PROMISING MARKER OF IRON DEFICIENCY ANEMIA IN
PREVALENT HEMODIALYSIS PATIENTS

MO788 ERYPTOSIS AND PARATHORMONE IN PATIENTS WITH END Khaled Abouseif1, Hussein Abdallah1, Marwa Abdulhady2, Shaimaa Zaki
STAGE RENAL DISEASE TREATED BY HEMODIALYSIS abdelmegied1
1
faculty of medicine ain shams university, internal medicine and nephrology, cairo,
Aya Hefny1, Fatima El-Tahir1, Abeer Fikry2, Ali M Shendi1 Egypt and 2elsheikh zayed specialized hospital, nephrology , Egypt
1
Faculty of Medicine, Zagazig University, Nephrology Unit, Egypt and 2Faculty of
Medicine, Zagazig University, Clinical Pathology department, Egypt BACKGROUND AND AIMS: End stage renal disease (ESRD) is chronic
inflammatory condition which affects iron parameters. Serum soluble transferrin
BACKGROUND AND AIMS: Eryptosis (Red cell apoptosis) has been recognized as receptor (sTfR) is a reliable indicator for assessing iron status in inflammatory
one of the mechanisms that mediate anaemia in patients with chronic kidney disease conditions. This study evaluates the usefulness of serum sTfR in iron deficiency anemia
whether pre or on dialysis. Phosphorus (Ph) and parathormone (PTH) can be detection in prevalent hemodialysis patients.
considered as uremic toxins which are associated with renal anaemia, and both were METHOD: This case-control study included 40 ESRD patients on conventional
suggested to be associated with shortened red blood cell (RBC) life span. We aimed to hemodialysis with CRP>10, 40 ESRD patients with CRP<10 and 8 apparently healthy
assess the relation between each of PTH and phosphorus levels and eryptosis in a controls. Serum sTfR was measured for all patients and controls.
cohort of patients with end stage renal disease (ESRD) treated by haemodialysis. RESULTS: STFRs predicts iron deficiency anemia in prevalent hemodialysis patients at
METHOD: We studied a cohort of 85 patients with ESRD on conventional cut off value 12.5 mg/l with area under curve 0.949, sensitivity 88.75, specificity 100,
hemodialysis for at least 3 months. Blood was drawn prior to the mid-week dialysis PPV 100% and NPV 47.1%. The prevalence of STFRs in patients with CRP<10 was
session. Patients are dialysed on Fresenius 4008s machines. The percent of Annexin V- 85%, while in patients with CRP>10 was 92.5% (P-value 0.288). Patients who have
binding RBCs was assessed by flow cytometry in fresh blood samples and was used to elevated STFRs have risk 1.22 times to have iron deficiency anemia if CRP <10 (odds
indicate the percent of Eryptotic RBCs. Data were represented as median (interquartile ratio: 1.22) and 3.14 times if CRP>10 (odds ratio: 3.14). There was significant
range). difference on comparing patients with CRP<10, CRP>10 and control as regard
RESULTS: The study included 85 patients on prevalent hemodialysis for a median of 8 haemoglobin and STFR with P-value 0.0001 and 0.0001 respectively. Post Hoc analysis
(3-12) years, 52.9% females. Hypertension was the most common cause of ESRD showed significant difference between the patients with CRP<10 and control also in
(49.4%). The median hemoglobin was 10.9 (9.3 - 13) gm/dl and most patients received patients with CRP>10 and control as regard haemoglobin and STFR (p value
erythropoietin therapy (83/85) at a median dose of 8000 (4000 – 8000 units/weak). The <0.0001). on comparing patients with CRP<10 with patients with CRP>10 there was
median percent of Annexin V- binding RBCs was 2.3 (1.4 – 4.7%). On multilinear significant difference in STFRs p value 0.0001 despite no significant difference in
regression analysis, only PTH was independently associated with the percent of haemoglobin (p value 0.642) and classic iron markers (s.iron, TIBC, TSAT) with p
Annexin V- binding RBCs (standardized b= 0.630; 95.0% CI: 0.001 – 0.003; p<0.001). value 0.701, 0.192, 0.382 respectively. Serum STFRs was negatively correlated with
Patients were then stratified according to the PTH level into: low PTH (< 150 ng/dl; s.iron and Kt\v in patients with CRP <10 (r -0.372, P-value 0.018) and (r-0.416, p value
25/85, 29.4%), target PTH (150 – 600 ng/dl; 33/85, 38.8%) and high PTH (> 600 ng/dl; 0.008) respectively.
27/85, 31.8%) groups. The 3 groups differed significantly in the percent of Annexin V- CONCLUSION: Serum soluble transferrin receptor is a highly sensitive and specific
binding RBCs (1.2 (0.7-1.7); 2.5 (1.8-3.6) and 4.8 (3.2-5.6) % respectively; p<0.001) marker of iron deficiency anemia in hemodialysis patients especially with high CRP
(Figure). The percent of Annexin V- binding RBCs was similar in patients with high level.
(>5.5) and target (<5.5 mg/dl) Ph levels (p=0.318). It was higher in patients with
above-target CaXPh product (>55) than those with target CaXPh product (<55 mg2/
dl2) (5 (2-5.4) % vs 2.3 (4.1 – 1.2) %), yet this was not statistically significant (p=0.068).
CONCLUSION: Patients with ESRD treated by hemodialysis express high rates of
eryptosis. Parathormone excess in those patients may result in further eryptosis
enhancement, and this represents a potential pathogenic mechanism linking
hyperparathyroidism with the anemia of CKD. Larger interventional studies are thus
warranted to further explore the association between parathormone and eryptosis.

MO789 Figure 1: ROC curve of STFRs in prediction of iron deficiency anemia

MO788 Figure 1: The per cent of annexin V-binding RBCs stratified by the PTH
level. Results expressed as median (interquartile range).*P < 0.05 vs High PTH group;
** P < 0.05 vs both High and target PTH groups.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
MO790 PREDICTORS OF ERYTHROPOIETIN HIPORESPONSIVENESS MO791 HIGH-SENSITIVITY CARDIAC TROPONIN I CORRELATES
IN PREVALENT PATIENTS ON PERITONEAL DIALYSIS: A WITH THE CARDIAC DYSFUNCTION AND WITH THE
CROSS-SECTIONAL STUDY SEVERITY OF ANEMIA IN DIALYSIS PATIENTS

Marisa Rolda~o1, Rachele Escoli1, Hern^ ani Gonçalves1, Francisco Ferrer1, Caterina Vita1, Davide Bolignano1, Pierangela Presta1, Mariateresa Zicarelli1,
Karina Lopes1 Irma Figlia2, Paola Cianfrone1, Valentina Arcidiacono1, Alessandro Comi1,
1
Centro Hospitalar Médio Tejo, Nephrology Giuseppe Coppolino1, Giorgio Fuiano1, Michele Andreucci1
1
Magna Græcia University, Nephrology and Dialysis Unit, Catanzaro, Italy and
2
BACKGROUND AND AIMS: Anemia resistant to recombinant human Ospedale Civile, Nephrology and Dialysis Unit, Cetraro, Italy
erythropoietin (EPO) is a risk factor for mortality in dialyzed patients with chronic
kidney disease. Identifying the causes of hyporesponsiveness may help overcome this BACKGROUND AND AIMS: Several evidences demonstrate that chronic dialysis
resistance. The aim of this study was to investigate the risk factors of EPO treatment alters troponin levels, even in the absence of an acute myocardial event,
hyporesponsiveness in a prevalent population of patients on peritoneal dialysis (PD). although the underlying causes remain largely unclear. In this small pilot study, we
METHOD: Cross-sectional study involving 50 prevalent DP patients. To evaluate the aimed at analyzing high sensitivity troponin T (HsTnT) in a cohort of dialysis patients
dose–response effect of EPO therapy, we used the erythropoietin resistance index to identify the potential clinical predictors.
(ERI), calculated as the average weekly weight-adjusted dose of EPO (U/Kg per week) METHOD: HsTnT levels were measured together with common laboratory and
divided by the average hemoglobin level (g/dL), over a 3-month period. Patients were clinical parameters in 39 chronic dialysis patients (middle age: 65612 aa; 82% M; 30 in
classified in two groups according to ERI: ERI  10 and ERI > 10. We compared hemodialysis and 9 in peritoneal dialysis). The patients underwent also a complete
clinical, analytical and demographic data among groups. Body composition and fluid echocardiography assessment.
volume were evaluated by bioimpedance using the body composition monitor (BCM). RESULTS: HsTnT levels were higher than normal reference values (median 46.1 ng/L
Logist regression analysis was performed to identify predictors of EPO IQR 33.5-84.3),but showing no differences between hemodialysis and peritoneal
hyporesponsiveness. Statistical analysis was executed using SPSS (Version 23 for Mac dialysis patients (p=0.19). At correlation analyses, HsTnT were strongly associated
OSX). with beta2-MCG (R=0.43; p=0.008), Hemoglobin (r=-0.47; p=0.002) and, in particular,
RESULTS: The average age of 50 prevalent DP patients was 52.04 6 15.98 years, 29 with some echocardiography parameters such as ejection fraction (R=-0.29; p=0.05), E/
(58%) were male, 29 (58%) were diabetic and 31 (64%) were treated with angiotensin- E’ratio (R=0.56; p=0.006) and LAVI (R=0.41; p=0.05) Figure 1.
converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). Average
hemoglobin level (Hb) was 10.99 6 0.81g/dL and average ERI was 7.64 6 7.25. Eleven
patients (22%) had hyporesponsiveness to EPO therapy (ERI>10). There was no age,
gender, cause of chronic kidney disease or PD modality difference among groups.
There was also no difference in the use of ACEIs or ARBs. Hyporesponsive patients
had lower body mass index (BMI) (22.94 6 2.89 vs 26.74 6 4.53Kg/m2, p=0.01) and
lower lean tissue index (LTI) (9.96 6 1.94 vs 16.23 6 18.51Kg/m2, p=0.02), but not fat
tissue index (FTI). Weekly creatinine clearance (peritoneal plus urinary), but not Kt/V,
was also significantly lower in this group (68.76 6 37.29 vs 87.84 6 35.35L/1.73m2,
p=0.028). Hyporesponsive patients had lower urine volume (0.73 6 0.63 vs 1.39 6
0.67L, p=0.005) and residual kidney function (3.43 6 3.04 vs 6.13 6 3.69mL/min/
1.73m2, p=0.044). The proportion of patients with fluid overload, defined as
overhydration (OH)/extracellular water (ECW) > 15%, was significantly higher in this
group (p=0.04). No difference was observed in albumin, c-reactive protein, serum iron,
serum ferritin, transferrin saturation index or parathormone among groups. In a logist
regression analysis, BMI [(OR) 0.56 (CI: 0.364-0.849)] and LTI [(OR) 0.315 (CI: 0.130-
0.767)] were predictors of hyporesponsiveness to EPO therapy.
CONCLUSION: Lower BMI and lower LTI were predictors of resistance to EPO
therapy in our study. Body composition, fluid status and residual kidney function seem
to be the main factors influencing the response to EPO therapy in prevalent patients on
PD, emphasizing the importance of strategies oriented to preserve residual kidney CONCLUSION: In a small cohort of dialysis patients, high HsTnt levels were at the
function in these patients. crossroad between the severity of functional heart dysfunction and anemia. Larger
studies are advocated to further clarify the role of HsTnT as a potential biomarker
reflecting the anemic cardiorenal syndrome which characterizes uremic subjects.

10.1093/ndt/gfab095 | i443
Nephrology Dialysis Transplantation 36 (Supplement 1): i444–i453, 2021
10.1093/ndt/gfab096

DIALYSIS. BONE DISEASE

MO792 CONTEMPORARY MINERAL AND BONE DISORDER


MARKERS AND TREATMENT AMONG HEMODIALYSIS
PATIENTS IN THE EUROPEAN DIALYSIS OUTCOMES AND
PRACTICE PATTERNS STUDY (DOPPS)*

Brian Bieber1, Indranil Dasgupta2, Pieter Evenepoel3, Stefan H. Jacobson4,


Piergiorgio Messa5, Almudena Vega6, Thomas Weinreich7, Angelo Karaboyas1,
Bruce Robinson1, Ronald Pisoni1
1
Arbor Research Collaborative for Health, Ann Arbor, United States of America,
2
University Hospitals Birmingham NHS Foundation Trust; Heartlands Hospital, Renal
Medicine, Birmingham , United Kingdom, 3University Hospitals Leuven, Department of
Nephrology and Renal Transplantation, Leuven, Belgium, 4Karolinska Institutet,
Danderyd University Hospital, Division of Nephrology, Department of Clinical Sciences,
Stockholm, Sweden, 5Universita degli Studi di Milano, Director of the Nephrology,
Dialysis, and Renal Transplant Unit, Milan, Italy, 6Hospital General Universitario
Gregorio Mara~ on, Nephrology Department, Madrid, Spain and 7Nephrologisches
n
Zentrum, Villingen-Schwenningen, Germany

BACKGROUND AND AIMS: Chronic kidney disease mineral and bone disorder
(CKD-MBD) is characterized by abnormalities in serum calcium, phosphorus, and
parathyroid hormone (PTH) and associated with morbidity and mortality. Previous
publications from the Dialysis Outcomes and Practice Patterns Study (DOPPS) have
demonstrated country differences in the prevalence and treatment of CKD-MBD
among hemodialysis patients in participating European countries. We aim to compare
the distribution of CKD-MBD related labs and treatments across countries in a
contemporary population of European hemodialysis patients.
METHOD: DOPPS is an international prospective cohort study of hemodialysis
patients 18 years of age. Patients are enrolled randomly from a representative sample
of dialysis facilities within each nation at the start of each study phase. The current
analysis includes n=1,701 patients from 91 facilities in the initial prevalent cross section
of Europe DOPPS phase 7 (2019-present; Belgium, Germany, Italy, Spain, Sweden,
UK). Results from Belgium should be considered preliminary as initial questionnaire
completion is ongoing. MO793 COMPARATIVE STUDY BETWEEN THE IMPACT OF
RESULTS: The % of patients with a high PTH (>600 pg/mL) ranged from 6% in Italy ETELCALCETIDE AND CINACALCET ON LEVELS OF IPTH,
to 24% in the UK, with 12-17% having high PTH in all other countries. Mean serum FGF-23, KLOTHO PROTEIN, SCLEROSTIN, CA AND P IN
total calcium ranged from 8.7 in Germany to 9.1 mg/dL in the UK (Table). Mean DIALYSIS PATIENTS WITH SECONDARY
serum phosphorus varied from 4.5 in Belgium to 5.3 mg/dL in Germany. Dialysate HYPERPARATHYROIDISM. RESULTS FROM A PROSPECTIVE
calcium of 2.5 mEq/L was predominant in Germany, Sweden, and the UK while 3.0 RANDOMIZED TRIAL
mEq/L was the most common prescription in Belgium, Italy, and Spain. Calcimimetic
prescription ranged from 13% in the UK to 32% in Spain. Etelcalcetide prescription Evgeny Shutov1,2, Galina Kotlyarova2, Ksenia Lysenko2, Galina Ryabinskaya3,
ranged from 1% in the UK to 12% in Spain and 14% in Italy. Active vitamin D Sergey Lashutin2
prescription ranged from 27% in Belgium to 75% in Sweden. Nearly all vitamin D 1
Russian Medical Academy of Continuous Proffessional Education, Moscow, Russia,
prescriptions were administered intravenously in Spain versus about half in Italy; in all nephrology, Moscow, Russia, 2Clinical Hospital named after S.P. Botkin, Moscow, Russia,
other countries, the route of active vitamin D administration was primarily oral. nephrology, Moscow, Russia and 3Clinical Hospital named after S.P. Botkin, Moscow,
Patient age and dialysis vintage varied by country, potentially contributing to some of Russia, laboratory, Moscow, Russia
the observed country differences in MBD marker levels and treatment practices.
CONCLUSION: CKD-MBD related abnormalities in PTH, serum phosphorus and
calcium remain common in European dialysis patients, with prevalence varying BACKGROUND AND AIMS: The treatment of secondary hyperparathyroidism is
considerably by country. Substantial international variation in CKD-MBD treatments one of the main tasks in the correction of mineral and bone disorders (MBD) in
was also observed in prescription of vitamin D and calcimimetics. Uptake of the patients with chronic kidney disease (CKD). However, the results of therapy for
secondary hyperparathyroidism are still unsatisfactory. In our prospective randomized
relatively new calcimimetic, etelcalcetide, varied considerably by country. A detailed
controlled trial were evaluated the effect and safety of 26 weeks of treatment with
understanding of the effect of treatment variation on CKD-MBD marker levels and
etelcalcetide (intravenous route of administration) compare with cinacalcet (oral
patient outcomes is needed to provide important insights for the European HD
administration) on CKD-MBD parameters in patients on program hemodialysis with
community in optimizing management of secondary hyperparathyroidism.
secondary hyperparathyroidism.
METHOD: The study group included 50 stable patients receiving hemodialysis with
secondary hyperparathyroidism (PTH > 300 pg/ml) and corrected Ca level greater
than 2.2 mmol/L, who were randomized in a 1: 1 ratio for treatment with etelcalcetide
(n = 25) or cinacalcet (n = 25) for 26 weeks. All patients were monthly evaluated the
levels of P, Ca, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP); the
levels of FGF 23, Klotho protein and sclerostin were assessed once in 3 months. The
dose of both drugs was adjusted according to the serum iPTH level. The nature,
frequency, and severity of treatment-emergent adverse events were assessed.
RESULTS: Therapy with cinacalcet and etelcalcetide led to a significant decrease in the
level of iPTH in the blood serum from 613.1 6 235.1 to 302.2 6 205.1pg/ml (p< 0.01)
and from 671.2 6 272.3 to 358,6 6 292.5 pg/ml (p <0.01), by 49.2% and 53.4%,
respectively. A significant decrease in the levels of corrected Ca was noted in both
groups: in the etelcalcetide group from 2.20 6 0.12 to 2.06 6 0.18 mmol/L (p <0.05),
in the cinacalcet group from 2.25 6 0.12 to 2.04 6 0.21 mmol/l (p <0.05). There was
no significant change in the P levels. The alkaline phosphatase level significantly
decreased in the cinacalcet group from 178.7 6 116.8 to 78.9 6 34.1 U/L, p <0.05) and
in the etelcalcetide group from 170,3 6 115.7 to 87.1 6 30.8 U/L, p <0.05. There was a
significant increase in Klotho protein levels by the end of the study from 17.9 6 5.0 to

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
57.1 6 39.3 (p <0.05) and from 17.6 6 3.7 to 91.6 6 56.2 pg/ml (p <0.05),
respectively, in the cinacalcet and etelcalcetide group. Changes in FGF-23 and
sclerostin by 6 months reached statistically significant changes only in the etelcalcetide
group, a decrease from the FGF-23 level from 42.7 6 22.2 to 23.0 6 12.3 pg/ml and an
increase in the level of sclerostin from 1, 59 6 0.31 to 2.20 6 0.33 ng/ml (p <0.05).
During the study, 2 patients in the cinacalcet group dropped out due to dyspeptic
symptoms and 1 patient in the etelcalcetide group dropped out due to hypocalcemia.
CONCLUSION: Etelcalcetide and cinacalcet are effective PTH-lowering drugs with a
comparable safety profile. Treatment with etelcalcetide, in contrast to cinacalcet, was
associated with significant increases in sclerostin and decreases in FGF-23, which may
have beneficial effects on outcomes and requires further study.

MO794 EVALUATION OF THE BONE ELASTIC STRUCTURE IN


PERSONS WITH AND WITHOUT CHRONIC KIDNEY DISEASE
ON DIALYSIS

Pietro Manuel Ferraro1,2, Alessandra Nicolosi3, Alessandro Naticchia1,2,


Nicola Panocchia1,2, Giuseppe Grandaliano1,2, Francesca Cosmi3,4
1
Fondazione Policlinico Universitario A. Gemelli IRCCS, U.O.C. Nefrologia, Dipartimento
di Scienze Mediche e Chirurgiche, Rome, Italy, 2Universit a Cattolica del Sacro Cuore,
Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Rome, Italy, 3M2TEST
srl, Trieste, Italy and 4Universit
a degli Studi di Trieste, Dipartimento di Ingegneria e
Architettura, Trieste, Italy

BACKGROUND AND AIMS: Chronic kidney disease is a frequent condition,


characterized, especially in its more advanced stages, by an array of derangements in
bone structure and density, resulting in a higher rate of bone fractures. Current MO795 CALCIUM BALANCE AND CKD-MBD PARAMETERS
strategies to monitor the bone status and assess the risk of bone fractures in CKD DIFFERENCES OF CITRATE VS. ACETATE DIALYSATE
patients are limited.
The Bone Elastic Structure (BES) test is a recently-developed non-invasive tool that Jose Jesus Broseta Monzo1, Luis Carlos Lo pez Romero2, Diana Rodrıguez1,
measures the elastic characteristics of the trabecular bone by simulating the application Elena Guillen Olmos1, Pilar Sa nchez-Pérez2, Julio Hernandez Jaras2
of loads on a virtual biopsy obtained from radiographic images of the proximal 1
Hospital Clınic de Barcelona, Department of Nephrology and Renal Transplantation,
epiphyses in the patient’s hand fingers. The simulation results are combined to obtain a Barcelona, Spain and 2Hospital Universitario y Politécnico de La Fe, Department of
parameter defined Bone Structure Index (BSI). The aim of our study is to explore Nephrology, València, Spain
whether the BES test could be a useful monitoring tool of bone status in patients with
CKD on dialysis by exploring whether such patients have different BSI values BACKGROUND AND AIMS: Dialysate composition is an essential feature of
compared with persons without CKD. hemodialysis treatment. The use of acetate as the dialysate buffer and its calcium
METHOD: The BES test was performed on a sample of 41 patients undergoing concentration are still topics of debate. Calcium transfer during dialysis sessions is
chronic hemodialysis (HD) and the BSI compared with a group of 374 persons with related to short-term (hemodynamic tolerance and arrhythmias) and long-term effects
normal renal function who had undergone the BES test in previous studies. Differences (cardiovascular calcification and mortality). This study aims to identify the potential
in BSI and 95% confidence intervals (CIs) between the two groups were obtained and benefits derived from acetate-free dialysis by using citrate as a buffer in terms of
tested for statistical significance with a linear regression model including BSI as the calcium balance and CKD-MBD biomarkers.
dependent variable and kidney status (HD vs no HD) as the independent variable, METHOD: We performed a prospective crossover study that analyzed 24 dialysis
adjusted for age and sex. Subgroup effects were explored by including interaction terms sessions, 12 with each dialysate buffer, on every patient. Ionized calcium and CKD-
(age x kidney status, age x sex, kidney status x sex) in the model. Finally, to further MBD parameters were analyzed with each acidifier. Both dialysates had a calcium
remove the potential confounding by age and sex, each HD patient was individually concentration of 1.5 mml/L. The remaining hemodialysis patients’ parameters were
matched with up to 4 non-HD participants based on sex and age (with a 5-year caliper) unchanged during the study period.
and a matched analysis was conducted on BSI values. RESULTS: No differences were found between pre-dialytical ionized calcium (iCa)
RESULTS: Average (SD) age was 64 (17) years in the HD group and 60 (12) years in (1,11 6 0,12 vs. 1,08 6 0,12 mmol/L) in both groups. However, we identified a
the non-HD group, with a prevalence of males of 49% and 16%, respectively. significant iCa increase in the sessions were acetate dialysate was used, both in
The individual values of BSI divided by kidney status and sex in Figure. The immediate (1,29 6 0,07 mmol/L) and in 30-minutes post-dialytical blood analysis
multivariate linear regression model showed that, after adjustment for age and sex, the (1,22 6 0,07 mmol/L). Whereas iCa levels remained stable during the immediate (1,07
BSI in the HD group was significantly lower compared with the non-HD group (HD 6 0,06 mmol/L) and 30-minutes post-dialytical analysis (1,08 6 0,11 mmol/L) when
145, 95% CI 140, 154; non-HD 179, 95% CI 177, 181; absolute difference 32, 95% CI using citrate. On the other hand, pre-dialysis albumin-corrected total calcium was
40, 25; p-value < 0.001). There was no significant interaction between age, sex and higher with acetate (8,9 6 0,6 vs. 8,31 6 0,75 mg/dL, p = 0,003) and PTH was lower
kidney status on BSI values (all p-values > 0.05). with acetate (169 vs. 267 pg/mL, p < 0,001).
Individual matching was successful for 36 out of 41 HD patients, who were matched to CONCLUSION: Acetate-free dialysis using citrate as an acidifier stabilizes iCa levels
127 non-HD participants; matched analysis confirmed the results (absolute difference during dialysis sessions while maintaining a neutral or negative effect in calcium
31, 95% CI 40, 23; p-value < 0.001). balance. This analytical benefit may translate into better cardiovascular long-term
CONCLUSION: The output of a non-invasive tool to determine the bone elastic outcomes.
structure appeared to be strongly associated with kidney function after control for
differences in age and sex. Further studies are needed to determine the potential
application of the BES test in patients with CKD.

MO796 IMPACT OF ACTIVE VITAMIN D AND CALCIUM


PREPARATION ON VASCULAR CALCIFICATION MARKERS IN
HEMODIALYSIS PATIENTS WITH HYPOCALCEMIA INDUCED
BY CALCIMIMETICS

Yusaku Hashimoto1, Sawako Kato1, Masato Tsuboi2, Makoto Kuro-o3,


Yachiyo Kuwatsuka4, Masahiko Ando4, Shoichi Maruyama1
1
Nagoya University Graduate School of Medicine, Nephrology, Japan, 2Kaikoukai
Healthcare Group, 3Jichi Medical University, Anti-Aging Medicine, Japan and 4Nagoya
University Hospital, Advanced Medicine, Japan

BACKGROUND AND AIMS: Recently, we demonstrated the efficacy of etelcalcetide


for control of secondary hyperparathyroidism (SHPT) in the DUET trial; a 12-week
multicenter, open-label, randomized (1:1:1), parallel-group study treated with
etelcalcetide þ active vitamin D (Group EþD), etelcalcetide þ oral calcium

10.1093/ndt/gfab096 | i445
Abstracts Nephrology Dialysis Transplantation

preparation (Group EþCa), or control groups (Group C) in 124 subjects undergoing improving CKD-MBD parameters compared with non-calcium phosphate binders
maintenance hemodialysis. Moreover, we also showed that active vitamin D was useful (sevelamer) in DD-CKD patients. The parameters compared in this study are changes
in correcting hypocalcemia induced by calcimimetics, but the oral calcium preparation in serum phosphate (P), serum calcium ions (Ca), fibroblast growth factors-23
was superior for suppression of hyperphosphatemia. In this post hoc analysis, we (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (calcidiol), and
evaluated vascular calcification markers, fibroblast growth factor 23 (FGF23) and 1,25-dihydroxyvitamin D (calcitriol). Bias risk was accessed by using the revised
calciprotein particles (CPPs), in patients using etelcalcetide (n = 77) extracted from the Cochrane Risk-of-bias (RoB-2) tool. Analysis was performed to provide standard mean
registrants of the DUET trial. difference (SMD) with 95% confidence interval (CI) using random-effect heterogeneity
METHOD: Serum levels of FGF23 and CPPs were measured at baseline, 6 weeks and test.
12 weeks after start of the trial. Skewed data (FGF23 and CPPs) were transformed to RESULTS: Ten RCTs with total of 1,139 participants were included in this analysis.
natural logarithm to achieve normal distribution prior to statistical analysis. The The sucroferric oxyhydroxide decreases FGF23 although not statistically significant
changes in log CPPs and log FGF23 were estimated in a linear mixed model with each (SMD = 0.22. 95% CI = -0.49 to 0.05, p = 0.11, I2 = 52%), but ferric citrate (SMD = -
treatment group, time point, and interaction of the treatment group and time point as 0.92. 95%CI = -1.56 to -0.29, p = 0.004, I2 = 69%) and the overall estimate (SMD = -
the fixed effects. We compared these changes between treatment the groups using a 0.45. 95% CI = -0.82 to -0.09, p = 0.02, I2 = 79%) showed significant FGF23 decline
linear mixed model and also the Tukey-Kramer method to correct for multiplicity. compared with sevelamer. The sucroferric oxyhydroxide showed no significant
Additionally, we exploratory examined the correlations among changes of FGF23, improvement of calcidiol (SMD = 0.08. 95%CI = -0.02 to 0.17, p = 0.13, I2 = 0%) and
CPPs and other biomarkers related to bone mineral metabolisms, iPTH, Ca, P, and calcitriol (SMD = 0.02. 95% CI = -0.08 to 0.12, p = 0.74, I2 = 0%) compared with
calcium-phosphate product, tested by Spearman’s rank correlation coefficient. selevamer. There is also no significant improvement of iPTH in sucroferric
RESULTS: The decreases at the 12-week time point after the trial start in log FGF23 oxyhydroxide subgroup (SMD = -0.14. 95%CI = -0.43 to 0.14, p = 0.32, I2 = 85%),
were estimated -1.13 pg/mL in Group EþCa and -0.10 pg/mL in Group EþD in a ferric citrate subgroup (SMD = -0.02. 95%CI = -0.16 to 0.12, p = 0.80, I2 = 0%), and
linear mixed model, respectively. Similarly, the decreases in CPPs were estimated -1.60 pooled group analysis (SMD = -0.10. 95%CI = -0.27 to 0.07, p = 0.27, I2 = 75%).
AU in Group EþCa and -0.82 AU in Group EþD, respectively. Changes of both Besides, this study also suggests no significant improvement comparison of serum P
FGF23 (P = 0.017) and CPPs (P < 0.001) in Group EþCa significantly decreased (SMD = -0.09. 95%CI = -0.19 to 0.02, p = 0.12, I2 = 38%) and Ca (SMD = 0.04. 95%CI
compared with those in in Group EþD by Tukey-Kramer multiple-comparison test at = -0.12 to 0.20, p = 0.61, I2 = 57%).
12 weeks after the trial start, while both changes in CPPs and FGF23 could not reach CONCLUSION: There is no significant efficacies differences between iron-based and
the significant differences between two groups at 6 weeks after the trial start (Figure 1). non-calcium phosphate binders for improving serum phosphate, serum calcium ions,
Reductions in FGF23 positively correlated with reductions in calcium (q = 0.42, P < iPTH, calcidiol, and calcitriol in dialysis-dependent chronic kidney disease patients,
0.01) and phosphate (q = 0.48, P < 0.01) at 6 weeks after the trial start, and in calcium except for the FGF-23 parameter. However, further trials are needed to establish the
(q = 0.30, P < 0.01) and phosphate (q =0.70, P < 0.01) at 12 weeks after 6 weeks of the juxtaposition.
trial start), but there was no correlation with reductions in iPTH at any time point.
Reductions in CPPs positively correlated with reductions only in phosphate at 6 weeks
after the trial start (q = 0.47, P < 0.01) and at 12 weeks after 6 weeks of the trial start (q
= 0.54, P < 0.01).
MO798 ORAL CALCITRIOL USE, VERTEBRAL FRACTURES AND
VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS:
RESULTS FROM VITAMIN K ITALIAN (VIKI) STUDY.

Maria Fusaro1,2, Andrea Aghi3, Cristina Politi4, Thomas Nickolas5,


Giuseppe Cianciolo6, Gaetano La Manna6, Lorenzo Gasperoni6, Maria
Cristina Mereu7, Maurizio Gallieni8, Maura Ravera9, Sandro Giannini3,
Stefania Sella3, Gaetano Arcidiacono3, Giovanni Luigi Tripepi4
1
Institute of Clinical Physiology (IFC), National Research Council (CNR), Pisa, Italy,
2
University of Padua, Department of Medicine, Padova, Italy, 3Clinica Medica 1,
Department of Medicine, University of Padua, Padova, Italy, 4Clinical Epidemiology and
Physiopathology of Renal Diseases and Hypertension, CNR, Institute of Biomedicine,
Reggio Calabria, Italy, 5Division of Nephrology, Columbia University Irving Medical
Center, Department of Medicine, New York, United States of America, 6Nephrology,
Dialysis and Renal Transplant Unit, S. Orsola Hospital, Department of Experimental
Diagnostic and Specialty Medicine (DIMES), Bologna, Italy, 7Independent Researcher,
Cagliari, Italy, 8Sacco Hospital, Department of Biomedical and Clinical Sciences ‘Luigi
Sacco’, Universit a di Milano, Milano, Italy and 9IRCCS AOU San Martino, Clinica
MO796 Figure 1: Changes in vascular calcification markers. Nefrologica, Dialisi e Trapianto, Universita’ di Genova, Genova, Italy

CONCLUSION: In this analysis, vascular calcification markers were significantly BACKGROUND AND AIMS: In patients with Chronic Kidney Disease (CKD)
decreased in Group EþCa compared to those in Group EþD. Further studies should mineral, bone, and calcific cardiovascular abnormalities are associated to adverse
be needed, our study suggests that oral calcium preparation may have an advantage clinical outcomes, including fractures, cardiovascular events and mortality. Vitamin D
against vascular calcification rather than active vitamin D for the correction of hormonal system along with alteration levels that occur in calcium, phosphate, PTH,
hypocalcemia induced by etelcalcetide in hemodialysis patients with SHPT. FGF23/Klotho are the main responsible of the bone and vascular metabolism changes,
particularly in hemodialysis (HD) patients that experienced the very negative clinical
consequences (decreased bone mass, increased fragility fractures and vascular
calcification). In the setting of a comparative effectiveness study, we investigated the
effect of oral calcitriol on fractures in HD patients taking into account a series of
MO797 JUXTAPOSING THE EFFICACIES BETWEEN IRON-BASED potential confounders.
AND NON-CALCIUM PHOSPHATE BINDERS FOR IMPROVING METHOD: We conducted a secondary analysis of the VIKI database, a cross-sectional
MINERAL AND BONE DISORDER PARAMETERS IN DIALYSIS- study involving 387 HD patients from 18 Italian dialysis centers. Routine biochemistry
DEPENDENT CHRONIC KIDNEY DISEASE PATIENTS: A and bone biochemical markers such as vitamin K levels, VKDPs, vitamin 25(OH)D,
META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS ALP, PTH, Ca, P, osteocalcin (BGP), Matrix Gla Protein (MGP) were assessed. The
presence of Vertebral Fractures (VF) and Vascular Calcification (VC) was determined
Boby Pratama Putra1, Felix Nugraha Putra2 through spine radiograph. Reduction of >20% of vertebral body height was considered
1 a VF. The severity of the vertebral fractures was estimated as mild, moderate and severe
Medical doctor, Blitar, Indonesia and 2Faculty of Medicine, Universitas Airlangga, (reduction: 20-25%, 25-40% or >40%, respectively). VC were quantified by measuring
Surabaya, Indonesia the length of calcific deposits along the arteries (mild 0,1-5 cm, moderate 5,1-10 cm
and severe >10 cm).
BACKGROUND AND AIMS: Hyperphosphatemia is a serious complication in RESULTS: 177 out 387 patients (45.7%) were treated with oral calcitriol. Oral
chronic kidney disease (CKD) patients that serves as the main risk factor of CKD– calcitriol-treated and untreated patients did not differ as for Ca, P, PTH, Albumin,
mineral and bone disorder (CKD-MBD) progression. Previous studies suggested that BGP, MGP, and ALP. The prevalence of VF was significantly lower in patients
iron-based phosphate binder showed better improvement in CKD-MBD parameters receiving oral calcitriol than in those untreated (48.6% vs 61%, P=0.015), whereas the
although the results were still inconclusive. This study aims to juxtapose the efficacies presence of aortic and iliac calcifications was similar between the two groups (aortic:
between iron-based and non-calcium phosphate binders for improving CKD-MBD 81.9% vs 79.5% respectively, P=0.552; iliac: 52.0% and 59.5%, P=0.167). No significant
parameters in dialysis-dependent (DD)-CKD patients. between-groups differences were observed in terms of calcification severity. In a
METHOD: We did comprehensive searching to screen all relevant literature until multivariable logistic regression analysis, after adjustment for all potential
November 2020 in online databases of Pubmed, EMBASE, ScienceDirect, and The confounders, oral calcitriol was associated with a marked reduction (-40.2%) of the
Cochrane Library. We included all randomized controlled trials (RCTs) accessing the odds of fractures (OR: 0.598, 95% CI: 0.363-0.985, P=0.043) (see Table).
efficacies of iron-based phosphate binders (sucroferric oxyhydroxide, ferric citrate) in CONCLUSION: A significant association was found between oral calcitriol and lower

i446 | Abstracts
Nephrology Dialysis Transplantation Abstracts
VF rate in HD patients. Such an effect remained significant also after data adjustment MO800 EFFICACY AND SAFETY OF CINACALCET IN CHINESE
for a large series of potential confounders. Further prospective and interventional MAINTAINANCE HEMODIALYSIS PATIENTS WITH
studies are needed to confirm these findings. DIFFERENT STAGES OF SECONDARY
HYPERPARATHYROIDISM: RESULTS OF ACTIVE STUDY

Active Study Group1,2


1
Jinling Hospital, Nanjing University School of Medicine, National Clinical Research
Center of Kidney Diseases, Nanjing, P.R. China and 2Kyowa Kirin China Pharmaceutical
Co., Ltd, Medical Affairs, Shanghai, P.R. China

BACKGROUND AND AIMS: Secondary hyperparathyroidism (SHPT), as a common


complication in advanced chronic kidney disease (CKD) has become a global public
health problem. Published literatures showed higher risk of bone fracture,
cardiovascular events and all-cause mortality was associated with uncontrolled SHPT
in patients with CKD. Cinacalcet, a calcimimetic agent was reported to reduce intact
parathyroid hormone (iPTH) levels in patients with SHPT. However, there is no large-
cohort study and stratified analysis of cinacalcet based on the level of iPTH in China.
The ACTIVE study was designed to test the efficacy and safety of cinacalcet in treating
Chinese maintenance hemodialysis patients with mild-to-severe SHPT, as well as to
investigate the benefit of long-term, continuous medication with cinacalcet in the real-
world setting.
METHOD: ACTIVE study was a phase IV, open-label, multicenter clinical trial
including two phases: Phase 1 was a cohort study with 32 weeks’ follow-up. Phase 2
was a real-world study of 20 additional weeks in which patients who completed the
cohort study decided independently whether to continue taking cinacalcet at their own
cost. Eligible maintenance hemodialysis (MHD) patients with baseline iPTH 300 pg/
mL from April 2017 to September 2019 in 23 centers in China were treated with
cinacalcet orally. Patients were grouped based on their iPTH level as mild (300-600 pg/
MO799 IS COMBINATION OF MAINTENANCE HEMODIALYSIS WITH mL), moderate (600-900 pg/mL) or severe (900 pg/mL) SHPT.
HEMOPERFUSION AN EFFECTIVE METHOD IN RESULTS: 911 patients were screened and of 750 eligible patients, 275 were identified
MANAGEMENT OF RENAL OSTEODYSTROPHY AND as mild, 224 were considered as moderate and left 251 were grouped as severe SHPT.
INFLAMMATION IN HEMODIALYSIS PATIENTS? The number of people who completed all 52-week follow-up in the mild, moderate and
severe SHPT groups were 184 (66.91%), 164 (73.21%), and 166 (66.14%),
Amela Beciragic1, Alma Mutevelic-Turkovic1, Amela Dervisevic2, respectively(Fig 1). The baseline and interim analysis results was published on 2020

Badema Aœengi €† Roljia
a ۠1, Fahrudin Masnic1, Aida Coric1, Selma Ajanovic1, EDTA. The number of patients achieving iPTH target (150-300 pg/mL) was 85
Nejra Prohic1 (31.02%) in mild group, 56 (25.00%) in moderate group and 27 (10.76%) patients in
1
Clinical Center University of Sarajevo, Clinic for hemodialysis, Sarajevo, Bosnia and severe group at 20-week visit, and the proportion of patients achieving iPTH target was
Herzegovina and 2Institute for human physiology, Faculty of Medicine, Sarajevo, Bosnia 33.94% (n=93), 24.11% (n=54) and 13.55% (n=34) at 32-week visit. The trends of the
and Herzegovina proportion of patients achieving iPTH target increased in all 3 different groups (Fig 2).
The number of patients who reached both targets of serum calcium (Ca2þ) and serum
BACKGROUND AND AIMS: Some of the conditions which occur in maintenance phosphorus (P) in the mild, moderate and severe SHPT group was 61 (22.26%), 42
hemodialysis (MHD) patients with a high incidence resulting in a decline in their (18.75%), 37 (14.74%) at 20-week visit, and 44 (16.06%), 34 (15.18%), 41 (16.33%) at
quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and 32-week visit, respectively. At the end of the 20th and the 32nd week of treatment,
chronic systemic inflammation. In developing countries, due to the low level of serum Ca2þP and fibroblast growth factor-23 (FGF-23) decreased significantly
economic development, low-flux dialysis is the main means of extracorporeal blood compared with their baseline values (Table 1). In the extension 32-52 weeks study, the
purification therapy. But it can hardly remove the middle and large molecule uremic corresponding proportion of patients who achieved iPTH target in the three SHPT
toxins and protein-bound toxins; as a result, the patients suffer from long-term groups was 11.41%, 6.06%, and 4.81%, respectively. The safety analysis showed the
complications and poor quality of life. In this study, we attempted to investigate most common treatment-related AE were hypocalcemia, hyperlipidemia and loss of
whether the combination of maintenance hemodialysis (MHD) with hemoperfusion appetite. This study is sponsored by Kyowa Kirin China Pharmaceutical Co., Ltd.
(HP) could improve the clearance rate of middle and large molecule uremic toxins so
as to improve their uremic complications.
METHOD: A total of 54 patients, who underwent routine hemodialysis, were assessed
in this study. Those patients were randomly divided into two groups: Group 1 (27
patients) received combined treatment of HD with hemoperfusion (HP) in this
regimen: HD 2 times a week with HDþHP once a week two times in a row, then after
two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27
patients) was only undergoing maintenance HD 3 times a week. The clinical and
laboratory properties of both groups were followed up for 18 months, whereas the
primary outcomes included normal clinical data, high sensitive C-reactive protein
(hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium
(Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses
and types of hypertensive drugs.
RESULTS: At the end of the 18-month observation, the serum concentration of
albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP)
were lower with Group 1 than with Group 2 (p<0.05). Whereas, higher levels of iPTH
were noticed in group 1, but when the laboratory and clinical data are analysed of the
group 1 alone a statistically significant lower values after the observational period are
noticed especially in the serum values of iPTH (p<0.05), P04 (p<0.001), CRP
(p<0.011), SBP and DBP (p<0.05).
CONCLUSION: HDþHP was superior to HD in regularly eliminating middle and
large molecule uremic toxins accumulated in the body which is mostly shown through
reducing the values of iPTH and hsCRP. These findings suggest a potential role for MO800 Figure 1: Study flowchart.
HDþHP in the treatment of inflammation and renal osteodystrophy as well, because
lowering these values of iPTH leads to a normalization of other minerals which is
expected and therefore leads to a stabilization of this long-term uremic complications,
which can improve the overall general condition of the MHD patient.

10.1093/ndt/gfab096 | i447
Abstracts Nephrology Dialysis Transplantation

metabolism were monitored, and Qualitative UltraSonography (QUS) or


Computerized Bone Mineralometry (CBM) were used alternatively, every 30 months
and every 2 years, respectively (depending on guidelines recommendation for both
radiological methods and timing).
RESULTS: 7/19 patients completed at least 30 months of follow-up, observing a
substantial stability of blood calcium and phosphorus values, against a reduction in the
mean values of B-CrossLaps and ostase (respectively from 2975.32 to 1852.25 pg/ml
and from 28.13 to 11.93 mcg/L). Comparison of QUS exams demonstrated improved
T-score (-4.71 to -4.17) and reduced fracture risk (13% to 8%). The results of the CBMs
confirmed the stability of the bone disease at the spine and the improvement of the
Tscore at the femoral level (from -3.5 to -3).
It should be noted that in our samples two patients achieved the longest observation
period (48-month follow-up in continuous therapy), in which the stability of bone
damage was observed at CBM compared to the start of treatment.
Only one fracture has been recorded.
CONCLUSION: We underline that close biochemistry monitoring and careful
evaluation of the therapeutic procedures before and after DMab administration helped
us to minimise and promptly correct adverse effects due to hypocalcemia. In addition
we are particularly satisfied to report in most patients a significant reduction of pain
and an improvement of mobility.
MO800 Figure 2: The trends of the proportion of patients achieving iPTH target in The results collected are consistent with acceptable safety and demonstrated efficacy of
3 groups. P <0.05 for comparisons between three groups at 4th, 8th, 12nd, 16th, 20th, 26th denosumab in hemodialysis patients.
and 32nd weeks. iPTH, intact parathyroid hormone.
*, compare with mild group, there was statistically significant difference(p<0.001);
#
, compare with moderate group, there was statistically significant difference(p<0.001).

CONCLUSION: Oral cinacalcet HCl was effective and safe in reducing iPTH in
patients receiving HD with mild-to-severe SHPT.

MO800 Table 1: Outcomes of laboratory tests in 3 groups.

Ca2þ, calcium; P, phosphorus; ALP, alkaline phosphatase; FGF-23, fibro-


blast growth factor-23.
*paired-test with significant difference(p<0.001);

MO801 SAFETY AND EFFICACY OF DENOSUMAB IN


HEMODYALISED PATIENTS UP TO 48 MONTHS TREATMENT
FOLLOW-UP

Rita Chiara Ierace1, Alessandra Moioli1, Francescaromana Festuccia1,


Claudia Fofi1, Simona Barberi1, Paolo Mene’1
1
Universita Sapienza di Roma, Department of Clinical and Molecular Medicine, Rome,
Italy
MO802 DOES ETELCALCETIDE REVERSE MYELOFIBROTIC BONE
CHANGES DUE TO HYPERPARATHYROIDISM? A CASE
BACKGROUND AND AIMS: Osteoporosis in hemodialysed (HD) patients with REPORT
Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) is a debilitating clinical
condition with complex therapeutic management. In fact, most of the drugs commonly Vincenzo Antonio Panuccio1, Rocco Tripepi2, Silvia Lucisano1, Adele Postorino1,
used to counteract osteoporosis are generally contraindicated when Glomerular Giovanna Parlongo1, Maria Rosaria Fazio1, Francesco Catalano1, Dario Pazzano1,
Filtration Rate (GFR) is lower than 30 ml/min. Denosumab (DMab) is a monoclonal Bruna Greve3, Elena Sabattini4, Esther Oliva3, Francesca Mallamaci1
antibody approved for the treatment of osteoporosis and does not require dose 1
adjustment in case of impaired renal function. For this reason, since 2014 this drug has Grande Ospedale Metropolitano “Bianchi Melacrino Morelli”, Nephrology, Dialysis and
been used by nephrologists for the treatment of osteoporotic patients also in Transplantation Unit, Reggio Calabria, Italy, 2Institute of Clinical Psychology, National
hemodialysis. Although the interest and diffusion in this specialized clinical field are Research Counsil, Reggio Calabria, Italy, 3Grande Ospedale Metropolitano “Bianchi
growing, only few data are still available in literature. Melacrino Morelli”, Hematology Unit, Reggio Calabria, Italy and 4Istituto di Ematologia
The aim of the study was to evaluate the efficacy and safety of denosumab in long-term “Seragnoli”, Policlinico S. Orsola, Sezione emolinfopatologica, Bologna, Italy
therapies in hemodialysed patients.
METHOD: Since November 2013, a total of 19 hemodialysed patients have been BACKGROUND AND AIMS: A 21 year old boy with a diagnosis of Autosomal
treated with denosumab annually (4) or semi-annually (15) for up to 48 consecutive Recessive Polycystic Kidney Disease and Caroli disease reached a final stage of chronic
months. During the course of therapy, the laboratory parameters of osteo-mineral kidney disease (CKD) and started haemodialysis.

i448 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: After 3 years in haemodialysis he underwent a kidney transplant from a MO803 THE UTILITY OF BONE HEALTH INDEX SDS SCORES IN
cadaveric donor. His transplanted kidney worked fairly well until the patients was 31 MEASURING BONE DENSITY IN CHILDREN WITH END
year old when he developed graft dysfunction (serum creatinine from 2.7 to 5 mg/dL in STAGE KIDNEY DISEASE
a very short period). There was a concomitant increase in serum phosphate levels (8.3
mg/dl) and iPTH that progressively increased to 1032 pg/ml despite a traditional Shazia Adalat1, Moira Cheung1
1
therapy. Evelina London Children’s Hospital, United Kingdom
RESULTS: At age 32, the patient returned to haemodialysis treatment thrice weekly
with a concomitant a progressive worsening of hyperparathyroidism with bone pain . BACKGROUND AND AIMS: Decreased bone mineral density (BMD) is well
Cinacalcet at a dosage of 30 mg daily treatment was initiated, then it was increased to recognised in patients on dialysis. Lower DXA-BMD predicts incident fractures in
120 mg daily without any benefit. Two years later, being the clinical situation without patients with CKD 3a-5D. However while bone age (BA) Xrays are routinely
any improvement and being the patient scarcely compliant to the therapy and because performed to assess delays in bone age and density, DXA scans are not available widely.
a further enlargement of parathyroid glands was observed, a Parathyroidectomy (PTX) We compared the utility of bone density findings using automated measurements
was advised. performed on routine BA Xrays and DXA scans.
Nevertheless, PTX was not performed because of patient’s refusal. Furthermore, METHOD: In our tertiary paediatric renal unit, patients on renal replacement therapy
despite Erythropoietic Stimulating Agent (ESA) therapy, he developed severe anemia are reviewed within a joint dialysis/endocrine clinic by an nephrologist and
that required regular and frequent blood transfusions. iPTH increased to 4500 pg/ml endocrinologist,with annual radiological bone health assessment using hand and wrist
[Fig.1] with a parallel rise in alkaline phosphatase >600 UI/L [Fig.2]. A Computed Xray using Bone XpertTM software. This automates assessment of BMD on hand Xrays,
Tomography scan showed multiple bone-thickening lesions. He thus initiated correcting for delays in bone age and calculates bone health index standard deviation
Etelcalcetide 5 mg e.v. 3 times a week, after the HD session but without any benefit. score (BHI-SDS) using measurements of cortical thickness and mineralisation of
The dosage was then increased to 7.5 mg but the patient gradually became frail and metacarpal bones. In any patient with abnormal BMD on BA Xray or uncontrolled
developed pancytopenia and low-grade fever. Hematological evaluation with bone hyperparathyroidism, DXA was performed (measured as whole body (minus head)
marrow biopsy was performed in December 2019. Bone marrow histology showed and in lumbar spine (L1–L4)). DXA-BMD Z scores were automatically calculated using
severe fibrosis [Myelofibrosis (MF) grade 3] with normal bone marrow cytogenetics. normative data. A review of the results obtained was performed to compare these
Blood samples for mutations in JAK-2, CALR, and MPL and BCR-ABL rearrangement investigations of bone mineralisation status in our paediatric dialysis patients.
were negative. There was no evidence for a myeloproliferative neoplasm (MPN) or RESULTS: 14 patients with ESRD on renal replacement therapy had both BHI-SDS
metastatic lesions. and DXA BMD Z scores measured. Median chronological age was 12.6 years at DXA
densitometry (range 5.1-16.3 years) with median BA of 11.5 years (range 4.4-14.8
years). All patients where BA Xray was performed had evidence of renal
osteodystrophy radiographically. Median BHI-SDS was -1.2 (range -3.56 to 1.5).
Median lumbar spine Z-score was -0.5 (range-3.6-2.9) and median WBMH Z-score
was -1.2 (range -2.6-1.5).

Pearson correlation coefficients with BHI-SDS were 0.77 and 0.8 respectively. Only 4/
15 (27%) who had DXA performed had reported low BMD. Only one had objectively
measured loss of vertebral height on vertebral fracture assessment. However there were
two patients with undiagnosed scoliosis and one patient with an anterior wedge shaped
fracture identified on DXA. These patients were referred for orthopaedic management.
CONCLUSION: The utility of BHI- SDS to measure bone density in paediatric
patients with ESRD has not been reported. There appears to be good correlation
between BHI SDS scores and DXA scan Z score measurements in paediatric patients
with ESRD on renal replacement therapy. The advantages of using BHI SDS is that it is
less expensive, more easily performed, more widely available and takes into account the
delay in bone age often found in these children.
BHI-SDS is a measure derived from assessment of the peripheral skeleton, in contrast
to DXA, which measures bone health in the total skeleton or spine. BHI-SDS appears
to be a useful initial measure to quantify bone density in patients with radiological
changes consistent with renal osteodystrophy in the peripheral skeleton. However all
children with low BHI-SDS should proceed to DXA scan as this may detect spinal
abnormalities in addition.

MO804 CLINICAL CHARACTERISTICS OF PATIENTS WITH


SECONDARY HYPERPARATHYROIDISM UNDERGOING
HEMODIALISYS IN SPAIN: AN ANALYSIS OF ELECTRONIC
HEALTH RECORDS USING NATURAL LANGUAGE
During the following months, while on a 7,5 mg dose of etalcalcetide, there was a PROCESSING
gradual reduction in iPTH [Fig.1] and serum alkaline phosphatase [Fig.2], up to 500
pg/dl and 200 IU/L respectively. The patient developed asymptomatic, often severe, Alberto Ortiz1, Jose’ M. Portoles1, MA Dolores Del Pino Y Pino2, Jesus Barea3,
hypocalcemia which was managed with therapy. Carlos Del Rio3, Maria Lopez3, Hugo Casero3, Jose-Vicente Torregrosa4,
The patient’s clinical conditions gradually improved, anemia responded to lower doses Mariano Rodriguez2
1
of ESAs. A bone marrow biopsy was repeated after one year (December 2020) and it Madrid, MADRID, Spain, 2, 3Savana, Spain and 4Barcelona, Barcelona, Spain
showed a reduction in fibrosis (MF grade varying from 1-2). Then etelcalcetide dosage
was reduced while serum calcium and phosphate levels were in the normal limit. BACKGROUND AND AIMS: Secondary hyperparathyroidism (SHPT) is common in
CONCLUSION: Myelofibrosis secondary to renal osteodystrophy is an uncommon patients suffering from chronic kidney disease (CKD) and worsens over time in
complication. It has been rarely reported and usually is associated with primary patients undergoing haemodialysis (HD). The clinical management of SHPT in HD
hyperparathyroidism. Marrow fibrosis and pancytopenia is related to the excessive patients is challenging. In this context, the SENEFRO-BD-SHPT study aims to access
iPTH that upregulates production of cytokines and paracrine factors in the bone and analyse the free-text narratives in the electronic health records (EHRs) of patients
marrow (IL-1a, IL-6, FNF-a, TGF–b, and platelet-derived growth factor) and it has an with SHPT undergoing HD to characterize their demographic and clinical
important stimulatory effect on fibroblast proliferation. It is known that surgical characteristics, including comorbidities, medication use, and control of relevant
parathyroidectomy is associated with a reduction of bone marrow fibrosis in primary biochemical parameters.
hyperparathyroidism. To our knowledge, this is probably the first case of tertiary METHOD: SENEFRO-BD-SHPT was an observational, retrospective, and multicentre
hyperparathyroidism in which the effect of etelcalcetide is comparable to study based on the secondary analysis of EHRs from 8 hospitals from the Spanish
parathyroidectomy as far as on calcium-phosphate balance, and a significant National Healthcare Network (Figure 1A). The unstructured clinical data in patients’
improvement in bone marrow fibrosis and hemoglobin. In conclusion, etelcalcetide at EHRs between January 1st 2014 and December 31st 2018 were analysed using the
least in this patient seems as effective as PTX on bone balance, bone marrow and EHReadV R technology, based on Natural Language Processing (NLP) and machine
anemia. learning. We conducted a cross-sectional analysis of all patients at the time of
inclusion, hereafter referred to as index date (Figure 1A). For HD patients, the index
date was defined as the timepoint when diagnostic criteria for either HD or SHPT were
first met, namely a) PTH > 300 pg/ml and/or b) documented use of drugs for the
management of SHPT such as calcimimetics, vitamin D or vitamin-D analogues.
Follow-up analyses were performed at 6- and 12-months following the index date.

10.1093/ndt/gfab096 | i449
Abstracts Nephrology Dialysis Transplantation

Crucially, to guarantee the homogeneity and quality of the data, we only considered representative patient. Figure 1(a) shows the longitudinal data for the aforementioned
HD patients with SHPT with available PTH values at baseline and at least at one time clinical parameters. Using a subset of the data (1 year was used), we extracted causal
point during follow up. relationships between the clinical (Fig. 1(b)). As shown in Fig. 1(c), some of the
relationships are physiologically consistent with current knowledge of the PTH, Ca,
and PO4 disturbances on CKD-BMD, vascular calcification being one of the axes. Also,
NLR is a measure of inflammation, which is also known to promote vascular
calcification. Further, potential pathways were also detected, namely the direct or
mediated effects of Alb and PTH on PP (as shown in Figs. 1(b)-(c)). Using these
pathways, a dynamic model describing these interactions can be used to prescriptive
investigate the impact of the dynamics on the progression of calcification.

RESULTS: From a source population of 3,290,365 EHRs in the hospitals catchment


area, a total of 623 patients with SHPT undergoing HD were found. Of these, 282
patients had available PTH data (Figure 1A). Regarding demographic characteristics,
68.4% patients (n = 193) were male, with a mean (6SD) age of 67.1 (615.4) years. The
most common causes of CKD were diabetic nephropathy (29%; n = 81), hypertensive/
renal vascular disease (24.4%; n = 68), tubulointerstitial disease (19.3%; n = 54), and
glomerular disease (12.5%; n = 35) (Figure 1B). The most frequent comorbidities in
patients’ EHRs at index date were hypertension (83.7%, n = 236), type 2 diabetes
(43.6%; n = 123), and heart failure (34.8%; n = 98) (Figure 1B). The percentage of
patients with controlled PTH, calcium (Ca), or phosphorus (P) values at index date and MO805 Figure 1: (a) A representative clinical data used to construct. (b) causal
during follow up is shown in Figure 1C; overall, these values remained stable across the pathway. (c) shows the representation of (b) with very likely and potential causal
study period. Finally, Figure 1D displays the use of selected SHPT-related medications pathways to PP.
at index date, namely vitamin-D and analogues (63.1%; n = 178), phosphate binders
(46.8%; n = 132), and calcimimetics (9.6%; n = 27).
CONCLUSION: SENEFRO-BD-SHPT represents the first attempt to use clinical NLP CONCLUSION: From the clinical variables, the method was able to extract both
and big data analytics to offer an updated picture of patients with SHPT undergoing known and potential drivers for changes on PP for the representative patients.
HD in Spain based on unstructured clinical data. NLP holds great potential to Additional study is needed to confirm these relationships both prospectively, clinical
characterize the epidemiology and clinical management of CKD using real-world investigation of potential pathways, and to further observe the long-term clinical
evidence in EHRs. However, free-text narratives in the EHRs may be suboptimal to manifestation of vascular calcification.
study analytical variables. Funding: Unrestricted grant from Amgen to SENEFRO

MO806 SAFETY OF INTRAVENOUS PARICALCITOL TREATMENT IN


MO805 CAUSAL PATHWAY-BASED PHYSIOLOGICAL MODELING OF CHINESE HEMODIALYSIS PATIENTS: A REAL-WORLD
VASCULAR CALCIFICATION IN HEMODIALYSIS PATIENTS DATABASE ANALYSIS

Alhaji Cherif1, Jakob Voelkl2,3, Peter Kotanko1,4 Niansong Wang1, Gengru Jiang2
1 1
Renal Research Institute, Research Division, New York, United States of America, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Department of
2
atsmedizin Berlin, Berlin, Germany, 3JKU Johannes Kepler Universit€
Charité – Universit€ at Nephrology, Shanghai, P.R. China and 2Xinhua Hospital Affiliated to Shanghai
Linz, Linz, Austria and 4Icahn School of Medicine at Mount Sinai, New York, United Jiaotong University School of Medicine, Department of Nephrology, Shanghai, P.R.
States of America China

BACKGROUND AND AIMS: Vascular calcification (VC) is common sequelae in BACKGROUND AND AIMS: The aim of this analysis based on the real-world
chronic and end-stage kidney diseases (CKD/ESKD), and is associated with multiple database was to observe the effect of paricalcitol on the safety profile in Chinese
risk factors, including disturbed bone metabolism and mineral disorders (CKD-BMD), hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT) under
uremia, leading to increased morbidity and mortality. The mechanism involves routine clinical practice.
multiple physiological processes and is not well understood. The study aims to develop METHOD: From the Better Life for Future database, a total of 668 Chinese
a causal pathway-based physiological model describing patient-specific drivers of hemodialysis patients from 104 dialysis centers between January 2015 and May 2019
vascular calcification. were included in the analysis set. Intact parathyroid hormone (iPTH), total serum
METHOD: We develop a causal pathway-based physiological modeling that utilizes calcium (Ca), phosphate (P), dosage of intravenous (IV) paricalcitol (ZemplarV R ) were

clinical data to identify patients with high risks of progression of VC and analyzed and discussed via retrospective analysis of the database during the treatment.
cardiometabolic diseases to provide multifactorial intervention strategies targeting the RESULTS: Patients were divided into five groups according to the duration of follow-
risk factors. We investigate the response of pulse pressure (PP, a proxy for pulse wave up. Median iPTH levels decreased from 1183 pg/ml at baseline to 676 pg/ml at the final
velocity) to parathyroid hormones (PTH), calcium (Ca), phosphate (PO4), calcium- visit, or 30.88% (p < 0.0001). Serum Ca levels shown significantly increased just in the
phosphate product (CaPO4), neutrophil-lymphocyte ratio (NLR), and albumin (Alb). group of Month 12–24 (P=0.0479) (Table 2). The incidence of hypercalcemia for three
Pulse pressure may account for both cardiac and vascular conditions (e.g., atrial consecutive blood draws was significantly lower than the incidence of hypercalcemia
fibrillation, aortic insufficiency, arterial stiffness or arteriovenous malformation, aortic for at least once or two draws in all groups (Table 3). Subgroup analyses of patients
valve stenosis, cardiac insufficiency or cardiac tamponade). with hyperphosphatemia showed a rapid phosphate reduction, within the first few
RESULTS: We demonstrate the causal pathway of PTH, Ca, PO4, NLR, and Alb on weeks, along with the reduction in the iPTH level (Figure 1).
PP, and find that there are likely paths from PTH, Ca, PO4, CaPO4, NLR to PP, where
the strength of the relationships vary from patient to patient. Figure 1 shows a

i450 | Abstracts
Nephrology Dialysis Transplantation Abstracts

MO806 Figure 1: Changes of iPTH and P from baseline to last measurement in the
subgroup of hyperphosphatemia (Mean 6 SD); (Hyperphosphatemia, P>1.78 mmol/l)

MO806 Table 1. Summary of baseline clinical characteristics

Parameter Month Month Month Month Month All subjects


0.5-3 3-6 6-12 12-24 24-48
n (%) 203(30.39%) 205(30.69%) 150(22.46%) 85(12.72%) 25(3.74%) 668(100%)
Female, n (%) 92(45.32%) 85(41.46%) 70(46.67%) 40(47.06%) 11(44.00%) 298(44.61%)
Age, years a 51614 52614 53615 50614 49610 51614
Dialysis centers, n 74 74 59 45 21 104
iPTH<1000 pg/ml, n 65 90 67 29 4 255
iPTH1000 pg/ml, n 138 115 83 56 21 413
a
Mean 6 SD; n, number of patients/dialysis centers

MO806 Table 2. Baseline to last measurement in Ca and P (mmol/L) (Mean 6 SD)

Parameter Month Month Month Month Month All


0.5–3 3–6 6–12 12–24 24–48 Subjects
At Baseline
Calcium 2.2660.22 2.2860.21 2.2860.17 2.2760.18 2.2960.19 2.2760.20
Phosphate 1.6460.37 1.6460.38 1.6160.34 1.5660.36 1.5460.39 1.6260.37
At Last Measurement
Calcium 2.2960.16 2.2960.18 2.2960.15 2.3160.15* 2.3160.17 2.2960.16
Phosphate 1.5960.39 1.6460.33 1.5860.33 1.6260.33 1.4860.33 1.6060.35

*p=0.0479, there was a statistically significant increase in serum Ca levels in the group of Month 12–24 (P<0.05).

MO806 Table 3. Events of elevated serum calcium (>2.5 mmol/L) from baseline to last visit (n, %)

Parameter Month Month Month Month Month All


0.5–3 3–6 6–12 12–24 24–48 Subjects
Patients with hypercalcemia at baseline (n, %) 14(6.90%) 24(11.71%) 13(8.67%) 4(4.71%) 3(12.00%) 58(8.68%)
Patients with hypercalcemia at last visit (n, %) 15(7.39%) 23(11.22%) 10(6.67%) 4(4.71%) 3(12.00%) 55(8.23%)
Documented events of elevated serum calcium(n) 30 54 54 45 28 211
Hypercalcemia at least once during treatment (n, %) 22(10.84%) 42(20.49%) 28(18.67%) 21(24.71%) 13(52.00%) 126(18.86%)
Hypercalcemia for two consecutive blood draws (n, %) 6(2.96%) 10(4.88%) 12(8.00%) 7(8.24%) 5(20.00%) 40(5.99%)
Hypercalcemia for three consecutive blood draws (n, %) 1(0.49%) 1(0.49%) 6(4.00%) 5(5.88%) 1(4.00%) 14(2.10%)

10.1093/ndt/gfab096 | i451
Abstracts Nephrology Dialysis Transplantation

CONCLUSION: This is the first national retrospective real-world observational study


since intravenous paricalcitol is available in China since 2014. This study adds valuable PTH< PTH> p-value
information to real-world data investigating the use of paricalcitol in Chinese HD 50 pg/mL 50 pg/mL
patients and demonstrated the use of paricalcitol as an effective and well-tolerated
treatment for the control of PTH during its use in routine practice. The occurrence of (N=24) (N=16)
hypercalcemia is mostly transient, followed by continuous treatment, the blood Bone Formation Markers
calcium level tends to be stabilized, and the blood phosphorus level will be improved
with the control of PTH.
Bone Specific Alkaline 12 þ/-5 37þ/-28 <0.0001
Phosphatase (10-40 ug/L)
Osteocalcin (6.8-32.2 ug/L) 116þ/- 106 1594þ/- 404 <0.0001
P1NP (ug/L) 224 þ/- 200 753 þ/- 487 <0.0001
MO807 CORRELATIONS BETWEEN THE INFLAMMATORY AND THE
BIOCHEMICAL BONE PROFILE OF PATIENTS ON Osteoprotegerin (pmol/L) 0.5 þ/- 1.3 0.3 þ/- 0.3 0.9
HEMODIALYSIS

Pascale Khairallah1, Thomas Nickolas2, Stylianos Panagoutsos3,


Bone Resorption Markers
Ploumis Pasadakis3, Fiona McCann4, William Fraser5, Vassilis Vargemezis3, CTX (ug/L) 1 þ/- 0.5 3.3 þ/- 1.4 <0.0001
Michael Pazianas6 TRACP5b (U/L) 1.3þ/- 0.5 2.1 þ/- 1.0 0.0006
1
Baylor College of Medicine, Section of Nephrology, Houston, United States of America,
2
Columbia University Medical Center, Department of Nephrology, New York, United
States of America, 3University Hospital of Alexandroupolis, Democritus University of Inflammatory Markers
Thrace, Department of Nephrology, Faculty of Medicine, 4University of Oxford, Botnar Albumin (g/L) 38 þ/- 4.0 41 þ/- 1.6 0.007
Research Centre, The Kennedy Institute of Rheumatology, NDORMS, United Kingdom,
5
University of East Anglia, United Kingdom and 6University of Oxford, Musculoskeletal
IL-6 (pg/mL) 589þ/- 90 7.7 þ/- 19 0.06
Institute, NDORMS, United Kingdom IL-8 (pg/mL) 0.1 þ/- 0.1 0.1 þ/- 0.1 0.9
TNF (pg/mL) 24 þ/- 64 0 þ/-0 0.1
BACKGROUND AND AIMS: End stage kidney disease (ESKD) is associated with a
malnutrition-inflammation complex that results in several endocrine, musculoskeletal,
and metabolic abnormalities. Despite the known resultant derangements from this Adipokines
process, few studies have evaluated the associations between inflammation and skeletal Adiponectin (ug/mL) 9.3 þ/- 4.3 11.6 þ/- 5.2 0.2
status in ESKD patients. Our goal is to evaluate correlations between inflammatory and
biochemical bone profile within and between dialysis patients and a healthy cohort.
Ghrelin (pg/mL) 19.1 þ/- 8.7 18.9 þ/- 6.0 0.7
METHOD: This analysis is a cross-sectional evaluation of a cohort of 40 dialysis Leptin (pg/mL) 2014 þ/- 1551 1522 þ/- 1479 0.2
patients and 20 healthy controls. IGF-1 (ng/mL) 109 þ/- 45 128 þ/- 43 0.1
RESULTS: Significant differences were found between the dialysis and healthy cohort
in biochemical bone profile, inflammatory markers and adipokine levels. Dialysis IGF-BP3 (ng/mL) 2053þ/-768 2399þ/-544 0.04
patients with low vs. high PTH (cutoff 50 pg/mL) had differences in bone turnover Mineral Metabolites
markers but no differences in inflammatory or adipokine levels (Table 1). More 25-OHD (ng/ml) 11þ/- 7 12 þ/- 5 0.1
specifically, bone-specific alkaline phosphatase (BSAP), osteocalcin (OCN) and
osteoprotegerin (OPG) were positively correlated with insulin-like growth factors but 1,25 OHD (43-144 ng/mL) 22 þ/-7 25 þ/-10 0.4
this correlation was not present after adjustment for parathyroid hormone (PTH) Adjusted calcium 2.2 þ/- 0.2 2.2 þ/-0.2 0.5
levels. C-terminal cross-linking telopeptide (CTX) positively correlated with IGF1 (p-
value 0.02, 95% CI (0.14-1.69)) and with IGFBP3 (p-value 0.007 and 95% CI (0.31-
(2.2-2.6 mmol/L)
1.84)) after multivariate adjustment for PTH, albumin and sex. Adiponectin positively Phosphorus (0.7-1.4 mmol/L) 1.5 þ/- 0.5 1.8 þ/- 0.6 0.06
correlated with IGFBP3 and this remained significant after adjustment for PTH, FGF-23 (RU/ml) 1110 þ/- 230 990 þ/- 305 0.4
albumin and sex (p=0.02). IL6, IL8 and TNF did not correlate with bone turnover
markers or with adipokine levels after multivariate adjustments. Mg (mmol/L) 1 þ/- 0.1 1.1 þ/- 0.1 0.05
Zn (umol/L) 9.8 þ/- 1.6 10.3 þ/- 1.4 0.5
CONCLUSION: In this cross-sectional study, significant differences were found
PTH< PTH> p-value between the dialysis and healthy cohort in biochemical bone profile, inflammatory
markers and adipokine levels. In the dialysis cohort, inflammatory markers did not
50 pg/mL 50 pg/mL correlate with bone turnover markers or with adipokine levels in dialysis patients.
(N=24) (N=16) Dialysis patients with high vs. low PTH (cutoff 50 pg/mL) had higher levels of bone
formation and bone resorption markers. Inflammatory and adipokine levels did not
Bone Formation Markers differ between those with high vs. low PTH.
Bone Specific Alkaline 12 þ/-5 37þ/-28 <0.0001
Phosphatase (10-40 ug/L)
Osteocalcin (6.8-32.2 ug/L) 116þ/- 106 1594þ/- 404 <0.0001
MO808 THE IMPACT OF PARICALCITOL FOR PARATHYROID GLAND
P1NP (ug/L) 224 þ/- 200 753 þ/- 487 <0.0001 SIZE OF SHPT PATIENTS WITH LONG-TERM MAINTENANCE
Osteoprotegerin (pmol/L) 0.5 þ/- 1.3 0.3 þ/- 0.3 0.9 HEMODIALYSIS: AN OBSERVATIONAL STUDY

Chenghui Tao1
Bone Resorption Markers 1
the Peoplo’s Hospital of Fengdu County, Nephrology, Chongqing, P.R. China
CTX (ug/L) 1 þ/- 0.5 3.3 þ/- 1.4 <0.0001
TRACP5b (U/L) 1.3þ/- 0.5 2.1 þ/- 1.0 0.0006 BACKGROUND AND AIMS: This is an observational study to assess effectiveness of
paricalcitol for treating secondary hyperparathyroidism (SHPT) patients with long-
term maintenance hemodialysis, via changes in biochemical indexes, such as Calcium
Inflammatory Markers (Ca), Phosphate (P) and Parathyroid Hormone (PTH), and size of parathyroid gland
Albumin (g/L) 38 þ/- 4.0 41 þ/- 1.6 0.007 (PG).
METHOD: This single-centre and small sample study included 11 Long-term
IL-6 (pg/mL) 589þ/- 90 7.7 þ/- 19 0.06 maintenance hemodialysis patients with SHPT, who were undergoing SHPT treatment
IL-8 (pg/mL) 0.1 þ/- 0.1 0.1 þ/- 0.1 0.9 with paricalcitol in the Blood Purification Centre of Fengdu people’s hospital,
Chongqing, China, from December 2018 to October 2019. We collected biochemical
TNF (pg/mL) 24 þ/- 64 0 þ/-0 0.1
indexes including Ca, P and iPTH, and imaging parameters of PG via ultrasonography
(volume and number), evaluating variations between baseline and Month 11 of post-
Adipokines treatment.
RESULTS: Compared to baseline, the maximum diameter lines (Fig 1) of PG
Adiponectin (ug/mL) 9.3 þ/- 4.3 11.6 þ/- 5.2 0.2 decreased significantly (mean 15.727 mm vs 10.936 mm, P=0.005) after 11 months’
treatment, though the minimum diameter lines (Fig 2) decreased without statistical
Continued difference (mean 6.727 mm vs 5.255 mm, P=0.089). The number of glands was less in

i452 | Abstracts
Nephrology Dialysis Transplantation Abstracts
Month 11 than that of baseline (mean 2.455 vs 2.182, P=0.277) and iPTH declined
significantly (mean 1045.109 pg/ml vs 610.934 pg/ml, P=0.001). The overall effective
rate of paricalcitol was 90.9% after 11 months’ treatment. Moreover, there were no
significant changes in serum calcium and phosphorus levels during the whole
treatment.

MO808 Figure 1: Variations in Maximum Diameter

MO808 Figure 2: Variations in Minimum Diameter

CONCLUSION: Intravenous paricalcitol can decrease the size and number of


parathyroid gland, and reduce iPTH concentrations in SHPT patients with Long-term
maintenance hemodialysis, without significant influence for serum Ca and P levels.

10.1093/ndt/gfab096 | i453
Nephrology Dialysis Transplantation 36 (Supplement 1): i454–i483, 2021
10.1093/ndt/gfab098

DIALYSIS. EPIDEMIOLOGY AND OUTCOME RESULTS: The CG sample included 43 patients with a mean age of 75.8 years; 22
women (51%); mean Kt/v 1.53; mean Hb 11.5 and mean time on HD 60.46 months.
The GI sample included 47 patients with a mean age of 73.53 years; 18 women (38%);
mean Kt/v 1.47; mean Hb 11.3 and mean time on HD 63.34 months.
MO809 DOES LISTENING TO LIVE MUSIC DURING HEMODIALYSIS The results show that after the intervention, IG vs CG increased the mean score (pm)
SESIONS AFFECT THE QUALITY OF LIFE?* in all the scales significantly.
The End time and GI interaction showed a mean score increase of 15.78 (p <0.001) for
Miriam Serrano1, Alicia Garcia-Testal2, Inmaculada Rico-Salvador2, the Symptoms/problems scale; 14.96 (p <0.001) scale Effects of kidney disease; 16.36
Conrado Carrrascosa Lo pez1, Rafael Ortiz Ramo n3, Javier Villalo
n Coca3, (p <0.001) on the Kidney disease burden scale; 14.78 (p <0.001) on the Sleep scale;
Pilar Royo-Maicas2, Rafael Garcia-Maset2 25.46 (p <0.001) on the Vitality scale; 29.57 (p <0.001) on the Emotional well-being
1
Polytechnic University of Valencia, València, Spain, 2Hospital de Manises, servicio de scale; 41.92 (p <0.001) on the Pain scale and 23.39 (p <0.001) on the General Health
nefrologia, Manises, Spain and 3Hospital de Manises, Manises, Spain scale.
CONCLUSION: Live classical music intervention during hemodialysis sessions
improves self-perceived HRQL in patients with chronic kidney disease on HD
BACKGROUND AND AIMS: Patients with chronic kidney disease on hemodialysis
(HD) treatment have a health-related quality of life (HRQoL) lower than the reference
values of the Spanish population.
Previous studies have shown through music therapy reduce levels of pain, anxiety and
depression in chronic kidney disease patients on hemodialysis.
This study presents an intervention with classical music performed live during HD
sessions. It is the first time to study the effect of classical music heard live on HRQL.
METHOD: Randomized clinical trial by groups. 90 patients agreed to participate. They
were randomized into an intervention group (IG) and a control group (CG). The IG
listened to 30/45 minutes of live classical music in two of the three weekly HD sessions
for 1 month. The CG followed his usual treatment.
Different individual scales of the quality of life test in kidney diseases (KDQOL-SF)
were analyzed, in two times, baseline (Start) and after (End) the musical intervention in
both groups.
The analysis was performed using a mixed linear regression model for repeated
measures with independent variables (age, sex, months in HD, Kt/v, Hemoglobin
(Hb)) and dependent variables (individual KDQOL-SF scale scores).

MO809 Table 1. Temporal evolution of the analyzed scales of the KDQOL-SF questionnaire for the control group (CG) and the intervention group (IG).

Mean (SD)
Variable Group Pre-intervention Post-intervention Estimate* (CI 95%): Group time  interaction p-value
Symptoms/problems GC 64,63 (18,27) 63,07 (16,88) 15,78 (10,00 - 21,56) <0.001
GI 66,31 (17,97) 80,54 (13,09)
Kidney disease effects GC 42,51 (21,05) 39,31 (18,60) 14,96 (9,16 - 20,76) <0.001
GI 45,88 (24,11) 57,64 (19,10)
kidney disease burden GC 29,79 (14,99) 26,59 (15,79) 16,36 (7,76 - 24,96) <0.001
GI 30,31 (25,60) 43,48 (23,99)
Sleep quality GC 51,80 (22,14) 49,94 (23,32) 21,59 (15,13 - 28,05) <0.001
GI 50,47 (26,03) 70,21 (22,56)
Physical function GC 29,76 (26,79) 28,25 (27,03) 26,08 (19,32 - 32,84) <0.001
GI 30,31 (26,23) 54,89 (27,17)
Physical role GC 25,00 (40,08) 29,65 (40,18) 46,41 (28,09 - 64,72) <0.001
GI 26,06 (38,64) 77,12 (39,29)
pain GC 43,60 (34,78) 36,04 (31,49) 41,92 (29,04 - 54,79) <0.001
GI 42,44 (31,84) 76,809 (30,87)
General health GC 33,72 (13,23) 31,86 (13,00) 11,96 (7,14 - 16,78) <0.001
GI 30,42 (20,79) 40,53 (19,62)
Emotional well-being GC 54,60 (23,83) 51,07 (24,36) 29,57 (21,13 - 38,01) <0.001
GI 53,61 (30,73) 79,66 (20,88)
Emotional role GC 70,54 (45,54) 55,81 (47,54) 43,09 (22,92 - 63,26) <0.001
GI 58,15 (46,86) 86,52 (31,59)
Social function GC 61,62 (28,53) 50,87 (28,66) 43,20 (32,40 - 54,00) <0.001
GI 52,39 (31,67) 84,84 (23,15)
Vitality GC 28,95 (24,21) 23,48 (21,14) 25,46 (18,62 - 32,30) <0.001
GI 35,00 (27,28) 55,00 (24,71)
Overall Health (Total) GC 44,41 (18,68) 39,53 (15,88) 23,39 (15,26 - 31,52) <0.001
GI 45,31 (24,92) 63,83 (19,95)

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
MO810 INTERLEUKIN-6 (-174G/C) POLYMORPHISM, RS1800795, IN MO811 HEALTHY LIFESTYLE SCORE AND MORTALITY IN PATIENTS
ESRD PATIENTS’ OUTCOME* ON HEMODIALYSIS: AN ANALYSIS OF THE DIET-HD STUDY

Susana Rocha1, Maria Joa ~o Valente2, Susana Coimbra2,3, Cristina Catarino2, Guobin Su1,2,3, Valeria Saglimbene4,5, Germaine Wong4, Marinella Ruospo5,
Petronila Rocha-Pereira2,4, José Gerardo Oliveira5,6, José Madureira7, Joa ~o Patrizia Natale4,5, Jonathan Craig6, Jörgen Hegbrant7, Juan Jesus Carrero3,
Carlos Fernandes8, Maria do Sameiro Faria2,9, Vasco M.P. Miranda10, Luıs Belo2, Giovanni Strippoli4,5
2 2
Alice Santos-Silva , Elsa Bronze-da-Rocha 1
National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ
1
LAQV, REQUIMTE, Laborat orio de Quımica Aplicada, Departamento de Ci^encias Failure Research, Nanfang Hospital, Southern Medical University, Department of
Quımicas, Faculdade de Farm acia da Universidade do Porto, Porto, Portugal, 2UCIBIO, Nephrology, Guangzhou, P.R. China, 2Guangdong Provincial Hospital of Chinese
REQUIMTE, Laborat orio de Bioquımica, Departamento de Ci^encias Biol ogicas, Medicine, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine,
Faculdade de Farm acia da Universidade do Porto, Porto, Portugal, 3Instituto de Department of Nephrology, Guangzhou, P.R. China, 3Karolinska Institutet, Department
Investigaç~ao e Formaç~ ao Avançada em Ci^encias e Tecnologias da Sa ude (IINFACTS), of Medical Epidemiology and Biostatistics, Stockholm, Sweden, 4The University of
Cooperativa de Ensino Superior Politécnico e Universit ario (CESPU), Gandra, Paredes, Sydney, Sydney School of Public Health, Sydney, Australia, 5University of Bari,
4
Portugal, Centro de Investigaç~ ao em Ci^encias da Sa ude, Universidade da Beira Interior, Department of Emergency and Organ Transplantation, Bari, Italy, 6Flinders University,
Covilh~a, Portugal, 5Clınica de Hemodi alise do Porto, Porto, Portugal, 6CINTESIS, College of Medicine and Public Health, Adelaide, Australia and 7Lund University,
Faculdade de Medicina da Universidade do Porto, Porto, Portugal, 7NefroServe, Clınica Department of Nephrology, Lund, Sweden
de Hemodialise de Barcelos, Barcelos, Portugal, 8NefroServe, Clınica de Hemodi alise de
Viana do Castelo, Viana do Castelo, Portugal, 9Clınica de Hemodi alise de Felgueiras, BACKGROUND AND AIMS: A healthy lifestyle promotes cardiovascular health and
10
Felgueiras, Portugal and Clınica de Hemodi alise de Gondomar, Gondomar, Portugal reduces cardiac-related mortality in the general population, but its benefits in patients
treated with hemodialysis are uncertain. The aim of this study was to evaluate the
BACKGROUND AND AIMS: Chronic inflammation plays an important role in the association of a modified American Heart Association (AHA) healthy lifestyle score,
progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). The and its individual components, with all-cause and cardiovascular mortality in a large
single nucleotide polymorphism (SNP) in the promoter region (-174G/C) of multinational cohort of patients treated with long-term hemodialysis.
interleukin-6 (IL6) gene regulates the levels of this cytokine, which have been METHOD: Based on the AHA’s recommendations for cardiovascular prevention, a
associated with a poor outcome in several pathologies. Our aims were to determine, modified healthy lifestyle score was derived from non-smoking, being physically active,
according to the genotype distribution of this polymorphism, the association between higher body mass index (BMI, obesity paradox of higher BMI being protective of death
the inflammatory mediators, high sensitivity C-reactive protein (hsCRP), IL6, and in dialysis patients), healthy diet, and well-controlled systolic blood pressure for
pentraxin 3 (PTX3), shown to be increased in ESRD, and to estimate the risk for all- participants in the DIET-HD study, a multinational cohort study of adults on
cause mortality over a period of one year. hemodialysis. Hazard ratios (aHR) were estimated to evaluate the association between
METHOD: 289 ESRD patients on hemodialysis (high-flux hemodialysis and the healthy lifestyle score [low (0 -3 points) as the referent, medium (4-6), and high (7-
hemodiafiltration) were included in this study. Real-Time PCR TaqMan SNP 10)] and cardiovascular and all-cause mortality by using cox model.
genotyping assays were used to assess allelic frequencies of IL6 (rs1800795). We RESULTS: 5483 out of 9757 (56%) patients with complete lifestyle data were followed
evaluated the circulating levels of PTX3, hsCRP and IL6 using commercially available for a median of 3.8 years (17450.9 person-years). There were 2,163 deaths, of which
kits. Deaths occurring along 1-year follow-up period were recorded, and the all-cause 826 cardiovascular-related. Compared with patients with a low lifestyle score (963,
mortality hazard ratio (HR), according to IL6 polymorphisms in this patient cohort 18%), the aHRs (95%CI) for all-cause mortality among those with medium (3,621,
were determined by Cox regression analysis. A p < 0.05 value was considered 66%) and high (899, 16%) were 0.70 (0.63-0.78) and 0.57 (0.49-0.66), respectively.
statistically significant. Cardiovascular death was 17% [aHR, 0.83 (0.68-0.99] and 30% (0.70, 0.55-0.90) lower
RESULTS: In all IL6 (-174G>C) genotypes, hsCRP was positively and significantly in patients with medium and high lifestyle score, respectively. Results were consistent
correlated with IL6. For hsCRP and PTX3, a positive correlation with significance was in stratified or complete-case analyses, and after excluding early deaths. Risk
only found for the GG genotype. All genotypes showed positive correlations between reductions were largely driven by being a non-smoker, physically active and having a
IL6 and PTX3 circulating levels, although only the GG genotype achieved a significant higher BMI. 20% of deaths were attributed to a medium/low lifestyle score (population
value. The Cox regression survival analysis for all-cause mortality in ESRD patients, attributable fraction; 95% CI 12-28%).
using as reference the heterozygous patients for IL6 polymorphism, showed that CC CONCLUSION: A healthier lifestyle, especially non-smoking, regular physical activity,
patients presented a significant higher mortality risk, with a HR of 3.275 [1.165 to and a higher BMI, is dose-dependently associated with lower all-cause and
9.204]. Moreover, the median survival time of CC patients (100 [54 - 138] days) was cardiovascular mortality in hemodialysis patients.
lower than that presented by the GG genotype patients (211 [83 - 290] days, p < 0.05
vs. CC) and by the heterozygous patients (291 [72 - 332] days, p = 0.157 vs. CC).
CONCLUSION: We observed different correlation profiles between inflammatory
biomarkers within each IL6 (-174G>C) genotype. The association of the CC genotype
of the IL6 polymorphism with a poorer outcome and shorter survival time for ESRD
patients was also observed. However, further studies are required and must consider
the underlying individual genetic background, since the inflammatory state appears to
be influenced by IL6 polymorphisms, which, in turn, might be determinant for disease
progression and outcome.
ACKNOWLEDGMENTS: This work was supported by Applied Molecular Biosciences
Unit-UCIBIO, financed by national funds from FCT/MCTES (UIDB/04378/2020), by
North Portugal Regional Coordination and Development Commission (CCDR-N)/
NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-
Rede de Quımica e Tecnologia-Associaç~ao in the form of a researcher (S. Rocha) –
project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and
FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).

10.1093/ndt/gfab098 | i455
Abstracts Nephrology Dialysis Transplantation

MO812 THE COMPARISON OF HIGH-DOSE HAEMODIAFILTRATION (RRT) is an important decision that determines the quality of life and survival. A single
WITH HIGH-FLUX HAEMODIALYSIS (CONVINCE) STUDY: therapy option might not be adequate across a patient’s entire lifespan and a majority
BASELINE CHARACTERISTICS AND PROOF OF PRINCIPLE of patients change from one RRT modality to another to adapt RRT to clinical and
OF THE CONVECTION VOLUME DELIVERED psychosocial needs. Transitions should be considered as an expected progression in the
patient’s treatment options.
Robin Vernooij1,2, Mei-Man Lee3, Mark Woodward4,5,6, Jörgen Hegbrant7, In these circumstances, there are new questions about the best sequence of techniques.
Bernard Canaud8,9, Krister Cromm8, Marietta Torok10, Kathrin Fischer11,12, METHOD: This observational study examined a cohort of all incident patients from
Claudia Barth13, Giovanni Strippoli14,15, Peter J. Blankestijn1, Michiel Bots2 the Madrid Registry of Renal Patients (REMER), who initiated RRT between January
1
University Medical Center Utrecht, Department of Nephrology and Hypertension, 2008 and December of 2018. This study used the proportional hazards models and
Utrecht, The Netherlands, 2University Medical Center Utrecht, Utrecht University, Julius competitive risk models to examine the impact of transitions between RRT modalities
Center for Health Sciences and Primary Care, Utrecht, The Netherlands, 3The George on survival.
Institute for Global Health, University of Oxford, Oxford, United Kingdom, 4University of We performed an intention-to-treat (ITT) analysis, according to the initial RRT chosen
Oxford, The George Institute for Global Health, Oxford, United Kingdom, 5University of and an as treated (AT) analysis, by RRT received (Only HD, Only PD, PD then HD or
New South Wales, The George Institute for Global Health, Sydney, Australia, HD then PD).
6
Johns Hopkins University, Department of Epidemiology, Baltimore, United States of RESULTS: A total of 8,971 patients started RRT during this period in Madrid (6.6
America, 7Lund University, Department of Nephrology, Clinical Sciences, Lund, Sweden, Million population): 7,207 on hemodialysis (HD), 1,401 on peritoneal dialysis (PD)
8
Fresenius Medical Care Deutschland GmbH, Global Medical Office, Bad Homburg and 363 received a pre-emptive kidney transplantation (KTX). Incident HD-patients
v.d.H, Germany, 9Montpellier University, School of Medicine, Montpellier, France, were older and had more comorbidities. They presented higher mortality (HD group
10
Diaverum, Corporate Medical Office, Malmö, Sweden, 11Charité Universit€ atsmedizin 40.9% vs PD group 22.8% vs 8.3% KTX group, p <0.001) and less access to a transplant
Berlin, corporate member of Freie Universit€ at Berlin, Humboldt-Universit€
at zu Berlin, (HD group 30.4% vs DP group 51.6%; p <0.001). Transitions between dialysis
12
Germany, Berlin Institute of Health, Center of Internal Medicine and Dermatology, techniques define different groups of patients with different clinical outcomes. Those
Department of Psychosomatic Medicine, Berlin, Germany, 13B. Braun Avitum AG, who change from HD to PD do it earlier (66% in less than 6 months), are younger and
Medical Scientific Affairs, Melsungen, Germany, 14University of Bari Aldo Moro, behave like those treated only with PD. Those who change from PD to HD do so later
Department of Emergency and Organ Transplantation, Bari, Italy and 15University of (1.5 years on average), are older (61.6 vs 53.5 years) and present higher mortality and
Sydney, School of Public Health, Sydney, New South Wales, Australia less access to kidney transplantation than the group who initiates in HD and transfer to
PD. Survival analysis by competitive risks is essential for integrated RRT models,
BACKGROUND AND AIMS: Although high-dose haemodiafiltration (HDF) has especially in groups such as PD patients, where 58.6% of the patients were considered
shown some promising survival advantage compared with high-flux haemodialysis as lost follow-up (received a KTX after during the first 2.5 years on PD). This analysis
(HD), the evidence remains controversial. In view of these discrepant results, a reflects how patients who change dialysis modality share more characteristics with the
definitive trial is required to determine whether high-dose HDF is superior to high-flux second technique than the original one.
HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will CONCLUSION: Our data suggest that transitions between RRT-techniques describes
assess the benefits and harms of high-dose HDF versus conventional high-flux HD in different patients, who associate different risks, and should be analyzed in an integrated
adults with end-stage kidney disease (ESKD). Here we provide information on the manner to define improvement actions. This approach should be incorporated into the
baseline characteristics of the included patients and evaluate whether the patients analysis and repports of renal registries.
randomised to HDF were able to reach a high-dose convection volume.
METHOD: This international, prospective, open label, randomised, controlled trial is
aiming to recruit 1800 ESKD adults treated with high-flux HD in 9 European
countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of
conventional high-flux HD. High-dose HDF is defined as a convection volume per
session of 23 L (range 61 L). The trial is designed with a follow-up time for each
patient of at least 24 months and will assess all-cause mortality, cause-specific
mortality, cardiovascular events, hospitalisation, patient-reported outcomes, and cost-
effectiveness. For this study we tabulated the baseline characteristics for all randomised
participants by treatment groups. For the patients randomised to HDF, we calculated
the proportion of the patients reaching a convection volume of  23L. session on the
first visit after baseline (i.e. 3 months) and compared baseline and treatment
characteristics with the patients with a convection volume of <23L/session.
RESULTS: CONVINCE has recruited, until the start of January 2021, 1139 patients in MO813 Figure 1: (1A) Cumulative incidence curve until change of technique for
eight European countries. The mean age was 62.4 (SD: 13.2) years and 62% (n=709) those patients who switch from peritoneal dialysis to hemodialysis and from
patients were men. The mean dialysis vintage was 5.0 (6.1) years. The mean systolic hemodialysis to peritoneal dialysis. (1B) Kaplan-Meier cumulative incidence curve of
blood pressure (BP) was 141 (22) mmHg, the diastolic BP was 73 (14) mmHg, and the all-cause mortality according to RRT sequence. The HR adjusted for age, sex and
body mass index (BMI) was 27.6 (5.7) kg/m2. Approximately one-third the patients diabetic nephropathy is shown, with TXR being the reference technique (HR = 1).
had diabetes mellitus and 21% had a history of coronary heart disease at baseline. Of
the patients randomised to HDF, over 85% achieved a convection volume of 23L/
session. There were no apparent differences in baseline and treatment characteristics
between the patients who reached a convective volume of 23L/session versus those
who did not: the vascular access was, respectively, a fistula (82% vs 81%), catheter (13%
vs 14%), and graft (5% vs 5%) access. MO814 RISK PREDICTION OF COVID-19 INCIDENCE AND
CONCLUSION: The CONVINCE study will run up to 2023 and addresses the MORTALITY IN A LARGE MULTI-NATIONAL HAEMODIALYSIS
question of benefits and harms, regarding survival, hospitalisation, patient-reported COHORT: IMPLICATIONS FOR MANAGEMENT IN
outcomes, and cost-effectiveness of high-dose HDF compared with high-flux HD in OUTPATIENT SETTINGS
patients with ESKD. This first analysis shows that achievement of high-dose HDF is
feasible for most patients and, most importantly, could be maintained during the Mathias Haarhaus1,2, Carla Santos1,3, Michael Haase1,4, Pedro Mota Veiga5,6,
present trial period. Carlos Lucas1, Fernando Maca rio1
1
Diaverum AB, Malmö, Sweden, 2Division of Renal Medicine, Department of Clinical
Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden,
3
Cardiovascular Research and Development Unit, Faculty of Medicine, Porto, Portugal,
4
Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany,
5
Polytechnic Institute of Viseu, School of Education, Viseu, Portugal and 66 NECE
MO813 ANALYSING TRANSITIONS IN THE INTEGRATED MODEL OF Research Unit in Business Sciences, University of Beira Interior, Covilh~
a, Portugal
RENAL REPLACEMENT THERAPY IN A REGIONAL HEALTH
SYSTEM BACKGROUND AND AIMS: Experiences from the first wave of the 2019
coronavirus disease (COVID-19) pandemic can aide in the development of future
Beatriz Gil-Casares Casanova1,2, Jose Portoles3, Paula Lo pez3, preventive strategies. To date, risk prediction models for COVID-19-related incidence
Fernando Tornero Molina1, Maria Marques Vidas3, Jose Luis Rojo Alvarez2 and outcomes in haemodialysis (HD) patients are missing.
1
Hospital Universitario del Sureste, Department of Nephrology, Arganda del Rey. METHOD: We developed risk prediction models for COVID-19 incidence and
Madrid, Spain, 2Universidad Rey Juan Carlos, Department of Communications Signal mortality among HD patients. We studied 38 256 HD patients from a multi-national
Theory and Telematic and Computing Systems, Fuenlabrada. Madrid, Spain and dialysis cohort between March 3rd and July 3rd 2020. Risk prediction models were
3
Hospital Universitario Puerta de Hierro, Department of Nephrology, Majadahonda. developed and validated, based on predictors readily available in outpatient
Madrid, Spain haemodialysis units. We compared mortality among patients with and without
COVID-19, matched for age, sex, and diabetes.
BACKGROUND AND AIMS: Every year 83,000 Europeans and 6,500 Spanish CKD RESULTS: During the observational period, 1 259 patients (3.3%) acquired COVID-
patients require dialysis or transplantation. The choice of renal replacement therapy 19. Of these, 62% were hospitalised or died. Mortality was 22% among COVID-19

i456 | Abstracts
Nephrology Dialysis Transplantation Abstracts
patients with odds ratios 219.8 (95% CI 80.6-359) to 342.7 (95% CI 60.6-13595.1), the future, we consider that is important to perform multicenter studies focused on
compared to matched patients without COVID-19. Since the first wave of the patients-outcomes. We also think that it’s important to understand the patient and
pandemic affected mostly European countries during the study, the risk prediction family perspective in terms of quality of life and symptom burden associated to each
model for incidence of COVID-19 was developed and validated in European patients treatment option.
only (N=22 826, AUCDev 0.64, AUCVal 0.69). The model for prediction of mortality
was developed in all COVID-19 patients (AUCDev 0.71, AUCVal 0.78). Angiotensin
receptor blockers were independently associated with a lower incidence of COVID-19
in European patients.
CONCLUSION: We identified modifiable risk factors for COVID-19 incidence and
outcome in HD patients. Our risk prediction tools can be readily applied in clinical
practice. The current study can aid in the development of preventive strategies for
future waves of COVID-19.

MO815 Figure 1: Kaplain Meyer curves comparing CM group vs HD group

MO815 BEYOND SURVIVAL: COMPARISON OF HEMODIALYSIS AND


CONSERVATIVE MANAGEMENT IN ELDERLY AND FRAIL
STAGE 5 CHRONIC KIDNEY DISEASE PATIENTS

^s Sala1, Jo~
Ine ao Oliveira1, Joana Freitas1, Joana Tavares1, Josefina Santos
Lascasas1, Andreia Campos1, Ana Castro1, Anto nio Cabrita1
1
Centro Hospital Universit
ario do Porto, Nephrology, Portugal

BACKGROUND AND AIMS: With the geriatric population increasing, the patients
reaching stage 5 chronic kidney disease (CKD) are older, frailer and have multiple
comorbidities. Technological advances in renal replacement therapy (RRT) and easier
access to dialysis resulted in an expansion on geriatric dialysis population.
Conservative management (CM) is an option that should be considered in this
population, where is crucial to balance the survival and quality of life. Beside mortality,
with this study we aim to evaluated patient-outcomes (hospitalization, falls and
functional capacity) in older and frailer stage 5 CKD patients receiving hemodialysis
(HD) and in CM.
METHOD: We conducted a single center retrospective study in older ( 75years),
frailer (Clinical Frailty Scale – CFS  5) and with multiple comorbidities (modified
Charlson comorbidity index – mCCI  5 and) stage 5 CKD patients, admitted in our
Nephrology department between January 1, 2014 to December 31, 2020. The eGFR was
calculated through Chronic Kidney Disease Epidemiology Collaboration formula
(CKD-EPI) at the time of decision or at the time of starting HD. The comorbidities
were stratified using the mCCI and frailty was assessed with CFS at the time of decision
in CM group (CMG) and at the start of HD (HDG). We evaluated hospitalizations,
falls, CFS one-year later and survival in each group. Survival analysis was performed
using the Kaplan–Meier method and was calculated at the beginning of RRT or eGFR
 15ml/min/1.73m2 in CMG. Differences between the two groups were tested with
Mann-Whitney U method.
RESULTS: A total of 76 patients with indication to start RRT were included: 61.8%
(n=47) initiated HD and 38.2% (n=29) were in CM. The reasons for CM decision were
deterioration of clinical condition (n=11), expected survival less than 6 months (n=8),
patient option (n=5) and cognitive impairment (n=5). Clinical characteristics are
presented in Table 1. The CMG was older [median, IQR: 88 (85.5-90.5) vs 80 (77.0 –
83.0), p < 0.001] and had a lower BMI [23.44 (21.08 - 25.08) vs 26.23 (23.26 – 29.20),
p=0.006]. Both groups did not differ significantly in terms of sex, CKD etiology,
comorbidity or frailty. A total of 66 patients died at the end of the study [CMG 100%
(n= 29) vs 78.7% HDG (n=37)]. The overall survival has higher on the HDG compared
to the CMG with a median survival rate of 503 days (Fig 1). One-year survival rate was
53.5% in HDG vs 24% CMG (p <0.001). The median (IQR) of number of
hospitalizations per patient was greater in the HDG [4 (1.5-6.5) vs 3 (0.5-5.5) CMG]. In
HDG 17% patients had at least one fall vs 3.4% in CMG. In both groups there was a
general deterioration associated to a higher CFS at one-year follow up (p=0.003 HD
group vs p=0.015 CMG).
CONCLUSION: In our study, hemodialysis was associated to improved survival in
older and frailer stage 5 CKD patients compared to CM. However, this group had more
hospitalizations, falls and poor functional status. These outcomes have a crucial impact
on quality of life in this population and should be consider at the time of treatment
decision. One of the limitations of our study was small sample size in both groups. In

10.1093/ndt/gfab098 | i457
Abstracts Nephrology Dialysis Transplantation

MO816 PULSE PRESSURE IS AN INDEPENDENT PREDICTOR OF METHOD: We searched the Cochrane Kidney and Transplant Register of Studies up
THE RISK OF RECURRENT ALL-CAUSE HOSPITALIZATION to 29 July 2019 using search terms relevant to this review. Studies in the Register are
IN CHRONIC HEMODIALYSIS PATIENTS identified through searches of CENTRAL, MEDLINE, and EMBASE, conference
proceedings, the International Clinical Trials Register Search Portal and
Ariella Mermelstein1, Alhaji Cherif1, Hanjie Zhang1, Xiaoling (Janice) Ye1, ClinicalTrials.gov. We included individual and cluster randomised controlled trials
Peter Kotanko1, Jochen Raimann1 (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with
1
Renal Research Institute, Research Division, New York, United States of America placebo or standard care in patients with CKD requiring dialysis. We used a random-
effects model meta-analysis to perform a quantitative synthesis of the data. We used
BACKGROUND AND AIMS: Pre - and peri-dialytic systolic blood pressures (SBP) the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated
have been linked to heightened cardiovascular morbidity and mortality in hemodialysis summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95%
(HD) patients. High pulse pressure (PP) is clinically associated with increased arterial confidence interval (CI). We assessed the certainty of the evidence for each of the main
stiffness and atrial fibrillation, while low PP is associated with cardiac insufficiency. We outcomes using the GRADE (Grades of Recommendation, Assessment, Development,
studied the relationship between PP and all-cause hospitalization in patients and Evaluation) approach.
undergoing maintenance HD. RESULTS: We included 16 trials (14 parallel RCTs and two cross-over trials) involving
METHOD: This retrospective cohort study was performed in HD patients from a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to
January 2015 to May 2020. To be included in the study, patients were required to be 18 placebo or standard care and one trial compared eplerenone to a placebo. Most studies
or older, dialysis vintage of at least a year, and must have received treatment within the had an unclear or high risk of bias. Compared to control, aldosterone antagonists
first 30 days after dialysis initiation. We developed Cox proportional hazards models reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials,
with spline corrected terms for recurrent all-cause hospitalizations. 95% confidence 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence).
interval (CI) were also computed. Further, we stratified the patient population into 4 Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6
SBP categories, namely: SBP < 120, 120  SBP < 150, 150  SBP < 180, and SBP  trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and
180 mmHg, and investigated the mediating effects of SBP on hospitalization risk. cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI
RESULTS: We studied 2453 HD patients (age 58.9616.1 years, 58% male) dialyzed 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an
between January 2014 and October 2018 in Renal Research Institute facilities. We apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients:
observe that PPs between 45 and 70 mmHg were associated with lower risk of RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of
recurrent hospitalization (Figure 1a), possibly driven by the behavior of SBPs between hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR
120 to 180 mmHg (Figure 1c-e). No statistically significant association was seen 1.41, 95% CI 0.72 to 2.78; low certainty of evidence).
between PP and hospitalization for patients with SPB <120mmHg and >180mm CONCLUSION: Based on moderate certainty of the evidence, aldosterone antagonists
(Figures 1b-d). A decreasing trend with PP greater than 90mmHg is noted but could reduce the risk of all-cause and cardiovascular death and morbidity due to
rendered negligible, and a statistical artifact caused by a case mix at these unusually cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in
high levels. The lack of significant associations between inflammatory (NLR) and patients with CKD requiring dialysis.
nutritional (Albumin and phosphorus) factors renders PP a significant and
independent predictor of recurrent hospitalization adding to the current knowledge in
the field.

MO818 SURVIVAL ON DIALYSIS: SWITZERLAND IN COMPARISON


WITH OTHER COUNTRIES – A FOLLOW UP
MO816 Figure 1: Risk of recurrent hospitalization in the overall population and
after stratification into groups of systolic blood pressure (SBP). Horizontal line at y=1 Rebecca Winzeler1, Patrice Max Ambühl1
indicates hazard ratio and both graphs display 95% confidence intervals. 1
Institute of Nephrology, Zurich, Switzerland

BACKGROUND AND AIMS: Survival in dialysis patients is substantially reduced


CONCLUSION: Our analysis found associations between PP (with and without SBP
compared to the general population. The aim of the present analysis was to compare
stratification) and the risk of recurrent hospitalization and all-cause mortality. Even
the survival of dialysis patients in Switzerland with other countries with an additional
after adjustment for hospitalization risk and other clinical, inflammatory, and
year of follow up and a higher number of patients.
nutritional parameters at baseline PP remained an independent predictor of recurrent
METHOD: Incident dialysis patients (hemo- or peritoneal dialysis; N=5’406) from the
hospitalizations. Further investigations into the relationship are needed to better
Swiss dialysis registry were followed up from 2014 to December 31, 2019 (median
understand the mediating effects of PP as a driver of hospitalization and mortality risk.
follow up days=658). Deaths occurring during this time (N=1’353) were recorded and
survival was examined using the Kaplan Meier method, censored for transplantation.
RESULTS: Characteristics of the dialysis population stratified according to survival
status are provided in Table 1.
Dialysis patients in Switzerland have an approximately 8% higher survival in the first
and second year and about 10% higher 5 years after start of dialysis, compared to other
MO817 ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH European countries (Annual ERA-EDTA Report 2017).
CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS In the first two years, the proportion in survival rates between genders is similar in
Switzerland, as well as in Europe. After 5 years, however, a difference in survival rates
Takeshi Hasegawa1,2, Hiroki Nihiwaki3, Erika Ota4, William Levack5, between genders becomes apparent, with women having a 5-year survival probability
Hisashi Noma6 of 56.6%, compared to a lower 5-year survival probability of 49.7% in men.
1
Showa University, Showa University Research Administration Center (SURAC), Tokyo, CONCLUSION: The markedly better survival in dialysis patients in Switzerland
Japan, 2Showa University, Division of Nephrology, Department of Medicine, School of compared to other European countries could be confirmed with an additional year of
Medicine, Tokyo, Japan, 3Showa University Fujigaoka Hospital, Division of Nephrology, follow up and more patients. Also, causes of death vary widely among European
Department of Medicine, Yokohama, Japan, 4St. Luke’s International University, countries. 5-year survival was calculated for the first time, with Switzerland showing
5
University of Otago, New Zealand and 6The Institute of Statistical Mathematics almost 10% better survival rates than other European countries.

BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD)


undergoing dialysis are at a particularly high risk of cardiovascular mortality and
morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and
harms of aldosterone antagonists, both non-selective (spironolactone) and selective
(eplerenone), in comparison to control (placebo or standard care) in patients with
CKD requiring haemodialysis or peritoneal dialysis.

i458 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO818 Table 1: Characteristics (given as mean6SD or percentage) in incident
dialysis patients according to their survival status

Non-Survivors, Survivors, p-value


n=1’353 n=4’053vor
Age, years 74.2 6 12.0 65.0 6 16.4 0.000
Male gender, % 68.1 65.6 0.094
Body mass 24.5 6 5.8 26.2 6 5.6 0.000
index, kg/m2
Dialysis vintage, days 673 6 479 810 6 578 0.000
Dialysis duration, 11.2 6 1.5 11.5 6 1.5 0.000
h per week
Kt/V 1.49 6 0.40 1.59 6 0.44 0.000
Hemoglobin, g/dL 10.5 6 1.8 11.1 6 1.4 0.000
Ferritin, ng/mL 568 6 644 490 6 405 0.000 MO818 Figure 1: Comparison of causes of death between hemodialysis patients in
Calcium, mmol/L 2.22 6 0.23 2.22 6 0.19 0.913 Switzerland and Europe (DOPPS)

Phosphate, mmol/L 1.53 6 0.50 1.63 6 0.48 0.000


PTH, ng/L 300 6 323 364 6 311 0.000
Iron substitution, % 73.6 71.7 0.184
EPO substitution, % 82.1 80.0 0.114 MO819 RISK FACTORS FOR COVID-19 MORTALITY IN
Comorbidities, n 3.6 6 2.1 2.1 6 1.9 0.000 HEMODIALYSIS PATIENTS
CCI* 6.0 6 2.7 4.1 6 2.1 0.000

*Charlson Comorbidity Index Vasilije Tomanoski1, Gordana Gjorgjievska1, Margarita Nakovska1,


Vasiliki Krecova1, Gojard Kjamili1, Aleksandar Andonoski1, Katerina Ristoska1,
Angela Kachakova1, Jasminka Zvezdakovska1, Bejane Ferati1, Liljana Vasileva1,
Ana Tomanoska1, Albnora Nasufi1, Irena Borisova1
1
Nefroplus, Hemodialysis, Skopje, Republic Of North Macedonia
MO818 Table 2: One-, two and 5-year survival probability (%) of incident dialysis
patients, unadjusted, stratified by age, gender and cause of renal failure BACKGROUND AND AIMS: The global pandemic with SARS-CoV-2 virus and
Covid-19 threatened hemodialysis patients as vulnerable category with high risk for
1 year 2 year 5 year fatal outcome. The aim of the study was to determine the prevalence and risk factors
srrqap ERA- srrqap ERA- srrqap ERA- for mortality in hemodialysis (HD) patients with confirmed Covid-19.
METHOD: This study was retrospective, multicentric, and included all HD patients
EDTA EDTA EDTA with positive PCR test for SARS-CoV-2 during the period of 10 months from March 1
0-19 yrs (N=59) 90.9 96.0 86.1 93.4 86.1 88.9 – December 31/2020. The outcome of patients with positive PCR test for SARS CoV-2
was evaluated. The following clinical parameters were compared in two groups of
20-44 yrs (N=450) 97.4 96.5 91.9 93.0 86.2 82.3 patients (the deceased and alive): age, sex, hemodialysis vintage, type of vascular access,
45-64 yrs (N=1’467) 93.6 90.1 87.0 82.3 70.2 59.4 BMI, Hemoglobin, WBC, Platelets, CRP, LDH, D-dimer, s-albumin, radiological
65-74 yrs (N=1’419) 90.2 82.1 78.9 70.0 51.8 40.7 findings, smoking abuse, therapy with ACE and ARBs, presence of symptoms and
comorbidities: hypertension (HTA), diabetes mellitus (DM), coronary artery disease
75þ yrs (N=2’011) 87.6 72.8 74.5 57.0 39.4 23.9 (CAD), chronic pulmonary disease (CPD), dyslipidemia, atrial fibrillation (AFF),
malignancy, treatment in hospital and intensive care unit (ICU) with oxygen support
Men (N=3’579) 90.6 82.8 80.0 71.0 49.7 41.4 and mechanical ventilation, and anticoagulant therapy. Statistical analysis was
performed by SPSS, continued variables with ANOVA and categorical variables with
Women (N=1’827) 90.7 82.7 80.5 71.6 56.6 43.7 Pearson Chi- square test and logistic regression.
RESULTS: Of total 631 hemodialysis patients during the period of 10 months 162
patients (113 M and 49 F) or 25,67% were with positive PCR test for SARS-CoV-2, they
Diabetes (N=1’092) 90.2 84.0 79.3 71.2 45.6 38.7 have had mean age 62,47613,14 years and HD vintage 71,93668,01 months. During
Renal vascular 90.5 81.7 77.4 68.2 44.1 36.7 the observed period 38 patients with Covid-19 (25 M and 13 F) deceased, that
disease (N=1’244) represents mortality of 23,45%, 8 patients deceased at home and 30 patients in hospital.
The mortality in patients with age range 18-49 years was 8%, with 50-59 years 18,9%,
Glomerulonephritis 94.6 91.2 89.8 84.1 68.1 62.1 with 60-69 years 22,2%, with 70-79 years 31,2% and in patients with  80 years was
(N=809) 50%. Clinical parameters showed that the deceased patients compared with alive
Other causes 89.5 81.1 78.9 70.3 55.1 43.4 patients have had statistically significant higher age (67,7610,57 vs 60,85613,46 years;
p=0.004), biochemical findings WBC (9,1364,07 vs 6,4563,0; p<0.001), LDH
(N=2’261) (39464,07 vs 2946143; p=0.032), D-dimer (369964,07 vs 202562628; p=0.041),
lower s-albumin (25,0364,0 vs 34,5766,89; p<0.001), and less hospital days
(9,87612,15 vs 16,24614,31; p=0.04). Regarding comorbidities the mortality in the
All (N=5’406) 90.7 82.8 80.1 71.2 51.8 42.2 deceased patients was significantly higher in patients with chronic pulmonary disease
(CPD) in comparison to patients without CPD (56,3% vs 19,9%; p=0.001), and in
patients with malignancy in comparison to patients without malignancy (57,1% vs
21,9%; p=0.032). The mortality in hospitalized patients was significantly higher in
comparison to treated patients at home (25,8% vs 10,5%; p<0.001) and was
significantly higher in patients treated in ICU in comparison to patients treated at
hospital (40,7% vs 25%; p<0.001). By logistic regression model it was determined that
presence of chronic pulmonary disease (HR=6,178; p=0.008), ICU treatment
(HR=5,311; p=0.01) and malignancy (HR=16,766; p=0.01) were the most predictive
risk factors for mortality.
CONCLUSION: Our study showed that mortality is high in HD patients with Covid-
19 and amounts 23,45%, which is in accordance with other larger studies of
ERACODA and ERA-EDTA registry regarding mortality of hemodialysis patients with
Covid-19 (25% vs 20%). The mortality in HD patients with Covid-19 was associated
with advanced age, high level of WBC, LDH and D-dimer, and low level of s-albumin.
In contrast to general population, no association with gender, diabetes and

10.1093/ndt/gfab098 | i459
Abstracts Nephrology Dialysis Transplantation

cardiovascular disease, but significant association of mortality with presence of chronic


pulmonary disease, malignancy, hospital and ICU treatment was found. MO820 Table 2. Univariate and multivariate Cox regression analysis of factors
related to all-cause mortality in HD patients.

Univariate Multivariate
MO820 INTRACELLULAR WATER BEFORE HEMODIALYSIS Exp (B) P Exp (B) 95% CI P
PREDICTS ALL-CAUSE MORTALITY IN HEMODIALYSIS Age 0.990 0.381 0.992 0.967-1.018 0.563
PATIENTS
Dialysis vintage 0.996 0.228 0.995 0.987-1.002 0.156
Robert Ekart1,2, Gasper Keber2, Nina Vodosek Hojs3, Eva Jakopin3, Nejc Piko1, Pulse pressure before HD 1.005 0.646 1.014 0.990-1.039 0.256
Sebastjan Bevc2,3, Radovan Hojs3
1
Hemoglobin 0.982 0.128 0.989 0.963-1.016 0.410
UKC MARIBOR, CLINIC FOR INTERNAL MEDICINE, DEPARTMENT OF DIALYSIS, Maribor,
Slovenia, 2UNIVERSITY OF MARIBOR, FACULTY OF MEDICINE, Maribor, Slovenia and CRP 0.994 0.434 0.994 0.979-1.010 0.484
3
UKC MARIBOR, CLINIC FOR INTERNAL MEDICINE, DEPARTMENT OF NEPHROLOGY, Serum albumin 1.127 0.051 1.047 0.907-1.209 0.528
Maribor, Slovenia Overhydration before HD 1.05 0.636
BACKGROUND AND AIMS: Several factors may be responsible for the increased
ECW before HD 1.062 0.077
mortality in dialysis patients, but volume overload is considered among the main ICW before HD 1.089 0.018 1.102 1.010-1.202 0.029
mechanisms of this association. Volume status is usually estimated using clinical ECW/ICW before HD 0.314 0.369
criteria, i.e., patien’s signs and symptoms, peridialytic blood pressure measurements,
and intradialytic hemodynamic instability. Bioimpedance analysis (BIA) is another Overhydration after HD 0.973 0.722
way to measure volume status in dialysis patients. BIA can measure overhydration ECW after HD 1.053 0.162
(OH), extracellular water (ECW), intracellular water (ICW) and ECW/ICW ratio. ICW after HD 1.037 0.136
The aim of our study was to analyze the role of BIA parameters before and after
hemodialysis (HD) on all-cause mortality. ECW/ICW after HD 0.423 0.404
METHOD: Eighty-three patients (mean age 64.2 years; 51 men) on maintenance HD
were included. BIA was performed and blood pressure was measured before and after
the HD session. Patients were followed for assigned time, until transplantation or
death. The mean follow-up time was 11816564 days.
RESULTS: Descriptive statistics of our patients are shown in Table 1. During the
follow-up period, 6 (7.2%) patients were transplanted and 39 (47%) patients died.
Univariate Cox regression analysis showed that only ICW before HD was a significant MO821 OXYGEN EXTRACTION RATIO AND MORTALITY RISK IN
predictor of all-cause mortality (HR=1.089; 95%CI: 1.01-1.17, p=0.018). OH, ECW, HAEMODIALYSIS PATIENT: A MULTICENTRE STUDY
ECW/ICW ratio before and after HD and ICW after HD were not associated with
survival. In multivariate Cox regression analysis including ICW before dialysis, age, Silverio Rotondi1, Lida Tartaglione 2 , Maria Luisa Muci 2 , Nicola Panocchia3,
dialysis vintage, pulse pressure before HD, hemoglobin, CRP and serum albumin, ICW Antonio Gesuete4, Teresa Papalia5, Luigi Solmi 2 , Sandro Mazzaferro6
before dialysis was an independent predictor of all-cause mortality (HR=1.102; 95%CI: 1
Sapienza, Department of Public Health and Infectious Diseases, Sapienza University of
1.01-1.20, p=0.029) (Table 2). Rome, Rome, Italy, 3Policlinico universitario A. Gemelli, Nephrology, Rome, Italy, 4Casa
CONCLUSION: ICW before HD predicts all-cause mortality in HD patients. Sollievo della sofferenza, Nephrology, San Giovanni Rotondo, , 5Azienda ospedaliera di
Cosenza, Nephrology, Cosenza, Italy and 6Sapienza, Department of Public Health and
Infectious Diseases, Sapienza University of Rome, rome, Italy

MO820 Table 1. Descriptive statistics of 83 HD patients presented as mean6SD BACKGROUND AND AIMS: Patients on haemodialysis (HD) suffer a very high rate
of cardiovascular mortality with some evidence suggesting a possible association with
decreasing blood oxygen saturation (SO2) during sessions. The ratio between arterial
SO2 (SaO2) and central venous SO2 (ScvO2) or Oxygen Extraction Ratio (OER),
HD patients which represents an estimate of the amount of oxygen claimed by peripheral tissues
(N=83) and of the haemodialysis related hypoxic stress, might represent a new prognostic
Dialysis vintage (months) 60 658 factor.
METHOD: We evaluate the relationship between OER values and mortality risks in
BP syst before HD (mmHg) 150621 HD patients in a prospective multicentre observational study. We enrolled chronic HD
BP diast before HD (mmHg) 78613 patients with permanent central venous catheter (CVC) and no fistula, in whom ScvO2
measurement is at hand and SaO2 is available with a peripheral oxymeter. OER
Pulse pressure before HD (mmHg) 72622
([(SaO2ScvO2)/SaO2]100) was measured before and after HD at enrolment (HD
BP syst after HD (mmHg) 153632 OER sessions) in each patients, and a one-year follow-up was planned to record the
BP diast after HD (mmHg) 78615 number of deaths.
RESULTS: In 101 patients (age 71.5 6 14 years on dialysis for 47 6 38 months),
Pulse pressure after HD (mmHg) 74627 during 9 6 6 months of follow up, we recorded 35 deaths. Patients were then divided
Overhydration before HD (L) 2.0861.78 into two groups, above or below the median value of pre-HD OER, which was 30%. In
ECW before HD (L) 18.1364.22 these groups, the average incidence of deaths was 12% (24 deaths) and 5,5% (11 deaths)
respectively (p<0.05), with significantly different survival curves (Kaplan-Meier log
ICW before HD (L) 18.9264.55 rank test = 0.04, fig). No difference in mortality was evident if we divided patients
ECW/ICW before HD 0.9760.14 according to the median intradialytic change in OER value.
CONCLUSION: Patients with pre-HD OER > 30% have a higher mortality risk, most
Overhydration after HD (L) 0.2962.07
probably secondary to reduced capability to respond to HD related oxygen
ECW after HD (L) 16.4663.85 requirements. OER is novel biomarker to identify patients at greatest clinical risk.
ICW after HD (L) 19.5565.94
ECW/ICW after HD 0.8760.17
Hemoglobin (g/L) 111612
CRP (mg/L) 10.16617.35
Serum Albumin (g/L) 38.962.85

i460 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO822 POLYPHARMACY NEGATIVELY AFFECTS HEALTH-RELATED MO822 Figure 1: Physical Component Summary (PCS) scores (A), Mental
QUALITY OF LIFE IN DIALYSIS PATIENTS Component Summary (MCS) scores (B), number of symptoms (C) and self-rated
health (D) per number of medications for crude results
Julia Colombijn1, Anna Bonenkamp1, Anita Van Eck van der Sluijs2,
Alferso C. Abrahams2, Joost Bijlsma1,3, Brigit Van Jaarsveld1,4
1
Amsterdam University Medical Centres, Amsterdam Cardiovascular Sciences,
Amsterdam, The Netherlands, 2UMC Utrecht, Nephrology and Hypertension, Utrecht,
The Netherlands, 3Dianet Dialysis Centre, Amsterdam, The Netherlands and 4Diapriva
Dialysis Centre, Amsterdam, The Netherlands
MO823 EARLY MORTALITY IN INCIDENT HEMODIALYSIS PATIENTS
BACKGROUND AND AIMS: Dialysis patients are often prescribed a large number of
Rita Verıssimo1, Luıs Leite de Sousa1, Catarina Mateus1, Pedro Fidalgo1,
medications to improve metabolic control and manage co-existing comorbidities.
André Weigert1
However, several studies suggest that a large number of medications can also 1
detrimentally affect their health-related quality of life (HRQoL). Therefore, this study Centro Hospitalar Lisboa Ocidental - Hospital de Santa Cruz, Nefrologia, Carnaxide,
aims to provide insight in the association between the number of medications and Portugal
various aspects of HRQoL in dialysis patients.
METHOD: A multicentre study was conducted among dialysis patients from Dutch BACKGROUND AND AIMS: Chronic kidney disease (CKD) is known to have
dialysis centres three months after initiation of dialysis as part of the ongoing significant morbi-mortality worldwide. Patients with CKD and in particular those with
prospective DOMESTICO study. The number of medications, defined as the number ESRD normally carry a large burden of comorbidities and the beginning of
of concomitantly prescribed types of drugs, was obtained from electronic patient hemodialysis leads to a higher risk of decompensation. In fact, annual mortality rates
records. Primary outcome was HRQoL measured with the Physical Component among hemodialysis patients is 10 to 30 times higher than those of the general
Summary (PCS) score and Mental Component Summary (MCS) score (range 0-100) of population. Various studies have demonstrated that incident patients experience the
the Short Form 12. Secondary outcomes were number of symptoms (range 0-30) higher mortality rate within the first 3 to 4 months of dialysis. Predicting early
measured with the Dialysis Symptoms Index and self-rated health (range 0-100) mortality is important to help the decision of initiating hemodialysis versus
measured with the visual analogue scale of the EuroQol-5D-5L. Data were analysed conservative care. Therefore we conducted a case control study to evaluate early
using linear regression and adjusted for possible confounders, including age, sex, mortality predictors in incident hemodialysis patients in our hemodialysis center.
dialysis modality, and comorbidity. Analyses for MCS and number of symptoms were METHOD: This is a retrospective case–control study, which to evaluate early mortality
performed after categorising patients in tertiles according to their number of predictors in incident hemodialysis patients from January 2013 to December 2018.
medications because assumptions of linearity were violated for these outcomes. Descriptive statistics were calculated and expressed as mean (6standard deviation
RESULTS: A total of 162 patients were included. Mean age of patients was 58 6 17 [SD]) or median (intraquartile range [IQR]) for parametric and non-parametric
years, 35% were female, and 80% underwent haemodialysis. The mean number of continuous variables and count (%) for categorical variables, respectively. We
medications was 12.2 6 4.5. Mean PCS and MCS were 36.6 6 10.2 and 46.8 6 10.0, compared variables between survivors and non-survivors at 3 months after initiation of
respectively. The mean number of symptoms was 12.3 6 6.9 and mean self-rated hemodialysis by using Student’s t-test, Mann-Whitney U test, or Fisher’s exact test
health 60.1 6 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional where appropriate. Multivariate logistic regression was used to calculate the adjusted
medication (95%CI -0.9 – -0.2; p=0.002). MCS was 4.9 point lower (95%CI -8.8 – -1.0; odds ratio (OR) with 95% confidence intervals (CI) for the variables associated with
p=0.01) and 1.0 point lower (95%CI -5.1 – 3.1; p=0.63) for the highest and middle early mortality.
tertiles of medications, respectively, compared to the lowest tertile. Patients in the RESULTS: From a total of 559 incident hemodialysis patients, 43 cases were identified
highest tertile of medications reported 4.1 more symptoms compared to the lowest (7.7%), and three controls were obtained for each case. From the 172 pts in the study
tertile (95%CI 1.5 – 6.6; p=0.002) but no significant difference in the number of mean (SD) age was 72.4 years (614), 58.1% were male, and the most common
symptoms was observed between the middle and lowest tertile. Self-rated health was etiologies of CKD were unknown etiology (22.1%, n=38) and diabetic nephropathy
1.5 point lower for each medication (95%CI -2.2 – -0.7; p<0.001). (16.9%, n=29). 34.4% (n=59) were dependent of assistance in daily living activities,
CONCLUSION: After adjustment for comorbidity and other confounders, a higher median (IQR) Charlson Comorbidity Index was 8 (6.10). The non survivors compared
number of medications was associated with a lower PCS, MCS, and self-rated health in to the survivors were older (78.8 6 9.2 vs 70.3 6 14.7, p < 0,001), had more AKI or
dialysis patients and with more symptoms. This suggests that it may be relevant to acute-on-chronic CKD (18 (41.9%) vs 18 (14%), p <0,001), emergency start of
weigh expected therapeutic benefits of medication against their possible harmful effects hemodialysis (29 (67.4%) vs 48 (37.2%), p= 0.001), more catheter use as vascular access
on HRQoL. An unfavourable balance between expected benefits and impact on (38 (88.4%) vs 92 (71.3%), p=0.024), congestive heart failure (30 (69.8%) vs 32 (24.8%),
HRQoL might be ground to deviate from clinical guidelines, especially for patients with p < 0.001), ischemic cardiomyopathy (20 (46.5%) vs 30 (23.3%), p=0.004), COPD (13
a limited life-expectancy and for whom a kidney transplant is unattainable. (30.2%) vs 11 (8.5%), p<0.001), peripheral vascular disease (14 (32.6%) vs 20 (15.5%),
p=0.015), Charlson comorbidity index (10 (8-11) vs 7 (6-9), p<0.001), dependence of
assistance in daily living activities (22 (51.2%) vs 37 (28.7%), presence of nephrology
appointments for >3 months before ESRD (23 (53.5%) vs 102 (79.1%), p=0.01), eGFR
(12.3 (6.1) vs 9.1 (4.2), p<0.001), serum albumin (3.1 (2.9-3.5) vs 3.5 (3-3.8), p=0.002).
A multivariable analysis was performed and the most suitable model to predict early
mortality was age (p=0.003, OR 1.07, 95% C.I. 1.023-1.121), emergency start of
hemodialysis (p<0.001, OR 8.35, 95% CI 3.385-20.606), congestive heart failure
(p=0.004, OR 3.65, 95% CI 1.519-8.776), peripheral vascular disease (p=0.035, OR 2.97,
95% CI 1.081-8.134). Hosmer-Lemeshow goodness-of-fit performed well (X2 6.67 DF
8; p =0.57), Nagelkerke R2 0.46; AUROC (95% CI) 0.86 (0.80-0.92).
CONCLUSION: The percentage of early mortality in our population (7.7%) was
compatible with national and European rates. Our model identifies as independent
mortality predictors age, emergency start of hemodialysis, congestive heart failure and
peripheral vascular disease with an AUROC 0,86. This could help identify patients that
could benefit from a more conservative care.

MO824 PREDICTORS OF MORTALITY OF COVID-19 IN CHRONIC


HEMODIALYSIS PATIENTS

Catarina Almeida1, Marina Sofia Rodrigues Reis1, Daniela Alferes1, Catarina


Isabel Ribeiro1, Sara Daniela Rodrigues1, Carla Moreira1, Rute Carmo1,
Daniela Lopes1, Maria Clara Santos1, Susana Pereira1, Ana Marta Gomes1,
Sonia Sousa1, Ana Ventura1, Clara Almeida1, Joa ~o Carlos Fernandes1
1
Centro Hospitalar Vila Nova Gaia Espinho, Nephrology, Vila Nova de Gaia, Portugal

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) has affected the
care of patients on chronic hemodialysis (HD). It has been reported that older adults
and those with comorbidities, such as diabetes mellitus, hypertension, cardiovascular
disease and chronic kidney disease are prone to develop severe disease and poorer
outcomes. By virtue of their average old age, multiple comorbidities,
immunosuppression and frequent contact with other patients in dialysis facilities,

10.1093/ndt/gfab098 | i461
Abstracts Nephrology Dialysis Transplantation

chronic HD patients are at particular risk for severe COVID-19 infection. The aim of ESKD patients, the absolute survival gain can vary greatly between individuals. Our
this study was to compare clinical presentation, laboratory and radiologic data and results indicate that the effects of HDF on survival can be predicted using a
outcomes between HD and non-HD COVID-19 patients and find possible risk factors combination of readily available patient and disease characteristics, which could guide
for mortality on HD patients. shared decision-making.
METHOD: A single center retrospective cohort study including patients on HD
hospitalized with a laboratory confirmed COVID-19 infection, from March 1st to
December 31st of 2020 and matched them to non-dialysis patients (non-HD) (1:1).
Data regarding patient baseline characteristics, symptoms, laboratory and radiologic
results at presentation were collected, as well as their outcomes. Categorical variables
are presented as frequencies and percentages, and continuous variables as means or
medians for variables with skewed distributions. A paired Student’s t-test was
performed on parametric continuous values or Mann-Whitney for non-parametric
continuous variables. Chi-squared test was performed for comparing categorical
variables. Logistic regression was used to identify risk factors for mortality on HD
patients. A p-value of less than 0,05 indicated statistical significance.
RESULTS: A total of 34 patients HD patients were included, 70,6% male, mean age of
76,5 years, median time of dialysis of 3,0 years. Among them 85,3% were hypertensive,
47,1% diabetic, 47,1% had cardiovascular disease, 30,6% pulmonary chronic disease
and 23,5% cancer. The most frequent symptoms were fever (67,6%), shortness of
breath (61,8%) and cough (52,9%). At admission, 55,9% of patients needed oxygen
supply, one required mechanic ventilation and was admitted to intensive care unit.
Regarding laboratory data, the most common features were lymphopenia in 58,9%
(median- 795/uL), elevated LDH in 64,7% (median- 255 U/L), raised C-reactive
protein in 97,1% (median-6,3 mg/dlL, raised D-dimer in 95,8% (median 1,7 ng/mL),
and all patients presented high ferritin (median 1658 ng/mL) and elevated Troponin T
(median 130ng/mL). The majority presented with radiologic changes, particularly
bilateral infiltrates in 29,4%. Concerning clinical outcomes, the median hospitalization
time was 11 days and 13 patients (38,2%) developed bacterial superinfection. Mortality
rate was 32,4%. When matched to 34 non-HD patients there was no statistical
significant differences in sex, age and comorbidities. The HD group had a tendency to
more ventilator support need (p=0,051), higher ferritin and troponin levels (p=<0,001
for both), whereas the non-HD group presented with greater levels of transaminases MO825 Figure 1: Histograms for the distribution of (A) predicted gain in median
(p= 0,017). There was o significant difference in hospitalization time (median of 11 vs 7 survival for hemodiafiltration (HDF) versus hemodialysis (HD) in months, (B)
days, p=0,222) neither in mortality (median of 32,4 vs 35,3%, p=0,798). When the predicted gain in median survival per year for HDF versus HD in days, (C) predicted
logistic regression was performed, only bacterial superinfection was a predictor for gain in median survival for HDF with a convection volume of 23L per 1.73m2 (body
mortality on hemodialysis patients (p=0,004). surface area-adjusted), i.e. high-volume HDF, in months, and (D) predicted gain in
CONCLUSION: Our study compared outcomes for COVID-19 patients on chronic median survival per year for high-volume HDF in days, in the pooled data.
HD to non-dialysis patients and showed no difference in hospitalization time nor in
death rate. In spite of these results, the mortality in patients on chronic HD is still not
negligible, with up to 32% of in-hospital mortality. Bacterial superinfection is a
predictive risk factor for mortality. Hence the importance of interventions to mitigate
the burden of COVID-19 in these patients, by preventing its spread, particularly in
hemodialysis centers.

MO826 INSIGHTS INTO CURRENT PRACTICES, ATTITUDES AND


UNMET MEDICAL NEEDS RELATING TO THE DIAGNOSIS
AND TREATMENT OF CHRONIC KIDNEY DISEASE-
ASSOCIATED PRURITUS: RESULTS FROM AN
MO825 PERSONALIZING TREATMENT IN END-STAGE KIDNEY INTERNATIONAL NEPHROLOGIST SURVEY
DISEASE: DECIDING BETWEEN HAEMODIAFILTRATION AND
HEMODIALYSIS BASED ON INDIVIDUALIZED TREATMENT James Burton1, Sebastian Walpen2, Sandrine Danel2, Lucy Snowdon3,
EFFECT PREDICTION Bernd Schroeppel4
1
Rob Van Kruijsdijk1, Robin Vernooij1, Michiel Bots2, Sanne Peters3, University of Leicester, Department of Cardiovascular Sciences, Leicester, United
Jannick Dorresteijn4, Frank L. J. Visseren4, Peter J. Blankestijn1, Thomas Debray2 Kingdom, 2Vifor Pharma Group, Glattbrugg, Switzerland, 3Vox.Bio, Cambridge, United
1 Kingdom and 4University Hospital, Section of Nephrology, Ulm, Germany
University Medical Center Utrecht, Nephrology and Hypertension, Utrecht, The
Netherlands, 2University Medical Center Utrecht, Julius Center for Health Sciences and
Primary Care, Utrecht, The Netherlands, 3Imperial College London, The George Institute BACKGROUND AND AIMS: Chronic kidney disease-associated pruritus (CKD-aP)
for Global Health, London, United Kingdom and 4University Medical Center Utrecht, is a common yet under-recognised condition in patients with CKD undergoing
Vascular Medicine, Utrecht, The Netherlands haemodialysis (HD), in whom it is associated with reduced health-related quality of life
(HRQoL), poor sleep quality, and a greater risk of depression. This real-world study
obtained insights from nephrologists in Europe and Australia into the current
BACKGROUND AND AIMS: An individual participant data (IPD) meta-analysis of practices, attitudes and unmet medical needs relating to the diagnosis and treatment of
four randomized controlled trials (RCTs) demonstrated that hemodiafiltration (HDF) CKD-aP.
reduced overall mortality compared to hemodialysis (HD) in patients with end-stage METHOD: Qualitative data were obtained from structured interviews conducted Oct–
kidney disease (ESKD). It remains, however, difficult to translate these average results Nov 2019 with 72 nephrologists from France, Germany, Italy, Spain, UK and Australia
into clinical practice as absolute treatment effects may substantially differ between (n=12 in each country). Quantitative data relating to diagnostic/treatment practices for
individuals. The aim of this study was to develop and validate a treatment effect CKD-aP were collected May–July 2020 by a 20-minute physician survey and collection
prediction model to determine which patients would benefit the most from HDF or of patient record forms (PRF). The survey was completed by 301 nephrologists from
HD in terms of all-cause mortality. France (n=50), Germany (n=56), Italy (n=58), Spain (n=55), UK (n=52), and Australia
METHOD: We used an IPD meta-analysis based on four RCTs comparing HDF with (n=30). Respondents’ level of agreement was assessed using a 7-point scale, from 1 (do
HD on mortality endpoints to derive a Royston-Parmar model for prediction of not agree at all) to 7 (strongly agree). PRF data were also captured for 1435 HD
absolute treatment effect of HDF based on pre-specified patient and disease patients with CKD-aP from all countries. All nephrologists who completed the
characteristics. Validation of the model with regard to model discrimination, interviews and surveys were currently treating >5 HD patients with CKD-aP.
calibration and net benefit was performed using internal-external cross validation. RESULTS: Most nephrologists (75%) agreed that CKD-aP is under-diagnosed in HD
RESULTS: The median predicted gain in median survival was 44 (Q1-Q3: 44-46) days patients, which is mainly driven by the lack of systematic screening by nephrologists
for every year of treatment with HDF compared to HD. The overall gain in median and under-reporting of the condition by patients. The main barriers to screening for
survival with HDF ranged from 2 to 48 months (Figure). Patients who benefited most CKD-aP identified by nephrologists included the lack of diagnostic guidelines and
from HDF were younger, less likely to have diabetes or a cardiovascular history and absence of standardised pruritus intensity scales to consistently diagnose and classify
had higher serum creatinine and albumin levels. Internal-external cross validation CKD-aP severity. The majority (74%) agreed new clinical guidelines for nephrologists
showed adequate calibration and discrimination. Decision curve analysis indicated that
prediction-based treatment allocation improved the net clinical benefit compared to
treating all with patients HDF or treating all with HD.
CONCLUSION: Although overall mortality is reduced by HDF compared to HD in

i462 | Abstracts
Nephrology Dialysis Transplantation Abstracts
are needed to aid diagnosis. Nephrologists perceived that on average 34% of their HD close-contact settings, such as close-range conversations).
patients experienced CKD-aP, and that 55% of them had moderate-severe symptoms. CONCLUSION: We found that Japanese patients on HD had a lower prevalence of
However, most nephrologists (79%) do not use any itch scales in clinical practice and SARS-CoV-2 antibodies compared to those in the United Kingdom. Serological testing
71% agreed a consistent international scale to diagnose CKD-aP is needed. 80% of identified HD patients with asymptomatic disease. Avoiding the ‘three Cs’ is very
nephrologists agreed diagnosis of CKD-aP is usually patient-driven, indicating there is important in minimizing the risk of COVID-19 among HD patients.
a reliance on patients mentioning their symptoms. Less than half of nephrologists
(46%) agreed that CKD-aP was easy to diagnose by clinical observation alone. The lack
of targeted treatment guidelines and approved therapies for CKD-aP leads to an
inconsistent, fragmented approach to management. Analysis of prescription data
captured in the PRFs of 1435 HD patients with CKD-aP showed treatment in current
clinical practice relies on incremental add-on therapy. The majority of patients (85-
MO828 INTENSIFIED TREATMENT FOR PREGNANCY IN
90%) receiving second- or subsequent lines of therapy for CKD-aP were prescribed
HEMODIALYSIS PATIENTS, ANALYSIS OF 13 CASES: IS
combinations of different treatments. Commonly prescribed (off-label) medications
THERE A GENDER ADVANTAGE?
for CKD-aP included antihistamines, moisturizers/emollients, corticosteroids and
gabapentinoids. However, there was no single standard of care for the treatment of
Daniele Marcelli1, Olga Rybakova2, Valery Shilo2, Luisa Wohn1, Claudia Barth1
CKD-aP, highlighting the uncertainties nephrologists face relating to best treatment 1
practice. Most nephrologists (72%) agreed that treatment options are very limited for B. Braun Avitum, Medical Scientific Affairs, Melsungen, Germany and 2B.Braun Avitum
patients with bothersome CKD-aP, and the survey responses indicated a high unmet Russland, Moscow, Russia
need for novel treatments. The majority of nephrologists felt a major improvement was
needed over current treatments, particularly in terms of improved efficacy for BACKGROUND AND AIMS: Pregnancy in dialysis patients is rare but challenging
reduction of itch intensity (62%) and the ability to improve the patient HRQoL (57%). for nephrologists and obstetricians, because pregnancy has a significant maternal and
CONCLUSION: This real-world international survey study of nephrologists showed fetal risk in these patients. Although intensified hemodialysis is effective to achieve
that CKD-aP is a frequent, but under-diagnosed condition affecting many HD patients, favorable clinical outcomes, the evidence concerning reliable parameters for the
with a lack of effective treatment options. Furthermore, there is an urgent need to optimal dialysis prescription is scarce. Herein, we report the management on
develop guidelines to assist in the diagnosis of CKD-aP and new targeted treatment hemodialysis and outcome of pregnancies occurring in the B. Braun dialysis network in
options that are both effective and well tolerated. Russia.
METHOD: We performed retrospective analysis of all pregnancy cases in B. Braun
dialysis chain in Russia from 2013 to 2020. Cases were reported by the involved Renal
Care Centers by a common questionnaire. All patients were treated with B. Braun
Dialogþ, AV set Dialog þ, SolCart bicarbonate cartridge and Xevonta dialyzers.
RESULTS: 13 pregnancies were reported, all achieved without infertility treatment: 1
was interrupted by voluntary termination of pregnancy, 9 resulted with living birth (6
MO827 ASSESSMENT OF SARS-COV-2 ANTIBODIES IN PATIENTS
females and 3 males) after a mean of 24 gestational weeks (7 cesarean and 2 vaginal
ON HEMODIALYSIS
deliveries), 2 with stillbirth and 1 with spontaneous abortion after 8 gestational weeks.
Mothers with positive pregnancy outcome were significantly younger (27.965.1 vs.
Takayasu Taira1
1
36.365.6 years), without differences in dialysis vintage, previous successful or
Yokohama Dai-ichi Hospital, Nephrology, Yokohama, Japan unsuccessful pregnancies and during follow-up blood pressure was well controlled.
Females newborns had borderline significant greater body weight (1.960.6 vs. 1.160.1
BACKGROUND AND AIMS: Strategies to minimize the risk of transmission of kg, p=0.076). 5 newborns had respiratory distress syndrome, 1 jaundice.
coronavirus disease 2019 (COVID-19) infection in hemodialysis (HD) patients have CONCLUSION: : Prompt increase of treatment frequency and time on high-flux/HDF
been rapidly implemented worldwide (Nature 16: 311, 2020). Serological testing of 356 dialysis were associated with successful pregnancy outcome. Considering that
HD patients revealed that 129 (36.2%) patients were positive for SARS-CoV-2 cardiovascular system and endogenous metabolism dynamically alter during
antibodies. Out of these 129 patients, 52 (40.3%) patients were asymptomatic (JASN pregnancy, various clinical parameters, i.e. body weight and blood pressure, should be
31:1969, 2020). In this study, we investigated the seroprevalence of SARS-CoV-2 closely monitored to modify dialysis settings accordingly. Female gender of the
antibodies in HD patients who were managed per Japanese Society for Dialysis- newborn seems to be associated with a better outcome. This study shows the safety of
Therapy guidelines in the context of COVID-19. high-flux hemodialysis and hemodiafiltration treatments in pregnancy and the benefit
METHOD: Study (1): A total of, 55 patients that underwent HD (41 males, 14 females; of enhanced prescription in dialysis time and frequency.
mean age: 66.3612.8 years, HD duration: 72.2668.4 months) between August 1 and ACKNOWLEDGEMENT: The authors express their gratitude to the entire medical
December 14, 2020, were included. We measured SARS-CoV-2 antibodies with a fully multidisciplinary team from B. Braun Russia Renal Care Centers and other local
automated cobas e801 analyzer using an ElecsysV R Anti-SARS-CoV-2 medical institutions directly and indirectly involved in the treatment of each case
electrochemiluminescence immunoassay (Roche Diagnostics) to qualitatively detect described.
SARS-CoV-2 antibodies in human plasma. The ElecsysV R assay uses a modified double-

antigen sandwich immunoassay with recombinant nucleocapsid protein (N), which is


geared towards the detection of late, mature, high-affinity antibodies independent of
the subclass. Study (2): We tested the plasma of 8,982 adult with normal renal function
for SARS-CoV-2 antibodies between July 1 and November 18, 2020.
RESULTS: Study (1): Using serological testing, only 2 out of 55 (3.64%) HD patients
MO829 INSTITUTIONAL TRANSPORT AS RISK FACTOR FOR COVID-
tested positive for SARS-CoV-2 antibodies. In total 54 patients were asymptomatic
19 IN HEMODIALYSIS PATIENTS
during the study period and did not have a polymerase chain reaction (PCR) test. Only
1 out of the 54 (1.85%) patients that were asymptomatic had SARS-CoV-2 antibodies.
Line Heylen1, Margaretha Van Kerrebroeck1, Els Oris2, Liesbet Hendrickx1,
Case 1 was an 89-year-old, male who had undergone HD for 53 months because of end
Eline Macken1, Christoph Metalidis1, Jacques Peeters1, Ann Van Mieghem1,
stage kidney disease (ESKD) secondary to diabetic nephropathy. His blood type was O
Deborah Steensels2
Rh (þ). This patient tested positive for SARS-CoV-2 antibodies on August 11, 2020. 1
Serological testing showed that this patient had an asymptomatic disease. Case 2 was a ZOL Genk, Nephrology, Genk, Belgium and 2ZOL Genk, Microbiology, Genk, Belgium
74-year-old, male that had undergone HD for 62 months due to ESKD secondary to
diabetic nephropathy. He was hospitalized because of bradycardia-tachycardia BACKGROUND AND AIMS: Hemodialysis patients face an exceptional risk in the
syndrome on November 14, 2020. On that day, his PCR test was negative. He current COVID19 pandemic, both for infection/transmission as well as for mortality.
underwent surgery to insert a cardiac pacemaker on November 18, and had a fever All efforts to reduce potential risk factors are needed to protect this vulnerable group.
(37.7 C) on November 24. A chest CT scan revealed that he had bilateral lung We aimed to evaluate risk factors for SARS-CoV-2 infection and transmission during
pneumonia. On that day, his PCR test was positive. Blood tests showed that his white the first COVID19 wave, in order to tackle these factors in the second.
blood cell count was 4300/lL (lymphocyte 30.4%), and C-reactive protein (CRP) levels METHOD: We included all hemodialysis patients who were dialyzed at our central
was 2.8 mg/dL. He was not treated with antiviral medication, the PCR test was repeated institution on March 19, 2020 (date of first COVID19 diagnosis). External low care and
and was positive on December 4,7, and 9. However, his PCR test was negative on home hemodialysis patients were excluded. Our central hemodialysis center has 5
December 13. This patient tested positive for SARS-CoV-2 antibodies on December 14. dialysis shifts in 6 units located next to each other, with a separate seventh dialysis unit
He recovered from a COVID-19 infection 21 days after the onset of the disease. Study dedicated for COVID19 isolation. COVID19 infections were diagnosed with
(2): Using serological testing, 47 out of 8,982 (0.52%) adults tested positive for SARS- nasopharyngeal swab PCR at the discretion of the treating nephrologist. On May 18
CoV-2 antibodies. In Japan, the population of Kanagawa prefecture is 9,216,009. The and 19, after the first wave, all hemodialysis patients were evaluated for presence of
number of PCR-confirmed patients with COVID-19 infection was 13,340 (0.14%) on SARS-CoV-2 antibodies using ELISA to screen for previous asymptomatic infections.
December 6, 2020. The estimated number of asymptomatic SARS-CoV-2 infection was Chi square and logistic regression were used for statistical analyses.
47,923 (0.52%). The total estimated number of patients with COVID-19 infection was RESULTS: 216 hemodialysis patients were included in this study, with a mean age of
61,263. In study 1, more than 90% of HD patients wear face masks, wash their hands, 72 years old (IQR 65-83). COVID19 was diagnosed in 17 patients during the first wave:
and maintain social distance of 2 m in dialysis facilities. Almost all patients avoided the in 15 symptomatic cases through nasopharyngeal swab PCR and in two additional
three Cs (closed spaces with poor ventilation, crowded places with nearby people, asymptomatic cases through SARS-CoV-2 IgG positivity. Interestingly, we observed

10.1093/ndt/gfab098 | i463
Abstracts Nephrology Dialysis Transplantation

MO828 Table1. Vascular access and dialysis parameters prescription in the 12 pregnant patients are reported in the table below.

Variable Week 16 Week 20 At delivery


Living birth Abort./stillbirth Living birth Abort./stillbirth Living birth Abort./stillbirth
Vascular access AV-Fistula 9 2 9 2 9 2
Modality LF HD 0 2 0 0 0 2
HF HD 7 0 0 7 7 0
HDF 2 0 0 2 2 0
Treatment frequency (No./wk) 3 3 2 0 2 0 2
4 0 0 1 0 1 0
6 6 0 8 0 8 0
Treatment length (hours/wk) 12.0 2 2 0 2 0 2
13.5-18.0 2 0 2 0 2 0
21.0-30.0 5 0 7 0 7 0
Body weight incr. (kg) 2.62þ2.38 1.47þ0.92 7.72þ3.73 4.70þ3.25 12.44þ5.53 5.45þ0.78

MO828 Table 2. Pre-dialysis blood pressure, anti-hypertensive prescription, hemoglobin levels and EPO dose are reported in the following table:

Variable Week 16 Week 20 At delivery


Living birth Abort./stillbirth Living birth Abort./stillbirth Living birth Abort. /
stillbirth
Pre-HD BP (mmHg) Systolic 131þ15 146þ7 128þ15 148þ0 134þ19 169þ22
Diastolic 87þ22 92þ11 83þ13 101þ16 84þ11 106þ16
Anti-hypertensive Methyldopa 2/9 0/3 2/9 0/2 2/9 0/2
Nifedipine 1/9 2/3 1/9 1/2 1/9 0/2
Hemoglobin (g/dL) 9.1þ1.6 8.2þ1.1 9.5þ1.4 8.0þ1.4 10.4þ0.9 7.5þ0.8
EPO dose (U/wk) 8000þ3742 6000þ0 8333þ3082 4000þ2828 9375þ5423 6000þ0

that 58.8% of COVID19 patients were transported by the same transport company,
while this company transports only 20.4% of hemodialysis patients (p=0.005) (Figure
A). As such, 22.7% of patients transported by this company became infected (OR 6.93,
95% CI 2.49-20.34, p=0.0002).
CONCLUSION: Institutional transport was the most significant risk factor for SARS-
CoV-2 infection among hemodialysis patients at our center. After stringent prevention
measures we were able to prevent transmission during transport in the second wave of
the COVID19 pandemic.

i464 | Abstracts
Nephrology Dialysis Transplantation Abstracts
31 HD patients admitted to ICU, 19 (61%) died.
CONCLUSION: Despite the fact the HD population represents only a small fraction of
the total population, they represent a sizable proportion of the total COVID-19 positive
cases and a significant percentage of the total COVID-19 related mortality. This study
highlights the increased susceptibility of HD population to COVID-19 infection, which
is associated with high rate of mortality, although lower than mortality rates reported
in Europe and the united states. 5,6

References
1. Ulu S, Gungor O, Gok Oguz E, Hasbal NB, Turgut D, Arici M. COVID-19: a novel
menace for the practice of nephrology and how to manage it with minor devasta-
tion?. Ren Fail. 2020;42(1):710–725. doi:10.1080/0886022X.2020.1797791
2. https://coronavirus.jhu.edu/map.html
3. Public Authority for Civil Information: https://www.paci.gov.kw/stat/
StatIndicators.aspx.
4. Ministry of Health Twitter Account: @KUWAIT_MOH
5. Ng JH, Hirsch JS, Wanchoo R et al. Outcomes of patients with end-stage kidney dis-
ease hospitalized with COVID-19. Kidney Int. 2020;98(6):1530–1539. doi:10.1016/
j.kint.2020.07.030
6. - Jager KJ, Kramer A, Chesnaye NC et al. Results from the ERA-EDTA Registry indi-
cate a high mortality due to COVID-19 in dialysis patients and kidney transplant
recipients across Europe. Kidney Int. 2020;98(6):1540–1548. doi:10.1016/
j.kint.2020.09.006

MO831 PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN


HEMODIALYSIS PATIENTS

Yoshiyasu Ogura1, Takamasa Ohki2, Kenta Sato3, Hideaki Aihara1,


Sayaka Yabushita1, Hiroyuki Tsukada1, Satoshi Furuse1, Nobuo Toda2,
Naobumi Mise1
1
Mitsui Memorial Hospital, Nephrology, Chiyoda ward, Japan, 2Mitsui Memorial
Hospital, Gastroenterology, Chiyoda ward, Japan and 3Mitsui Memorial Hospital, Total
Quality Management, Chiyoda ward, Japan

BACKGROUND AND AIMS: The aim of this study was to compare the prognosis of
hepatocellular carcinoma (HCC) between dialysis and non-dialysis patients.
MO830 COVID-19 INFECTION IN HEMODIALYSIS POPULATION METHOD: In this retrospective observational study, we examined consecutive patients
with naı̈ve localized HCC, who were treated with radiofrequency ablation (RFA)
between February 2000 and December 2017. The patients were categorized into two
Ali AlSahow1, Ahmed AlQallaf2, Hamad Bahbahani2, Anas Alyousef3, subgroups based on whether they were on maintenance dialysis (Dialysis Group,
Yousif Bahbahani4, Bassam Alhelal5, Heba AlRajab6, Abdullah Almuhaiteeb3, n=458) or not (Non-dialysis Group, n=13), and were followed until December 2019.
Heba Shalaby1, Mohamed Elabbadi6, Mohammad Elsebaei3, Emad Abdallah5, The primary endpoint was overall survival using Kaplan-Meier analysis. As for
Medhat Ayoub4, Aissar Abou Trabeh4, Mariam AlSarraji4, Abdullah AlAwadhi4 propensity score matching, we matched 13 pairs of cases by using age, sex, Child-Pugh
1
Jahra Hospital, Nephrology, Al Jahra, Kuwait, 2Jaber Al Ahmad Al Sabah Hospital, score, tumor size, number of tumors and HCV positivity. We also compared causes of
Nephrology, Kuwait, 3Al-Amiri Hospital, Al Kuwayt, Kuwait, 4Mubarak Al-Kabeer death between the 2 groups.
Hospital, Jabriya, Kuwait, 5Adan Hospital, Hadiya, Kuwait and 6Farwaniya Hospital, RESULTS: The study cohort were aged 69.969.1 years and included 328 male patients
Kuwait, Kuwait (70%). Hepatitis B was positive in 37 patients (7.9%), C in 322 (68.4%) and co-infection
of HBV and HCV was detected in 3 (0.6%). Ninety-five (20.2%) were heavy alcohol
drinkers. In Dialysis Group, patients were younger (p=0.004), total bilirubin, AST, ALT
BACKGROUND AND AIMS: A third novel coronavirus leading to severe respiratory
levels were significantly lower and PT level was significantly higher. In the entire
infection (coronavirus disease 2019, COVID-19) was first identified in Wuhan, China
cohort, overall survival was comparable between Dialysis Group and Non-dialysis
in December 2019; 1 as of January 2021, more than 90 million person infected and
Group (5-year survival rate 55.2% vs 52.7%, respectively; p =0.144). In the propensity
more than 2,000,000 died worldwide. 2 Hemodialysis (HD) patients are at risk of
score matching analysis, however, Dialysis Group showed significantly worse overall
COVID-19 infection but reported infection rates are variable. 1 We report results of
survival than Non-dialysis Group (5-year survival rate 52.7% vs 92.3%, respectively; p
prospectively collected data on HD patients who contracted COVID-19 infection in
=0.018). During the observational period, 255 (54%) patients died. As for causes of
Kuwait.
death, liver-related death occurred in 44% in Dialysis Group and 67% in Non-dialysis
METHOD: Demographics, comorbidities, and mortality data for HD patients who got
Group, whereas cardiovascular death was 22% in Dialysis Group and 5% in Non-
infected with COVID-19 in Kuwait from 1/March/2020 to 31/July/2020 were collected
dialysis Group. Procedure-related major complication in the first RFA session of each
and analyzed.
patient was 0% in Dialysis Group.
RESULTS: Kuwait population during that same period was 4,600,000 (63% Males and
CONCLUSION: Prognosis of hepatocellular carcinoma was poorer in dialysis patients
37%Females). 3 Total number of HD patients was 2000 (representing only 0.04% of the
compared to non-dialysis ones, which may be explained by a higher rate of non-liver-
total population with 52% Males and 48% Females). Total number of COVID-19 cases
related death in dialysis population. Since RFA, per se, has been safely preformed in
confirmed by PCR from nasopharyngeal swab was 66,957. Total number of infected
dialysis patients, prognostic improvement may be expected by treating HCC in dialysis
HD patients was 141 (representing 7% of the total HD population and 0.2% of the total
patients as aggressively as in non-dialysis cases.
number of people infected with COVID-19 in Kuwait). All COVID-19 positive cases
were treated for free in ministry of health hospitals
Mean age for HD patients with COVID-19 was 57 (54 for males and 62 for males). DM
was present in 70%, HTN in 95%, CV disease in 61%, respiratory illness in 20.5%, and
ICU admission was required for 31 patients (22%), with 80% requiring intubation and
assisted ventilation. Conventional HD was switched to CRRT in 61 patients (43%).
Steroids were used for 23%, convalescent plasma in 1 patient, lopinavir/ritonavir in 7
patients, tocilizumab in 3 patients.
Total number of mortality due to covid-19 infection in Kuwait was 447 (0.7% of the
total cases). 4 Total mortality in HD population during that period for any reason was
100 (5% of the total HD population), however, total mortality due to COVID-19
infection was 30% of the total mortality in the HD population (and 7% of the total
COVID-19 related mortality in the country). Patients who died were older with mean
age of 63 vs 56 for survivors and had respiratory illness more frequently (27% vs 18%)
and 60% were males. Of those who were switched to CRRT, 21 of 61 (34%) died. Of the

10.1093/ndt/gfab098 | i465
Abstracts Nephrology Dialysis Transplantation

MO833 PSYCHOLOGICAL REPERCUSSIONS OF THE LOCKDOWN


AND THE COVID-19 EPIDEMIC IN HEMODIALYSIS PATIENTS
AND CAREGIVERS IN FRANCE

Mathilde Prezelin-Reydit1,2, Abdallah Guerraoui3, Thibault Dolley-Hitze4,


Benoı̂t Vendrely5, François Chantrel6,7, Anne Kolko-Labadens8, Lynda Azzouz9,
Marc Bouillier10, Solenne Pelletier11, Hafedh Fessi12, Cécile Vigneau13,
Christian Combe14, Agnes Caillette-Beaudoin3, Philippe Chauveau1,
Catherine Lasseur1, Laetitia Idier1,14
1
AURAD AQUITAINE, GRADIGNAN, France, 2INSERM U1219 BPH, Bordeaux Population
Health, Biostatistic team, Bordeaux, , 3CALYDIAL, VIENNE,, 4AUB Santé, SAINT MALO,,
5
Hôpital privé St Martin, PESSAC, France, 6CH Mulhouse, Service de Néphrologie,
MULHOUSE, France, 7AURAL Mulhouse, MULHOUSE, France, 8AURA Paris, IVRY SUR
SEINE, France, 9ARTIC 42, Saint-Priest-en-Jarez,, 10CHG Le Puy en Velay, Service de
Néphrologie, Le Puy-en-Velay,, 11CHU de Lyon, Service de Néphrologie, Pierre-Bénite, ,
12
CHU de Tenon, Service de Néphrologie, PARIS,, 13CHU de Rennes, Service de
Néphrologie, RENNES, and 14CHU de Bordeaux, Bordeaux,

BACKGROUND AND AIMS: The health crisis linked to the COVID-19 epidemic has
required lockdown measures in France and changes in practices in dialysis centers. The
objective was to assess the depressive and anxiety symptoms during lockdown in
hemodialysis patients and their caregivers, to assess their coping strategies during this
period and to assess the symptoms of depression, anxiety and post traumatic stress
beyond confinement.
METHOD: We sent, during lockdown period, between April and May 2020, self-
questionnaires to voluntary subjects (patients and caregivers), treated by hemodialysis
MO832 SYMPTOM BURDEN AND QUALITY OF SLEEP IN or who worked in hemodialysis in one of the 14 participating centers in France. We
MAINTENANCE HAEMODIALYSIS PATIENTS analyzed their perception of dialysis sessions (beneficial or worrying), their stress level
(VAS rated from 0 to 10), their anxiety and depressive symptoms (HADS). Factors
Jasna Trbojevic Stankovic 1,2, Sasa Milosevic 3, Branislav Andric3, associated with stress, anxiety and depression were analyzed with multiple logistic
Edvin Hadzibulic4, Fatmir Bird-ozlic 4, Zoran Marjanovic 2, Snezana Pesic5 regression models. We will look for associations between coping strategies, participant
1 characteristics and symptoms of stress, anxiety and depression using chi-square tests.
Faculty of Medicine, University of Belgrade, 2Clinical Hospital Center “Dr Dragisa A second questionnaire was sent out in October to collect symptoms of depression,
Misovic”, Department of Hemodialysis, 3General Hospital Krusevac, Department of anxiety and post-traumatic stress beyond confinement. Symptoms will be described
Nephrology and Hemodialyis, 4General Hospital Novi Pazar, Department of Nephrology and factors associated with stress, anxiety and depression will be analyzed with
and Hemodialyis and 5Clinical Hospital Center “Zvezdara”, Department of Nephrology multiple logistic regression models.
and Metabolic Disorders with Dialysis RESULTS: 669 patients and 325 caregivers agreed to participate. 70% of participants
found it beneficial to come to dialysis during confinement. The proportions of subjects
BACKGROUND AND AIMS: The number of patients with end-stage renal disease is with a stress level  6 linked to the epidemic, confinement, fear of contracting COVID-
growing rapidly worldwide and their survival on haemodialysis (HD) is increasing as a 19 and fear of infecting a loved one were respectively 23.9%, 26.2%, 33.4% and 42%.
result of technique and treatment improvements. Nevertheless, longer survival and 39.2% presented with certain (13.7%) or doubtful (19.2%) anxious symptoms. 21.2%
increasing complexity of the comorbid disorders contribute to a series of symptoms presented a certain (7.9%) or doubtful (13.3%) depressive symptomatology. Age,
which affect patients’ physical and mental health. In the present study we aimed to gender, history of psychological disorders and perception of dialysis sessions were
examine the symptom distress and quality of sleep in patients treated with chronic HD. associated with levels of stress, anxiety and depression. 685 subjects participated in the
METHOD: In this cross-sectional study, we recruited 304 (179 males and 125 females, second part of the study (68.9% of the participants of the first part). Analyzes of this
age range 20 - 85 years, time on dialysis 3 - 324 months) out of 372 HD patients from data are in progress.
five centres. All patients were under stable condition, without any severe acute CONCLUSION: During the lockdown period, in France, the majority of hemodialysis
comorbidities, and able to understand and fill-in the self-administered questionnaires. patients and caregivers found it beneficial to come to dialysis. One in 3 subjects had
Standard laboratory parameters and Kt/V were determined in all patients. Quality and anxiety symptoms and one in 5 subjects had depressive symptoms. It will be interesting
patterns of sleep were assessed by the Pittsburgh Sleep Quality Index (PSQI), while to investigate if there was an association between the coping strategies implemented by
physical and emotional symptoms and their severity were evaluated by the Dialysis the participants and their level of stress, anxiety and depression during confinement
Symptom Index (DSI). Other relevant demographic and clinical data were obtained and to analyze the evolution of the anxiety-depressive symptoms over time.
from patients’ medical records. The results were analyzed with independent sample T
test and v2 statistic.
RESULTS: The average PSQI was 7.6264.44, average symptom burden 15.49612.85,
and average symptom severity 23.38618.78. Almost two thirds of the patients (63.8%)
had poor sleep quality. The average sleep duration, latency and efficiency were
6.8561.75 hours, 36.01634.99 minutes and 81.51621.57% respectively. Nearly half of
the patients (45%) used sleep medications. MO834 LOWER POST DIALYSIS POTASSIUM AND HIGHER
Women, unemployed and diabetic patients had significantly worse quality of sleep ULTRAFILTRATION RATE ARE INDEPENDENT PREDICTORS
than men (8.4164.33 vs. 7.0864.43; p=0.001), employed (7.7564.47 vs. 4.3861.89; OF ALL-CAUSE MORTALITY IN DIALYSIS PATIENTS
p<0.01) and nondiabetic (8.8964.59 vs. 7.3664.40; p=0.041) patients respectively.
Other demographic (age, level of education, marital status, smoking habit), clinical Elvana Rista1, Vilma Cadri2, Ilir Akshija3, Endri Harja4
1
(body mass index, comorbidities, dialysis vintage, shift, and adequacy, type of Hygeia Hospital, Nephrology-Dialysis-Transplantation, Tirana, Albania, 2University
membrane and vascular access) and standard laboratory parameters were not Hospital Center “Mother Theresa”, Department of Nephrology, Tirana, Albania,
3
significantly associated with sleep quality. University Hospital Center “Mother Theresa”, Department of Statistics, Tirana, Albania
Poor sleepers had significantly higher symptom burden (17.81612.97 vs. 11.4269.78; and 4Villa Maria, Department of Cardiac Surgery, Tirana, Albania
p<0.01) and symptom severity (27.67619.73 vs. 15.81614.16; p<0.01). The most
prevalent and at the same time the most bothersome symptoms were difficulty BACKGROUND AND AIMS: Dialysis is a life-saving procedure for the end-stage
becoming sexually aroused (63.2%), feeling tired or lack of energy (60.5%), decreased kidney disease, but mortality in this category of patients is still high. The survival of
interest in sex (57.6%), feeling nervous (57.2%) and dry skin (53.3%). Shortness of these patients is much lower compared to the general population. Factors affecting this
breath (p=0.011), dizziness (p=0.005), restless legs (p=0.011), tingling in feet (p=0.005), survival has been studied for years and still continue to be an important part of current
lack of energy (p=0.001), cough (p=0.001), dry mouth (p=0.017) and bone/joint pain studies. While ultrafiltration rate is known to be associated with mortality in prevalent
(p=0.016) were significantly more prevalent in poor sleepers. dialysis patients an important predictor of survival is the control of potassium profile.
CONCLUSION: Patients on HD experience high number of symptoms and often have The aim of our study was to assess the hemodynamic and biochemical data, and to
poor quality of sleep which may affect their well-being. These results support the likely identify any significant association between post-dialysis potassium and all-cause
importance of routine symptom assessment in dialysis centres to guide systematic mortality.
symptom management and provide appropriate psychosocial and clinical support. METHOD: This is a prospective study of 308 patients on maintenance dialysis,
followed for seven years, ending 2019. All patients are dialysis dependent for ESKD and
getting treatment in a single-center.
Hypokalemia was defined as a serum potassium level < 3.5 mEq/L and high
ultrafiltration rate (UFR) > 13 ml/kg/h. Other hemodynamic and metabolic data were
also evaluated

i466 | Abstracts
Nephrology Dialysis Transplantation Abstracts
The survival rate was analysed by Kaplan-Meier curves and Cox regression analysis. SARS-CoV-2 infection in the population undergoing dialysis treatment in Lazio
RESULTS: A total of 308 patients were enrolled in this study. Mean age was 52 6 15.6 Region.
years; 62.3% of pts were male; BMI 24.764.2. Of these, 55 patients (17.9%) died during METHOD: A cohort of patients treated in the dialysis units of Lazio Region was
the follow-up period. Our data showed the presence left ventricular hypertrophy enrolled. Prevalent dialysis patients at 1/1/2020 and incident patients during the period
(p=0.010), peripheral artery disease (p<0.0001), diastolic disfunction (p<0.01) and 01/01/2020-08/01/2020 were included. The LRDTR collects information on dialysis
ultrafiltration rate during dialysis >13ml/kg/h (p=0.002) were the most important patients from the start of chronic dialysis treatments with biannual update and
predictors of mortality. Metabolic abnormalities, low albumin (p<0.0005), immediately informing about the end of dialytic treatment (death, renal transplant,
hyperphosphatemia (p=0.011), post-dialysis potassium (p=0.037) were significantly etc). Infection was traced in the LRDTR from March 2020 to 08/13/2020. The
associated with higher mortality. information on vital status was obtained from LRDTR and the mortality Lazio registry
Logistic regression analysis of the metabolic data identified post-dialysis potassium up to 10/30/2020. Poisson models, crude and adjusted for sex and age, were used to
(OR 0.242, 95% CI 0.074 – 0.793, p=0.019), and logistic regression analysis of the estimate incident rate of infection and mortality rate on dialysis patients and on
hemodynamic data identified ultrafiltration ratio (OR 0.149, CI 0.033 – 0.673, p=0.013) dialysis patients who have developed SARS-CoV-2 infection, and respective confidence
as independent predictors of all-cause mortality. intervals of 95% (CI95%).
CONCLUSION: Lower post dialysis potassium levels and higher ultrafiltration rate are RESULTS: During the study period, the estimate of the number of patients undergoing
independently associated with higher all-cause and CV mortality in prevalent dialysis treatment was 5196 in Lazio Region, 65% were males with mean age of 70
hemodialysis patients. Therefore the potassium profile and the UFR of the dialysis years. Thirty-seven patients were infected with SARS-CoV-2: 70% males, mean age 73
patients needs close monitoring and optimal control. The individualization of the years. These patients were treated in 24 different dialysis units. The cumulative
dialysis prescription is recommended for each patient and it has an important role in incidence rate of SARS-CoV-2 infection was 0.71% (95% CI 0.52-0.98) and the
preventing the occurrence of complication with immediate and long term effects. adjusted incidence rate was 3.3 *100,000 Person Days (PD) (95% CI 2.4-4.7). The
Management of dialysis patients should focus especially on reducing the risk of distribution of positive swabs by month was: 21 in March 7 in April, 6 in May, 1 in
hypokalemia, not only that of hyperkalemia. June, 2 in July. Twenty-seven patients had symptoms while 10 patients, who have had
contact with infected individuals, had positive swabs in absence of symptoms. Infected
and hospitalised dialysis patients were 78%. Of the 29 hospitalized patients: 6 were in
sub-intensive care, 16 in intensive care, of these 7 needed intubations, 9 underwent
non-invasive ventilation. The adjusted cumulative mortality rate in dialysis patients
was 6.8% (95% CI 6.0-7.6), the same measure for SARS-CoV-2 infected patients was
37.4% (95% CI 19.8-70.4) with an average follow-up of 205 PD. The adjusted mortality
MO835 AFTERMATH OF FORTNIGHTLY UNIVERSAL TESTING FOR
rate was 3.3 * 10,000PD (95% CI: 2.9-3.7) among dialysis patients and 21.2*10,000PD
SEVERE ACUTE RESPIRATORY CORONA VIRUS-2
(95% CI: 11.1-40.7) among infected dialysis patients.
INFECTION IN MAINTENANCE IN HEMODIALYSIS PATIENTS
CONCLUSION: This study highlights a greater susceptibility of dialysis patients to
SARS-CoV-2 infection, with a rate three times higher than that observed in the general
Narayan Prasad1, Manas Ranjan Patel1, Dharmendra Bhadauria1,
population (source: Civil Protection Department). Mortality risk for dialysis patients
Anupama Kaul1, Ravi Sankar Kushwaha1
1
with SARS-CoV-2 infection is about 6 times higher than in the dialysis patients it
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Nephrology, Lucknow, suggesting a major impact of infection on this fragile population.
India

BACKGROUND AND AIMS: Asymptomatic maintenance hemodialysis patients


with SARS-COV-2are missed with pre-dialysis screening without testing. The possible
ideal strategy of testing each patient before each shift with RT-PCR was not feasible.
We aimed to study the effectiveness of fortnightly screening with RT -PCR for SARS-
MO837 IMPACT OF DOWNTIME ON CLINICAL OUTCOMES IN
CoV-2 in curbing transmission.
CRITICALLY ILL PATIENTS WITH ACUTE KIDNEY INJURY
METHOD: Between July 1, 2020, and September 30, 2020, all 273 patients receiving
RECEIVING CONTINUOUS RENAL REPLACEMENT THERAPY:
hemodialysis were subjected to fortnightly testing for SARS-Cov-2 in the unit to detect
A RETROSPECTIVE STUDY USING PROPENSITY SCORE-
asymptomatic patients. The cost and effectiveness of universal testing in preventing
MATCHED ANALYSIS
transmission were analyzed using Susceptible-Infectious-Removed (SIR) modeling
assuming R0 of 2.2.
Jungho Shin1, Hyun Chul Song1, Jin Ho Hwang1, Su Hyun Kim1
RESULTS: Of 273 MHD patients, 55 (20.1%) got infected with SARS-CoV-2 over 1
three months. Six (10.9%) were symptomatic, and 49 (89.1%) asymptomatic at the time Chung ang University Hospital, Internal Medicine, Seoul, Korea, Rep. of South
of testing. Six (10.9%) asymptomatic patients develop symptoms later; and 43 (78.2%)
remained asymptomatic. A total of 7(6.1%) HCWs also tested positive for the virus. BACKGROUND AND AIMS: Continuous renal replacement therapy (CRRT) is
With an assumption of R0 2.2 and isolation of symptomatic patients only, all 273 essential in treating critically ill patients with acute kidney injury, and circuit downtime
patients could have been affected by September 30, 2020; with the isolation of both is considered a quality indicator. However, it remains uncertain whether CRRT
symptomatic patients and those testing positive after pre-dialysis screen, only 52 (19%) downtime affects outcomes such as mortality and renal recovery. This study
infections could have been prevented. However, at the end of the study period, 218 investigated the impact of downtime on various clinical outcomes in critically ill
(80%) patients remained uninfected of SARS-CoV-2. Fortnightly universal testing is patients undergoing CRRT.
cost-effective, and SIR modeling proved effective in preventing person-to-person METHOD: A total of 216 patients who underwent CRRT were retrospectively
transmission. recruited. Downtime was calculated over 4 days from CRRT initiation, and patients
CONCLUSION: Repeated universal testing in maintenance hemodialysis patients were classified as downtime <20% or 20% of potential operative time. Patients with
detected 89% of asymptomatic SARS-CoV-2 patients over three months and appeared 20% downtime were matched to those with <20% downtime using 1:2 propensity
to be an effective strategy to prevent person-to-person transmission in the dialysis unit. score matching, adjusting for age, sex, comorbidity index, and severity score.
RESULTS: There were 88 patients with <20% downtime and 44 patients with 20%
downtime. The cumulative volume and median flow rate of effluent in patients with
20% downtime were lower than those in patients with <20% downtime (P<0.001
and 0.062, respectively). Daily fluid balance differed on days 2 and 3 (P=0.046 and
0.031, respectively), and the difference in levels of urea and creatinine widened over
time (P=0.004 and <0.001, day 4). The levels of total carbon dioxide were lower in
MO836 INCIDENCE AND OUTCOME OF SARS-COV-2 INFECTION IN
those with 20% downtime (P=0.038 and 0.020 at days 2 and 3). Based on our results,
THE POPULATION UNDERGOING DIALYSIS TREATMENT IN
20% downtime was not associated with increased 28-day mortality (P=0.944). On the
LAZIO REGION
other hand, a subgroup analysis showed the interaction between downtime and daily
fluid balance on mortality (P=0.004). In this study, downtime was not related to renal
Claudia Marino1, Laura Angelici1, Enrico Calandrini1, Silvia Cascini1,
recovery.
Santo Morabito2, Nicola Petrosillo3, Nera Agabiti1, Marina Davoli1
1
CONCLUSION: Increased downtime could impair fluid and uremic control and
, Department of Epidemiology of the Regional Health Service - Lazio, Rome, Italy, acidosis management in patients undergoing CRRT. Moreover, the adverse effect of
2
AOU Policlinico Umberto I - Rome, Hemodialysis Unit, Rome, Italy and 3National downtime on fluid control may increase mortality rate. Further studies are needed to
Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Rome, Rome, Italy verify the value of downtime as a quality indicator and its impact on outcomes in
critically ill patients requiring CRRT.
BACKGROUND AND AIMS: Patients with chronic kidney disease (CKD) represent a
frail population with severe co-morbidities and different degrees of immune
dysfunction. These patients might be at higher risk of SARS-CoV-2 infection and
might experience severe consequences of COVID-19. In March 2020, the Lazio
Regional Dialysis and Transplantation Registry (LRDTR) implemented a questionnaire
to obtain information on dialysis patients who have developed SARS-CoV-2 infection.
The aims of this study is to evaluate the incidence and the short-term lethality of

10.1093/ndt/gfab098 | i467
Abstracts Nephrology Dialysis Transplantation

associated with lower serum activity or concentration of paraoxonase, a PON1 protein


product. Assessing PON1 SNVs enables the prediction of cardiovascular mortality risk
in HD smokers and non-smokers and may help select patients for advanced prevention
against cardiovascular diseases.

MO839 URGENCY OF RENAL REPLACEMENT THERAPY INITIATION


AS A PREDICTOR FOR POOR PROGNOSIS IN PATIENTS
WITH KIDNEY DISEASE

Konstantin Vishnevskii1, Viktor Suchkov2


1
St. Petersburg State Healthcare Institution “City Hospital @ 15”, Dialysis department,
St.-Petersburg, Russia and 2Clinical Infectious Diseases Hospital named after S.P. Botkin,
Dialysis department, St.-Petersburg, Russia

BACKGROUND AND AIMS: It is known that mortality from COVID-19 among


patients with kidney disease is significantly higher than in general population. The
worst prognosis is seen for patients receiving renal replacement therapy (RRT). At the
same time, many patients undergo an urgency start of hemodialysis (HD) while
MO838 PARAOXONASE 1 GENE POLYMORPHISMS CONCERNING suffering from COVID-19. The aim of the study was to determine the significance of
CARDIOVASCULAR MORTALITY IN CIGARETTE SMOKERS the RRT urgency for the prognosis in patients with COVID-19.
AND NON-SMOKERS TREATED WITH HEMODIALYSIS METHOD: A retrospective analysis of case histories for 253 patients who received
RRT at the infectious ward of St. Petersburg State Healthcare Institution City Hospital
Alicja Ewa Grzegorzewska1, Kamila Ostromecka1, Monika Swiderska2, No. 15 from May to December 2020 was performed. All patients had a diagnosis of
Paulina Adamska1, Adrianna Mostowska1, Paweł Jagodzin ski1 COVID-19, confirmed by PCR and/or clinical symptoms. Urgency RRT was
1
Poznan University of Medical Sciences, Department of Biochemistry and Molecular performed in case of detection of indications, both in acute kidney injury (AKI), and in
n, Poland and 2Poznan University of Medical Sciences, Department of
Biology, Pozna the diagnosis of end-stage chronic kidney disease (esCKD). Kaplan-Meier curves and
Nephrology, Transplantology and Internal Diseases, Poznan, Poland multivariate Cox regression were used to perform cohort analyzes of survival and
relative risk of death. For the calculations, the applied statistical software package SPSS
21.0, SPSS Ink (USA) was used.
BACKGROUND AND AIMS: Paraoxonase 1 gene (PON1) single nucleotide variants
RESULTS: Of the 253 treated patients, 197 were patients with chronic outpatient HD,
(SNVs), known as associated with lipoprotein peroxidation, are related to
in 56 HD therapy was started urgently: 45 for AKI, 11 for esCKD. Totally 83 patients
atherosclerotic diseases, including coronary heart disease (CHD). Cigarette smoking,
died. The overall mortality rate was 33%, while in outpatient HD group it was 18% and
causing increased susceptibility to lipoprotein oxidation, contributes to cardiovascular
in the urgent HD start group - 84%. After adjusting for gender and age the fact of the
events, and its effects are linked with PON1 SNVs. We investigated the association of
urgency of starting RRT was an independent risk factor that increased the probability
PON1 rs705379 (-108C>T), rs854560 (163A>T), and rs662 (575A>G) SNVs with
of death by 2.5 times (95% Cl 1.6 3.9) compared to outpatients HD (Log Rank:
cardiovascular mortality in maintenance hemodialysis (HD) patients concerning
P<0.001, Fig. 1). The patients age over 60 was also a factor significantly worsening the
cigarette smoking status.
prognosis (Log Rank: P <0.001).
METHOD: In the HD group, there were 206 smokers and 659 non-smokers. Among
all patients who died (n = 542), cardiovascular mortality was similar in smokers and
non-smokers (59.0% vs. 59.3%, respectively). Deceased smokers were burning 20 (5 -
25) cigarettes daily. We obtained PON1 polymorphisms by HRM analysis (rs662) or
predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). All cardiovascular,
cardiac, CHD- and non-CHD-related deaths were analyzed in smokers and non-
smokers concerning PON1 SNVs and DM status. The Kaplan-Meier method with the
log-rank test and the Cox regression analyses were applied for the estimation of
survival. If computed P-values were below 0.05, the adjustment for sex, age, and HDL-
cholesterol was applied. We have shown only adjusted P-values for survival analyses.
RESULTS: HD cigarette smokers, who died from cardiovascular diseases, were
younger (63.5, 31.1 – 86.3 vs. 74.0, 26.8 – 95.9 years, P = 2.992e-10), predominantly
men (70, 85.3% vs. 91, 38.1%, P = 1.5e-13), had more atherogenic serum lipid profile
(atherogenic index estimated as the TG/HDL cholesterol ratio 4.90, 0.72 – 25.6 vs. 3.79,
0.66 – 49.7, P = 0.003; HDL-cholesterol level 34.8, 17.3 – 103 vs. 40.0, 7 – 103 mg/dL, P
= 0.0004; TG 167.0, 48.8 – 652 vs. 149.8, 40.0 – 856 mg/dL, P = 0.034), but similar RRT
duration compared to deceased HD non-smokers. Cigarette smoking status did not
influence cardiovascular mortality either in DM or non-DM group. DM smokers
showed similar cardiovascular mortality to non-DM smokers, but among HD non-
smokers, DM patients demonstrated higher cardiovascular mortality than non-DM
subjects (P = 0.029). Among all smokers, the rs705379 TT genotype was associated
with all cardiovascular (P = 0.028), all cardiac (P = 0.046), and cardiac non-related with
CHD (P = 0.001) mortality. The rs705379 TT genotype smokers, who died from
cardiac reasons, showed a higher frequency of myocardial infarction than CCþCT
bearers (66.7% vs. 29.2%, P = 0.047). Non-DM smokers showed similar qualitative
significance to all smokers concerning all cardiovascular, all cardiac, and cardiac non-
MO839 Figure 1: Risk of death from all causes among patients with renal disease
related with CHD death rates (P-values 0.011, 0.044, and 0.009, respectively). In DM
and COVID-19, depending on the urgency of initiation of hemodialysis therapy
non-smokers, the rs705379 T allele correlated with CHD related deaths (P = 0.020).
The rs854560 T allele, compared to the AA genotype, was associated with lower
cardiovascular mortality in non-DM smokers (P = 0.008). The rs854560 TT genotype
CONCLUSION: Among patients with COVID-19 and kidney disease the urgency of
showed a negative correlation with cardiac death non-related to CHD in all non-
RRT initiating is a factor that significantly worsens the prognosis, especially among
smokers (P = 0.079). In DM smokers, the rs662 G allele was associated with a higher
patients of the older age group.
risk of cardiac mortality (P = 0.005). In all non-smokers and non-DM non-smokers,
the rs662 G allele correlated with cardiovascular deaths (P = 0.020 and P = 0.018,
respectively).
CONCLUSION: The variant alleles of PON1 rs705379 (T) and rs662 (G) are
associated with cardiac mortality in HD patients. The rs854560 variant allele (T)
possessors present better cardiovascular survival than the AA genotype subjects.
Cardiovascular mortality is not merely related to polymorphic variants known as

i468 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO840 ADAPTIVE DESIGN METHODS IN DIALYSIS CLINICAL TRIALS METHOD: We performed a secondary analysis of 35 peritoneal dialysis (PD) patients
– A SYSTEMATIC REVIEW (age: 64611 years; 74% males; 17% diabetics) who participated to the Exercise
Introduction to Enhance Performance in Dialysis (EXCITE) trial, a 6-month
Conor Judge1,2,3, Robert Murphy1, Catriona Reddin1, Sarah Cormican1,2, randomized, multicenter trial testing whether a simple, personalized walking exercise
Andrew Smyth1, Martin O’Halloran1,3, Martin O’Donnell1 program at home, managed by dialysis staff, improves functional status in adult
1
National University of Ireland Galway, Medicine, Galway, Ireland, 2Wellcome Trust HRB patients on dialysis. The main study outcomes included change in physical
Irish Clinical Academic Training (ICAT), Galway, Ireland and 3Translational Medical performance at 6 months, assessed by the 6-minute walking test (6MWD) and the five
Device Lab NUIG, Galway, Ireland times sit-to-stand test (STS), and in quality of life, assessed by the Kidney Disease
Quality of Life Short Form (KDQOL-SF) questionnaire. Data are summarised as
BACKGROUND AND AIMS: Adaptive design methods are intended to improve median and interquartile range (IQR).
efficiency of clinical trials, and relevant to evaluating interventions in dialysis RESULTS: Out of 35 PD patients, 14 resulted to be allocated to the active arm and the
populations. We sought to quantify the use of adaptive design clinical trials in dialysis. remaining 21 to the control arm of the trial, and all completed the 6-month active
METHOD: We completed a full text systematic review and adhered to the Preferred phase of the trial. At baseline, the two groups did not differ as for age, gender, smoking,
Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Our diabetes, and NYHA class (p ranging from 0.41 to 1.00) as well as for baseline values of
review utilised included a novel machine learning classifier and full text systematic 6MWD (active group, median 344 m, IQR: 307-440 m versus control group, median
review. We searched MEDLINE (Pubmed) and performed a detailed data extraction of 302 m, IQR: 263-425m, P=0.12) and STS test (active group, median 18.2, IQR: 17.1-
trial characteristics and a narrative synthesis of the data. 18.8 sec versus control group, median 20.2, IQR 16.2-27.1, P=0.25). During the 6
RESULTS: 50 studies, available as 66 articles, were included after full text review. 31 month period, there was a 34.0 m median increase of 6MWD (IQR: from 16.3 to 61.3
studies were conducted in a dialysis population and 23 studies had renal replacement m) in the active group and only a modest increase of the same test in the control group
therapy as a primary or secondary outcome. Group sequential designs were the most (median: 14.0 m; IQR: from -39.5 to 38.5 m) and the between arms difference was
common type of adaptive design method used in dialysis randomized clinical trials and statistically significant (P=0.034). No between arms difference was found in the STS
in general adaptive designs usage is increasing over time. Acute Kidney Injury (AKI) test change (P=0.70). At 6 months, the quality of social interaction in the kidney
was studied in 27 (54%) of trials, End Stage Kidney Disease (ESKD) was studied in 22 disease component of the KDQOL-SF remained stable in patients of the active arm
(44%) of trials and Chronic Kidney Disease (CKD) was studied in one trial (2%). The (median change from baseline: 0.0, IQR: from -5.0 to 17.5) whereas it decreased in
most common country of lead author was the United States of America in n=20 (40%) patients in the control arm (median change from baseline: -5.8, IQR: from – 20.0 to -
of studies. 26 (52%) studies were supported by public funding. 41 studies (82%) did not 1.3) (between-arms difference, P=0.032).
report their adaptive design method in the title or abstract and would not be detected CONCLUSION: The results of this multicentre trial involving PD patients show that a
by a standard systematic review involving title and abstract searches. simple, personalized, home-based, low-intensity exercise program is feasible in PD
CONCLUSION: Adaptive design methods are infrequently used in dialysis patients and it may improve physical performance and quality of life in this high risk
randomized control trials. category of patients.

MO842 SARS-COV-2 INFECTION AMONG PATIENTS RECEIVING


MAINTENANCE HAEMODIALYSIS: SINGLE HAEMODIALYSIS
CENTER EXPERIENCE FROM BANGLADESH

Mohammad Mehfuz E Khoda1, Muhammad Abdur Rahim2, Ishrat Jahan Shimu3,


Md. Golzar Hossain1, Md. Abul Mansur1
1
BIRDEM General Hospital, Nephrology and Dialysis unit, Dhaka, Bangladesh, 2BIRDEM
General Hospital, Nephrology unit, Dhaka, Bangladesh and 3National Institute of
Cardiovascular Disease, Department of Cardiology, Dhaka, Bangladesh

BACKGROUND AND AIMS: Severe acute respiratory syndrome corona virus 2


(SARS-CoV-2) infections emerged in Wuhan, China in December 2019 and rapidly
became pandemic. Unfortunately, there is lack of evidence about the optimal
management of corona virus disease-2019 (COVID-19) and even less is available in
patients on maintenance haemodialysis. Patient receiving maintenance haemodialysis
are at increased risk for infection by SARS-CoV-2 with poor outcome. So, the purpose
of this study was to identify the incidence of SARS-CoV-2 infection among end-stage
kidney disease (ESKD) patients on maintenance haemodialysis.
METHOD: A cross-sectional study was conducted at a haemodialysis unit of tertiary
care hospital of Bangladesh from April to August 2020. All patients, who were on
maintenance haemodialysis, twice or thrice weekly, were screened by reverse
transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2, irrespective of
MO841 EFFICACY OF PHYSICAL EXERCISE IN PERITONEAL symptoms. All data were collected in case record forms and patients were followed-up
DIALYSIS PATIENTS: A SECONDARY ANALYSIS OF THE over phone.
EXCITE TRIAL RESULTS: During the study period, a total of 133 patients (males 70, 52.6%) were on
regular maintenance haemodialysis in the study centre. Most patients were in 5th and
Francesca Mallamaci1,2, Vincenzo Antonio Panuccio1, Maria Carmela Versace2, 6th decades of life. Twenty-one (15.8%) patients tested positive for SARS-CoV-2 by
Giovanni Luigi Tripepi2, Graziella D’Arrigo2, Carmine Zoccali3, On behalf of Excite RT-PCR with female (16, 76.2%) predominance. Eighteen (18/21, 85.7%) patients had
Working Group2 symptoms suggestive of SARS-CoV-2 infection and rest three (3/21, 14.3%) patients
1
Grande Ospedale Metropolitano BMM, Nephrology, Dialysis, and Transplantation Unit, were diagnosed during routine screening. Common presentations were fever (42.9%),
Reggio Calabria, Italy, 2IFC-CNR, Section of Epidemiology and Physiopathology of Renal cough (66.7%) and respiratory distress (66.7%) and most had multiple symptoms. The
Disease and Hypertension, Reggio Calabria, Italy and 3Associazione per le Ricerche su incidence of SARS-CoV-2 infection in blood group A was 8(38%) and blood group O
Ipertensione, Nefrologia e Trapianto Renale, IPNET, Reggio Calabria, Italy was 8(38%). There were no significant differences of mortality rate among blood
groups. Most patients (16/21, 76.2%) infected by SARS-CoV-2 were referred to
BACKGROUND AND AIMS: Although physical activity has been documented to be COVID-dedicated hospitals, five (5/21, 23.8%) were shifted to intensive care unit
effective in many categories of high-risk patients and more recently also in dialysis (ICU). Outcome was poor; 17 (17/21, 89%) patients died in hospitals and four (4/21,
patients, there are no studies specifically focused on Peritoneal Dialysis (PD) patients. 19%) patients became free of SARS-CoV-2 infection. Caregivers/relative of our patients
The peculiarity of this treatment modality for uremia is that it is carried out at the acquired COVID-19 in course of disease.
patient’s home while the vast majority of physical exercise in dialysis patients is carried CONCLUSION: One-sixth of patients on maintenance haemodialysis acquired SARS-
out during the hemodialysis (HD) session, then they are not applicable for PD patients. CoV-2 infection with nearly ninety percent fatality rates. Despite having risk factors for
The Excite trial (JASN 2017; 28:1259-1268) is a home-based, individualized, low- severe infection by SARS-CoV-2, patients on dialysis must visit health care facilities.
intensity exercise program. In this multicenter, randomized clinical trial, the EXerCise So, utmost care should be taken to reduce risk of COVID-19 among such vulnerable
Introduction To Enhance performance in dialysis patients trial (EXCITE), we aimed to group of patients.
investigate whether this home exercise program improves the degree of fitness and
quality of life in patients with CKD-5D (Hemodialysis and Peritoneal Dialysis
patients). The EXCITE home based clinical trial, is the first and may be the only one,
involving peritoneal dialysis patients and this is of unique importance for the scientific
community.

10.1093/ndt/gfab098 | i469
Abstracts Nephrology Dialysis Transplantation

MO843 PREVALENCE AND MANAGEMENT OF HYPERTENSION IN CONCLUSION: Interdialytic weight gain in our HD patients is excessive &
HEMODIALYSIS PATIENTS contributing to HTN. Patients must restrict salt & fluid intake & dialysis centers must
regularly & frequently assess dry weight, ensure thrice weekly schedule & 4 hours per
Ali AlSahow1, Anas Alyousef2, Bassam Alhelal3, Heba AlRajab4, session are met, so excess fluid is completely removed. Also, high sodium & high
Yousif Bahbahani5, Hani Nawar1, Mostafa Mohammed Elsayed calcium baths need to be avoided.
Mohammed Ibrahim2, Mohamed Elabbadi4, Vivian F Kamel5, Emad Abdallah3,
Rajeev Kumar6, Ebrahim AlSahu7
1
Jahra Hospital, Nephrology, Al Jahra, Kuwait, 2Al-Amiri Hospital, Nephrology, Al
Kuwayt, Kuwait, 3Adan Hospital, Nephrology, Hadiya, Kuwait, 4Farwaniya Hospital,
Nephrology, Kuwait, Kuwait, 5Mubarak Al-Kabeer Hospital, Nephrology, Jabriya, Kuwait,
6
Dr.BRA IRCH, Oncology, New Delhi, India and 7Jahra Hospital, Medicine, Al Jahra,
MO844 COVID-19 PANDEMIC IN DIALYSIS PATIENTS IN
Kuwait
SWITZERLAND

BACKGROUND AND AIMS: Hypertension (HTN) is common in hemodialysis Rebecca Winzeler1, Patrice Max Ambühl1
(HD) patients & diagnosed by pre-dialysis BP >140/90 mmHg. Causes include high 1
Institute of Nephrology, Zurich, Switzerland
salt intake, volume overload, & loss of residual kidney function. Therapy includes
achieving correct dry weight with each session, restricting interdialytic sodium & fluid
intake & medications. We review its prevalence, factors associated with it & its BACKGROUND AND AIMS: COVID-19 is an infectious disease that can result from
management in our patients. infection with the novel coronavirus SARS-CoV-2. The disease, was first described in
METHOD: Demographics, HD prescription & medications data collected for patients Wuhan at the end of 2019 and the first case in Switzerland was discovered in February
from 5 dialysis centers. 2020. This analysis gives an overview of dialysis patients in Switzerland that were tested
RESULTS: A total of 1585 files reviewed. Males were 51.8% & mean age was 59. Mean COVID-19 positive.
age significantly higher for females (61 vs 57). ESKD cause was DM in 51% & HTN in METHOD: All dialysis centers reported their cases with COVID-19 to the Swiss
35%. However, of files reviewed, adequate data on comorbidities in 1390 patients (table dialysis registry srrqap. All patients reported to the registry between March 5 (1st
1), 69% had DM, 92% had HTN, 47% had CVD & 31% had BMI > 25 (which was dialysis patient with COVID-19) and June 30, 2020 were included in this analysis and
significantly more frequent in females). HTN was more likely in older patients, comparisons were made with COVID-19-free dialysis patients (from 2019).
diabetics & females with odds of HTN in females nearly twice the odds of HTN in RESULTS: On March 5, 2020, the first dialysis patient was infected with COVID-19 in
males & odds of HTN with DM is 2.27 times odds of HTN without DM & one-year Ticino. The number of infected dialysis patients increased rapidly over the months of
increase in age would increase odds of HTN by nearly 4%. Mean pre-HD BP for those March and April, with the majority of patients in the cantons of Vaud (23.5%), Ticino
with HTN was 143/76 mmHg & for those without HTN was 136/75 mmHg. HD (22.3%) and Geneva (18.8%) and together making up almost 65% of the COVID-19-
frequency was thrice weekly in 94% & HD duration was > 3.5 hours in only 77% of infected dialysis patients in Switzerland. COVID-19 cases represented 2.4% of all
patients. HDF used in 81.5%. Mean interdialytic weight gain (IDWG) was 2.8 kg, with prevalent patients on dialysis (as of 31.12.2019).
no difference according to gender or presence of DM or HTN (Table 2). Higher IDWG Twenty-seven (12 female, 15 male) out of 93 dialysis patients died, which corresponds
associated with age < 65, Calcium bath of 1.75 & Sodium bath > 138 with 0.638 kg to a mortality rate of 29%. Mortality was highest in patients from Switzerland (together
higher IDWG with calcium of 1.75 compared to calcium of 1.25. Higher IDWG was with the Netherlands), and lowest in Romania with 8.5% (K. Jager and A. Kramer,
associated with higher BP. Mean volume of fluid removed per session was 2.74, which submitted for publication, 2020).
was less than mean IDWG, with no difference according to gender or DM, however, it Mortality was associated with advanced age in dialysis patients. In contrast to the
was higher in the higher dialysate sodium group, & lower in the shorter session group general population, male sex, diabetes and hypertension were no major risk factors for
(with trend towards statistical significance). CCB used to treat HTN in 62% followed mortality in our cohort.
by bB in 52%. Number of patients with HTN on 1 drug 21%, 2 drugs 27%, 3 drugs CONCLUSION: Although dialysis patients from Switzerland in general have a better
23%,  4 drugs 20% & 9% missing data. Number of antihypertensives did not correlate survival compared to those from other European countries, infection with COVID-19
with IDWG. in Switzerland results in the highest mortality compared to other European countries

MO843 Table 1. Patients characteristics & HD prescription

Demographics All Patients Group 1 Group 2 No Unadjusted p Value Adjusted


Total HTN Total HTN Total OR(95% CI] OR[95% CI]
Age (mean) 1390 59.47 49.96 <0.001
Female (mean) 582 61.88 48.82 1.04[1.02-1.05] <0.001 1.03[1.01-1.04]
Male (mean) 808 57.66 50.42 <0.001
Gender
F 582 94% 6% 1.84[1.21-2.79] 0.004 2.05[1.26-3.33]
M 808 90% 10% 1.0 1.0
Comorbidities
DM 1390 71% 42% 3.44[2.32- 5.09] <0.001 2.27[1.41- 3.66]
CVD 1390 49% 27% 2.69[1.74-4.14] <0.001 2.22[1.29-3.84]
Obesity (BMI > 25) 1390 31% 32% 0.96[0.64-1.45] 0.849
BP
Mean SBP 1371 143.4 135.73 1.02(1.01- 1.03) 0.001 1.01[1.00- 1.02]
Mean DBP 1371 75.83 75.07 1.00(0.99- 1.02) 0.514
HD Modality HD Prescription
Low Flux 133 123 10 1.0
High Flux 124 108 8 1.1(0.42-2.88] 0.850
HDF 1129 1035 89 0.95[0.48-1.87] 0.872
Calcium Bath
1.25 550 504 46 1.0 0.781
1.5 337 307 30 0.93[0.58-1.51] 0.409
1.75 500 465 35 1.21[0.77-1.92]
Sodium Bath
<138 535 491 44 1.0 0.652
138 704 651 53 1.10[0.73-1.67]

i470 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO843 Table 2. Factors relevant to mean IDWG.

Variable Number Mean IDWG* p-Value


Male vs Female 592 vs 571 2.80(1.09) vs. 2.81(1.16) 0.852*
Age < 65 vs  65 825 vs 535 2.86 (1.15) vs. 2.71(1.08) 0.013*
HTN vs no HTN 1255 vs 103 2.81(1.12) vs 2.79(1.19) 0.890*
DM vs no DM 939 vs 419 2.84(1.15) vs 2.74(1.05) 0.127*
Dialysate Na <138 vs  138 531 vs 682 2.70(1.16) vs 2.87(1.12) 0.009*
Dialysate Ca 1.25 vs 1.5 vs 1.75 2.46(1.02) vs 2.88(1.19) vs 3.12(1.08) <0.001$
Dialysate To <36.5 vs  36.5 684 vs 530 2.91(1.16) vs 2.64(1.09) <0.001*

*Unpaired Student t-test/$Oneway ANOVA F-test

in this population. In addition, male sex, diabetes and hypertension seem not to be
associated risk factors in our dialysis population.

MO844 Table 1. Characteristics (given as mean6SD or percentage) in dialysis


patients with COVID-19 and COVID-19-free dialysis patients

With Without p-
COVID-19 COVID-19 value
(n=93) (n=4619)
Age, years 70.0 6 15.5 68.9 6 14.7 0.103
Male gender, % 65.6 65.2 0.898
Body mass index, kg/m2 27.3 6 5.4 25.9 6 5.7 0.228
Dialysis vintage, years 5.5 6 12.7 4.0 6 4.0 0.624
Dialysis duration per week (h) 11.4 6 1.4 11.5 6 1.4 0.749
Kt/V 1.55 6 0.39 1.59 6 0.41 0.259
Hemoglobin, g/dL 10.9 6 1.4 11.1 6 1.4 0.506
Ferritin, ng/mL 507 6 416 510 6 434 0.448 MO844 Figure 1: Probability of death in dialysis patients in Switzerland
Calcium, mmol/L 2.21 6 0.19 2.22 6 0.19 0.822
Phosphate, mmol/L 1.50 6 0.46 1.62 6 0.48 0.769
PTH, ng/L 317.6 6 238.2 369.2 6 328.4 0.148
Comorbidities, n 2.9 6 2.3 2.6 6 2.0 0.047
CCI* 4.6 6 2.2 4.5 6 2.2 0.536 MO845 EUROQOL EQ-5D-3L IN DIALYSIS POPULATION IN
COLOMBIA
Hypertension, % 88.2 83.1 0.209
Diabetes Mellitus, % 43.5 37.7 0.273 Mauricio Sanabria1, Jasmin Vesga2, Angela Rivera3, Juan Guillermo Ariza4
1
Iron substitution, % 78.8 72.7 0.207 Baxter Renal Care Service Latinamerica, Research, BOGOTA D.C., Colombia, 2Baxter
Renal Care Services Colombia, Research, Bogota, Colombia, 3Baxter Healthcare
EPO substitution, % 81.2 79.7 0.732 Corporation, Medical, Deerfield Il, United States of America and 4Baxter Healthcare
Corporation, Medical, Bogota DC, Colombia, Colombia

BACKGROUND AND AIMS: The EuroQol-5D (EQ-5D-3L) is a generic


MO844 Table 2. Characteristics (given as mean6SD or percentage) in dialysis questionnaire to evaluate the quality of life related to health, and simultaneously
patients with COVID-19 according to their survival status facilitates the obtaining of preference values (utilities) In the economic evaluation of
health interventions. Quality-adjusted life year (QALY) is a commonly used metric.
Our objective is to evaluate the quality of life (QoL) and obtaining of utilities according
Non-Survivors, Survivors, p-value the dialytic treatment.
n=25 n=60r METHOD: This was an observational, multicentre cross-sectional study. Prevalent
Age, years 80.1 6 7.4 65.1 6 16.6 0.000 patients on dialysis for at least 90 days, older than 18, at the Baxter Renal Care Services
Colombia were included between August 2, 2019, to December 11, 2020. Socio-
Male gender, % 52.0 71.7 0.081 demographic and clinical characteristics of all patients were summarized descriptively,
Body mass index, kg/m2 28.3 6 6.4 26.9 6 4.9 0.282 additionally, all categorical variables were compared with Pearson’s v2 test or Fisher’s
exact test and continuous variables were analysed with Student’s t-test or Mann
Dialysis vintage, years 3.7 6 4.1 4.2 6 3.4 0.798
Whitney U test. The difference in the QoL by domains will be evaluated using
Comorbidities, n 3.4 6 1.7 2.7 6 2.4 0.046 Pearson’s v2 test or Fisher’s exact test. The EQ VAS provides a quantitative measure of
CCI* 4.9 6 1.9 4.5 6 2.3 0.341 the patient’s perception of their overall health.
RESULTS: A total 254 patients were evaluated, the median age was 55 years, 55% were
Diabetes, % 44.0 43.3 0.955 men. At enrolment the median dialysis vintage 3.2 years, and 63% were in peritoneal
Hypertension, % 76.0 93.3 0.024 dialysis treatment (Table 1). We did not find differences in the proportions by dialysis
treatment when exploring each of the 5 dimensions of the QoL (Table 2). We observed
that the patients perception of their overall health was similar median EQ VAS score
80 in HD and EQ VAS score 80 in PD (Figure 1). We did not find statistically
significant differences in health status 11111, which represents not having problems in
any dimension 46.8% versus 45.6%, HD and PD respectively, p-value= 0.855.

10.1093/ndt/gfab098 | i471
Abstracts Nephrology Dialysis Transplantation

MO845 Figure 1: EQ VAS score according therapy , sex, age amd dialysis vintage.

CONCLUSION: The quality of life reported by the patients and health status in
haemodialysis was similar to peritoneal dialysis.

MO846 THE SPECTRUM OF CLINICAL AND SEROLOGICAL


FEATURES OF COVID-19 IN URBAN HEMODIALYSIS
PATIENTS

Elena Goma -Garcés1, Teresa Stock da Cunha1, Alejandro Avello1,


Monica Pereira2, Sebastian Mas-Fontao1, Alberto Ortiz1, Emilio Gonz alez-Parra1
1
Hospital Universitario Fundaci on Jiménez Dıaz, Madrid, Spain and 2Fundaci
on I~
nigo
Alvarez De Toledo, M ostoles, Spain

BACKGROUND AND AIMS: The inherent immunosuppression of uremia increases


the susceptibility of hemodialysis patients to infection. There is still limited evidence on
hemodialysis patients and COVID-19. The clinical and analytical spectrum and
treatment responses and mortality are poorly characterized.
METHOD: Clinical and analytical features, chest X-ray, polymerase chain reaction
(PCR) and antibodies for SARS-CoV-2, treatment and outcomes were analyzed in 48
patients diagnosed with COVID-19 during March and April 2020 in two coordinated
Spanish hemodialysis units.
RESULTS: In 200 haemodialysis patients, COVID-19 was diagnosed in 48, of whom
22 were PCR positive, eight PCR negative but seroconverted and two were diagnosed
on typical clinical grounds. Despite a mean age of 72.6 years, the overall mortality rate
was 5/48 (10%). Among the PCR positive patients, 21 (55%) required admission and
five (13%) died. PCR positive patients were more often symptomatic and hospitalized
and had higher troponin I levels than PCR negative patients, but did not differ in
lymphocyte counts, D-dimer or interleukin-6 (IL-6) levels. Among PCR negative
COVID-19 patients, three out of 10 (30%) required admission, and none died. The
most frequent symptom among the 48 patients was fever (31%), followed by
asymptomatic patients (23%). A low number of lymphocytes was the only parameter
significantly different between hospitalized and ambulatory COVID-19 patients,
independently of PCR status.
CONCLUSION: COVID-19 hemodialysis patients are frequently asymptomatic, and
mortality may be lower than previously reported. Diagnosis may be retrospective,
based on seroconversion, as PCR may be negative. This information should guide
preventive and patient isolation strategies.

i472 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO847 PREVALENCE OF FATIGUE REPORTED BY PATIENTS ON
HEMODIALYSIS THERAPY

Mauricio Sanabria1, Cesar Mauricio Doria2, Edward Martinez2, Carlos Simon2,


Jasmin Vesga4, Magda Marin2
1
Baxter Renal Care Services Latinamerica, Research, BOGOTA D.C., Colombia, 2Baxter
Renal Care Services Colombia, Medical, Bucaramanga, Colombia and 4Baxter Renal
Care Services Colombia, Research, Bucaramanga, Colombia

BACKGROUND AND AIMS: Fatigue is a symptom with a high prevalence in


patients on hemodialysis therapy due to uremic toxins, anemia, associated
comorbidity, and hemodialysis treatment per se. Our objective is to evaluate the
prevalence of fatigue reported by patients and their association with the nutritional
status.
METHOD: This was a prospective observational, multicenter cohort study. Prevalent
patients on HD therapy for at least 90 days, older than 18, at the Baxter Renal Care
Services were included between September 1, 2017, to November 30, 2017 with one-
year follow-up. Socio-demographic and clinical characteristics of all patients were
summarized descriptively, the nutritional status was evaluated by protein Energy waste
(PEW). Patient reported fatigue was measured with high flux membrane and medium
cut-off membrane (Theranova). A generalized linear binomial multivariable model was
conducted to assess the effect of PEW on fatigue symptom controlling for some
confounding variables.
RESULTS: We found that the fatigue reported by the patients has a prevalence of 55% MO848 PREVALENCE OF COVID -19 IN CHRONIC HEMODIALYSIS
[95% CI: 52.2 to 57.7] in our population, there are no statistical differences due to the PATIENTS AT THE TARIJA DEPARTAMENTAL
use of different types of membranes p= 0.911, and neither did we find that the HEMODIALYSIS CENTER DURING THE PEACK OF THE
nutritional status is an independent factor that explains this symptom. If we find that ANDEMIC JULY - SEPTEMBER 2020
women and diabetics have a higher risk of fatigue; RR=1.17 [95% CI: 1.06 to 1.29] and
RR= 1.19 [95% CI: 1.00 to 1.42] respectively. Nelson Zamora1, Andrea Molina2, Jaime Arduz1
1
CONCLUSION: The fatigue is a prevalent symptom in the chronic hemodialysis Hospital Regional San Juan de Dios, Tarija, Tarija, Bolivia and 2Banco de Sangre,
population; being a woman and the diagnosis of diabetes are risk factors associated Tarija, Tarija, Bolivia
with this outcome. PEW and the type of dialysis membrane used were not associated
with this symptom. Studies evaluating the recovery time from post-dialysis symptoms BACKGROUND AND AIMS: Bolivia was the last country to enter in the list of Latin
and its relationship with the type of membrane are necessary. American countries to report cases for the worldwide pandemic of COVID-19,
reporting its first two confirmed cases on March 11, 2020 in the cities of Santa Cruz
and Oruro. In Tarija department, the peak of cases was registered in the months of
July, August and September. The Departmental Hemodialysis Center during this
period had 71 registered patients undergoing chronic hemodialysis sessions. In this
article we display the prevalence of patients who were infected with COVID-19 during
that period of time.
METHOD: This is a prospective cohort observational study in which 71 patients were
observed, who underwent hemodialysis sessions during the three shifts during the day
(morning, afternoon and evening, during the months of July, August and September,
months which were the peak of the pandemic in Tarija. Patients suspected of being
transmitted with the disease, underwent immunochromatography IgM/IgG, ELISA
anti SARS-CoV-2 and RT/PCR tests before confirming the diagnosis of COVID-19.
Patients who had hemodialysis sessions for a period of less than 3 months were
excluded from the study, and also those who changed their treatment modality for
peritoneal dialysis to hemodialysis.
RESULTS: 63 patients, 27 men and 36 women, who underwent hemodialysis sessions
during the observational period met the inclusion criteria of the study. 7 patients were
excluded for not meeting the inclusion criteria, 6 with a period less than 3 months
undergoing hemodialysis and 1 patient who had changed the treatment modality from
peritoneal dialysis to HD were excluded too. Of the 63 hemodialysis patients, 57
patients remained healthy and 6 were diagnosed with COVID-19 (Table 1). The
prevalence of patients who presented COVID-19 in the hemodialysis center was 9%,
with 33% of mortality and 83% who were able to recover and receive epidemiological
discharge (figure 1). Of the 6 patients who developed COVID-19, 3 were women and 3
were men, 4 patients with previous hepatitis B infection who were dialyzed in the room
with machines HBV þ and 2 patients without liver infections who were dialyzed in
negative machines. Three patients evolved asymptomatic during the SARS-CoV-2
infection, 2 presented thermal rises and mild cough, but without compromise in O2
saturation or ventilatory function, and one patient who died developed mild cough,
slight fever and a hemodialysis catheter-related bloodstream infection by
Staphylococcus aureus, confirmed in blood culture.
Clinical characteristics of study participants (N=63)

COVID COVID All


negative positive patients
N= 57 N= 6 N= 63
Age Mean 51.08 57,6 51.66
Gender F (m) % 58(42) 50(50) 57(43)
Ethnicity
Latin % 98 100 98
Black % 2 0 2
Reason of HD

Continued

10.1093/ndt/gfab098 | i473
Abstracts Nephrology Dialysis Transplantation

Continued had been asymptomatic raising doubts about whether there could have been false test
COVID COVID All results or an undetectable immune response.
negative positive patients
N= 57 N= 6 N= 63
Age Mean 51.08 57,6 51.66
MO850 OUTCOMES OF COVID-19 INFECTION IN DIALYSIS
Gender F (m) % 58(42) 50(50) 57(43) PATIENTS IN QATAR: A NATIONWIDE COHORT STUDY
Ethnicity
Tarek Abdellatif1, Abdullah Hamad1, Mohamad Alkadi1, Essa Abuhelaiqa1,
Latin % 98 100 98 Muftah Othman1, Rania Ibrahim2, Tabaseem Akl1, Fadumo Yasin1, Sahar Aly1,
Black % 2 0 2 Musab Eljaali1, Hassan Almalki1
1
Reason of HD Hamad general hospital, Nephrology, Doha, Qatar and 2Hamad general hospital,
Diabetes nephropaty % 35 50 36 Doha, Qatar

Hypertensive % 25 0 22 BACKGROUND AND AIMS: Patients on maintenance dialysis are more susceptible
nephropaty to COVID-19 and its severe complications. We studied outcomes of COVID-19
GMN % 26 50 29 infection in dialysis patients in the state of Qatar. Our primary outcome was to
determine the mortality rate of dialysis patients with COVID-19 infection and
PKD % 5 0 5 associated risk factors. Our secondary outcomes were to assess the severity of COVID-
Other % 9 0 8 19 in dialysis patients and its related complications such as the incidence of hypoxia,
Vintage on HD (m) mean 29 (3-108) 12 ( 6-18) (3-108) critical care unit admission, need for mechanical ventilation or inotropes, incidence of
acute respiratory distress syndrome (ARDS), and length of hospital stay.
METHOD: This was an observational, analytical, retrospective, nationwide study. We
included all adult patients on dialysis who tested positive for COVID-19 (PCR assay of
CONCLUSION: The prevalence of patients infected by SARS-CoV-2 was 9% with a nasopharyngeal swab) during the period from February 1, 2020 to July 19, 2020.
mortality of 17% (1 patient), validating that strict patient control and prevention Patient demographics and clinical features were collected from a national electronic
measures become a great support to avoid massive spread between patient prone to medical record. Laboratory tests were evaluated upon diagnosis and on day 7.
acquire this infectious disease. RESULTS: There were 76 out of 1068 dialysis patients who were diagnosed with
COVID-19 (age 56613.6, 56 hemodialysis and 20 peritoneal dialysis, 56 males). Eleven
patients (15%) died during study period. Mortality due to COVID-19 among our
dialysis cohort was 100 times higher than that in the general population for the same
period (15% vs. 0.15%; OR 114.2 [95% CI: 1.53 to 2.44]; p<0.001). Univariate analysis
MO849 COVID-19 AT THE HEMODIALYSIS UNIT OF FELGUEIRAS,
for risk factors associated with COVID-19-related death in dialysis patients showed
NORTH OF PORTUGAL
minor but statistically significant increases in risks with age (OR 1.07), peak WBC peak
level (OR 1.189), AST level at day 7 (OR 1.04), fibrinogen level at day 7 (OR 1.4), D-
Sofia Homem Melo Marques1, Martin Balboa1, Manuel Tomé2, Ana Beco1,
dimer level on day 7 (OR 1.94), and peak CRP level (OR 1.01). A major increase in the
Maria do Sameiro Faria1
1
risk of death was noted with atrial fibrillation (OR, 8.7; p=0.008) and hypoxia (OR: 28;
alise de Felgueiras, Felgueiras, Portugal and 2School of
CHF - Clınica de Hemodi p=0.001). High severity of COVID-19 illness in dialysis manifested as 25% of patients
Medicine, Braga, Portugal required admission to the intensive care unit, 18.4% had ARDS, 17.1% required
mechanical ventilation, and 14.5% required inotropes for intractable hypotension or
BACKGROUND AND AIMS: SARS-CoV-2 represents a challenge for hemodialysis shock. The mean length of hospital stay was 19.2610.4 days. Laboratory tests were
(HD) patients due to their multiple comorbidities, disturbed immune defenses in the remarkable for severely elevated ferritin, fibrinogen, CRP, and peak IL-6 levels and
setting of kidney disease and increased age. Furthermore, sharing collective spaces decreased albumin levels on day 7.
during HD sessions increases the risk of contamination. CONCLUSION: This is the first study to be conducted at a national level in Qatar
In March 2020, the first COVID-19 cases in Portugal occurred in Felgueiras, a exploring COVID-19 in a dialysis population. Dialysis patients had a high mortality
municipality belonging to the district of Porto. The HD unit that serves this population rate of COVID-19 infection compared to the general population. Dialysis patients had
has 69 in-center patients and, from March 2020 until January 2021, has had 14 severe COVID-19 course complicated by prolonged hospitalization and high need for
COVID-19 cases. We describe our experience concerning patient management and critical care, mechanical ventilation and inotropes. Special care should be done to
their clinical characteristics. prevent COVID-19 in dialysis patients to avoid severe complications and mortality.
METHOD: Clinical and laboratory data were collected. We aimed at assessing the
impact of the infection in hemoglobin, alanine transaminase, several electrolytes -
potassium, phosphorus, sodium and calcium - as well as the normalized protein
catabolic rate (nPCR) comparing results from the month before infection with those of
the month after cure. Statistical analysis used SPSSV R and variables were compared MO851 INCIDENCE AND MORTALITY OF CORONAVIRUS DISEASE
using paired-samples t-test. (COVID 19) IN HEMODIALYSIS PATIENTS
RESULTS: We used a dedicated room and staff for COVID-19 patients, disinfection
protocols and specific routes. Transportation was done with a maximum of 3 patients Nevena Grujic1, Snezana Pesic 1, Radomir Naumovic1,2
1
in a 9-seater vehicle, all patients used masks, practiced social distancing, were asked for Zvezdara Hospital, Nefrology, Belgrade, Serbia and 2University of Belgrade, Faculty of
symptoms and had their temperature measured on each HD session. SARS-CoV-2 medicine, Belgrade, Serbia
infection was established by reverse transcription polymerase chain reaction on nasal
and oropharyngeal swabs. Of the 14 cases, 3 occurred in March, 5 from October until BACKGROUND AND AIMS: In December 2019, an outbreak of coronavirus disease
Christmas and 6 from then onwards, accounting for approximately 20% of the unit’s 2019 (covid 19) due to SARS Cov2 began in China and spread worldwide.
patients. Of these, 2 were asymptomatic, 6 had predominantly respiratory symptoms, 1 Hemodialysis patients represent a unique group of patients, mostly elderly,
had fever and 1 had gastrointestinal symptoms. Three were hospitalized, 2 died due to imunocompromised, with numerous comorbidities. Patients with end stage renal
COVID-19 and 1 died 1 month after cure due to advanced cancer. Mean age of these disease are thought to be at increased risk of disease, severe disease and death from
patients was 70613.2; 5 were females and 6 had diabetic nephropathy. Only 7 patients Covid 19 infection. In addition, dialysis centers are a suitable place for an outbreak of
had post-COVID-19 results for comparison. The mean hemoglobin value before the epidemic. All of the above represents a group of hemodialysis patients particularly
COVID-19 was 10.561.7g/dL and did not change significantly after COVID-19. susceptible to infection and the development of serious disease.
Although phosphorous dropped from a mean 3.860.9mg/dL to 3.261.3mg/dL, this METHOD: We reviewed data of all maintenance hemodialysis patients in
difference did not reach significance (p=0.43). All other electrolytes remained stable. hemodialysis centar of Zvezdara Hospital, Belgrade, Serbia. We include all patients
nPCR dropped from 1.2360.47 to 0.9560.37 although not a significant difference with COVID 19 infection in period between April 1 2020 and January 10 2021.
(p=0.24). Five patients were tested for IgG/IgM antibodies against SARS-CoV-2 one RESULTS: Of 232 patients undergoing hemodialysis, 68 (29,31%) were infected
month after cure using ElecsysV R qualitative immunoassay and 4 tested positive.
with Sars-Cov-2. 46 (67,64%) patients were males and 22 (32,35%) females. The age
CONCLUSION: COVID-19 is a problem for HD patients where the percent of cases is range of the patients was 35 to 87 years, the mean age was 65,25. The underlyind
larger than in the general population. Our 3 first cases and the 4 last cases shared the cause of terminal renal failure in 25 patients was hipertensiv nefroangiosklerosis, 14
same HD shift and occurred in the same period confirming that, despite all protective diabetic nephropathy, 10 opstructiv nephropathy, 9 polycystic kidney disease, and
measures, sharing the facilities in close proximity is a risk factor. Respiratory 10 other cause of kidney failure. The average of hemodialysis duration was 70,70
symptoms predominated but were only severe requiring hospital admission in 3 months. The average durations of disease was 15 days. Mortality has been estimated
patients. Mortality represented 14% and the 2 patients whose death was attributable to at 33,82% (23 patients). Among patients who died 8 (34,78%) were females, and 15
COVID-19 had an increased burden of comorbidities and were old. Seroconversion (65,21%) males.
was high 1 month after the disease. The only patient who tested negative for antibodies

i474 | Abstracts
Nephrology Dialysis Transplantation Abstracts
CONCLUSION: The mortality among hemodialysis patients diagnosed with Covid 19 MO853 SEROLOGICAL RESPONSE AND FACTORS INVOLVED AFTER
is high. Hemodialysis patients typically present with multiple comorbidities and are A VACCINATION PROTOCOL FOR HEPATITIS B VIRUS IN A
considered to be a high-risk group for infections. Hemodialysis patients with Covid-19 HEMODIALYSIS UNIT
may have prolonged hospital stays and unfavorable prognoses and should be closely
monitored. Maria Paz Castro Ferna ndez1, Luis Guillermo Piccone Saponara1,
Nancy Giovanna Uribe Heredia2, Guillermo Ferrer Garcıa1, Agustın Carren ~o
Parrilla1, Sara Anaya Fernandez1, Casimiro Valle Dominguez1, Gloria Garcıa
Conejo1, Eliana Olazo Gutierrez1, Carmen Vozmediano Poyatos1
1
Ciudad Real University General Hospital, Nephrology, Ciudad Real, Spain and
2
Guadalajara University General Hospital, Cardiology, Guadalajara, Spain
MO852 MANAGEMENT OF PATIENTS UNDERGOING CHRONIC
HEMODIALYSIS DURING THE COVID-19 PANDEMIC: BACKGROUND AND AIMS: The population with chronic kidney disease (CKD)
FONDAZIONE POLICLINICO A. GEMELLI’S EXPERIENCE presents an increased risk of infection by hepatitis B virus (HBV). Usually, the
protective immunological response rate (considering HBV titer > 10 mIU/mL) is 90–
Federica Urciuolo1,2, Nicola Panocchia1,2, Alessandro Naticchia1,2, 95% after the 4th dose of vaccine; In CKD the immune response is lower and correlates
Viola D’Ambrosio1,2, Silvia Barbarini2,3, GianMarco De Luca1,2, Rocco Baccaro1,2, with the degree of CKD. In dialysis, this response is variable, less than 50% with three-
Massimo Liberatori1,2, Giuseppe Grandaliano1,2 dose regimens and higher with four doses. Cardiovascular risk factors have been
1 implicated in the response rate to vaccination.
Fondazione Policlinico Universitaro A. Gemelli IRCCS, UOC Nefrologia, Dipartimento di
The objective of this work is to analyze the efficacy of the HBV vaccine in hemodialysis
Scienze Mediche e Chirurgiche, Rome, Italy, 2Universit
a Cattolica del Sacro Cuore,
patients and to identify cardiovascular factors as predictors of response.
Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Rome, Italy and
3 METHOD: Retrospective observational study. We evaluated the response to a 4-dose
Ospedale Vito Fazzi, Dipartimento di Nefrologia e Dialisi, Lecce, Italy
vaccination protocol (0-1-2-6 months), determining the levels of HBVA 3 months after
the last dose. Demographic variables (age, sex), associated comorbidity, etiology of
BACKGROUND AND AIM: COVID-19 (COronaVIrus Disease 19) is an acute CKD, among others, were collected. Statistical analysis with SPSS 25.0. Categorical
respiratory disease caused by SARS CoV 2 virus. The correlation between SARS-CoV2 variables are expressed as percentages and have been compared using the Chi2 test.
infection and comorbidities is complex; patients with multiple comorbidities present The quantitative variables are expressed as mean þ/- standard deviation and the T-
often with the most severe symptoms that could potentially lead to death. Patients student was used to compare them. Statistical significance for a value of p <0.05.
undergoing hemodialysis are generally frail and immunodeficient. This leads to a RESULTS: 89 patients were included; 68.5% are male, with an average age of 65 years.
greater risk of contracting infectious diseases. In the literature, the estimated incidence 85.4% had arterial hypertension, and 39.3 were diabetic, the most frequent cause of
of SARS-CoV2 infection is 3.24% in chronic hemodialysis patients. CKD being renal vascular disease (20.8%), diabetic nephropathy (26.4%) and
METHOD: Fondazione Policlinico A. Gemelli is a COVID hospital. During the interstitial (9%). The immune response to HBV vaccination was 79.2%. When making
pandemic patients from several dialysis centers converged in our hospital. FPG has two statistical comparisons between the qualitative variables, we have not observed
dialysis centers, one for outpatients and one for inpatients. Patients admitted for differences between serological response and DM or sex; We did find a trend towards
COVID-19 infection have been treated in three different settings: 1. isolation room significance when comparing the serological response with the variable HT and
within the dialysis center; 2. Bedside; 3. In a COVID-19 dialysis center. We etiology of CKD (polycystic kidney disease), pNS. The comparison of means between
retrospectively collected data of patients treated from March 2020 to January 2021 and quantitative variables when performing the Student’s T-test did not show differences
analyzed the SARS-CoV2 incidence in our center’s chronic hemodialysis patients. for any of the study variables.
RESULTS: 66 hemodialysis patients affected by COVID-19 have been treated in our CONCLUSION: In our center, HBV vaccination on dialysis achieves a response rate of
hospital from March 2020 to January 2021, 60 patients undergoing chronic dialysis and 79.2%. HT may condition the immune response to vaccination in HD patients,
6 patients diagnosed with acute kidney injury (AKI) stage III non-intensive care unit. although significance was not reached. Hereditary pathology has been the one that has
Among chronic patients, 64 underwent chronic hemodialysis and 2 patients underwent shown the best serological response with respect to the rest of etiologies, perhaps
peritoneal dialysis. Median age was 68.19 (46 males, 20 females), all patients had associated with greater residual renal function.
multiple comorbidities: 37.8% of patients had diabetes mellitus; 72.7% cardiovascular
diseases and 16.6% a positive clinical history for cancer. Among the 6 AKI cases, 3
patients regained total kidney function; the other 3 had to continue renal replacement
therapy. The mean hospital stay length was 18.5 days with a mean time of COVID-19
infection of 21.23 days. The overall mean Charlson Comorbidty Index was 6.21.
Among the 66 treated patients, 43 were diagnosed with COVID-19-related pneumonia,
14 had the infection, no pulmonary involvement, but presented with other MO854 PHYSICAL ACTIVITY IN CHRONIC HEMODIALYSIS
complications, and 5 patients resulted positive although asymptomatic. Among the 116 PATIENTS: ABOUT 71 CASES
hemodialysis outpatients, only 4 presented with SARS-CoV2 infection, 3 were contacts
of a positive family member and 1 resulted positive during a hospital stay for Imen Chemli1, Amel Ayed2, Ayed Sinda 3 , Meriem Ben salem4, Manel Ben salah4,
Clostridium Difficile infection. All patients required hospitalization. 14 (21%) patients Insaf Handous4, Ahmed Letaief4, Mouna Hamouda4, Sabra Aloui4, Habib Skhiri4
1
died. Among the deceased patients, the mean age was 76.90 years (9 males, 3 females), hospital of Fattouma Bourguiba Monastir, nephrology, Monastir, Tunisia, 2Monastir,
mean Charlson Comorbidity Index was 7.3, mean hospital stay length was 9 days. nephrology, Monastir, Tunisia and 4hospital of Fattouma Bourguiba Monastir, nephrol-
Among patients who survived the disease the mean age was 76.92 years (34 males, 14 ogy, monastir, Tunisia
females), mean Charlson Comorbidty Index was 5.87 and mean hospital stay length
was 19.47 days. Statistical significance was reached for age (p value 0.005) and BACKGROUND AND AIMS: physical activity is generally impaired in the chronic
Charlson Comorbidty Index (p value 0.39), but not for mean hospital stay length (p hemodialysis patient. Studies confirm the benefit of maintaining or improving physical
value 0.13). All COVID-19 patients were treated with bicarbonate hemodialysis and a activity in these patients. For this reason, our study aims to assess physical inactivity in
Theranova 400 BaxterV R filter. This filter was chosen for its efficiency on medium-size
chronic hemodialysis patients using a physical activity score: DIJON score and to
molecules removal (between 25 kDa and 60 kDa) that may be associated with identify the factors linked to a decrease in physical activity .
inflammation. Bedside treatments were performed using the GeniusV C Fresenius
METHOD: this is a descriptive and analytical cross-sectional study carried out at the
system. Each treatment lasted 180 minutes, in order to reduce the time of exposure to hemodialysis center of Fattouma Bourguiba hospital in Monastir. We used the DIJON
COVID-19 of medical staff and the risk of virus spread on one hand, but still ensuring questionnaire to measure physical activity: daily activities, sports or leisure. The
an optimal and complication-free treatment to patients. reference values for the level of physical activity are 0-10 (low), 10-20 (medium); and
CONCLUSION: Our experience seems to confirm the national data collected so far, 20-30 (high).
both in terms of patients’ outcomes and mortality rate. Our study confirms that age is a RESULTS: our study included 71 patients. The middle age was 46.62 þ - 15.34 years.
risk factor for mortality. How to properly manage chronic hemodialysis patients 69% of patients were male. The overall physical activity level was high at 22.75 þ -1.99
affected by COVID-19 remains a challenging and burdensome question. However, in 28.2% of patients, medium at 13.75 þ -3.65 in 33.8% of patients and low at 5.56 þ -
there is the need of new flexible solutions that guarantee the patients and the medical 2.91 in 38% of hemodialysis patients. Analysis in multiple linear regression showed
staff’s safety on one hand and a personalized management on the other. that the variables that explained the DIJON score in our population are in order of
contribution: pre-dialytic uremia (b = 0.433; t = 2.99; p = 0.005), cardiac diseases(b =
0.305; t = 2.074; p = 0.044), the KT/V ratio (b = -. 858; p = -1.915; p = 0.063), the PRU
(b = 1.21; t = 1.885; p = 0.066) , anemia (b = 0.211; t = 1.704; p = 0.096), comorbidity
evaluated by Charlson score (b = -. 461; t = -1.414; p = 0.165).
CONCLUSION: our results showed that the level of physical activity is linked to many
factors, some of which are modified. So, prescribing an adapted and personalized
program will improve the prognosis and the quality of life of our patients.

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Abstracts Nephrology Dialysis Transplantation

MO855 PREVALENCE OF SELF-REPORTED KIDNEY DISEASE MO857 HEMOPERFUSION IN HEMODIALYSIS PATIENTS WITH
AMONG THE FIRST DEGREE RELATIVES OF SAUDI COVID-19 INFECTION: IMPACT ON CLINICAL COURSE
PATIENTS ON DIALYSIS AND ITS RELATIONSHIP TO
SPECULATIVE VERSUS DEFINITIVE CAUSES OF CKD IN THE Ioannis Griveas1, Antonis Schinas1, Anthoula Balitsari1,
INDEX CASE Gerasimos Asimakopoulos1, Evangelos Pratilas1
1
Army Share Fund Hospital 417 (NIMTS), Nephrology, Athens, Greece
Abdulla Al-Sayyari1
1
King Saud Bin Abdulaziz University for Health Sciences, Riyadh BACKGROUND AND AIMS: Our Nephrology Department during spring period on
the first wave of COVID-19 was the referral Dialysis Unit for Covid-19 positive
BACKGROUND AND AIMS: CKD is common in Saudi Arabia. This study evaluates hemodialysis (HD) patients in the district area of Athens, Greece. We used
and compares the prevalence and clinical characteristics of Saudi dialysis patients with hemoperfusion (HP) as a therapeutic option in our patients. The aims of this study are
a positive family history of kidney disease to those without such a history and to assess to report characteristics, rates and outcomes of all patients affected by infection with
certainty of the CKD diagnosis by their physicians. SARS-CoV-2 undergoing HD and were treated under our care focusing on the impact
METHOD: This is a cross-sectional survey-based study on adult Saudi hemodialysis of HP on them.
patients in six dialysis centers in four Saudi cities. The first part of the survey recorded METHOD: This is an observational study. Our Dialysis Unit has been assigned as a
the demographic variables and the degree of diagnostic certainty (completed by the referral unit for Covid-19 positive HD patients. Patients divided to 2 groups: first group
physicians) and the second part (completed by the patients) recorded first degree of patients underwent HD sessions with Hemoperfusion (A) and the second one
family history of kidney disease. received HD sessions without any other extracorporeal blood purification method (B).
RESULTS: A total of 1080 patients were included. The prevalence of positive family We used resin-directed hemoadsorption cartridges (HA-330 and HA-130)
history (FH) was 21.5%. The number of relatives affected was 285, (41%) were parents manufactured by the Jafron Biomedical Company, China. We registered all the data
and (57%) were siblings. More relatives of female patients had ESRD than in relatives regarding the clinical course of our patients population. Age, primary cause of end
of male patients (80.2% and 68.9% respectively) (p=0.0001). There were significantly stage renal disease, weight, clinical presentation, HD history, outcome, days of
more patients with “unknown” or “hypertensive” diagnostic labels among the patients hospitalization.
with FH of kidney disease than in the group without a family history (p=007 and 0.005 RESULTS: Group A 13 patients (4 males) have been enrolled in this group with mean
respectively). Dialysis vintage was significantly shorter and CKD vintage was age of 74 years old. 5 of them were presented asymptomatic at admission and 7 of them
significantly longer in positive FH patients (4.9 66.4 yrs.) than in patients without FH admitted with or developed during their stay pleural effusions. 4 of them were
(5.9 65.8yrs) (p=0.03). The duration since the diagnosis of CKD was made was asymptomatic without effusions during the whole hospital stay. 12 patients received
significantly longer in patients with FH of kidney disease (7.567.7 yrs.) than in patients HP for 3 hours in our Dialysis Unit during the planned HD session and one patient
without (2.064.5) (p=0.0001). Of all the diagnoses given to the patients, more than half received Hemoperfusion in ICU during CRRT. 6 patients had one session of
(57.8%) were either “unknown” (33%) or only speculative in nature (25.3%). In those Hemoperfusion (with HA130, 4 patients and with HA 330, 2 patients). 6 patients had 2
with a diagnostic label, the diagnosis was thought to be definitive in only 62.2% of the sessions (7 days interval) either with HA 130 both sessions (3 patients) or with HA 330
cases. followed 7 days after with HA 130 (3 patients). The patients that admitted in ICU
CONCLUSION: The prevalence of FH of kidney disease was 21.5%, and it was more started HP the third day of her admission. The pattern was as follows: We used HA330
prevalent with patients with “unknown” or “hypertension” (13%) diagnostic labels. in 3 consecutive days during CRRT. In Day 10 we used HA130 and in Day 13 HA330.
HP was performed for 3 hours. 24 days was the average hospitalization stay before
starting HP for the 12 patients in boards. 9 patients discharged from the hospital after
43 days of hospitalization (range: 35-56 days). 30 days were the mean hospitalization
stay for the diceased ones. We did not observe any side effects with HP cartridges
(hypotension, reduction of platelets, bleeding).
Group B 9 patients (7 males) with mean age of 75 years old did not receive HP during
MO856 IMPACT OF HEMODIALYSIS TIME PROLONGATION ON
their hospitalization. All of them were presented symptomatic. 8 out of 9 patients died
BLOOD PRESSURE CONTROL IN PREVALENT
after 6 days of hospitalization (range: 1-14 days), 2 of them in ICU.
HEMODIALYSIS PATIENTS
CONCLUSION: To sum up, HP seems to be a helpful, safe an quite efficient tool in the
battle against Covid-19 in HD patients. Despite the method is unspecific, our lack of
Nahla Teama1, Reem Elsharabasy1, Heba Soliman2, Magdy ElSharkawy3
1
strong evidence, our views are with the opinion that is an reliable alternative therapy.
Ain Shams University, Faculty of Medicine, Nephrology, Cairo, Egypt, 2Mansheit El However, the real impact of HP on the patient’s clinical course (time of initiation,
Bakry Hospital, Nephrology, Cairo, Egypt and 3Ain Shams University, Faculty of therapeutic protocols, tools to evaluate response) has yet to be determined. The above
Medicine, Nephrology, Cairo, Egypt notice does not minimize the great interest for the method that renal community
should give.
BACKGROUND AND AIMS: Hypertension prevalence among ESRD patients range
from 76% to 90%. Sodium & volume overload is among the main mechanisms.
Increasing theduration of dialysis time, either by longer session hours or increased
sessions, aiming at reducing the dry weight to achieve euvolemia, may be beneficial for
individuals who failed to achieve target BP or ideal volume status during standard HD
prescription hours.We aim to study the effect of increasing hemodialysis session time
on blood pressure control.
METHOD: This observational study was conducted on 50 adult clinically stable
hypertensive prevalent HD patients on thrice weekly maintenance HD. Patients with
secondary causes of hypertension and Patients with decompensated medical conditions
were excluded from our study.Patients were divided into 2 groups:(A) 25 patients who
received longer session hemodialysis session (4.5hour) and (B) 25 patients HD who
received the usual 4 hours session.
Revision of antihypertensive medications&dosages,dry weight was reassessed regularly,
andthey were instructed to restrict their salt intake as much as possible aiming at BP
<140/90mmHg.they werefollowed up for a period of 6 months assess changes of pre-
dialysis blood pressure to monitor response.
RESULTS: Patients in both groups were age matched, with male sex predominance
(64%in groupA&56% in groupB). Patients in both groups underwent their HD sessions
mostly through AVF (68% and 92% for group A and B respectively). Ultrafiltration
volume declined significantly with longer HD sessions compared to conventional
sessions (p-value <0.001 vs 0.523).
Longer HD session time session was associated with highly significant decline in mean
SBP, (p-value <0.001). Longer HD session time session was associated with highly
statistically significant decline in mean DBP, (p-value <0.001). The decline in mean
perdialysis SBP & DBP was -17.27 &-9 mmHg, respectively and the rate of decline of
postdialysis SBP & DBP was -6.45 & -12.38 mmHg, respectively at 6th month
compared to values in 1st month of follow up period.
CONCLUSION: Longer HD session duration is associated with better improvement in
UF volume, mean SBP&DBP, pre-dialysis SBP&DBP and post-dialysis SBP&DBP as
well.

i476 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO858 BIOCHEMICAL CHARACTERIZATION AND SURVIVAL OF
PATIENTS URGENT-START HEMODIALYSIS DURING COVID-
19 PANDEMIC: EXPERIENCE IN A GUATEMALAN CENTER

Celso Mazariegos1, José Vicente S anchez Polo1


1
Guatemalan Institute of Social Security (IGSS), Guatemala, Guatemala City,
Guatemala

BACKGROUND AND AIMS: The Coronavirus Disease 2019 (COVID-19) pandemic


has greatly impacted the world health system, affecting almost 20 million people with a
high fatality rate, mainly patients with comorbidities including patients with chronic
kidney disease (CKD) in all its stages and renal replacement therapy. The aim of the
present study was to evaluate the biochemical characteristics of the patients who
urgent-start hemodialysis during the pandemic and additionally to evaluate their
survival.
METHOD: Patients urgent-start hemodialysis were taken during the months of
August to November 2020, the admission laboratory data was recorded, including the
test to determine SarsCov-2, and Kaplan-Meier survival analysis was applied taking in
it counts variables such as sex, professional who placed the vascular access, COVID-19
test result and evaluation by nephrology in the pre-dialysis clinic.
RESULTS: 92 patients were including in the analysis, 65% male, the nephrologist
placed the vascular access in 54% of the patients, 71% had a negative result in the
COVID-19 test and 55% had no evaluation in the pre-dialysis clinic. Among the
biochemical results was found BUN 95.3mg/dl (SD 38.1), sCr 10.3mg/dl (SD 6.3), Na
130.6mg/dl (SD 7.5), K 5mmol/L (SD 1.1), Ca 7.8mg/dl (SD 1), P 6.5mg/dl (SD 3.3),
uric acid 8.3mg/dl (SD 10) and PTH 279pg/ml (SD 267). As prognostic markers of MO858 Figure 2: Survival by COVID-19 test
infection by COVID-19, the following results were found WC 12.3k/UL (SD 9.3),
hemoglobin 9.35g/dl (SD 2.5), hematocrit 28.7% (SD 9.4), platelets 291mcL (SD 137),
sedimentation 75mm/hr. (SD 37), CRP 81.8mg/L (SD 113.8), interleukin-6 232-6pg/ml
(SD 838.8), ferritin 1074.3mg/ml (SD 825.3), D dimer 4.3mcg/dl (SD 11.2), lactate
dehydrogenase 322U/L (SD 255) and procalcitonin 6.5ng/ml (SD 16.8). When
evaluating survival with the Kaplan-Meier analysis, no statistically significant
difference was found when analyzing the variable presence of COVID-19 infection
(Figure 2 - p: 0.89), sex (Figure 3 - p: 0.54), professional who placed vascular access
(Figure 4 - p: 0.1), and the pre-dialysis evaluation (Figure 5 - p: 0.33), having a survival
in general of 77% at 3 months (Figure 1).
CONCLUSION: The present study found a 77% survival rate in patients with urgent-
start hemodialysis. There are no other documented data in Guatemala, which is why it
provides guidelines for future studies in the country. Among the variables taken, no
one was found that would determine a better survival, including SarsCov-2 infection. It
will be necessary to carry out more studies with greater follow-up, more patients and
more centers to carry out a better analysis.

MO858 Figure 3: Survival by Sex

MO858 Figure 1: Overall Survival

MO858 Figure 4: Survival by vascular acces

10.1093/ndt/gfab098 | i477
Abstracts Nephrology Dialysis Transplantation

Parameter Group 1 Group 2


N 13 7
Male, N (%) 9 (69.2) 6 (85.7)
Median [25;75]
Age, years 62 [49;67] 56 [38;69]
PD duration, months 29 [13;50] 5 [3;15]
HD duration, months 3 [1;12] 23 [5;30]
Causes of end-stage renal disease
Hypertension, N (%) 4 (30.8) 1 (14.3)
Glomerulonephritis, N (%) 4 (30.8) 2 (28.6)
Diabetes mellitus, N (%) 2 (15.3) 0
Others, N (%) 3 (23.1) 4 (57.1)
Causes for transfer to other treatment modality
Peritonitis, N (%) 10 (76.9) -
Leakage, N (%) 2 (15.4) -
Vascular access problems, N (%) - 4 (57.1)
Poor hemodialysis tolerance, N (%) - 2 (28.6)
MO858 Figure 5: Survival by Follow-up Dialysis Clinic Patient’s preference, N (%) 1 (7.7) 1 (14.3)
Outcomes
Died, N (%) 7 (53.8) 2 (28.6)
Transplanted, N (%) 2 (15.4) 2 (28.6)
Alive, N (%) 2 (15.4) 3 (42.8)
MO859 TRANSITIONS BETWEEN THE DIFFERENT DIALYSIS
MODALITIES AND THEIR EFFECT ON SURVIVALS: A SINGLE-
Transfer to other treatment modality, N (%) 2 (15.4) -
CENTER STUDY Death place
Intensive care unit, N (%) 6 (85.7) 0
Krystsina Kurylovich1,2, Kirill Komissarov3
1 Home, N (%) 1 (14.3) 2 (100)
Governmental Clinical Hospital @1, Dialysis, Minsk, Belarus, 2Belarusian Medical
Academy of Postgraduate Education, Urology and Nephrology, Minsk, Belarus and Death cause
3
Minsk Research and Practice Centre of Surgery, Transplantology and Hematology, Cardiovascular accidents
Nephrology and dialysis, Minsk, Belarus
ardiac arrest, N (%) 1 (14.3) -
BACKGROUND AND AIMS: An integrated care approach available today, which Acute heart failure, N (%) 1 (14.3) -
implies that most patients will use different modalities at different time points of their Stroke, N (%) 1 (14.3) -
disease, creates a need to accumulate data on patient outcomes and survival when Sepsis
switching from one treatment modality to another. The aim was to compare survival
after the transition from hemodialysis (HD) to continuous ambulatory peritoneal Diabetic foot sepsis, N (%) 1 (14.3) -
dialysis (CAPD) and after the transfer from CAPD to HD. Gallbladder empyema, N (%) 1 (14.3) -
METHOD: A single-center retrospective trial included 20 (18.9%) from 106 initiating
CAPD between January 2016 and December 2020 patients, who were transferred from
Bleeding
CAPD to HD or from HD to CAPD through a follow-up period until December 2020. Essential thrombocythemia, N (%) 1 (14.3) -
2 groups of patients were identified: the 1st group included CAPD-to-HD transition Undiagnosed peptic ulcer, N (%) 1 (14.3) -
patients, the 2d group - HD-to-CAPD transition patients. At the end of a follow-up,
the transfer’s causes, outcomes, and cohort life expectancy (CLE) on the new treatment Chronic conditions
modality were evaluated. Uremia, N (%) - 1 (50)
RESULTS: A summary of patients’ characteristics are shown in the table below. The Congestive heart failure, N (%) - 1 (50)
patient’s number in the 1st group was 13, in the 2d - 7. Transfer causes in the 1st group
were peritonitis (76.9%), leakage (15.4%), in the 2d group - vascular access problems
(57.1%), poor hemodialysis tolerance (28.6%). In both groups in 1 case transfer cause
was the patient’s preference (7.7% and 14.3% respectively). In the 1st group CAPD
duration was 29 [13;50] months, transfer outcomes included death in 7 cases (53.8%),
renal transplantation (RT) in 2 cases (15.4%), in 2 cases (15.4%) patients were alive and
were on HD, in 2 cases (15.4%) patients later were transferred back to CAPD. In the 2d
group HD duration was 23 [3;30] months, transfer outcomes included death in 2 cases MO860 NEUTROPHILS /LYMPHOCYTES RATIO: IS THERE ANY
(28.6%), RT in 2 cases (28.6%), in 3 cases (42.8%) patients were alive and on CAPD. In RELATION WITH ARTERIOVENOUS FISTULA EARLY FAILURE
the 1st group in 6 from 7 cases (85.7%) patients died in the intensive care unit (ICU), ON HEMODIALYSIS
the main causes of death included cardiovascular accidents - 42.8% (cardiac arrest,
acute heart failure, stroke), sepsis - 28.6% (due to gallbladder empyema and diabetic Hanen Abid1,2, Salma Toumi1,2, Rania Lahouimel1, Emna Kharrat1, Rimeh Ben
foot sepsis), bleeding - 28.6% (due to essential thrombocythemia, undiagnosed peptic Brahim1, Ikram Agrebi1, Najla Dammak1,2, Hanen Chaker1,2,
ulcer). In the 2d group all patients died at home, causes of death involved congestive Khaoula Kammoun1,2, Soumaya Yaich1,2, Mohamed Ben Hmida1,2
heart failure - 50% and uremia - 50.0%. In the 1st group CLE was 3.4 months, in the 2d 1
Hedi Chaker Hospital, Nephrology department, Sfax, Tunisia and 2Faculty of Medicine
- 20.5 months.
of Sfax, Renal Pathology Laboratory Lr19es11, Sfax, Tunisia
CONCLUSION: Post-transfer mortality is higher in the CAPD-HD transition group.
In most cases, such patients die faster and in more severe condition and almost always
in the ICU. Almost half of the CAPD-to-HD transfer patients died due to BACKGROUND AND AIMS: The native arteriovenous fistula (AVF) is the vascular
cardiovascular complications. Therefore, when transferring a patient to HD, it is access point for hemodialysis (HD) in end-stage renal disease (ESRD) patients
necessary to take into account the load exerted on the heart and blood vessels, as well undergoing HD. The challenge in the follow up of any AVF is to reach a correct
as the risks of bleeding and sepsis. maturation state and a higher longevity. The neutrophils to lymphocytes ratio (NLR)
and the platelets to lymphocytes ratio (PLR) have been reported in many papers to be
prognostic indicators for the AVF failure which seems to be associated with high levels
of NLR or PLR. This study aimed to evaluate the role of preoperative NLR and PLR in
predicting early AVF failure.

i478 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: We conducted a retrospective study including 31 patients who are
hemodialysis (HD) in our center and who benefited from an AVF confection during MO861 Table 1. Primary indications for CRRT implementation -Survival rate
2019 and 2020.
The threshold ratios found in the literature from which the risk of AVF early failure is Indication Number of Survivors/
significant are NLR> = 2.5 and PLR> = 150. These values have been considered the
references in our work. patients (%) Survival rate
RESULTS: The average age of our patients is 50 years (20-84 years). The sex ratio is (%)
equal to 1,38 (18 men and 13 women). 20 patients started HD when they were under Oliguria (less than 30 ml/h) 41 (44.5%) 10/41 / 24.3%
60 years old and 11 patients after the age of 60.
We noticed smoking, obesity, hypertension and diabetes respectively in 16%, 45%, or Anuria (0 ml/8h)
77%, and 32% of our patients. The causal nephropathy is respectively undetermined in Acidosis 16 (17.3%) 2/16 / 12.5%
10 cases, interstitial in 7 cases, diabetic in 6 cases, glomerular in 5 cases and vascular in
3 cases.
Fluid overload 11 (11.9%) 9/11 / 81.8%
The type of AVF is proximal in 19 cases (61%) and distal in 12 cases (38%). Electrolytic Disorders 22 (23.9%) 18/22 / 81.2%
The AVF failure occurred in 19%. The causes of AVF early failure are respectively a Intoxications 2 (2.1%) 0/2 / 0%
thrombosis in 3 cases, a stenosis in 2 cases and non maturing AVF in one case. The
mean NLR is 4,47 (1,09 -17). The mean PLR is 193 (80-397). 74% of our patients have a
NLR 2,5 and 26% less than 2,5. 61% of the patients have a PLR 150 and 39% less
than 150. All the patients with an AVF failure have a NLR 2,5 however only 5
persons have a PLR 150.
Among the 6 patients with an AVF failure, the AVF is proximal in 5 cases and distal in MO862 COVID-19 INFECTION IN HEMODIALYSIS
one case. PATIENTS:FINDINGS-EXPERIENCE-OUTCOME
We divided our population in two groups: group1 patients with an AVF failure (6
patients) and group2 who don’t have an AVF failure (25 patients). Afterwards, we have Ioannis Griveas1, Antonis Schinas1, Anthoula Balitsari1,
studied the correlations between these 2 groups with the NLR interval and PLR Gerasimos Asimakopoulos1, Evangelos Pratilas1
1
interval. Army Share Fund Hospital 417 (NIMTS), Nephrology, Athens, Greece
We didn’t find any significant correlation between the occurrence of AVF
failure with the NLR interval (p=0,11) and PLR interval (p=0,22). We tried to find BACKGROUND AND AIMS: Our Nephrology Department during spring period on
values of NLR and PLR for which we found a correlation with the AVF failure using the first wave of COVID-19 was the referral Dialysis Unit for Covid-19 positive HD
the ROC curve. The best cut off to predict AVF failure is 3,45 for NLR and 204 patients in the district area of Athens, Greece. The aims of this study are to report
for PLR. characteristics, rates and outcomes of all patients affected by infection with
CONCLUSION: We demonstrate throw this study that a high preoperative SARS-CoV-2 undergoing HD and treated under our care
NLR and PLR can predict the early AVF less. These data may serve as a METHOD: This is an observational study. Our Dialysis Unit has been assigned as a
foundation to develop future research on the role of anti-inflammatory referral unit for Covid-19 positive HD patients. We registered all the data regarding the
medications in the prevention of AVF failure think that required a larger series clinical course of our patients population. Age, primary cause of end stage renal
and more prolonged follow up. disease, weight, clinical presentation, HD history, outcome, days of hospitalization.
RESULTS: 22 Covid-19 positive HD patients were treated under the care of our facility
during the period 8 April 2020-17 June 2020. 16 patients were symptomatic at
admission and 13 patients admitted with or developed during their stay pleural
MO861 THE PROGNOSIS OF PATIENTS RECEIVING CONTINUOUS effusions. 12 patients (8 male) of our group died during their hospitalization. 3 out of
RENAL REPLACEMENT THERAPY (CRRT) AFTER 12 were admitted to Intensive Care Unit (ICU). 6 patients were septic, 4 had
CARDIOVASCULAR SURGERY DEPENDS ON THE respiratory failure and 2 developed cardiovascular events. 14.5 days were the mean
INDICATION FOR ITS INITIATION hospitalization days (range: 1-38 days) for the diceased ones.
2 out of 3 patients that admitted to ICU had quick deterioration, incubated and stayed
Nikolaos Schizas1, Maria Smyrli2, Aikaterini Dedeilia3, Vasilios Patris1, in ICU for 48 hours. The third one with severe cormobidities (multiple myeloma,
Ilias Samiotis1, Panagiotis Dedeilias1, Michail Argiriou1 cancer of bladder) developed respiratory failure after 8 days of hospitalization,
1
General hospital of Euaggelismos, Cardiovascular and Thoracic Department, Greece, incubated, became septic and died after 20 days in ICU.
2
General hospital of Euaggelismos, Nephrology Department “Antonios G Billis, Greece Mean age of our patients was 74.5 years. It has to be pointed out that 13 patients were
and 3National and Kapodistrian University of Athens, Medical School, Greece over 75 years old. Mean age was higher in those who died compared with those who
were discharged with double negative Covid-19 tests (79 vs 74,5 years old respectively).
Median dialysis vintage for our patients was 63 months and for the diceased ones was
BACKGROUND AND AIMS: Continuous Renal Replacement Therapy is required in
89 months. Average weight of our patients was 69 kgrs. Weight of diceased patients
2.6% to 5% of patients who have undergone cardiovascular surgery. Although its
was 63 kgrs. 11 out of 22 patients and 5 out of 12 diceased patients were diabetic. 14
implementation is frequent, several aspects of this therapeutic measure still remain
patients were hypertensive and 16 had official cardiovascular backround. 10 out of total
uncertain.
22 patients under our care discharged after 43 days of hospitalization (range:35-56
METHOD: The data of all patients who were surgically treated during a 3-year period
days).
(2017-2019) at a single cardiovascular department were collected and the cases in
CONCLUSION: As a conclusion our data provide clues regarding out experience of
which continuous renal replacement therapy was used were identified. From this
caring HD patients with COVID-19. Mortality was high. It seems that despite the fact
group, the data of those that received dialysis for the first time were analyzed.
that immune response of this population has not been clearly clarified, age,
RESULTS: In about 5% of patients renal replacement was inevitable, and the mortality
cormobidities and above all end-stage renal disease by its self is a significant and
rate among them reached 57.6%. The mean duration of renal therapy was 8.4 days. The
unpredictable risk factor for clinical outcome of HD patients with COVID-19
investigation of laboratory parameters in different stages revealed certain aspects about
infection.
the expected outcomes. The survival rate varied significantly in relation to the
indication for CRRT. Fluid overload and electrolytic disorders were associated with
high survival rate, while oliguria or anuria, acidosis or intoxications were linked to
increased mortality rate. MO863 COMPARISON OF ALL-CAUSE-MORTALITY BEFORE AND
CONCLUSION: Despite CRRT being associated with high mortality rates, it is the AFTER COVID-19 PANDEMIC IN A HEMODIALYSIS CENTER:
only option for life-threatening conditions in clinical practice. The indication for A SUCCESSFUL PREVENTIVE PROTOCOL
CRRT is a key factor for the prognosis, decision-making and the overall management
of a patient. Vahideh Yavari1
1
Dr. Yavari Nephrology Day Clinic, Branch of Research, Shiraz, Iran

BACKGROUND AND AIMS: COVID-19 has exerted a lot of pressure and concern
on Hemodialysis ward managers. Being successful in patient education and,
simultaneously, protecting the personnel and patients with in-time provision of
sanitation and prevention protocols are mandatory to survive the pandemic. The aim
of this study was to assess the success of our preventive measures in the dialysis center
after application of our self-developed protocols.
METHOD: Crude and age-adjusted mortality rates of two time frames, i.e. 4th January
to 5th December 2019 and the same period in 2020 (before and after the start of
pandemic) were compared. The data were processed with SPSS software version 26.
RESULTS: During 4th January to 5th December 2019, the crude all-cause-morality
rate of our hemodialysis center was 20.23% (51 out of 252 patients). Likewise, between
4th January 2020 to 5th December 2020, the crude all-cause-morality rate was 18.25%

10.1093/ndt/gfab098 | i479
Abstracts Nephrology Dialysis Transplantation

(46 out of 252 patients). Same result was yielded after age adjustment of the morality and Beck depression inventory (BDI) scores with LH, FSH in both the genders. In
rates. males there was positive correlation between SF 36 scores and testosterone level (r=
CONCLUSION: Tailoring effective and timely preventive measures along with tireless 0.366), and in females positive correlation between SF 36 score and progesterone level
education of patients can control all-cause-mortality and possibly COVID-19 excess in women HD patients (r= 0.549) was seen. There was a negative correlation between
mortality rates in dialysis centers. BDI score and progesterone level in women (r=0. -510) and negative correlation
It seems that our preventive protocols which included strict patient and personnel between BDI score and testosterone in men (r= -0.371).
screening, early referral to infectious specialist, clear isolation-sanitation protocols of CONCLUSION: QOL as assessed by SF 36 in patients on HD is low. There was
COVID-19 positive cases and repeated patient and personnel education have been positive correlation between SF 36 scores and testosterone level in males and between
successful in surviving the pandemic till present. SF 36 score and progesterone in females.

MO864 PATIENT MEDICATION ADHERENCE ON HEMODIALYSIS MO866 SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR
RECEPTOR AND COVID-19 INFECTION IN HEMODIALYSIS
Marwa Omrane1, Amel Babchia1, Raja Jaballah1, Afef Mahersia1, Olfa Saidane1 PATIENTS
1
Regional hospital of Ben Arous, Hemodialysis, Ben Arous, Tunisia
Ioannis Griveas1, Antonis Schinas1, Anthoula Balitsari1,
Gerasimos Asimakopoulos1, Evangelos Pratilas1
BACKGROUND AND AIMS: Non-adherence to treatment is a major problem in 1
Army Share Fund Hospital 417 (NIMTS), Nephrology, Athens, Greece
patients with end stage renal disease and contributes to the significant increase in
morbidity, mortality and health costs.
METHOD: The objective of this work was to assess adherence to treatment BACKGROUND AND AIMS: Soluble urokinase plasminogen receptor (suPAR) is a
prescriptions protein in the blood that has been described to reflect the severity status of systemic
for hemodialysis patients and to identify the predictive factors of poor compliance. inflammation. At the same time an elevated level of suPAR has been independently
This is a cross-sectional study of 59 patients on chronic hemodialysis. Adherence to associated with incident chronic kidney disease. We investigated the association
treatment was evaluated by the adherence assessment test. between admission suPAR levels and severity and outcome of Hemodialysis (HD)
RESULTS: The mean age of our patients was 51.8 years, with an M/F sex ratio of 1.26. patients with Covid-19 infection.
The socio-economic level was considered low in 83% of cases. The mean duration of METHOD: In an observational study of adult HD patients hospitalized for Covid-19,
hemodialysis was 81.6 months [6 months-252 months]. Causal nephropathy was we measured suPAR levels in plasma samples. The time table for those measurements
dominated by vascular nephropathy (13 cases). Forty-two patients had high blood were as follows: at the beginning of admission, after hemoperfusion (HP) session for
pressure. A total of 23.9% of patients were good observers, 59.5% had minimal those patients that received them, and just before discharge.
compliance problems, and 16.7% were poor observers. Statistical analysis has shown RESULTS: Of the 17 patients (7 were male), 13 patients received HP (mean age: 74
that poor adherence to treatment is associated with male gender, low socioeconomic years old). The median suPAR level was 12.94 ng/ml. For those who undertook HP
and intellectual level, the presence of comorbidities, increased medication, number of median suPAR level was 10.55 ng/ml at the end of each session (p=NS). 3 patients had
medications taken per day, and less knowledge of the pathology and risks as side effects suPAR level below 7 ng/ml. 2 of them survived without developing pleural effusions. 7
of drugs. patients discharged from the hospital with median suPAR level 12.94 ng/ml which did
CONCLUSION: Treatment adherence is unsatisfactory in our population of patients not differ significantly from the median suPAR level of the diceased ones (13.68 ng/
on maintenance hemodialysis. Therapeutic education targeting the expected benefit of ml).
the treatments, their mode of action, their side effects as well as a simplification of the CONCLUSION: Admission of suPAR levels in HD patients hospitalized for Covid-19
intake would improve long-term adherence in patients. do not seem to be predictive for their clinical course in general. Chronic Kidney
Disease backround and its relation to suPAR levels independently of patients’
inflammation status may be the key component for our notice. Despite that, in patients
where low levels of suPAR combined with absence of pleural effusions the prognosis
MO865 SEX HORMONAL PROFILE OF PATIENTS ON MAINTENANCE was excellent.
HEMODIALYSIS AND CORRELATION WITH QUALITY OF LIFE
AND DEPRESSION: A CROSS-SECTIONAL STUDY FROM
SOUTH INDIA
MO867 THE SIGNIFICANCE OF THE MEAN PLATELET VOLUME AS A
Muzamil Latief1, Manzoor Parry2, Farhat Abbas3, Manjusha Yadla4 BIOMARKER IN HEMODIALYSIS PATIENTS
1
Government medical college Srinagar, Nephrology, Srinagar, India, 2Sheri Kashmir Abdulla Al-Sayyari1
institute of medical sciences, Nephrology, Srinagar, India, 3Government medical college 1
Srinagar, Pathology, Srinagar, India and 4Government medical college and hospital, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Secunderabad, Nephrology, Hyderabad, India
BACKGROUND AND AIMS: The mean platelet volume was found to be an
BACKGROUND AND AIMS: Hormonal abnormalities in haemodialysis (HD) important biomarker in certain medical conditions. We evaluate its significance in
patients contribute to quality of life including sexual dysfunction. Whereas Short Form patients on chronic hemodialysis
36 (SF 36) questionnaire deals with the holistic assessment of the quality of life in METHOD: Adult stable patients on chronic hemodialysis for at least six months were
patients, it is directly impacted by sexual dysfunction or erectile dysfunction in males. included. MPV together with certain demographic ( age, sex, BMI, dialysis vintage,
In this study we assessed the sex hormone levels in HD patients and its correlation with cause of CKD, medication taken, mode of dialysis, type of vascular access) and
quality of life (QOL). laboratory parameters (Hb, albumin, Kt/V, PTH, CRP serum lipids) were measured
METHOD: In this single center cross-sectional study, 100 patients (50 males and 50 and recorded
females) on maintenance HD for more than 6 months were included in the study. In The correlation between these parameters and MPV was evaluated using Pearson
female patients’ sex hormones that included Luteinizing Hormone (LH), Follicle correlation coefficient and the MPV in the absence or presence of the demographic
Stimulating Hormone (FSH), Prolactin, Estrogen, Progesterone was assessed in parameters was calculated independent t test
midweek early morning blood sample. In male patients LH, FSH and Testosterone RESULTS: One hundred and twenty- three patients were studied. The mean age was
were assessed in midweek early morning samples. QOL assessment was done using SF 60.06 18.4 and 48.7% were male and diabetes was the cause of CKD in 56.3% ; 72.6%
36 questionnaire. were on hemodialysis and 27.4% on hemodiafiltration , 52.1% used AV fistula and
RESULTS: Mean age of our study populations was 33.76þ/- 7.86 years with male 47.9% used permcath as vascular access; 50.9% were on aspirin Comparing the mean
female ratio of 1:1 and mean body mass index of 20.52 6 2.89 kg/m2. Presumed MPV above and below the 50th percentiles in different parameters revealed no
chronic interstitial nephritis in was the most common cause of end-stage renal disease significant differences. No significant correlation was found between MPV and
(76%) in our study followed by Diabetic Kidney disease (21%). In males, mean serum duration on dialysis, age, weight, BM, erythropoietin dose per week, PTH, hemoglobin,
LH, FSH and Testosterone were 8.58 6 3.56 mIU/ml, 8.9 6 4.05, 217.46 6 96.44 ng/dl albumin, CRP, number of admissions in the preceding year yea, LDL or HDL. However
respectively with 70% patients having testosterone deficiency. In females, mean serum , there was a mild positive correlation with triglyceride level (Pearson coefficient = 0.2
LH, FSH, Prolactin, estrogen and Progesterone levels were 8.616 3.86 mIU/ml, 8.08 6 (P=0.02).
3.70 mIU/ml, 12.35 6 5.70 ng/ml, 84.56 6 27.39 pg/ml and 0.31 6 0.22ng/ml CONCLUSION: No significant correlation or association was found between the MPV
respectively. Mean SF 36 score in our study was 55.37þ/-12.22, in males 54.82þ/-12.81 and any of the clinical demographic or laboratory parameter measured except that
and in females 55.93þ/-11.70. The prevalence depression was 53% (50% in males and there was a mild positive correlation with triglyceride level.
56% in females) in our study. There was no significant correlation between SF 36 scores

i480 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO868 CLINICAL OUTCOMES FOR INTRAVENOUS DRUG USERS MO869  DE COVID-
IMPACTO DE LA SEGUNDA OLA DE INFECCION
REQUIRING HAEMODIALYSIS 
19 EN PACIENTES DE HEMODIALISIS EXTREMADURA
~
(ESPANA)
Katy Burns1, Durga Kanigicherla1,2, Patrick Hamilton1,2,3
1
Manchester Institute of Nephrology and Transplantation, Manchester University NHS Rosa Marıa Ruiz Calero Cendrero1, Marıa Victoria Martın Hidalgo Barquero1,
Foundation Trust, Manchester, United Kingdom, 2Manchester Academic Health Science Eva Vazquez Leo1, Marıa Antonia Ferna ndez Solıs2, Marıa Cruz Cid Parra3,
Centre (MAHSC), The University of Manchester, Manchester, United Kingdom and OlgaMaria Sanchez4, Silvia Gonz-lez Sanchidria n5, Miguel Angel Su arez
3
Wellcome Centre for Cell-Matrix Research, Division of Cell Matrix Biology and Santisteban6, Javier Deira Lorenzo5, Nicola s Roberto Robles Pérez1
1
Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Infanta Cristina Hospital, Badajoz, Spain, 2Fresenius Medical Care, Villanueva de la
Health, The University of Manchester, Manchester, United Kingdom Serena, Spain, 3Fresenius Medical Care, BADAJOZ, Spain, 4Fresenius Medical Care -
Centro de dialisis, Mérida, Spain, 5Hospital Universitario de C
aceres, C
aceres, Spain and
6
BACKGROUND AND AIMS: Intravenous drug users (IVDU) face significant Hospital Virgen Del Puerto Plasencia, Plasencia, Spain
challenges when requiring long-term therapies such as dialysis and pose management
dilemma to clinicians. Many patients present late, complicated by erratic lifestyles and BACKGROUND AND AIMS: Hemodialysis patients are high-risk patients for severe
complex mental health needs, often requiring urgent renal replacement therapy (RRT). forms of SARS-Cov 2. Extremadura has two provinces Badajoz(B) and Caceres(C) with
Decisions regarding modality can be difficult due to the lack of evidence for outcomes one million of people. The incidence was small in the first part of the pandemic (2,6%)
in this cohort. We investigated the clinical outcomes of patients with history of IVDU compared with the national incidence, and it was higher in C than in B (5,6% vs 1,1%)
in our service who presented with ESRD. The aim of this study was to estimate the incidence of COVID-19 disease in the
METHOD: A single-centre retrospective analysis of ESRD patients with a background population of Extremadura’s hemodialysis patients and to study the clinical evolution,
of IVDU. Incidence of hospital and ICU admission, length of stay and frequency of treatment and mortality in patients with confirmed infection with Polymerase chain
culture positive sepsis following the initiation of RRT were investigated. Primary reaction(PCR) during the second wave.
outcome was days admitted versus days spent in the community, frequency of life- METHOD: Multicenter, retrospective, observational study of hemodialysis patients
threatening sepsis and tunnelled catheter replacement. Data was collected from the with COVID-19 disease between August and December of 2020. There were 683
date of first RRT (earliest April 2015 and latest November 2019) to last follow-up in hemodialysis patients in this period distributed in 5 hospital units and 7 out of hospital
September 2020 or patient death. An admission was included when the patient was Units.
admitted for at least an overnight stay in hospital. Admission days calculated do not RESULTS: Incidence: 6,8% (46 infected of SARS-Cov 2), with almost one patient in
include attendance for outpatient haemodialysis. Bacteraemia’s were included when a each center (the highest with 16,1%) and higher incidence in B than in C (8,1% vs
report confirming a positive culture associated with clinical features of infection; paired 4,1%). Males (58,7%), media age, (69,3611,9) and median renal replacement therapy
samples were counted as a single episode. time 29 months (RIC 47,4). The most frequent CKD was diabetic nephropathy (16%),
RESULTS: Six patients initiated RRT during the study period and included four males but 35% of the patients have diabetes, 86% hypertension and 56% cardiovascular
and two females. Mean age of 46.6 years (32-54 years). Cause of ESRD was Amyloid illness. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II
AA in 5) and IgA nephropathy in 1). Mean follow-up was 677 days till censor (range receptor blockers 40% and with vitamin D 62,8%. There were 42% patients who had
313 to 932 days). There was an average of nine inpatient admissions (range 3 to 17) contacted with positive people of hemodialysis unit and 37% with positive people
averaging 280 inpatient days (range 29 to 637 days) across the cohort. At last follow- outside. 67% have symptoms: the most frequent cough and fever (46%). Hospitalized
up, three patients died with an average time to death of 833 days from initiation of RRT patients: 41,6%, all of them with bilateral pneumonia. All had lymphocytopenia and
(range 664 to 932 days). Four patients required at least one admission to the Intensive high acute phase reactants: D -dimer 1195 ng/ml (RIC 1545), Ferritin 950,12ng/ml
Care Unit (ITU) with an average length of stay of 10.3 days (range 1 to 47 days). All (RIC 533,6) IL-6 30,11pg/ml (RIC 41,13) C-reactive protein 28 mg/l (RIC 62,10)
patients experienced at least two episodes of culture positive sepsis with a total of 72 Procalcitonin 0,42 ng/ml (RIC 0,44), all increased in the hospitalized period without
bacteraemia’s across the cohort (range 2 to 41). Four patients required tunnelled significant differences. Median hospitalized time was 10 days (RIC 11). Nine patients
catheter replacement ranging from 2 to 7 catheters. Results are summarised in Table 1. died (19,5%), 3 of them in intensive unit care with 15 days median. Most of them
CONCLUSION: IVDU patients represent a challenging patient population to manage needed antibiotic therapy, steroids and anticoagulation, 5 convalescent plasma and 5
with limited options available for RRT. This study highlights these difficulties tocilizumab. We stopped isolated room dialysis when they had negative PCR (56%) or
particularly with the use of tunnelled catheters for haemodialysis. Our results indicate IgG positive (54%), median insulation 17 days (RIC 7). We havent found differences in
RRT in IVDUs is associated with frequent and prolonged hospital stays with multiple hospitalized vs no hospitalized patients in age, gender, renal replacement therapy time,
bacteraemia’s, ICU admissions and significant mortality. Clinicians are faced with a etiology, DM, hypertension or cardiovascular illness and treatment, nor in relation
significant ethical dilemma as tunnelled catheters represent both a lifeline for with mortality.
continued survival and a perfect access to recreational drugs. If patients are to be CONCLUSION: We have observed an increase in the incidence of infection in this
offered haemodialysis via tunnelled access, more intensive and earlier multidisciplinary period compared with the first period of the pandemic, parallel to the increases in the
planning and counselling needs to be employed to ensure patients are aware of the incidence of the general population in Extremadura (more in B than in C). The
significance of the associated risks. Psychological therapy and social care input would mortality is high but similar to other publications. We have to do screening due to the
be essential to help reduce morbidity and mortality. possibility of asymptomatic patients that could have contributed to expand the
infection. The high number of hospitalized patients and the need of isolated rooms
dialysis for infections patients is a challenge for the organization of hemodialysis units
but having positive serologic reduce the isolation time.

MO870 HYPOCHLOREMIA IS ASSOCIATED WITH A GREATER


INCIDENCE OF PNEUMONIA IN CHRONIC HEMODIALYSIS
PATIENTS WITH COVID-19: A CENTER’S EXPERIENCE

Francisco Valga1,2, Tania Monzon3, Nicanor Vega-Diaz1,2,


Sergio Ruiz-Santana2,4, Rassoul Diallo-Saavedra5, Sara Aladro1,
Jose Carlos De la Flor6, Jose Carlos Rodriguez-Perez1,2
1
Gran Canaria Dr. Negrin University Hospital, Nephrology, Las Palmas de Gran Canaria,
Spain, 2University of Las Palmas de Gran Canaria, Doctoral School. Biomedicine
Research Program, Las Palmas de Gran Canaria, Spain, 3Avericum S.L Dialysis Centers,
Las Palmas de Gran Canaria, Spain, 4Gran Canaria Dr. Negrin University Hospital,
Intensive Care Unit, Las Palmas de Gran Canaria, Spain, 5Gran Canaria Dr. Negrin
University Hospital, Anesthesiology, Las Palmas de Gran Canaria, Spain and 6Central
Defense Gomez Ulla Hospital, Nephrology, Madrid, Spain

BACKGROUND AND AIMS: Recently, serum chloride has gained greater


importance in the assessment of patients with heart failure and sepsis. Hypochloremia
has been associated with higher mortality. On the other hand, COVID-19 pandemic
continues to be, to date, a threat to public health. Patients with cardiovascular
comorbidity or chronic kidney disease are particularly vulnerable. There are some
studies that show a trend towards a lower serum chloride concentration in patients
with a positive PCR test for SARS-CoV-2. Therefore, the objective of our study was to
determine if there is a relationship between serum chloride levels at the time of
diagnosis and a greater tendency to develop COVID-19 pneumonia in chronic
hemodialysis patients.
METHOD: Retrospective cohort study. We analyzed the serum chloride, C-reactive
protein (CRP), procalcitonin, neutrophil-lymphocyte (NLR) and platelet-lymphocyte

10.1093/ndt/gfab098 | i481
Abstracts Nephrology Dialysis Transplantation

(PLR) ratios of 11 chronic hemodialysis patients with a positive SARS-CoV-2 TMA administration. In addition to heparin withdrawal and treatment with alternative non-
PCR test during the second wave of the pandemic in our hospital (August-December heparin anticoagulation (fondaparinoux), 7 patients needed plasma treatment. 11
2020). We collected the length of hospital stay, the diagnosis of pneumonia (yes/no) patients on HD were transferred to peritoneal dialysis (PD), and 3 patients recovered
and the final state of the infection (cure or death). The patients were divided into two renal function. Overall mortality was 52%, and it was below 30% in hemodialysis
groups taking the median serum chloride as the cut-off point (1: <97 mEq / L and 2:> patients.
97mEq / L) CONCLUSION: HIT should be considered in patients at risk. It is necessary to abolish
RESULTS: The mean age was 57 6 13 years and 36.36% (N = 4) were women. All heparin treatment and use alternative method (PD) or alternative anticoagulation.
patients required hospital admission and mean hospitalization time was 19 6 13 days. Hemodialysis patients have better prognosis than other comparable patients
3 patients (27.3%) died. The medians of the parameters were the following: serum
chloride 97 mEq / L (IQR 94-99); CRP 29.04 mg / L (IQR 8.53-76.13); NLR 4.13 (IQR
2.67-8.48) and PLR 244.06 (IQR 208.08-320). 81.8% (N = 9) had COVID-19
MO872 INFLUENCE OF SARS-COV-2 INFECTION ON MORTALITY IN
pneumonia. Group 1 patients (Chloride <97 mEL / L) had a higher incidence of
PATIENTS UNDER RENAL SUBSTITUTE TREATMENT
pneumonia (p = 0.049) (Figure 1) and a greater tendency to be admitted to the
Intensive Care Unit (ICU) (p = 0.029). Despite not reaching statistical significance,
Guillermo Ferrer Garcıa1, Luis Guillermo Piccone Saponara1, Patricia Sanchez
there was also a higher mortality in patients with lower chloride levels.
Escudero1, Maria Paz Castro Ferna ndez1, Nancy Giovanna Uribe Heredia2,
Eliana Olazo Gutierrez1, Agustın Carren ~o Parrilla1, Sara Anaya Fernandez1,
Gloria Garcıa Conejo1, Marina Ugarte Camara1, Carmen Vozmediano Poyatos1
1
Hospital General Universitario Ciudad Real, Nephrology, Ciudad Real, Spain and
2
Hospital Universitario Guadalajara, Cardiology, Guadalajara, Spain

BACKGROUND AND AIMS: Dialysis patients constitute a risk group for


coronavirus infection due to their immunosuppressed condition, with the increased
risk of morbidity and mortality that this entails. We analyzed the factors associated
with mortality from coronavirus infection in a cohort of patients undergoing renal
replacement therapy at our center.
METHOD: Transversal study. We included patients in renal replacement therapy
(RRT) in our center. Demographic variables (age, sex), associated comorbidity, RRT
technique, clinical and laboratory parameters were collected. Statistical analysis with
SPSS 25.0. Categorical variables are expressed in percentages and are compared using
the Chi2 test. The quantitative variables are expressed as mean 6 standard deviation
and compared using Student’s T-test. Statistical significance p <0.05.
RESULTS: 38 patients, mean age 66 6 18 years, 51.4% men. 92.1% had arterial
hypertension, 39.5% diabetes mellitus (DM). 63.2% on hemodialysis, 2.6% peritoneal
dialysis, 34.2% transplanted. 84.2% presented fever, 63.2% cough, 73.7% pneumonia,
34.2% dyspnea, 15.8% digestive symptoms. 21.1% leukopenia, 73.7% lymphopenia,
money D 1509 6 1351, CRP 12.45 6 19.47, sodium 136 6 5.5. 81.% were admitted to
hospitalization, of which 2.6% required admission to the ICU. 44% died. Mortality was
statistically significantly related to DM (56.3% vs 43.8% p = 0.05), and with the need
for hospitalization (93.8 vs 6.3% p = 0.054).
MO870 Figure 1: Chloride levels and diagnosis of COVID-19 pneumonia in chronic CONCLUSION: In our experience, DM patients and those who required
hemodialysis patients hospitalization had a higher risk of mortality.

CONCLUSION: Chronic hemodialysis patients with SARS-CoV-2 infection and lower


serum chloride levels at hospital admission were more likely to develop pneumonia. MO873 THE STRUCTURE OF DEATH IN PATIENTS WITH ESRD ON
DIALYSIS

Olimkhon Sharapov1,2
MO871 HEPARIN INDUCED THROMBOCYTOPENIA AND 1
Tashkent Pediatric Medical Institute, Internal Disease, Tashkent, Uzbekistan and
HEMODIALYSIS - SINGLE CENTRE EXPERINCE 2
Republican Specialized Scientific Practical Medical Center of Nephrology and Kidney
transplantation, Nephrology, Tashkent, Uzbekistan
Ana Bulatovic1,2, Vesna Maslarevic Radovic1, Katarina Markovic3,
Jelena Bjedov1,2, Petar Djuric1, Aleksandar Jankovic1,2, Marina Paunovic4,
Tatjana Damjanovic1,2, Verica Stankovic Popovic1,2, Radomir Naumovic1, BACKGROUND AND AIMS: According to the ERA-EDTA, mortality from
Nada Dimkovic5 cardiovascular complications (CVC) among CKD patients on programmed
1 hemodialysis (HD) is about 30 times higher than in the same age groups in the general
Zvezdara University Medical Center, Nephrology and Dialysis, Beograd, Serbia,
2 population. More than 50% of deaths in patients with end-stage renal failure (ESRD)
University School of Medicine, Nephrology and Dialysis, Beograd, Serbia, 3Zvezdara
receiving renal replacement therapy are due to cardiovascular (CV) causes. The ratio of
University Medical Center, Hematology, Beograd, Serbia, 4Zvezdara University Medical
the remaining causes varies from country to country. In this regard, it is of interest to
Center, Laboratory Diagnostic, Beograd, Serbia and 5Medical Academy, Serbian
study the causes of death of patients with ESRD in Uzbekistan.
Medical Assosiation, Beograd, Serbia
METHOD: We prospectively followed the course of 200 patients with end-stage CKD
who received programmed hemodialysis in three different centers of the Republic of
BACKGROUND AND AIMS: Heparin-induced thrombocytopenia (HIT) is a Uzbekistan for 24 months (from January 2018 to January 2020). All patients received
potentially fatal adverse reaction after administration of unfractionated or fractionated hemodialysis according to the same scheme - 12 hours a week, through an
heparin, which underlies the generation of antibodies to the heparin complex and arteriovenous fistula in the forearm. During this period, 72 patients died (40 men and
platelet factor 4 (PF4). It occurs in 5% of patients treated with unfractionated heparin 32 women). The average age of the deceased was 53.6 6 1.6 years (M 6 m). The main
and 0.5 - 1.5% fractionated heparin. The aim of the study is to determine the incidence primary disease was chronic glomerulonephritis. It was 45.8% (n = 33) of all dialysis
and outcome of hemodialysis patients with HIT over 4-years period. patients. Diabetes mellitus ranked second - 27.8% (n = 20). Other causes were
METHOD: This retrospective study analyzed patients who were tested for evidence of urolithiasis - 9.7% (n = 7), pyelonephritis - 5.6% (n = 4), ADPKD - 4.2% (n = 3),
positive anti-heparin antibody in the period from 2015 to 2020 in Zvezdara University vasculitis - 4.2% (n = 3 ), lupus - 2.7% (n = 2). To identify the cause of death, the
Medical Center. The diagnosis was confirmed by the 4T clinical scoring system, a medical history and the results of the pathological examination were analyzed.
positive antiheparin-PF4 ELISA test and a positive platelet aggregation test with RESULTS: Among the deceased, 68.1% (n = 49) of patients had cardiovascular diseases
heparin. in their medical records, while 31.9% (n = 23) did not have CVD. 43.1% (n = 31) of
RESULTS: During observation period, total of 64 tests were performed, out of which patients died during the first year of follow-up, the remaining 56.9% (n = 41) died
23 patients were positive. Out of them, 14 patients were on HD, 7 patients (geriatric, within 2 years. The main cause of death of patients was sudden cardiac death, which
surgery and cardiology departments) received therapy due to peripheral thrombosis, accounted for 61.1% (n = 44) of all deaths. 18.1% (n = 13) of patients died as a result of
AIM or arrhythmia and 2 patients during 2020 due to SARS-CoV-2 bilateral acute respiratory failure. In 6.9% (n = 5) cases, the cause of death was acute myocardial
pneumonia. All patients treated at nephrology, started hemodialysis (HD) with infarction. Death due to hepatic coma and stroke accounted for 5.6% (n = 4) of patients
unfractionated heparin, while others were treated with LMWH. 4T scoring showed who died. 2 (2.7%) patients died as a result of acute bleeding(figure 1).
that 64% of patients had a moderate risk of developing HIT, while high risk was
assessed in 36% of patients. Thrombotic complications in the form of deep venous
thrombosis had 53% of patients and pulmonary thromboembolism had 17,5 % of
patients. The greatest decrease in Tr was the most commonly observed between 10th
and 14th day (61% of patients) and 39% from 4th to 10th day from start of heparin

i482 | Abstracts
Nephrology Dialysis Transplantation Abstracts
We report throw this work the experience of our unit of HD with the covid-19
infection and its outcomes on our patients.
METHOD: We conducted a prospective study since the beginning of the pandemic.
We have collected 26 HD patients reached of COVID 19 disease.
RESULTS: The sex ratio of our population was equal to 1,36 with female
predominance. The mean age of our patients was 61, 31 614,17 years. The co-
morbidities noted among these patients were respectively hypertension, diabetes, heart
diseases and obesity in 19, 17, 10 and 10 cases. The causal nephropathy was
respectively diabetic, undetermined, glomerular and interstitial nephropathy in 13, 9, 2
and 2 cases. The major symptoms associated to the COVID 19 were respectively
dyspnea, cough, asthenia, fever and chills, digestive manifestations, chest pain in 22, 19,
19, 15, 10, and 6 cases. 7 patients have been exposed to covid-19 infested person.
Symptoms appeared within an average of 4,3 6 2 days. Oxygen saturation was less
than 92% in 65% of the cases during hospitalization. 84% of the patients are
hospitalized including one among them who required the stay in a resuscitation unit
and intubation. The scannographic lesions of covid were estimated to more than 50%
in 8 cases and less than 50% in 4 cases. A biological inflammatory syndrome has been
noted in all of the patients with a mean CRP at 117þ/-127 mg/l and the mean
leucocytes count at 1024866592 elt/mm3. Lymphopenia was noted in 14 cases with
When analyzing the structure of death of the examined patients, depending on the lymphocytes count less than 1500 elt/mm3. The ratio of neutrophils / lymphocytes was
presence or absence of cardiovascular pathology, it was revealed that the main cause in more than 2,5 in 12 cases. The treatment was based on oxygen, corticosteroids,
both groups was also sudden cardiac death. But, at the same time, in patients with antibiotics, vitamins and anticoagulation for hospitalized patients (22 patients). The
CVD, sudden cardiac death was 63% (n = 30) of all causes of death, while in patients mean number of HD sessions realized per patient during hospitalization was 4 6 2,3
without CVD, it was 59% (n = 14) the cause of all deaths. Acute respiratory failure as a HD sessions. The perdialytic complications noted were alteration of the state of
cause of death was detected more in patients without CVD. 29% (n = 7) of patients consciousness in 3 cases and heart failure in 5 cases. The outcomes of our patients were
died from this complication, while in patients with CVD this indicator was 13% (n = marked by death in 38% and a recovery in 62% of the patients. Thus, the forms
6). All cases of acute myocardial infarction (n = 5) were observed in patients with CVD observed in our series are respectively moderate, severe, pauci-symptomatic and
(10%). Deaths due to stroke and coma were also more common in patients with asymptomatic in 12, 10, 2 and 2 cases.
CVD(figure 2). CONCLUSION: We highlight throw this study the severe consequences of COVID-19
on HD patients in whom mortality reached 38%. Until the pandemic is controlled and
a vaccine or a treatment are valid, we highlight the importance of the compliance with
confinement and develop home dialysis among our population.

MO875 SEROCONVERSION RATE AND PERSISTANCE OF IGG


RESPONSE TO SARS-COV2 IN HEMODIALYSIS PATIENTS. A
CASE SERIES STUDY

Nikolaos Tsikliras1, Aggelina Anagnostara2, Vasiliki Rekari3, Ilias Nikitidis3,


Apostolos Kyrgialanis2
1
General Hospital of Xanthi, Hemodialysis Unit, Xanthi, Greece, 2General Hospital of
Xanthi, Hemodialysis Unit, Xanthi, Greece and 3General Hospital of Xanthi, Blood
Donation Department, Xanthi, Greece

BACKGROUND AND AIMS: Higher incidence and worse outcome of coronavirus


disease (COVID-19) are observed in dialysis patients, mainly due to weak immune
CONCLUSION: According to our study, dialysis patients with CKD die mainly due to response. However, little is known about seroconversion ability and duration of
cardiovascular accidents (more than 80%). The main place in the structure of death is antibody response after COVID-19 in this group. The aim of this study was to estimate
taken by sudden cardiac death, which is the cause of death for more than 60% of the seroconversion rate and the persistence of IgG response to SARS-CoV2 in dialysis
deceased patients. Other causes were acute respiratory failure, acute myocardial patients.
infarction, coma, stroke, and acute bleeding. Patients who already had CVD more than METHOD: Four (4) dialysis patients previously infected with SARS-CoV2 were
2 times more often die from cardiovascular complications than patients who did not included in this study. Initially, all patients were tested for the presence of IgG
have CVD. antibodies 21-35 days after the onset of their symptoms. The cut-off value for positivity
was a ratio of  1.4. Those patients with at least two consecutive positive samples were
defined as seropositives. Seropositives were then having their antibodies tested monthly
for a maximum period of six months or until the first negative result. Duration of
MO874 COVID-19 IN HEMODIALYSIS PATIENTS: CLINICAL antibody persistence was defined as the time between the day IgG were last detected
PARTICULARITIES AND OUTCOMES and the day of onset of infection.
RESULTS: All four patients were seropositives after the initial test (seroconversion rate
Hanen Abid1,2, Salma Toumi1,2, Olfa Zini1, Amira Sai1, Ikram Agrebi1, = 100%) with a mean IgG ratio of 6.44 (61.28). Median follow up period was 128
Najla Dammak1,2, Hanen Chaker1,2, Mondher Masmoudi1,2, (range 96-193) days. Median duration of antibody persistence was 153 (range 103-193)
Khaoula Kammoun1,2, Soumaya Yaich1,2, Mohamed Ben Hmida1,2 days. By the sixth month, IgG had turned negative in two of four patients (rate = 50%).
1
Hedi Chaker Hospital, Nephrology department, Sfax, Tunisia and 2Faculty of Medicine CONCLUSION: In our study, dialysis patients showed a remarkable seroconversion
of Sfax, Renal Pathology Laboratory Lr19es11, Sfax, Tunisia rate after infection with SARS-CoV2. However, a rapid decline of IgG antibodies was
observed in half of them.
BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) has affected the
care and outcomes of patients treated with dialysis worldwide. Patients on
hemodialysis (HD) are at extremely high risk to develop COVID-19 because of their
multiple co-morbidities and immunosuppression.

10.1093/ndt/gfab098 | i483
Nephrology Dialysis Transplantation 36 (Supplement 1): i484–i493, 2021
10.1093/ndt/gfab100

DIALYSIS. HEALTH SERVICES RESEARCH

MO876 ESTIMATING THE BUDGET IMPACT OF DAPAGLIFLOZIN


FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE FROM
A UK PAYER PERSPECTIVE*

Oliver Darlington1, Phil McEwan1, Rebecca Boyce1, Gengshi Chen2,


Becky Martin2, Elisabeth Sörstadius2, Juan Jose Garcia Sanchez2, Naveen Rao2
1
Health Economics and Outcomes Research Ltd, Cardiff, United Kingdom and
2
AstraZeneca, Cambridge, United Kingdom

BACKGROUND AND AIMS: Chronic kidney disease (CKD) is a chronic and


progressive disease which imposes a significant burden on patients and healthcare
systems as the disease progresses, particularly in patients who reach end-stage kidney
disease (ESKD). Dapagliflozin was established to be an efficacious treatment for CKD
in the DAPA-CKD study, where it was associated with a significant reduction in the
incidence of CKD progression, ESKD, hospitalization for heart failure (HHF) and
MO876 Figure 1: Annual budget impact associated with the introduction of
death in comparison with standard care alone. A vital component of a new treatment’s
dapagliflozin for the treatment of CKD
health economic evaluation is to assess its potential budget impact, particularly in
conditions with high prevalence in the general population such as CKD. As such, this
study’s objective was to estimate the budget impact of introducing dapagliflozin for the
treatment of CKD in the UK from an NHS perspective.
METHOD: A model was developed to estimate the three-year budget impact of the
introduction of dapagliflozin in addition to standard care (angiotensin-converting
enzyme inhibitors and angiotensin II receptor blockers) vs. standard care alone for the MO877 PREVALENCE AND PERSISTENCE OF COVID-19
treatment of CKD in the UK. The size of the eligible patient population was estimated ANTIBODIES IN NEW YORK CITY HEMODIALYSIS CLINIC
based on overall CKD prevalence, and the proportion of all CKD patients who would
have been eligible for inclusion in DAPA-CKD. In total, 929,000 patients were Ohnmar Thwin1, Nadja Grobe1, Xiaoling (Janice) Ye1, Priscila Preciado Rojas1,
estimated to be eligible for treatment with dapagliflozin in the UK. The analysis Leticia M Tapia Silva1, Peter Kotanko1
1
assumed that 5% of CKD patients would receive treatment with dapagliflozin in the Renal Research Institute, Clinical Research, New York, United States of America
first year, increasing to 15% in the second year and 20% in the third year. The relative
market share of individual components of background standard care was assumed to BACKGROUND AND AIMS: Dialysis patients are at higher risk for severe acute
remain constant over time, with the distribution informed by the baseline respiratory syndrome coronavirus (SARS-CoV-2) infection. Longevity of antibody
characteristics from DAPA-CKD. Event rates from DAPA-CKD were used to predict response to SARS-CoV-2 infection remains unclear. It is reported that maintenance
the incidence of CKD progression (50% decline in estimated glomerular filtration hemodialysis (MHD) patients can mount an antibody response that is similar in
rate), ESKD, HHF, acute kidney injury, hyperkalaemia and death to estimate cost- intensity and timing to the non-dialysis population. We aim to investigate the
offsets associated with reduced event incidence. Published event and drug acquisition prevalence and persistence of antibodies in hemodialysis patients.
costs were applied to the incidence of modelled events. METHOD: We measured IgG and IgM antibodies in MHD patients as part of a quality
RESULTS: The introduction of dapagliflozin was estimated to reduce total three-year improvement project. Four New York City dialysis clinics participated in this study.
costs associated with CKD management by £114.0M, from £6.6B to £6.5B in the Strict policy of RT-PCR testing was implemented in clinics for patients with signs and
patient population eligible for treatment with dapagliflozin. Cost-savings were driven symptoms of Coronavirus Disease 2019 (COVID-19). Initial antibody testing was done
by a reduction in the incidence of CKD progression events (122.7K vs. 130.5K with and on June 10 and July 13, 2020 (phase 1) and retesting was done for previously positive
without the introduction of dapagliflozin, respectively), ESKD (99.2K vs. 103.8K) and patients between December 9 and 17, 2020 (phase 2). Upon obtaining verbal consent,
HHF (44.2K vs. 41.3K) over a three-year time horizon. Cumulative three-year drug 3.5 ml of pre-dialysis blood samples were taken via vascular access. SARS-CoV-2
acquisition costs were estimated to increase by £177.4M following the introduction of antibodies were determined using the emergency use authorized Diazyme DZ-Lite
dapagliflozin when used in addition to standard care. However, the cumulative cost- SARS-CoV-2 IgM / IgG CLIA assays with 100% sensitivity and 98% specificity.
offsets associated with reduced incidence of clinical events was £291.3M over the three- Detection of formed immune-complexes is achieved with N-(4-amino-butyl)-N-ethyl-
year model time horizon, with reduced incidence of ESKD resulting in the largest cost- isoluminol; the luminescence signal is reported as units per ml (AU/ml), values  1.00
saving (£4.8B vs. £5.0B). AU/ml are considered as “reactive” and < 1.00 AU/ml as “non-reactive.”
CONCLUSION: The introduction of dapagliflozin for the treatment of CKD is RESULTS: A total of 429 MHD patients were studied in phase 1. Antibodies were
estimated to be cost-saving over a three-year horizon in comparison with standard present in 130 (30.3%) and only 55 patients with Covid-19 diagnosis confirmed by RT-
care, even when considering additional drug acquisition costs. Dapagliflozin has the PCR test were reactive for IgG antibodies. The time to antibody testing was 73 days
potential to significantly ameliorate the clinical and economic burden imposed by CKD (median 77; range 30-111) days. In the phase 2 antibody testing, IgG antibodies were
on patients and the NHS. only detected in 47 patients (85.5%) 242 days (median 245, range 204 to 268) after
clinical diagnosis of Covid-19. Between the two phases of antibody testing, the
luminescence signal declined by 40.9 AU/mL (95% confidence interval 31.5 to 50.3)
from 54.1645.3 to 13.2620.9 AU/mL (P<0.0001 by paired t-test; Figure 1). In
univariate logistic regression, a higher number of days between clinical diagnosis of
COVID-19 and the second antibody measurement was associated with a lower
seropositivity rate (odds ratio 0.929, 95% confidence interval 0.864 to 0.998, P=0.044).
Antibody persistence was not associated with age, gender, race, and ethnicity.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
antianemic preparations whereas GPs prescribed more frequently analgesics and drugs
used in diabetes), they also had similarities (frequencies of beta blocking agents,
calcium channel blockers and lipid modifying agents).
Similarly, the interviews highlighted that despite the unique technical nature of a large
part of nephrologists’ practice (nephropathy aetiology, dialysis and kidney
transplantation, nephrotoxicity) another part was similar to GPs’, including the long-
term holistic care of patients with multiple comorbidities as well as diet and lifestyle
advices. This appears to blur the perimeter of the role of each professionals regarding
CKD care and favours an increased presence of nephrologists, as suggested by the
quantitative prescription analysis. In turn, as interviews revealed, some GPs expressed
a fear of losing their patients and regretted a decreased communication from
specialists. Nephrologists’ description of the role of GPs ranged from a strict addressor
to nephrologists, to an intermediary support to reduce uncertainties, to a constant
partner with transfer of therapeutic objectives.
CONCLUSION: Combining the crossed point of view of GPs and nephrologists and
robust prescription data, this study highlights an overlap in the roles and practices and
suggests a competition in the control of therapeutic strategies that might hinder an
optimal care trajectory for patients. Development of integrated renal care network
could address these obstacles

MO877 Figure 1: Quantitative change of IgG antibodies over time.


The antibody tests were done on average 171 days (range 154 to 189) apart. The
quantitative luminescence signal declined by 40.9 AU/mL (95% confidence interval
31.5 to 50.3) from 54.1645.3 to 13.2620.9 AU/mL (P<0.0001 by paired t-test).

CONCLUSION: We observed that about 6 out of 7 MHD patients maintain SARS-


CoV-2 antibodies over 6-9 months but there is a significant decline of IgG level. The
time between clinical diagnosis and IgG testing was associated with IgG decline. Follow
up study to understand antibody dynamics in MHD population is a crucial step once
vaccines become available.

MO878 THE DYNAMICS OF THE COLLABORATION BETWEEN MO878 Figure 1: Total number of drug prescription for 2015 incident dialysis patients
GENRAL PRACTITIONER AND NEPHROLOGIST DURING in France (N=8679)
PRE-DIALYSIS CARE: A MIXED METHOD STUDY

Maxime Raffray1, Cécile Vigneau2, Cécile Couchoud3, Campeon Arnaud4,


Laetitia Laude5, Sahar Bayat1
1
Univ Rennes, EHESP (French School of Public Health), REPERES (Recherche en phar-
maco-épidémiologie et recours aux soins) – EA 7449, RENNES, France, 2Univ Rennes, MO879 PROPOSAL OF A GERIATRIC ASSESSMENT TAILORED FOR
Inserm, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, OLDER CHRONIC KIDNEY DISEASE PATIENTS: RESULTS OF
CHU Pontchaillou, service de néphrologie, RENNES, France, 3REIN Registry, Biomedecine A PRAGMATIC CONSENSUS-BASED APPROACH
Agency, Saint-Denis-La-Plaine, France, 4EHESP, Arènes, CNRS, UMR 6051, Rennes,
France and 5EHESP, Health Organizations Management (MOS)-EA 7348, Rennes, France Carlijn Voorend1, Hanneke Joosten2, Noeleen Berkhout-Byrne1,
Adry Diepenbroek3, Casper Franssen3, Willem Jan W. Bos1, Marjolijn Van Buren1,
Simon Mooijaart1
BACKGROUND AND AIMS: Nephrologists and General Practitioners (GP) are 1
critical in the care trajectory of patients with CKD through the medical work they Leiden University Medical Center (LUMC), Leiden, Netherlands, 2Mumc+, Maastricht,
provide: screening, referral, follow-up, slowing down CKD progression and renal Netherlands and 3University Medical Center Groningen, Groningen, Netherlands
replacement therapy preparation. They often intervene simultaneously in a
collaborative context. Several guidelines define this medical work and collaborative BACKGROUND AND AIMS: Unidentified cognitive decline and other geriatric
care models. However, evidence suggests that the implementation of such models is impairments are prevalent in older patients with advanced kidney disease. Despite
limited and suboptimal. For example, 18% of patients who started dialysis in 2018 in guideline recommendation of geriatric evaluation, routine geriatric assessment is not
France did not see a nephrologist before.The objectives of this study were 1) to common in these patients. While high burden of vascular disease and existing pre-
quantitatively describe the practices of both French nephrologists and GPs through dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on
drug and biology lab test prescriptions for patients with CKD and its evolution before which instruments are most suitable in this population to identify geriatric
and after dialysis start, 2) to qualitatively describe how they see each other’s role and impairments. Therefore, the aim of this study was to propose a geriatric assessment,
from this 3) identify the factors interfering with optimal care trajectory based on multidisciplinary consensus, for older people with advanced chronic kidney
METHOD: All incident 2015 dialysis patients from France were identified using the disease.
national REIN registry. Healthcare consumption of those patients 2 years before and 1 METHOD: A pragmatic approach was chosen to reach agreement on a suitable set of
year after dialysis start was retrieved from the French national health insurance instruments to routinely identify major geriatric impairments in older patients with
database (SNDS) via indirect record linkage. The items of interest were drug and lab advanced chronic kidney disease. This approach included focus group meetings to
test prescriptions as well as the prescriber medical specialty. Prescription frequencies identify criteria for the assessment, literature review to identify potential instruments,
and percentages per months and per prescriber specialty were reported. Anatomical questionnaire to inventory currently used instruments, an expert consensus meeting to
Therapeutic Chemical (ATC) classification level 2 was used for drugs. Semi-structured ensure that the selection of tests was based on input from clinical experience in
interviews with general practitioners and nephrologists exploring their practices nephrology and geriatrics, and pilot testing to ensure practicability. In preparation of
surrounding CKD care were performed in a sample from the Bretagne region. the consensus meeting we composed a project team and an expert panel (n=33),
Thematic analysis was performed on the transcripts. drafted selection criteria for the selection of instruments, and assessed potential
RESULTS: A total of 2 263 935 drug prescriptions were found for 8679 patients who instruments for the test-set.
started dialysis in 2015 in France in the span of 2 years before and 1 year after dialysis RESULTS: Selection criteria related to general geriatric domains, clinical relevance,
start. The place of each professional changed through time: drug prescribed by GPs feasibility and duration of the assessment. The consensus-set contains instruments in
decreased from 83.6% of the total during the 2 years before dialysis start to 62.6% functional, cognitive, psychological, somatic, patient preferences, nutritional status,
during the year following dialysis start. Nephrologist’s place increased from 4.9% of the and social domains (Figure 1). Administration of (seven) patient questionnaires and
total prescriptions to 21%. Although GPs and nephrologists had differences between (ten) professional-administered instruments, by nurse (practitioners), takes estimated
the drugs they prescribe (nephrologists prescribed more frequently vitamins and 20 and 40 minutes, respectively. Results are discussed in a multi-disciplinary meeting

10.1093/ndt/gfab100 | i485
Abstracts Nephrology Dialysis Transplantation

including at least nephrology and geriatric expertise, informing nephrology treatment CI 0.47 to 0.91; p=0.01) see Table 2. Main cause of hospitalization was cardio-
decisions and follow-up interventions amongst which comprehensive geriatric cerebrovascular (Table 3). We observed no differences in hospitalization duration or
assessment. survival.

MO879 Figure 1: Abbreviations: P, patient; I, interviewer; C, clinician; CG, caregiver;


SPICC, Self-perceived pressure from informal care; PROMS, patient-reported outcome
measures.

CONCLUSION: This first multi-disciplinary consensus on nephrology-tailored


geriatric assessment intent to benefit clinical care and enhance research comparability
for older patients with advanced chronic kidney disease. The proposed geriatric
assessment is currently implemented in multiple hospitals and studies. Future
initiatives and studies should provide insights on effectiveness, feasibility, patient’s
satisfaction and, value for shared treatment decision making and outcome
improvement.

MO880 EFFECTIVENESS OF MEDIUM CUT-OFF VS HIGH FLUX


DIALYZERS: A PROPENSITY SCORE MATCHING COHORT
STUDY

Alejandra Molano-Trivin ~o1, Mauricio Sanabria2, Jasmin Vesga3,


Giancarlo Buitrago4, Ricardo Sa nchez4, Angela Rivera5
1
Baxter Renal Care Services- Fundaci
on Cardioinfantil, Bogota, Colombia, 2Baxter Renal
a, Colombia, 3Baxter Renal Care Services-Colombia,
Care Services Latin-America, Bogot
Bogota, Colombia, 4Universidad Nacional de Colombia, Clinical Research Institute,
School of Medicine, Universidad Nacional de Colombia., Bogot a, Colombia and 5Baxter
Healthcare Corporation, Deerfield, IL, United States of America

BACKGROUND AND AIMS: According to emerging evidence, medium cut-off


membrane improves clearance of molecules larger than 25 kDa, including larger
uremic toxins. There is growing evidence on clinical effectiveness outcomes associated
with the use of these membranes.
Our aim was to evaluate clinical effectiveness of medium cut-off (HDx) versus high
flux (HF-HD) dialyzers in terms of hospitalization rate and duration, cardiovascular
event rate and survival in a HD prevalent cohort in Colombia through an
observational, multicenter retrospective cohort analysis.
METHOD: Adult Prevalent HD patients (> 90 days in HD) at Baxter Renal Care
Services Colombia were included between September 1st, 2017 to November 30th,
2017 (follow-up until 2 years). Socio-demographic and clinical characteristics of all
patients were summarized descriptively. Inverse probability of treatment weighting on
the propensity score was used to balance comparison groups on indicators of baseline
socio-demographic and clinical characteristics. Weighted incidence rate ratios (IRRs)
and rates and duration of hospitalization and cardiovascular events according to
dialyzer type were obtained using binomial negative regression with the weighting
sample.
RESULTS: We evaluated 1098 patients (37.7% women): 534 in HF-HD vs 564 in HDx
(Table 1), median age was 60.6 years. Mean time on HD was 5.6 years (SD 5.51) for
HF-HD and 5.88 for HDX (SD 5.48)
We observed lower hospitalization rates in HDx group, (IRR HDx/HF-HD: 0.82 95%
CI 0.69 to 0.98; p=0.03); and cardiovascular events rate, (IRR HDx/HF-HD: 0.65 95%
CI 0.47 to 0.91; p=0.01) see Table 2. Main cause of hospitalization was cardio-
cerebrovascular (Table 3). We observed no differences in hospitalization duration or
survival.
CONCLUSION: We evaluated 1098 patients (37.7% women): 534 in HF-HD vs 564 in
HDx (Table 1), median age was 60.6 years. Mean time on HD was 5.6 years (SD 5.51)
for HF-HD and 5.88 for HDX (SD 5.48)
We observed lower hospitalization rates in HDx group, (IRR HDx/HF-HD: 0.82 95%
CI 0.69 to 0.98; p=0.03); and cardiovascular events rate, (IRR HDx/HF-HD: 0.65 95%

i486 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO882 PATIENTS’ UNDERSTANDING AND EXPERIENCE OF COVID-
19 PANDEMIC AMONGST IN-CENTRE HAEMODIALYSIS
POPULATION IN A SINGLE UK CENTRE

Khai Ping Ng1, Lisa Crowley1, Yogita Aggarwal1, Jyoti Baharani1


1
University Hospitals Birmingham NHS Foundation Trust, Renal medicine (Heartlands),
Birmingham, United Kingdom

BACKGROUND AND AIMS: Patients with end-stage kidney disease on dialysis are
susceptible to severe COVID-19 infections. However, during the pandemic, many renal
patients were unable to ‘shield’ fully due to the ongoing need to attend the dialysis unit
for treatment. With a significant proportion of our haemodialysis population coming
from socially deprived and ethnic minority background (38%), we aimed to explore
patients’ understanding and experience of COVID-19 pandemic.
METHOD: This was a cross-sectional survey of patients receiving in-centre
haemodialysis from one centre in England conducted during July 2020, three months
after the first UK national lockdown. The questionnaire consisted of 18 questions
exploring patients’ awareness of COVID-19 pandemic, understanding of ‘shielding’,
use of face covering, and their experience of haemodialysis treatment as well as
accessing healthcare during COVID-19 pandemic. Those with language barriers were
offered assistance and verbal translation by haemodialysis nurses, if possible, to
complete the questionnaire.
RESULTS: In total, 232 patients (of a total of 479 in-centre dialysis patients, 48%
response rate) completed and returned the questionnaire. Of these, 29 (12.5%) patients
required help with the questionnaire due to language barrier. Mean age was 62 (SD 16)
years, 63% were male, 53% were from ethnic minorities and 45% were from the most
deprived area (MDI Decile 1). A third of the respondents lived with 3 or more adults at
home and a quarter lived with one or more child.
Majority of the patients (97%) were aware of COVID-19 pandemic, and most received
information on COVID-19 from the news (87%). Dialysis staff (43.1%), family and
friends (32.6%), internet (31%) and general practitioners (20.3%) were also key sources
of information. Despite this, 17.2% of the patients did not know about ‘shielding’.
MO881 LUNG ULTRASONOGRAPHY AND BIOIMPEDANCE IN Even though 3 in 4 patients stated that they were ‘always’ or ‘often’ able to ‘shield’,
ASSESSMENT OF VOLUME STATUS OF HEMODIALYSIS when prompted with scenarios, significant number of patients in fact felt that they were
PATIENTS: A COMPARISON BETWEEN BOTH METHODS unable to shield when travelling to dialysis (56%), during dialysis (35%) or when
shopping (17%). Majority of the patients (89%) said that they wore face covering and
Catia Figueiredo1, Marisa Rolda ~o1, Ana Rita Valerio Alves1, Hern^ ani Gonçalves1, 28% self-isolated from the rest of household during the first peak of pandemic. 83%
Flora Sofia1, Karina Lopes1 practised ‘social distancing’ at dialysis units but 5% did not and 6% felt unable to do so.
1 Almost a quarter of the patients (23%, 54 patients) felt unwell during the first wave of
Rainha Santa Isabel Hospital - Centro Hospitalar Médio Tejo, EPE, Nephrology, Torres
Novas, Portugal COVID-19. Majority (50%) of them sought medical help by informing the dialysis
unit, whilst 26% contacted their GP and 38% attended emergency departments. Of
BACKGROUND AND AIMS: Assessment of volume status is an important these 54 patients, 35% had difficulties accessing medical help, especially from primary
prognostic factor in hemodialysis (HD) patients. Several methods have been suggested care. One in four patients felt that their dialysis experience had changed during the
to estimate it: bioimpedance analysis, brain natriuretic peptide levels (BNP) and lung pandemic: 10% increased use of private taxis or used different travel services, 3.5%
and inferior vena cava (IVC) ultrasonography (US), which are emerging as a valuable reported increased travel time, 8% dialysed at a different unit, 5% experienced longer
technique in this field. Our aim was to evaluate effectiveness of lung US in assessment waiting time to start dialysis sessions and 4% had dialysis frequency reduced . Almost
of volume status in chronic HD patients and compare it with the gold standard a third (29%) of the patients knew of someone in the dialysis unit who had COVID-19
bioimpedance technique. infection during the first wave of pandemic.
METHOD: Cross-sectional study of 58 prevalent HD patients. Several analytical data CONCLUSION: COVID-19 posed significant challenges for patients receiving in-
were analyzed, including BNP, albumin and sodium levels. Lung and IVC US were centre haemodialysis. Despite their high susceptibility to severe COVID infection,
performed to assess the presence and distribution of B-lines and the diameter and significant number of patients was not aware of ‘shielding’ or able to ‘shield’ effectively.
respiratory collapsibility of IVC, respectively. FreseniusVR body composition monitor Some also experienced difficulties accessing medical help and a quarter reported
(BCM) was the bioimpedance technique used. It defines hyperhydration as relative change of transport or dialysis arrangement during the pandemic.
fluid overload (RFO) >15%. Both US and BCM were performed at the same day,
immediately before the middle week HD session. Categorical variables are presented as
frequencies and percentages, continuous variables as means and standard deviations,
or medians and interquartile ranges (IQR) for variables with skewed distributions.
Statistical analysis was performed using SPSSV R version 25 for Windows.

RESULTS: The average age was 75.361.6 years and 56.9% were male. The average MO883 FATIGUE IS THE PREDOMINANT PATIENT-REPORTED
time in HD was 36.664.1 months. Half of the patients (n=29) presented B-lines in lung OUTCOME MEASURE IN HEMODIALYSIS PATIENTS:
US. The diameter of IVC was significantly higher in this group of patients, both RESULTS OF A MULTICENTER CROSS-SECTIONAL EPROMS
inhaling (1.360.4 vs 0.960.4; p=0.001) and exhaling (2.060.4 vs 1.660.5; p<0.001). STUDY
Similarly, most patients with B-lines at lung US presented collapsibility of IVC < 50%
(n=25; 89.3%). Abdallah Guerraoui1, Anne Kolko-Labadens2, Mathilde Prezelin-Reydit3,
Although not statistically significant, the RFO was higher in patients with presence of Philippe Chauveau3, Catherine Lasseur3, Marie Lino-Daniel1, Julie Haesebaert4,
B-lines compared to those who did not present it (10.2610.6% vs 5.466.9%; p=0.061). Agnes Cailette-beaudoin1
Considering the mean RFO value in patients with B-lines, we observed that its presence 1
Calydial, Nephrology-Dialysis, Vienne, France, 2AURA Paris, Nephrology-Dialysis, Paris,
was significantly higher in patients with RFO > 10% compared to those with RFO < France, 3Aurad-aquitaine, Nephrology-Dialysis, Gradignan, France and 4Universitaire
10% (58.6% vs 31%; p=0.035). Besides, patients with RFO > 10% also presented higher Lyon, HESPER, Lyon, France
BNP (9878634646 pg/mL vs 394568634 pg/mL; p=0.009) and lower albumin levels
(3.460.5 vs 3.760.4; p= 0.039) than other group.
CONCLUSION: Lung US seems to be a valuable tool to diagnose overhydration earlier BACKGROUND AND AIMS: End Stage renal disease (ESRD) and hemodialysis are
than BCM, which currently defines hyperhydration as RFO >15%. In this study we associated with a decrease in quality of life (QOL). Self-reported QOL symptoms are
verified that patients with lower levels of RFO (>10%) already presented signals of not always prioritized by the medical team, potentially leading to conflicting priorities
fluid overload, such as presence of B-lines at lung US, higher BNP and lower albumin with patients. Electronic patient-reported outcome measures (ePROMs) allow
levels. These findings support the benefit of lung US in guiding fluid removal and may physicians to better describe these symptoms. The objective was to describe the
change the practice in our HD unit to probe the ideal dry weight for chronic dialysis prevalence of symptoms self-reported by HD patients.
patients. METHOD: A multicenter cross-sectional study was conducted in three HD centers.
Patients were included if they were 18 years old or over and treated with HD for at least
three months in a center. Data were collected by the patient via a self-administered
ePROMs questionnaire. Data included patient characteristics, post-dialysis fatigue and
intensity, recovery time after a session, perceived stress, impaired sleep the day before
the dialysis session, current state of health, and the one-year change.
RESULTS: In total, we included 173 patients with a mean age of 66.2 years, a mean 6

10.1093/ndt/gfab100 | i487
Abstracts Nephrology Dialysis Transplantation

SD hemodialysis duration of 48.9 6 58.02 months, mainly treated in self-dialysis unit


(67%) and having at least one comorbidity (72.5%). The prevalence of fatigue was
72.1% [IC 95% 64.7% to 78.7%] with a mean severity score of 5.846 2.12. 66.4% had a
high level of stress (level B or C). Recovery time was more than 6 hours for 24.9% of
patients and 78 % declared they had a better or unchanged health status than the
previous year. The self-perceived health status of patients was 6.26 2.12 and 77.5% [IC
95% 70.5% to 83.5%] of patients stated that they had not a worsened health status than
the year before. No statistical differences were observed between centers for the
PROMS. Despite significant differences in patient characteristics from the three centers
including age, comorbidities or type of dialysis, no differences were found on the
prevalence of the various PROMs, in favor of internally
CONCLUSION: Fatigue and stress were the main symptoms reported by HD patients.
There was no association between symptoms reported and comorbidities clinical
results of patients. The patient’s care teams should better consider these symptoms.

MO884 ASSOCIATION BETWEEN QUADRICEPS ISOMETRIC


STRENGTH AND SLEEP DISTURBANCES AMONG PATIENTS
ON HEMODIALYSIS

Shun Yoshikoshi1, Yuta Suzuki1,2,3, Shohei Yamamoto1,4, Manae Harada2, MO884 Figure 1: Multivariable-adjusted restricted cubic splines examining the
Keigo Imamura1, Haruka Ito1, Takumi Noda1, Sachi Yamabe1, Atsushi Yoshida2, association of quadriceps isometric strength with sleep disturbance
Kentaro Kamiya1, Atsuhiko Matsunaga1
1
Kitasato University Graduate School, Rehabilitation Sciences, Sagamihara, Japan,
2
Sagami Circulatory Organ Clinic, Sagamihara, Japan, 3National Institute of Public
Health, Wako, Japan and 4National Center for Global Health and Medicine,
Epidemiology and Prevention, Shinjuku, Japan
MO885 APP BASED DOCUMENTATION AND SUPPORT OF A
BACKGROUND AND AIMS: The muscle strength of patients on hemodialysis (HD) GERMAN HOME DIALYSIS PROGRAMM - A PILOT STUDY
is lower than that of community-dwelling older adults. Because decreased muscle
strength, especially quadriceps isometric strength (QIS), has been reported to be a risk Severin Schricker1, Moritz Schanz1, Tina Oberacker1, Silke Merz1,
factor for increased mortality rate among patients undergoing HD, the prevention and Martin Kimmel2, Dominik M. Alscher1, Markus Ketteler1
correction of decreased QIS are very important in this population. Although some 1
Robert-Bosch-Hospital, Nephrology, Stuttgart, Germany and 2ALB FILS KLINIKEN
factors associated with decreased QIS among patients on HD have been reported, these GmbH, Nephrology, Göppingen, Germany
factors remain unclear because patients on HD have many comorbidities with
increasing age and prolonged HD vintage. In community-dwelling older adults, sleep
BACKGROUND AND AIMS: Telemedicine is advancing. However, studies that
disturbance is reported to be a factor associated with reduced muscle strength. In
examine the integration into home dialysis care are still scarce. This multicenter,
addition, the prevalence of sleep disturbance is higher in patients on HD. Therefore, it
Germany-wide prospective observational pilot-study investigated the effects,
is necessary to investigate these associations in this population. We examined the
acceptance and usability of an app as a new care concept compared to conventionally
association between QIS and sleep disturbances among patients receiving HD.
cared-for patients.
METHOD: This cross-sectional study included 211 outpatients undergoing HD three
METHOD: Here, we employed the “DiaApp”, a tablet based documentation,
times a week. To evaluate QIS, a handheld dynamometer (ltas F-1; Anima, Tokyo,
communication, information and supply ordering system developed by the PHV – a
Japan) was used. Patients were asked to sit on a bench with their hip and knee flexed at
non-profit dialysis network in Germany with around 7,000 patients. During a pilot
an angle of 90 . They performed isometric voluntary contraction of the quadriceps for
rollout phase of the app between 2018 and 2019, 25 patients participated in four
a maximum of 5 seconds, thrice, for both legs. The average of the right and left
dialysis practices. Participants were free to choose between app use (app) and the
maximal QIS divided by the dry weight (%DW) was used in the analysis. Sleep
previous paper-based documentation (control). We collected prospective data on
disturbances were measured using the Athens Insomnia Scale (AIS), a self-
demographics, adverse events as well as questionnaires regarding quality of life (KDQL
administered questionnaire consisting of eight questions, each scored from 0 to 3. The
v1.3), affinity for technology (TA-EG), satisfaction with the app (UTAUT), and self-
total scores range from 0 to 24, with higher scores indicative of worse sleep quality.
confidence in dealing with chronic illness (SES6G). Furthermore, 5 app users were
Clinical characteristics, including age, sex, body mass index, HD vintage, comorbidity
interviewed in a qualitative interview over 90 min about their attitude towards
score, serum albumin, C-reactive protein, and the Mini-Mental State Examination,
technology, illness and the app.
were investigated. Multiple linear regression analysis and multivariable-adjusted
RESULTS: Of the 25 participants, 13 used the app (52%). App users tended to be
restricted cubic splines with four knots were used to examine the association between
younger, more likely to be male (60.0%) and on peritoneal dialysis (n=15, 60.0%).
QIS and sleep disturbances.
Median age and dialysis vintage for app users and controls were 51 (38-60; 0) vs. 59
RESULTS: The median age was 68 (interquartile range: 59–76) years, and 62% of the
(37-64; 1) years and 51.5 (34-68; 3) vs. 38 (28-66; 5) months, respectively. Mean follow-
patients were men. In multiple linear regression analysis, the AIS score was extracted as
up durations were 6.5 months and 12 months. All participants continued to use the
a significant factor related to QIS after adjusting for clinical characteristics (regression
app. One exit site infection (app), 3 hospitalizations (peritonitis and shunt revision,
coefficient: -0.45, 95% confidence interval: -0.84 to -0.05, p = 0.028). In the
controls; inguinal hernia, app) and no serious app-related adverse event occurred.
multivariable-adjusted restricted cubic splines, a nonlinear relationship was found
App users exhibited small trends (n.s.) towards lower quality of life (median SF-12
between QIS and the AIS score even after adjusting for clinical characteristics. In
physical composite app: 43, IQR 40-48 controls: 47, IQR 38-50; SF-12 mental
addition, it was shown that QIS decreased significantly as the AIS score increased up to
composite median app: 53, IQR 35-55; controls: 56, IQR 42-59;) greater self-confidence
6, which is the cutoff value for discriminating sleep disturbances (Figure).
in managing chronic illness (SESG6 Score app: 7.33, IQR: 6-8.83; controls:7.17, IQR 6-
CONCLUSION: Higher AIS scores were independently associated with decreased QIS
7.83) and higher affinity for technology (in all four TA-EG dimensions). App users
among patients on HD. Future studies should investigate the causality between QIS
were more likely to have completed a master’s degree, while non-users mostly had a
and sleep disturbance in patients undergoing HD.
bachelor’s degrees (Chi-square 14.183, df 6, p=0.028). Overall, the educational level of
participants was high. There was a tendency (n.s.) for actual app users to have slightly
lower performance expectations (median control arm 5.5 vs. app arm 5.88 on a Likert
scale 1-7), a slightly higher assessment of their own and other available resources
(supportive conditions median control arm 6 vs. app arm 6.67 on a Likert scale 1-7).
In the qualitative interviews, all app users surveyed stated that they regularly used
digital offerings in all areas of their lives. Therefore, expectations were similar to other
apps to be more efficient in terms of time, material and effort than paper-based
documentation. The attitude towards the app was that towards an auxiliary tool, “it
should simply work”, and found it to be useful. Patients disliked the necessity of a
dedicated (in this case a tablet) device for running the app. Information about the
disease was more likely to be outside of the app in e.g. the internet.
CONCLUSION: In this study, we found no significant differences between app users
and controls. No adverse events occurred. Via trends and interviews, the picture
emerges that an upcoming, younger generation of dialysis patients appreciates the

i488 | Abstracts
Nephrology Dialysis Transplantation Abstracts
advantages of flexible home dialysis procedures and, as in other areas of life, expects MO887 THE IMPACT OF A MULTI-DISCIPLINARY CLINIC ON THE
simple, digital and thus resource-saving options for self-management and OUTCOMES OF INCIDENT DIALYSIS PATIENTS IN A
communication. At the same time, such applications are also subject to the REGIONAL HOSPITAL IN SINGAPORE
expectations of digital user experiences from other areas of life. This poses enormous
challenges for the often-costly development of such applications by non-commercial Boon Cheok Lai1, Mayank Chawla2, Shashidahar Baikunje2, Lee Ying Yeoh2,
providers and limited number of target audiences. Marie Tan3, Elianna K.g3
1
Sengkang General Hospital, Renal Medicine, Singapore, Singapore, 2Sengkang General
Hospital, Renal Medicine and 3Sengkang General Hospital, Singapore

BACKGROUND AND AIMS: Institution of a pre-dialysis programme has been


shown to improve the outcome of the chronic kidney disease (CKD) patients
MO886 ASSESSMENT OF HEALTH-RELATED QUALITY OF LIFE IN approaching end stage renal disease (ESRD). A renal multidisciplinary clinic (MDC)
PATIENTS ON HEMODIALYSIS USING RAND36 SCORE aimed at reducing unprepared dialysis initiation is known to reduce morbidity in such
patients and reduce the risks of complications once the patient initiates dialysis. The
Manisha Dassi1, Anupama Janardhana2, Sampoorna Hegde3, Garima Aggarwal4, design of this service is of paramount importance to ensure efficient delivery and to
Girish Namagondlu5, Kishan A6, Krishnam Raju Penmatsa7, Amit Langote8, achieve optimal utilization of the resources.
Karthikeyan Balasubramanium9, Arvind Conjeevaram10 The number of patients requiring urgent initiation of dialysis is alarmingly high in
1
Max Super Speciality Hospital, Vaishali, Department of Nephrology and Renal Singapore as compared to elective initiation, and our hospital was no exception when
Transplantation, Ghaziabad, India, 2Nanjappa Hospital, Department of Nephrology we started the renal service in 2018. Patients with unplanned initiation of RRT either
and Renal Transplant, Shivamogga, India, 3Bloom Value Corporation, Bloom Value because of lack of referral/late referral, infrequent follow up with the nephrologist or
Corporation, Bengaluru, India, 4Columbia Asia Hospital Whitefield, Bangalore, because of other factors such as inadequate knowledge of disease trajectory, or poor
Department of Nephrology and Renal Transplantation, Bengaluru, India, 5Columbia compliance to medications, tended to have worse outcomes.
Asia Hospital Hebbal, Bangalore, Department of Nephrology and Renal METHOD: We recruited the patient who initiated dialysis between July 2018 to July
Transplantation, Bengaluru, India, 6Trustwell Hospitals Pvt. Ltd., Department of 2020 in our Quality Improvement (QI) project.
Nephrology and Renal Transplantation, Bengaluru, India, 7Queen’s NRI Hospital, In the MDC group, the patient will be reviewed by a dedicated team of nephrologists, renal
Department of Nephrology and Renal Transplantation, Visakhapatnam, India, 8Apollo coordinators (RC) and medical social workers (MSW) and comprises of 2 mutually
Hospitals, Department of Nephrology and Renal Transplantation, Navi Mumbai, India, exclusive components: low clearance clinic (LCC) and transitional care clinic (TCC).
9
Saveetha Medical College and Hospital, Chennai, Department of Nephrology and In the MDC, nephrologist takes a lead role for the patient’s overall medical assessment
Renal Transplantation, Chennai, India and 10The Bangalore Hospital, Department of and treatment. Renal coordinator provides the CKD and dialysis education to
Nephrology, Bengaluru, India empower patient to make the correct RRT choice. MSW provides psychosocial support
and financial counselling.
BACKGROUND AND AIMS: Evaluation of Health-related quality of life (HRQoL) is The LCC became operational from 07th September 2018 while the TCC was initiated
an important, albiet neglected component of health care in patients with End Stage on 12th July 2019. CKD patients who are deemed likely to need RRT in the coming one
Renal Disease (ESRD). RAND-36 is a validated scoring system for evaluating HRQoL. year by the primary nephrologist are scheduled to attend LCC. Upon initiation of
Patients on hemodialysis experience decrease in various aspects of HRQoL. Various haemodialysis, all patients are referred to the TCC in the first month of their discharge.
disease related and socio-economic factors influence HRQoL. There is limited data on In the conventional group, we recruited the patient who have not attended MDC
HRQoL among patients of ESRD on hemodialysis from Indian subcontinent. In the before or after dialysis initiation.
present study, we aim to evaluate the HRQoL using RAND-36 score & the factors Retrospectively, their data including baseline demographic and morbidity parameters
which influence it’s various aspects. In addition, we aim to evaluate patient perception were collected in the MDC group and conventional group.
of ease of access to dialysis related health care and its impact on RAND-36 score. Morbidity outcome like definitive dialysis access, needs of intensive care unit (ICU)
METHOD: This cross sectional, multi-centric study was performed in Nov 2020. A admissions, complications like catheter related blood stream infections (CRBSI) and
random sampling was employed to select the study participants. Patients with history other infections, stroke and myocardial infarction (MI) were analysed.
of psychiatric illness, significant impairment of hearing, speech, or cognitive RESULTS: There are 130 patients initiated on RRT between July 2018 to July 2020.
disturbances were excluded. RAND 36-Item Health Survey (Version 1.0) was used and The percentage of patient started dialysis with a definitive access was greater in the
circulated amongst dialysis patients across 10 dialysis centres in hospitals across India. MDC group (25%) as compared to the conventional group (9%) (p=0.03). Although
Final scores were calculated using standard guidelines. A proprietary software from statistically not significant, the incidence of intensive care unit (ICU) admission was
Bloom Value Corporation was used for data capture by electronic means and Power BI also lower in the MDC group (10%) than the conventional group (31%) (p=0.06).
was used for analysis. After initiation of dialysis, the patients in the MDC group had lower rates of CRBSI
RESULTS: 257 ESRD patients on hemodialysis completed the survey. Mean age was (5.6%) than the conventional group (14%) (p=0.17). These patients also had lower
52.9 years. 65.4 % participants were males, 39.69% were Diabetics and 75.88% had rates of other infections and major adverse cardiovascular outcomes (13% in MDC
hypertension. Accessibility to healthcare was reported by 36% and 27.7% patients as group versus 37% in conventional group) (p=002). The rate of recurrent admission,
‘excellent‘ and ‘very good’ respectively. The mean scores in various scales were Physical defined as frequent admissions up to 3 times per year, was lower as well in the MDC
Functioning (PF) 47.27627.87 %, Role limitations due to physical health (RP) 54.18 6 group (13%) as compared to the conventional group (35%) (p=0.003).
40.97 % , Role limitations due to emotional problems (RE) 55.38 6 43.57 %, Energy/ CONCLUSION: This QI project has demonstrated the benefit of MDC in improving
fatigue (EF) 49.80 6 19.38 %, Emotional wellbeing (EW) 57.71 6 22.04 %, Social the lives of the incident dialysis patients. Moving forward, we aim to continue to evolve
functioning (SF) 58.02 6 25.32%, Pain (BP) 68.28 6 23.52 % and General Health (GH) this clinic in order to match the changing needs of our patients, with a view to increase
48.11 616.43%. Lower PF Scores were seen with higher age (NS),  2 comorbidities its uptake, and to increase the percentage of patients having elective starts with a
(NS). PF scores were higher in patients with Government insurance and higher definitive dialysis access to at least 65% as per target set in NKF-KDOQI 2009
perception of healthcare accessibility (NS). RP Scores were higher in males and with guidelines, in order to help them achieve the maximum benefit out of this endeavour.
advancing age (NS). Employed patients had lower RP scores (p=0.009). RE scores were
lower in patients with  2 comorbidities (NS) and among Employed patients (p=0.04).
EF Scores were higher in males (p=0.07) and lower in patients with  2 comorbidities
(NS). EW scores were higher in males (p=0.09) and among patients with higher
perception of healthcare accessibility (NS). SF Scores were higher in males (p=0.08)
and with higher perception of healthcare accessibility (NS). BP Scores were higher
among patients with 2 comorbidities (p=0.04) and higher perception of healthcare
accessibility (NS). GH scores were higher with Government Insurance availability and
higher perception of healthcare accessibility (NS).
CONCLUSION: To our knowledge this is the first multi-centric study conducted
amongst ESRD patients in India, evaluating HRQoL using RAND36 scores. There is
significant heterogeneity in patient reported outcomes and it’s determinants.
Government Insurance support and a higher perception of healthcare availability have
positive impact on many aspects of HRQoL. This is a valuable tool in executing patient
centred care.

10.1093/ndt/gfab100 | i489
Abstracts Nephrology Dialysis Transplantation

MO888 QUALITY OF LIFE AND QUALITY OF SLEEP IN RESULTS: The sample included a total of 160 patients: 102 non-dialysis CKD patients,
MAINTENANCE HEMODIALYSIS PATIENTS: REPORTS FROM 40 hemodialysis, 8 peritoneal dialysis and 10 kidney transplant patients. Their mean
TWO HEMODIALYSIS CENTERS IN IRAN age was 66.74 615.36 years, 57.5% were males and 42.5% diabetics. The mean number
of daily medications was 8.75 63.38, mean frequency of blood tests per year 6.86 66.4
Samaneh Hashemi1, Roya Rezaee2, AmirHossein Saeedi2, Hazhir Hojati2, and mean number of hospital admissions per year 0.79 61.43. The mean total annual
Reza Yahyavi Sahzabi2, Fatemeh Maghsudi3 cost of CKD per patient across all categories was assessed at 19,900,164 627,893,591
1
Abadan University Of Medical Sciences, Internal medicine, 2Abadan Faculty of Lebanese Pounds (1 $USD= 1515 LP in 2019). Statistical analysis showed a higher total
Medicine, Medical School and 3Abadan Faculty of medical science, Public health cost among dialysis patients compared to other categories of CKD (p<0.001), higher
cost of medications in transplant patients (p<0.001) and higher cost of technique
BACKGROUND AND AIMS: Patients with End Stage Kidney Disease (ESKD) modality in peritoneal dialysis patients (p<0.001). These differences are summarized
usually tend to have lower Quality of Life (QoL) compared to the general population. in Figure 1.
The purpose of this study was to determine the QoL and quality of sleep in patients on CONCLUSION: Similar to previous studies from other countries, this cost of illness
maintenance hemodialysis (MHD) and its relation with medical factors. analysis showed a high burden of dialysis annual costs compared to non-dialysis CKD
METHOD: This descriptive-analytical study was performed on 145 patients on MHD and transplant patients. It revealed as well a great burden of medications’ costs at the
in two hospitals affiliated to Abadan University of Medical Sciences. Patients’ QoL was level of dialysis and transplantation. It is thus crucial that governments and health
assessed via KDQOL-SF questionnaire. For sleep quality, Pittsburgh Sleep Quality policies in low- and middle-income countries target interventions that prevent end-
Questionnaire (PSQI) was used. Demographic information of patients, type of vascular stage kidney disease, reduce medications’ costs and most of all create programs that
access, history of dialysis, and frequency and duration of each dialysis session were encourage kidney transplantation.
collected. The average results of related laboratory tests in the last six months, were also
recorded for each patient.
RESULTS: Of 145 MHD patients, 81 (55%) were men and 64 were women. Most
patients (53%) were between 30 and 60 years old. Illiteracy was present in 48 (33%)
patients. Unemployed patients accounted for 70% of patients (99) and most of the
participants (83.44%) lived in the city. Of 145 patients, 102 (70.34%) were married, 20
(13.79%) were single, and the rest were widows. The mean dialysis adequacy of patients
was 1.14, and 53% had dialysis adequacy less than 1.2. The average quality of life score
was 66.00 613, suggesting a high QoL in this group of patients. literacy was
significantly associated with QoL score (P<0.001). Likewise, there was significant
association between QoL score and income level (p <.001), the effect of Kidney disease
on life (p <.001), working status (p <.009), social functioning (p <.046), and marital
status (p <.001). The quality of social interactions was significantly associated with
residence location (p <.001). On the other hand, the presence of Kidney disease
burden, sexual dysfunction, unemployment, role emotional and role physical, was
associated with low QoL scores. We found a significant relationship between
hemoglobin level and cognitive function (p <.001, r= .075). In addition, significant
relationships between phosphorus levels and physical function (p=.021) and role
emotional (P:0.04) were observed. Seemingly, phosphorus levels were inversely related
with sexual function in our patients (p <0.001, r= - .013). Our data also suggested that
serum calcium levels may have an impact on the patients’ social function (p=.038). The
mean score of sleep quality was 7.0064.00. Most of the patients (61%) had a PSQI>5,
MO889 Figure 1: Cost of illness of different CKD categories
indicating a poor sleep quality. High sleep quality (PSQI<5) is significantly associated
with low age and high-income level. There was also a significant relationship between Note. 1 US dollar=1515 Lebanese Pounds (LBP) in 2019. HD=Hemodialysis.
the average sleep quality and general health (p <0.001, r= -0.206), social function PD=Peritoneal Dialysis.
(p= 0.018, r=-0.208), and energy fatigue (p <0.001, r= -0.309).
CONCLUSION: Our study showed that a wide range of determinants, including
demographic, socioeconomic and disease-related factors can significantly influence the
QoL and sleep quality in ESKD patients undergoing hemodialysis. Among them,
modifiable factors including laboratory test results, socioeconomic determinants and
psychosocial status should be addressed and accordingly treated and solved. Hence, an
MO890 HOW CAN MODERN DIALYSIS TECHNOLOGIES HELP TO
improvement in both the QoL and sleep quality of maintenance hemodialysis patients
COUNTERACT STAFFING SHORTAGES IN HAEMODIALYSIS
will be expected.
UNITS?
KEYWORDS: Hemodialysis, Quality of life, Sleep quality, Sociodemographic
characteristics.
Turahan Turan1, Matthias Keil2, Marjelka Trkulja2, Raquel Ribeiro2,
Carsten Hornig2, Thorsten Bruce2
1
Frankfurt University of Applied Sciences, International Business Information Systems,
Frankfurt am Main, Germany and 2Fresenius Medical Care Deutschland GmbH, Bad
Homburg v. d. H., Germany
MO889 COST OF ILLNESS OF CHRONIC KIDNEY DISEASE IN
BACKGROUND AND AIMS: Dialysis units face an increasing shortage in qualified
LEBANON: FROM THE SOCIETAL PERSPECTIVE
healthcare professionals (HCPs). Multiple studies1,2 have suggested that staffing
shortages and the clinic work environment affect both patient and organizational
Mabel Aoun1, Elie Helou2, Ghassan Sleilaty3, Dania Nehme Chelala1
1
outcomes, resulting in higher workloads and more stressful work environments. This
Faculty of Medicine, Saint-Joseph University, Nephrology, Beirut, Lebanon, 2Faculty of may lead to staff disengagement, burnout, absenteeism, voluntary turnover, reduced
Medicine, Saint-Joseph University, Urology , Beirut, Lebanon and 3Faculty of Medicine, patient satisfaction and potentially adverse patient outcomes.
Saint-Joseph University, Beirut, Lebanon Nurses have a significant role in the delivery of haemodialysis (HD) therapy for end-
stage renal disease patients. While supporting patients in navigating their everyday
BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is the 12th leading lives, including HD therapy, nurses balance a variety of challenges related to care and
cause of death worldwide and a high societal burden. Cost-of-illness studies of CKD coordination. This study analyses how four main categories of dialysis technologies
are scarce in developing countries. Identifying factors associated with the highest cost (HD machines, digital technologies, water treatment systems, and other medical
can help decision makers adapt health policies and sustain kidney health services, devices) can reduce the complexity in daily haemodialysis process steps, relieving nurse
especially in limited resources’ settings. This study aims to estimate the cost of illness of workload and thus freeing up more time for patient care.
CKD in Lebanon, from the early stages of CKD until dialysis and kidney transplant and METHOD: This observational study was conducted in three phases. First, we analysed
identify cost components related to the highest financial burden. the process steps in a typical working day in a haemodialysis care facility, mapping
METHOD: This is a cross-sectional study of all CKD patients who presented to two them to the best practice standards3. In a second phase, we analysed the data via a
nephrology clinics during the first two weeks of November 2020. The sample size Delphi panel of 19 experts (international multidisciplinary team). The initial mapping
required for the study to be representative was 154 patients. The medical and was discussed in 10 moderated rounds (2 moderators) to quantify the process step
administrative records were reviewed to collect the demographics and CKD improvements resulting from four main categories of modern HD technologies: HD
characteristics of patients as well as the direct medical costs (medications, diagnostic machines (HDM), digital technologies (DT), water treatment systems (WT), other
tests, hospitalizations, inpatient care, outpatient care), direct non-medical costs medical devices including motorized chairs/beds & digital weighing scales
(transportation) and indirect costs (productivity losses) for one year between 1st June (Miscellaneous). In phase 3 an assessment was performed to determine how modern
2019 and 1st June 2020. Kruskal Wallis test was used to compare the costs between HD technologies and the combination of the four main categories (Setup B) could
different CKD stages and categories. The study got the approval of the ethics potentially improve daily process steps versus a conventional dialysis clinic set-up
committee of Saint-Joseph University. (Setup A).

i490 | Abstracts
Nephrology Dialysis Transplantation Abstracts
RESULTS: A total of 146 daily process steps were identified over the course of a single wave as far as inflammatory markers IL6 (51.9 6 44.8 vs 55.45 6 40.52 pg/mL; ns) and
HD session. Table 1 shows, how the four main categories of dialysis technologies C-reactive protein (4.74 6 3.8 vs 6.70 6 5.44 mg/L; ns) as well as the hospital stay
individually contribute to improving the number of process steps, when applying (21.1610 vs 24.4.8610 days; ns) and in-hospital mortality (28.1% vs 18.2%; ns).
modern technologies (Setup B) versus a conventional setup (Setup A). Additional Overall, 354 bedside treatments were performed; mean session time and mean weekly
process step improvements were identified that result from the specific combinations sessions were 3.64 6 0.40 hours, and 3.4 6 0.45 HD/week, with no differences between
of the four technology categories. The maximum improvement that can be achieved FW and SW patients.
through a combination of all 4 categories is 95 out of 146 process steps. Overall, the CONCLUSION: Our data show that the higher spread of Sars-cov2 during the second
biggest contributors to process step improvements were HD machines (39 steps wave has infected younger and less comorbid HD patients, with no significant
improved) followed by digital technologies (25 steps improved). In terms of technology differences in clinical and laboratory parameters. Our organizational model based on
combinations Digital Technologies and Water Treatment Systems lead to the highest the HD bedside with the Genius system, allowed a personalized treatment with efficacy
number of process step improvements. In Setup A, a total of only 10 out of 146 process and safety for the patients and staff.
steps were improved, while in Setup B 95 out of 146 process steps were improved.
Hence, the net improvement achieved with Setup B vs. Setup A was 85 process steps.
This equates to a 58% improvement of total number of process steps.
MO892 DIALYSIS SERVICE MANAGEMENT DURING COVID-19
CONCLUSION: Our results indicate that a 58% net improvement in daily process
PANDEMIC IN EUROPEAN CITY AREA
steps could be achieved versus a conventional setup. These findings suggest that
investments in modern technologies may reduce the complexity in dialysis clinics,
Laurynas Rimsevicius1, Feliksas Jankevicius2, Ausra Motiejuniene Bilotiene2,
easing stress levels, improving the overall working environment, and freeing up more
Marius Miglinas1
time for patient care. Changes in the work environment in renal care facilities have 1
been observed to have several beneficial effects: a higher job satisfaction, lower stress Vilnius University, Nephrology Center, Vilnius, Lithuania and 2Vilnius University
and burnout levels, reduced intention to leave and higher staff retention can be Hospital Santaros Klinikos , Vilnius, Lithuania
achieved1,2. Further studies are required to validate the findings of this analysis.
BACKGROUND AND AIMS: Many countries across Europe experience the second
1) Applebaum D et al. J Nurs Adm (2010); 40: 323-328. wave of CoVid-19 pandemic. Lithuania is a country situated on the eastern shore of the
2) Hayes B et al. J Nurs Manag (2015); 23: 588-98. Baltic Sea. Until January 15, Lithuania had 165560 confirmed positive cases, 100495
3) EDTNA/ERCA Nurses Best Practice Guidelines. https://www.edtnaerca.org/ recoveries, and 2376 deaths.
education/publications. Accessed: 10th Jan 2021 METHOD: In this abstract, we describe reorganization in dialysis service in Vilnius,
the capital and largest city of Lithuania, with urban population of 700,275 inhabitants.
RESULTS: At the pandemic start in March 2020, Vilnius had 3 public nephrology
departments each running a hemodialysis unit, and 4 private hemodialysis centers,
with total of 250 end-stage kidney disease patients. Vilnius University Hospital
Santaros Klinikos, as the main hospital in the country and national CoVid-19
coordinator, restructured dialysis service in city area. Chronic hemodialysis programs
in public hospitals were cancelled and patients were shifted to private centers. In the
threat of infection and multiple outbreaks in two hospitals, nephrology units were
closed and CoVid-19 negative nephrology patients were located in a satellite hospital in
other city, whilst all city hospitals served as CoVid-19 centers. In Santaros Klinikos, we
treated severe CoVid-19 patients who needed chronic or acute dialysis, while
asymptomatic and mild to moderate-symptom patients carried their dialysis
procedures in isolated shafts and/or facilities in private centers. In cases with
unsatisfactory self-isolation, isolation sites were located in hotels or other premises
provided by the municipal administration. Transportation to dialysis center was
provided by municipality as well. Rapid antigen testing was set in a case of suspected
outbreak or for all outpatient hemodialysis patients in some centers in circumstances of
high community transmission. During the pandemic, we had ongoing transplant
activities, continued wait-listing for kidney transplant and increased peritoneal dialysis
program. Most peritoneal dialysis patients were trained at home by a mobile nurse
team, also home visits we carried instead of inpatients visits. We started CoVid-19
vaccination during the first week of January for all dialysis patients and transplant
recipients who had no contraindications and gave informed consent.
CONCLUSION: In conclusion, the rapid release and adoption of recommendations
and action plan helped to identify and locate CoVid-19 outbreaks in dialysis facilities.
Dialysis service reorganization is needed to maintain ongoing treatment for chronic
patients who vitally depend on renal replacement therapy. Private dialysis centers and
municipality should assist with physical resources operating the patients flow. The
MO891 HEMODIALYSIS PATIENTS AMID COVID-19 PANDEMIC: A growth of peritoneal dialysis program serves as a significant subsidiary factor when
COMPARISON BETWEEN FIRST AND SECOND WAVE patients need more social distancing. Vaccination data and outcomes in end-stage
renal disease patients is coming soon.
Carlo Lomonte1, Piero Lisi2, Simone Corciulo2, Elisabetta Manno2,
Bianca Covella2, Luigi Rossi2, Annalisa Teutonico2, Pasquale Libutti2, Vito Pepe2
1
Miulli General Hospital, Nephrology, Acquaviva delle Fonti, Italy and 2Miulli General
MO893 ASSESSMENT OF PHYSICAL ACTIVITY IN CHRONIC
Hospital, Nephrology, Acquaviva delle Fonti, Italy
HEMODIALYSIS PATIENTS IN THE NEPHROLOGY AND
HEMODIALYSIS DEPARTEMENT CHU IBN ROCHD
BACKGROUND AND AIMS: Data about HD patients and how to best dialyze them
during the COVID-19 pandemic are scarce. The aim of the study is to describe the Imane Failal1, Sanae Ezzaki1, Marouane Sayeh1, Salma Elkhayat1,
organizational model and clinical outcomes of patients confirmed COVID-19 needing Ghizlaine Medkouri1, Benyounes Ramdani1
renal replacement therapy, admitted in a COVID Hospital in Southern Italy during the 1
CHU ibn rochd, nephrology, casablanca, Morocco
first and second pandemic wave.
METHOD: All the consecutive patients requiring chronic HD, during the first and
second wave were considered. Due to local resources, we have implemented an BACKGROUND AND AIMS: Physical activity is often reduced in chronic
organizational model based on the HD bedside with Genius system. The machine was hemodialysis patients. Studies having evaluated hemodialysis reveal a significant
prepared in the Dialysis Unit and then transferred to the COVID Hospital. After sedentary lifestyle. which is associated with excess mortality. Conversely, the benefits in
treatment, the monitor was sterilized and carefully cleaned with chlorine wipes and re- terms of morbidity and mortality from physical activity are numerous. The fight
transferred into the dialysis Unit to be prepared for the next dialysis. Demographic against sedentary lifestyles in hemodialysis patients must be one of the objectives of
data, clinical symptoms at presentation, and laboratory results were extracted by the healthcare teams. For this reason, our study aims to assess physical inactivity using a
electronic medical record. Patients hospitalized during the first wave (FW) and second physical activity score from DIJON in chronic hemodialysis patients and to identify the
wave (SW) were compared. factors linked to a decrease in physical activity in them and to propose programs aimed
RESULTS: From March 10 through December 31 2020, we enrolled a cohort of 40 at to encourage PA as well as exercises adapted to the hemodialysis patient.
patients (37.5% F), with COVID-19 infection requiring HD; 11 (27.5%) during first METHOD: This is a descriptive and analytical cross-sectional study conducted during
and 29 (72.5%) during second wave. The phenotype and clinical symptoms at the the month of January 2020, in the nephrology and hemodialysis department of CHU
admission were not different between two groups. Compared to FW, the SW patients IBN ROCHD. We used the Dijon questionnaire translated into Arabic to measure the
were younger (70.169.5 vs 77.365.9 years; p<0.03) with lower dialysis vintage (35618 PA taking into account daily, sports or leisure activities. The PA level benchmarks are
vs 60648 months; p<0.05), and lower Charlson Comorbidity Index scores (2.8 6 1.8 0–10 (low), 10–20 (medium), and 20–30 (high).
vs 5.09 6 2.0; p<0.05). No differences were observed between the first and second RESULTS: Our study included 71 patients. The average age was 46.5 years with

10.1093/ndt/gfab100 | i491
Abstracts Nephrology Dialysis Transplantation

extremes ranging from 16 to 93 years, there is a slight male predominance with a sex kidney disease and especially those on the hemodialysis program have an increased risk
ratio of 1.1. Initial nephropathy was undetermined nephropathy in 53.5%, glomerular of severe morbidity and mortality caused by the novel coronavirus.
in 29.5%, diabetic in 7% and hypertensive in 1.4%. The age of the periodic hemodialysis AIM OF STUDY: was to determine the prognosis and mortality risk in hemodialysis
treatment in our patients varied from 1 month to 44 years, with an average duration of patients hospitalized for symptomatic COVID-19 infection, using the ALAMA age
17.3 years. 91.5% of patients had an arteriovenous fistula as a vascular approach, 8.4% score and the COVID-GRAM critical illness risk score.
of patients were dialyzed on a catheter. METHOD: Prospective and retrospective study that included 74 patients undergoing
The overall level of physical activity was high only in 4.5% of patients, while it was low chronic hemodialysis, hospitalized in the Constanta County Emergency Clinical
in 61.3% and moderate in 34% of patients.The study of the relationship between the Hospital between March 2020 - December 2020, confirmed with SARS-CoV 2
decrease in physical activity and different demographic, clinical and paraclinical infection by RT-PCR testing.
parameters had revealed that the decrease in physical activity was significantly RESULTS: Out of the total number of 74 hospitalized patients (64.58% M, 35.41% F;
correlated with seniority on hemodialysis, gender, l he advanced age, the different mean age = 66.64 years), having moderate and severe forms of the disease. 56.25%
degrees of anemia, and the cardiovascular affections, on the other hand no significant needed conventional oxygen therapy, 22.9% non-invasive mechanical ventilation and
correlation was found between the decrease in physical activity and hypocalcemia, 12.5% intubation and ventilation. All patients underwent specific treatment according
hyperphosphatemia, and hyperparathyroidism. to the national protocols, updated with the rapid changes and increasing informations
CONCLUSION: Our results show that the level of physical activity is linked to many regarding the disease management. The mean duration of hospitalization was 12.33
parameters, some of which can be modified. Prescribing an adapted and personalized days. 94.7 % of patients had additional risk factors (diabetes mellitus-47.56%, arterial
program would improve the prognosis related to co-morbidities and the quality of life hypertension-87.3%, COPD – 7.8%, systemic aterosclerosis – 35.4%,
of our patients. immunosuppression – 11.6%, malignant tumors – 4.8% ). Mean ALAMA score was
more than 85 years (p<0.01) and mean COVID-GRAM critical illness risk score was
202 (92.1% risk for critical illness). Fatal outcome affected 37.8% of the patients, mainly
due to severe respiratory failure, myocarditis, arrhythmias and stroke.
MO894 EVALUATIONS OF TOXIC HEAVY METALS LEAD AND
CONCLUSION: Hemodialysis patients with SARS-CoV 2 infection have an
MERCURY IN REGULAR HEMODIALYSIS SMOKER AND
unfavorable evolution and a reserved prognosis with a high risk of death, depending
NONSMOKER PATIENTS BY COMPARISON WITH OTHER
especially on the need for ventilatory support. 6.25% of the patients followed had post-
HEALTHY CONTROL SUBJECTS IN EGYPTIAN POPULATION
COVID syndrome (disseminated intravascular coagulation, severe bacterial infections,
enterocolitis), but these long-term complications of the survivors will need further
Ezzeldin Shalaby1, Hisham Abdelmawgoud2
1
studies.
Cairo university, Department of Forensic Medicine and Clinical Toxicology, Cairo, Egypt
and 2Almokatem Insurance Hospital, Head of Nephrology Department, Cairo, Egypt

MO896 EMERGENCY HEMODIALYSIS DURING THE CORONAVIRUS


BACKGROUND AND AIMS: Around worldwide population, 10% are affected by
PANDEMIC: ABOUT 68 CASES
chronic kidney diseases (CKD); hemodialysis is the common choice of renal
replacement therapy. Cigarette smokers have higher Lead level than non-smoker
Imen Chemli1,2, Ouni Amal3, Faouzi Haoula2, Meriem Ben salem2, Manel Ben
population. As Tobacco leaves are grown on polluted soil, it is proven that Mercury
salah1, Insaf Handous1, Ahmed Letaief1, Mouna Hamouda1, Sabra Aloui1,
poisoning depends on dose and duration of exposure. Aim of the study was to
Habib Skhiri2
determine two important toxic heavy metals elements Lead and Mercury 1
concentrations in regular hemodialysis patients smoker and non-smoker by hospital of Fattouma Bourguiba Monastir, nephrology, Monastir, Tunisia, 2Monastir,
comparison with normal subjects and its correlation to anemia. nephrology, Monastir, Tunisia and 3Monastir, nephrology, monastir, Tunisia
METHOD: Blood samples were collected from CKD patients on maintenance
hemodialysis for more than 6 months divided into non-smoker and smoker to be BACKGROUND AND AIMS: The emergency hemodialysis is a very common
compared with samples from a control group of non-CKD, non-smoker persons. This situation in nephrology and is characterized by high morbi-mortality.
study was conducted in September 2019 in Al Mokattam Insurance Hospital – The aim of this work was to determine the indications for emergency hemodialysis, the
Cairo and involved 60 persons of both sex. They were divided into 3 groups: CKD stage clinical and paraclinical profiles of the patients, as well as the parameters of the session
5 patients on hemodialysis 40 patients and sub-divided into 2 groups; (smoker) 20 of hemodialysis and the perdialytic complications.
patients and (non-smoker) 20 patients and the history of eating fish and seafood was METHOD: This is a prospective descriptive and analytical study carried out over a
taken. The third group was a control group included 20 healthy non-smoker period of 3 months (March 3, 2020 - June 6, 2020). This period coincides with the
participants. Lead and Mercury were analyzed by electro thermal atomic absorption coronavirus pandemic. This study was included all patients who have undergone
spectrophotometer in Al Borg central Laboratory. The complete blood count (CBC), Emergency hemodialysis. The study was done in the hemodialysis unit of the
kidney function tests and Iron parameters were also detected. nephrology department of the CHU Fattouma Bourguiba Monastir.
RESULTS: duration on hemodialysis did not raise Lead or Mercury level in blood, RESULTS: We collected 68 patients, the majority are male (70%). The average age was
while smoking raises Lead level in blood, and eating fish and sea food more than once 60 þ -14.4 years. The original department was the emergency room in 42.6% of cases,
per week increased Mercury level in blood. There was a relation between raised Lead the intensive care unit in 10.29% and a surgical department in 13.23% of cases. 40% of
level and anaemia in hemodialysis patients. patients were diabetic and 22% had coronary insufficiency. 60.5% were a chronic renal
CONCLUSION: Lead Prolonged and Mercury measurement is important in failure, 16% were end-stage and 34% were on hemodialysis. The indications for
hemodialysis patients with possible symptoms of heavy metal toxicity. Lead level emergency hemodialysis were acute lung edema, hyperkalaemia and metabolic acidosis
monitoring is recommended in resistant anemia in hemodialysis patients. in 31%, 50% and 50% of cases, respectively. Poorly tolerated uremia and anuria more
than 12 hours were the indication in 11.8% and 10.3% of cases, respectively, drug or
toxic intoxication (methanol) was in 5.9% of cases and hypercalcaemia in 4.4% of
cases. The average duration of the sessions was 2.95 hours [2–4 hours]. Ultrafiltration
was necessary in 44.11% of cases. Per-dialysis anticoagulation was used in 38.23% of
patients. The vascular access was a femoral catheter in 67.6% of cases and an
arteriovenous fistula in 28% of cases. The per-dialytic complications were hypotension
in 10 cases (14.7%) and the session was stopped in 4 cases. hypoglycemia was noted in
2 cases (2.9%) and seizures in 2 cases. Cardiopulmonary arrest was reported in 2.9% of
sessions.
The incidence of bleeding complications occurring within 72 hours after the
hemodialysis session was 5.8%.The death rate was 13.2%.
Our univariate analysis concluded that diabetes, heart failure and coronary artery
disease, history of gastrointestinal bleeding and active infection are risk factors for
mortality.
MO895 EVOLUTION AND PROGNOSIS OF HEMODYALISIS PATIENTS The multivariate analysis showed that diabetes and a history of gastrointestinal
WITH MODERATE AND SEVERE COVID INFECTION: SINGLE bleeding was the two factors of mortality.
HOSPITAL CENTRE EXPERIENCE CONCLUSION: The confinement period has affected the medical activity in our
department. So, it has increased the cases of emergency hemodialysis with more
Camelia Pana1, Alexandru Iordache2, Campineanu Bogdan3,
complications.
Alina Mihaela Sburlan (Stanigut)4, Liliana-Ana Tuta1
1
Ovidius University of Constanta, Internal Medicine- Nephrology, Constanta, Romania,
2
Constanta County Emergency Hospital, Nephrology, Constanta, Romania, 3Ovidius
University of Constanta, Internal Medicine- Nephrology, Constanta, and 4Ovidius
University of Constanta, Medical Semiology, Constanta, Romania

BACKGROUND AND AIMS: One of the major challenges of our century seems to be
the SARS-COV2 virus pandemic that has resulted, at least until now, in over 2 million
deaths worldwide. Multiple observational studies showed that patients with chronic

i492 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO897 ANXIETY AND DEPRESSIVE DISORDERS IN CHRONIC Finally, the environmental burden of the HD procedures may be significantly reduced,
HEMODIALYSIS PATIENTS with a CO2 EE saved up to 6.6 ton/year patient (equal to 3 round-trip flights Venice-
NY).
Sanae Ezzaki1, Imane Failal1, Rania Elafifi1, Salma Elkhayat1, CONCLUSION: Home HD enable patients and their families to substantially improve
Ghizlane Elmedkouri1, Benyounes Ramdani1 their quality of life, provide a safe and effective dialysis treatment for the patients,
1
CHU ibnrochd, nephrology, CASABLANCA, Morocco contribute to operational efficiency of the healthcare system, and reduce both the
economical impact and the environmental burden of hemodialysis. In conclusion, we
BACKGROUND AND AIMS: Hemodialysis is experienced as a vital need and is a believe both HHDs are exellent solution, in particular NHHD for active young patients,
heavy strain that is causing psychological distress expressed by anxiety and depression. and AHHD for fragile patients without a caregiver, resulting in a better management
The aim of our study was to estimate the prevalence of anxiety and depression in and outcome.
chronic hemodialysis patients.
METHOD: This is an observational cross-sectional study, carried out within the unit
CASABLANCA CHU ibnrochd of hemodialysis in January of 2020 of 71 chronic
hemodialysis patients, in collaboration with a psychiatrist, the scale of anxiety and
depression (HAD) has been used to diagnose and assess the severity of anxiety and
depression in this population.
RESULTS: Our study included 71 chronic hemodialysis adult patients, the average age
of our patients was 46.5 years, ranging from 16 to 93 years, with a sex ratio M / F 1.1,
seniority average hemodialysis is 17.3 years; patients are single, married, widowed,
divorced in 66%, 26%, 5% and 3% of cases, 72.5% of our patients are without
profession.
None of the patients is followed by a psychiatrist or under antidepressant or anxiolytic
during the study, 46% of our patients have anxiety and depression with a male
predominance in 56% of cases, anxiety was found in 15% of patients, 1 case of major
anxiety, the average score of anxiety is 10 6 2, depression was found in 36% of cases
and 1 case of major depression, the average depression score was 11 6 2.
CONCLUSION: Anxiety and depression are common in patients on periodic
hemodialysisThese results emphasizes the importance of collaboration between
nephrologists and psychiatrists in order to offer hemodialysis patients psychological
support and guarantee a better quality of life.

MO898 NEW ORGANISATIONAL MODEL OF HOME HEMODIALYSIS:


THE EXPERIENCE OF THE PROVINCE OF BELLUNO

Lucrezia Carlassara1, Giordano Pastori1, Umberto Savi1, Marco Pasqualetto1,


Morena Giozzet1, Andrea Bandera1
1
ULSS1 Dolomiti, Unit of Nephrology and Dialysis, Belluno, Italy

BACKGROUND AND AIMS: Belluno is a mountainous province of 3610 Km2, with a MO899 PRURITUS IN CHRONIC HEMODIALYSIS PATIENTS ANDS
low population density (56 people/Km2), and an high ISTAT old age index of 228. ITS IMPACT ON QUALITY OF LIFE
Four HemoDialysis (HD) Centers assist 112 patients, who spend up to 8 hours/week by
ambulance to arrive at the HD Center, with a CO2 estimated emission (EE) up to 6.6 Faten Ghabi1,2, Salma Toumi1,2, Asma Amouri1,2, Hanen Chaker1,2,
ton/year patient. The cost of in-Center HD may reach up to 61.000 e/year patient. Ikram Agerbi1,2, Najla Dammak1,2, Khawla Kammoun1,2, Soumaya Yaich1,2,
Giving these premisis, we consider as first choice either Peritoneal Dialysis or Home Abdelrahmen Masmoudi3, Mohamed Benhmida1,2
1
HD (HDD), otherwise than in-Center HD. HHD can be Not assited HHD (NHHD), university hospital center hedi chaker, nephrology, Sfax, Tunisia, 2Medical school Sfax,
performed by the patient himself, or Assisted HHD (AHHD), the new HHD service Renal pathology reserch laboratory UR12ES14, Sfax, Tunisia and 3university hospital
which involves a nurse assistance at home. Both HHDs enables patients to stay at center hedi chaker, Dermatology service, Sfax, Tunisia
home, may improve patient’s quality of life, reduce the HD costs (32.000-34000 e/year
patient), and may reduce the environmental burden of the healthcare procedures (CO2 BACKGROUND AND AIMS: Pruritus is a common symptom in chronic
EE of 0-2.3 ton/year patient). hemodialysis patients, its intensity varies from patient to patient and which plays a
METHOD: One patient have undertaken NHHD and other two the AHHD. Patient 1, major role in impairing their quality of life. Its pathophysiology is poorly understood
on NHHD, is a 50 year old (y.o.) male, on HD since 9/2013. His Past Medical History and its management remains a challenge.
(PMH) encompasses End Stage Renal Disease (ESRD) due to IgA Nephropathy, a The main objective of our study is to estimate the frequency of pruritus in our
previous kidney transplant, and hypertensive cardiopathy. Patient 2, on AHHD, is a population and its impact on their quality of life.
88y.o. woman, on HD since 01/2020. Her PMH includes ESRD due to multiple MATERIAL AND METHODS: This is a cross-sectional study involving 53 patients
myeloma, and hypertension. Patient 3, on AHHD, is a 95y.o. male on HD since 09/ carried out in the dialysis unit of the CHU Hédi chaker in sfax. The DLQI
2009. His PMH includes ESRD due to hypertensive nephropathy, atrioventricular (Dermatology Life Quality Index), the Pittsburgh Sleep Quality Index (PSQI) and the
block with pacemaker, hepatopathy. verbal analogue scale to specify the intensity of pruritus were used to assess the impact
HHD is performed utilising: the NxStage System (FreseniusV R ) for NHHD, and the
of pruritus on quality of life.
Dialog iQV R System (B.BRAUNV R ) for AHHD. The HD prescription plans 2 hours
RESULTS: The mean age of our patients was 48 6 28 years with a predominance of
treatment for 6 times/week for NHHD, and 4 hours treatment for 3 times/week for men (60%). The mean duration on hemodialysis was 5.4 years. The prevalence of
AHHD. pruritus was 28% of cases. Pruritus affects 75% of the body surface in 90% of patients,
The total amount of the economical resoureces employed for HD comprise: HD an intensity greater than or equal to 5 in 93.33% of cases on an intensity scale of 0 to
equipment, healthcare-worker, and ambulance transportation (Figure). 10, the impact was moderate on the quality of life according to the DLQI in 66.66% of
The EE of CO2 have been determined using a calculator (www.myclimate.org). The EE the cases, 86.66% of the patients presented a nocturnal recrudescence of the pruritus,
of CO2 for in-Centre HD comprise both those caused by patients and nurses (Figure). and an alteration of the quality of sleep was present in 73.33% of the cases according to
We assumed the same fuel consumption of a diesel Van for the ambulances one. We the PSQI.
assumed that nurses use a diesel compact car to commute. The Comparison of the groups with (G1) or without pruritus (G2) showed the
RESULTS: All patients reported a significantly improved quality of life because they predominance of hyperposphoraemia in the first group with averages of 1.92mmol / l
were able to avoid many hours of travel to reach the HD Center. Moreover, the patient and 1.4mmol / l respectively in G1 and G2
on NHHD, appreciated an increased subjective wellness, a greater independence in CONCLUSION: Pruritus remains the most frequent complaint for hemodialysis
setting the daily work and personal appointments, and a wider freedom in the eating patients, which in our patients was linked mainly to hyperposphoraemia requiring
and drinking habits. optimization of phosphorus chelators and hemodialysis measures.
The economical resources that may be riallocated by the Healthcare System are up to
30.000 e/year patient.

10.1093/ndt/gfab100 | i493
Nephrology Dialysis Transplantation 36 (Supplement 1): i494–i501, 2021
10.1093/ndt/gfab102

MO901 ASSOCIATION OF MALNUTRITION AND INFLAMMATION


DIALYSIS. PROTEIN ENERGY WASTING, WITH ERYTHROPOIETIN RESISTANCE INDEX
INFLAMMATION AND OXIDATIVE STRESS Vitor Sa Martins1,2,3, Teresa Adragao4, Leila Aguiar1, Catarina Dias1,
Rita Figueiredo1, Pedro Lourenço1, Tania Pascoal1, Juliana Pereira1,
Tatiana Pinheiro1, In^ es Ramia~o1, Brıgida Velez1, Nuno Borges2,
Conceiça ~o Calhau3,5,6, Fernando Mac ario1
MO900 ENHANCED EXPRESSION OF THIOREDOXIN-INTERACTING
1
PROTEIN (TXNIP) RESULTS IN REDUCED TRX ACTIVITY AND DIAVERUM Portugal, Sintra, Portugal, 2Faculdade de Ci^encias da Nutriç~ ao e
INCREASED OXIDATIVE DNA-DAMAGE IN PERITONEAL Alimentaç~ao da Universidade do Porto, Porto, Portugal, 3CINTESIS - Centro de
4
DIALYSIS PATIENTS* Investigaç~
ao em Tecnologias e Serviços de Sa ude, Porto, Portugal, Hospital de Santa
Cruz, Serviço de Nefrologia, Lisboa, Portugal, 5 NOVA Medical School j Faculdade de
Tina Oberacker1, Severin Schricker2, Moritz Schanz2, Dominik M. Alscher2, Ci^encias Médicas da Universidade Nova de Lisboa, Lisboa, Portugal and 6Unidade
Markus Ketteler2 Universitaria Lifestyle Medicine José de Mello Sa
ude by NOVA Medical School, Lisboa,
1
Dr. Margarete Fischer-Bosch - Institute of Clinical Pharmacology, Stuttgart, Germany Portugal
and 2Robert-Bosch Hospital, Department of General Internal Medicine and Nephrology,
Stuttgart, Germany BACKGROUND AND AIMS: Erythropoietin Resistance Index (EPORI) has been
previously associated with higher risk of mortality and morbidity in hemodialysis (HD)
BACKGROUND AND AIMS: Peritoneal dialysis (PD) is an effective method of renal patients (pts). The objectives of this study were to identify which factors, such as the
replacement therapy (RRT). The long-term use of PD as a RRT is limited due to risk of malnutrition, are associated with EPORI and to assess its association with
adverse effects of high glucose-based PD solutions to the structure and function of the mortality and hospitalization risk.
peritoneal membrane. PD patients show excessive oxidative stress compared to healthy METHOD: Historical cohort study in a group of high-flux HD pts from 25 outpatient
controls. However, there are only scare information on pathophysiological HD clinics, starting from a baseline group of 2975 pts. We evaluated EPORI,
mechanisms leading to oxidative DNA-damage in PD patients. Therefore, the aim of interdialytic weigh gain (IDWG), Malnutrition Inflammation Score (MIS) and the
this study was to elucidate the mechanism leading to excessive oxidative stress in other parameters at the study baseline. For a better understanding of weight gain
human samples of the peritoneal membrane. patterns, we calculated the average of the IDWG at the day of monthly blood sample
METHOD: Human peritoneal biopsies of healthy controls, PD patients and patients collection of the previous 3 months, values >4% were considered high. A MIS>5
with EPS were collected. Protein expression of TXNIP was analysed by ELISA using indicated nutritional risk.
plasma samples and by immunohistochemistry of peritoneal biopsies using a Histo- RESULTS: We analyzed 2044 pts, 1148 (56%) males, 642 (31%) diabetic, with a mean
Score. Protein expression of TRX was examined by immunohistochemistry. To age 68.4614.12 years, a mean HD vintage 105674 months and mean EPORI
measure TRX activity a kit based on the reduction of insulin by reduced TRX was used. 7.2367.51 (U/week/kg)/(g/dL). During a follow-up of 48 months, 719 pts (35%) died
The resulting oxidative DNA-damage was investigated by immunohistochemistry and 1291 pts (63%) were hospitalized at least once after baseline assessment, 531 pts
using a Histo-Score or by ELISA using plasma samples of patients. and 400 pts were excluded because follow up was not possible and EPORI data was not
RESULTS: Biopsies from the peritoneum of 8 healthy controls, 11 uremic patients, 22 available, respectively.
patients on PD < 12 months or 29 patients on PD > 12 months and of 13 patients with ROC curve analysis identified different cut-off values for EPORI in relation with all-
EPS were collected. The age of the uremic patients was higher (median 65.0 years, IQR: cause mortality and hospitalizations.
49.0-75.0) than in the other subgroups (PD < 12 months: median 62.0 years, IQR: UNIVARIABLE ANALYSIS: An EPORI>5 was associated with higher MIS
52.25-68.25, PD > 12 months: median 60.0 years, IQR: 39.5-70.5 and EPS: median (7.0663.9, vs 6.0263.48, p<0.001), higher IDWG (3.1561.23 vs 1.2661.09, p<0.001),
51.00 years, IQR: 40.0-57.5). In general, there were more female participants in the lower Hematocrit (Htc) (33.2663.17 vs 33.6962.61, p<0.001), higher C-Reactive
control-group (75 %) compared to all other groups (uremic group: 27%, PD < 12 Protein (CRP) 14.94624.45 vs 10.4618.9, p<0.001), female gender (57% vs 48%,
months: 18 %, PD >12 months: 41% and EPS group 33 %). Time on PD was longer in p<0.001), death (58% vs 49%, p<0.001) and hospitalization (55% vs 47%, p<0.001).
EPS patients (median 72.0 months) than in PD patients (PD <12 months: median 10.0 When analyzing with Kaplan-Meier estimator using log-rank test to compare survival
months and PD > 12 months: 39.0 months). curves, mortality and hospitalizations were increased in all sub-groups with higher
The ELISA study of plasma samples showed that TXNIP is upregulated in all groups values for EPORI (cut-offs of 5 to 8) when compared, respectively, with lower EPORI
compared to healthy controls. Immunohistochemically studies of peritoneal biopsies values.
showed also an upregulation of TXNIP upon exposure to high glucose-based dialysis
fluids (PD and EPS group). Interestingly, a glucose-related change in protein
expression of its interacting partner and cellular anti-oxidant TRX was only observed
in EPS samples. TRX activity in uremic patients was almost unchanged compared to
Mortality Hospitalizations
healthy controls except for one patient. However, enhanced TXNIP expression Log-Rank (x2) p-value Log-Rank (x2) p-value
correlated with a reduced activity of TRX in samples of PD as well as EPS patients. EPORI>5 16.663 <0.001 25.808 <0.001
Reduced TRX activity resulted in an increase of produced ROS. Therefore, the effect on
the generation of oxidative damage was analysed by ELISA of plasma samples and by EPORI>6 21.905 <0.001 28.847 <0.001
immunohistochemistry on peritoneal sections. Both analysis showed an increase in the EPORI>7 23.698 <0.001 29.847 <0.001
oxidative DNA-damage marker 8-Hydroxydesoxyguanosin (8-OHdG) in all PD EPORI>8 27.022 <0.001 44.673 <0.001
samples and samples of EPS patients compared to the control group.
CONCLUSION: Here, we show that high glucose-based peritoneal dialysis solutions MULTIVARIABLE ANALYSIS: The predictors of EPORI were MIS>5 (OR 1.564,
lead to an upregulation of TXNIP expression in human peritoneal samples. This p<0.001), IDWG (OR 1.234, p< 0.001), CRP (OR 1.010, p<0.001) and Htc (OR 0.948,
increase in TXNIP expression reduces the activity of its interacting partner an p<0.001).
antioxidant TRX leading to an increase in ROS production and enhanced levels of In similar models, adjusting for MIS>5 (p<0.001), gender (p<0.001), age (p<0.001),
DNA-damage. CRP (p<0.001) and dialysis vintage (p<0.001), different EPORI cut-off values were
In this study, we elucidate for the first time a novel mechanism showing that glucose- associated with higher risk of mortality and hospitalizations.
dependent upregulation of TXNIP induces a perturbation of the intracellular redox
equilibrium leading to alterations of the peritoneal membrane. Therefore,
manipulation of TXNIP expression may be a promising therapeutic target to improve
peritoneal membrane function. Mortality Hazard ratio (HR) 95% CI p-value
estimate
Lower limit Upper limit
EPORI>5 1.378 1.179 1.611 <0.001
EPORI>6 1.418 1.216 1.654 <0.001
EPORI>7 1.419 1.215 1.658 <0.001
EPORI>8 1.466 1.248 1.723 <0.001

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
Hospitalization Hazard ratio (HR) 95% CI p-value Further in-depth examinations should be verify our findings, determining whether
estimate therapeutic measures targeting cFLC balance, such as hemodiafiltration and expanded
dialysis, would be helpful to reduce the “inflammunity” process, characterizing
Lower limit Upper limit dialyzed patients.
EPORI>5 1.301 1.160 1.458 <0.001
EPORI>6 1.316 1.174 1.476 <0.001
EPORI>7 1.370 1.219 1.540 <0.001
EPORI>8 1.468 1.300 1.658 <0.001
MO903 THE ASSOCIATION BETWEEN VITAMIN K, CALCIUM,
CONCLUSION: In the modern hemodialysis era, higher EPORI cut-off values were PHOSPHORUS LEVELS AND NUTRITIONAL STATUS IN
associated with a progressive higher risk of mortality and of hospitalization. The HEMODIALYSIS PATIENTS
modification of the EPORI predictors that are susceptible to improvement, such as the
nutritional and inflammation status, may contribute for a better prognosis in this Sylwia Małgorzewicz1,2, Ewelina Puchalska-Reglin ska3, Lucyna Konieczna4,
population. Katarzyna Krzanowska5, Alicja Debska-Slizien1
1
Medical University of Gda
nsk, Nephrology, Transplantology and Internal Diseases,
Gdansk, Poland, 2Medical University of Gda nsk, Clinical Nutrition, Gdansk, Poland, 37
Szpital Marynarki Wojennej, Dialysiis Unit, Gdansk, Poland, 4Medical University of
Gdansk, Department of Pharmaceutical Chemistry, Gda nsk, Poland and 5Uniwersytet
Jagiello
nski Collegium Medicum, Department of Nephrology, Krak ow, Poland
MO902 SERUM FREE LIGHT CHAINS IN HEMODIALYSIS PATIENTS:
A BRIDGE BETWEEN INFLAMMATION, IMMUNE SYSTEM BACKGROUND AND AIMS: Vascular calcification is highly prevalent in dialysis
DYSFUNCTION AND MORTALITY RISK patients. The most common postulated cause, apart from calcium and phosphorus
disorders, is sub-clinical vitamin K deficiency. It results in the failure of the GLA-
Antonio Lacquaniti1, Susanna Campo1, Teresa Casuscelli Di Tocco1, matrix protein (MGP) to undergo carboxylation. The lack of functional carboxylated
Paolo Monardo1 MGP may contribute to increased vascular calcification. Aim: We assessed the
1
Papardo Hospital, Nephrology and Dilsysi Unit Internal Medicine Department, relationships between vitamin K, MGP, calcium, phosphorus levels and nutritional
Messina, Italy status in hemodialysis patients.
METHOD: The study included 58 hemodialysis patients in stable clinical condition
(mean age 64.1 6 15.6 yr) . We determined plasma levels of: vitamin K1 and K2 (LC-
BACKGROUND AND AIMS: Uremic toxins, poor removed by conventional MS method), GLA -matrix protein (ucMGP and cMGP), osteocalcin (ELISA methods),
hemodialysis (HD), represent independent risk factors for mortality in end-stage renal parathyroid hormone (iPTH), calcium (Ca), phosphorus (P), CRP and routine
disease (ESRD). biochemistry. Echocardiography was performed and BMI was calculated. Nutritional
Middle uremic toxin molecules were associated to pathological features of uremia, such status was assessed by SGA and s-albumin – malnutrition was diagnosed based SGA
as immune dysfunction and inflammation. These two entities are not mutually 5 and s-albumin  38g/l. FFQ-6 was used to dietary assessment. Patients with HPT
exclusive, but they could represent two sides of the same coin. ESRD-associated (n=17; 32%) were treated by active vitamin D/paricalcitrol and calcium carbconicum.
inflammation is closely related to the activation of innate immune system. Free light RESULTS: Malnourished patients (n=11; 20%) presented statistically significantly
chain (FLC) may be a specific assessment of inflammation, representing a direct higher CRP, age and lower phosphorus, iPTH, BUN, creatinine, cholesterol and
function of adaptive immunity through B-cell lineage production rather than a general potassium. Also, malnourished patients presented significantly higher ucMGP and
marker of inflammation. lower cMGP and lower both vitamin K forms in comparison to well-nourished
While several studies have assessed the relation between FLCs and mortality risk in (ucMGP 18.9 vs 13.2 ng/dl; p=0.0005; cMGP 150.1 vs 332.4 ng/dl; p=0.0002). Diet in
chronic kidney disease (CKD), FLCs, as uremic toxins in non-multiple myeloma both groups malnourished and well-nourished not differ significantly, though
dialyzed patients, were marginally analyzed. malnourished patients ate less amount of nutrients. Additionally, phosphorus level
The aim of this prospective study was to evaluate the clinical impact of FLCs levels in positively correlated with Kt/V, SGA and vitamin K2 (R Spearman =- 0.3;p=0.01,R
HD patients, during a 2-years follow-up analysing the relations with biomarkers of Spearman = 0.4;p=0.05;R Spearman = 0.3; p=0.001, respectively).
inflammation, such as C-reactive protein (CRP) and procalcitonin (PCT), main CONCLUSION: Vitamin K deficiency, as expressed by high ucMGP levels is
lymphocytes subsets, such as CD4þ and CD8þ T cell count and high mobility group associated with nutritional status. Low albumin and chronic inflammation might
box (HMGB) -1 levels, as expression of the innate immune system. The potential link increase risk of calcification in spite relatively low iPTH and phosphorus levels.
between FLCs levels and mortality risk was assessed.
METHOD: 190 patients on chronic hemodialysis at the Nephrology and Dialysis Unit
of Papardo Hospital in Messina, Italy, were enrolled and followed for 2 years. Inclusion
criteria were: age >18 years, absence or <200 ml/die residual diuresis, j/k ratio within
the renal reference range (0.37–3.1).
Receiver operating characteristics (ROC) analysis was performed to estimate the cut-
off points of HMGB-1 and cFLC. Kaplan-Meier survival analysis and Cox proportional MO904 DIETARY PATTERNS IN HEMODIALYSIS PATIENTS:
multivariate hazards model were used for clinical outcome. RELATIONSHIP WITH CLINICAL AND NUTRITIONAL
RESULTS: HD patients were characterized by high FLC levels. jFLC values were 182.3 PARAMETERS
(IQR: 140.2 – 216.1) mg/L, whereas kFLC levels were 108.2 (IQR: 72.7 – 143.2) mg/L.
The median combined (c) FLC concentration was 182.9 mg/L (IQR = 207.8 – 330.2), Cristina Garagarza1,2, Ana Valente1, Cristina Caetano1, Ine ^s Ramos1,
which was extremely greater than the median reported in the general population Joana Sebastia ~o1, Mariana Pinto1, Telma Oliveira1, Anibal Ferreira3,4,
(normal range = 9.3 – 43.3 mg/L) and in CKD patients [68.9 mg/L (IQR = 49.4 – Catarina Sousa Guerreiro2
1
100.9)]. Nephrocare Portugal, Nutrition Department, Lisboa, Portugal, 2Faculdade de Medicina
No differences in cFLC levels were revealed according to dialysis techniques. da Universidade de Lisboa, Laborat ao, Lisboa, Portugal, 3Nephrocare
orio de Nutriç~
HD patients showed significant reduction of CD4þ and CD4þ/CD8þ ratio. High Dialysis Unit, Vila Franca de Xira, Nephrology Department, Lisboa, Portugal and
HMGB1 levels were detected in HD patients (161.3 6 39.7 ng/ml) and positively 4
Faculdade de Ci^encias Médicas, Nova Medical School, Lisboa, Portugal
related to PCT and cFLC (r = - 0.38; p < 0.001), with an inverse relation to CD4þ/
CD8þ ratio. BACKGROUND AND AIMS: Nutritional recommendations for hemodialysis (HD)
cFLC positively correlated with b2 microglobulin, hemoglobin, and HMGB1. patients focus on the achievement of a sufficient energy and protein intake without
Conversely, an inverse correlation was revealed with surrogate markers of exceeding phosphorus, potassium, sodium and/or fluids intake limits. This study
inflammation, such as CRP, procalcitonin, neutrophil counts. aimed to identify different dietary patterns of HD patients and analyze their
There were 49 deaths during the follow-up. The majority (23/49) of deaths were relationship with clinical and nutritional parameters.
attributed to cardiovascular disease, the remainder to infection and malignancy. METHOD: This was a longitudinal prospective multicenter study with 582 HD
cFLCs and sHMGB-1 levels in this group were significantly elevated. By ROC analysis, patients from 37 dialysis centers. Dry weight, Kt/V, serum potassium, phosphorus,
HMGB-1 levels > 100.9 ng/mL and cFLC > 223.4 mg/l were associated with a calcium, sodium, creatinine and C-reactive protein were measured. Dietary intake was
significantly lower survival rate (p < 0.02 by log-rank test) than for patients with lower obtained using the Food Frequency Questionnaire. Dietary patterns were derived from
levels when using Kaplan-Meier analysis. After adjusting for confounding factors, by principal component analysis based on 20 food groups which were adjusted for total
Cox proportional hazards method, the difference remained statistically significant (p = energy intake. Linear regression was used to analyze patterns and the variables of
0.02) interest. All statistical tests were performed using SPSS 26.0 software. A p-value lower
CONCLUSION: Our study demonstrated an independent relation between high cFLC than 0.05, was considered statistically significant.
levels and mortality in HD patients. cFLCs represent a potential biomarker of RESULTS: Patients’ mean age was 67.8617.7 years and median HD vintage was 65
“inflammunity”, a physiopathological process playing a pivotal role in ESRD, based on (43-104) months. Three different dietary patterns were identified: “Western” (31.3% of
a vicious circle between inflammation and immune dysfunction.

10.1093/ndt/gfab102 | i495
Abstracts Nephrology Dialysis Transplantation

the patients) with high intake of soft drinks, home-made fried potatoes, caffeinated
drinks, red and processed meat, and low intake of fruit and vegetables soup;
“Mediterranean” (33.5% of the patients) with high intake of vegetables, beans, fish,
olive oil, eggs, and low intake of milk and milk products. Finally, “Low animal protein”
(35.2% of the patients) with high intake of whole grain bread, cookies and sweets,
vegetables soup and low intake of white bread, rice, pasta and potatoes. Regarding
clinical parameters, the Mediterranean pattern was predictor of a higher dry weight
(p=0.001), higher creatinine (p=0.032) and lower serum calcium (p=0.024), whereas
Western pattern predicted higher phosphorus (p=0.006), sodium (p=0.014) and
creatinine (p=0.001). Low animal protein pattern predicted lower creatinine levels
(p=0.011). After adjusting for age, gender, presence of diabetes, HD vintage and Kt/V,
serum calcium was the only parameter which remained statistical significant within the
Mediterranean pattern. Comparing the nutritional parameters studied, the
Mediterranean pattern was the strongest predictor of a higher intake of protein (%)
(p<0.001), folate (p<0.001), vitamin B12 (p<0.001), vitamin B6 (p<0.001), vitamin C
(p<0.001), vitamin D (p<0.001), potassium (p=0.015) and omega 3 fatty acids
(p<0.001) and a lower intake of carbohydrates (%) (p<0.001), calcium (p<0.001) and
sodium (p=0.006).
CONCLUSION: Three different dietary patterns were identified in these HD
population. The pattern which was closer to the well-known Mediterranean diet was MO905 Figure 1: Time trends of pro- and anti-inflammatory cytokines in HD patients
associated with a better nutritional intake profile, which, at least theoretically, are with COVID-19. A) IL-6 showed a trend to decrease in the first week after the
associated with better clinical outcomes. diagnosis of COVID-19, reaching statistical significance in PLD group. B) IL-10
presented a significant increase in the first week after the diagnosis of COVID-19 in
HDx group. C) IL-8 circulating levels, as well as D) sTLR4 levels, did not present
significant modifications during the study. Expanded hemodialysis (HDx): black lines;
Protein-leaking dialysis (PLD): red lines.
* = p<0.05 vs T0
MO905 EFFECTS OF DIFFERENT DIALYSIS TECHNIQUES ON
INFLAMMATION IN MAINTENANCE HEMODIALYSIS
PATIENTS WITH COVID-19: A RANDOMIZED STUDY

Pasquale Esposito1,2, Leda Cipriani1, Daniela Verzola1, Maria


Antonietta Grignano3, Fabrizio Grosjean3, Elisa Russo1, Teresa Rampino3, MO906 DIAGNOSIS OF SARCOPENIA ACCORDING TO THE
Francesca Viazzi1,2 EWGSOP2 STEPS IN VERY ELDERLY HEMODIALYSIS
1
University of Genova, Department of Internal Medicine, Genova, Italy, 2IRCCS Ospedale PATIENTS
Policlinico San Martino, Genova, Italia. Clinica Nefrologica, Dialisi, Trapianto and 3Unit
of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Maria Luz Sa nchez-Tocino1, Blanca Miranda1, Sebastia n Mas2,3, Ana Maria De
and University of Pavia, Italy Alba-Pen ~aranda1, Antonio Lopez-Gonzalez4, Monica Pereira1, Alberto Ortiz2,5,
Emilio Gonzalez Parra2,5, Carolina Gracia-Iguacel2
1
BACKGROUND AND AIMS: Uncontrolled inflammation plays a relevant role in the Fundaci nigo Alvarez de Toledo, Madrid, Spain, 2IIS-Fundaci
on Renal I~ on Jiménez Dıaz,
pathogenesis of Coronavirus Disease-19 (COVID-19) and has been related to disease Madrid, Spain, 3CIBERDEM, Madrid, Spain, 4Complejo Hospitalario Universitario A
5
severity and unfavorable outcomes. Here, we studied the time trend of pro-and anti- Coru~
na, A Coru~na, Spain and Universidad de Autonoma de Madrid, Medicina, Madrid,
inflammatory markers in a population of patients undergoing hemodialysis (HD) Spain
affected by COVID-19, evaluating the potential modulating effects of two different
dialysis approaches. BACKGROUND AND AIMS: Sarcopenia, defined as the loss of muscle mass and
METHOD: For this prospective randomized study, we recruited maintenance strength, is common in patients with chronic kidney disease. The variability of the
hemodialysis patients with confirmed COVID-19 infection. After diagnosis, the prevalence of sarcopenia depends in part on the diagnostic criteria applied. In 2019, the
patients were randomized to two different dialysis modalities, expanded HD (HDx), European Working Group on Sarcopenia in Older People 2 (EWGSOP2) proposed
performed by use of a medium cut-off membrane, and standard treatment based on the four steps to diagnose and assess sarcopenia. The concept of sarcopenia is
use of a protein-leaking dialyzer (PLD). Clinical and laboratory data were collected, encompassed within the broader concept of frailty.
including circulating pre and post-dialysis levels of interleukin-6 (IL-6), interleukin-8 The aim of this study was to analyse the incidence of sarcopenia in very elderly patients
(IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-g). on haemodialysis following the criteria recently established by the European Working
Samples were collected at diagnosis (T0), one and two weeks after the diagnosis (T7 Group on Sarcopenia in Older People EWGSOP2. Additionally, to assess the
and T14, respectively). usefulness of the diagnostic algorithm in the very elderly haemodialysis population,
RESULTS: Twenty-seven HD patients with COVID-19 (69.7 616.6 years, 14 males) and its association with functionally scales related to sarcopenia, such as dependency,
were compared with 14 non-infected HD patients, as the control group. COVID-19 frailty, and nutrition.
patients presented a significantly reduced number of lymphocytes, including CD4 METHOD: In a prospective study of 60 patients on chronic hemodialysis aged 75- to
andCD8 subpopulations, and higher levels of ferritin and lactate dehydrogenase. 95-years, sarcopenia was assessed according to the 4 EWGSOP2 steps: Find-Assess-
Moreover, COVID-19 patients had higher levels of IL-6 [35.5 (59.4) vs 12 (43) pg/ml, Confirm-Severity, using Strength, Assistance walking, Rise from a chair, Climb stairs,
p=0.048] and IL-10 [9.3 (20.8) vs 1.2 (1.4) pg/ml, p=0.02], while the levels of IL-8 and and Falls (SARC-F) to find, grip strength by dynamometry (GFD) and sit to stand to sit
sTLR4 were comparable. Then, twenty-five patients were randomized to undergo HDx 5 (STS5) test to assess, appendicular skeletal muscle mass by bioimpedance to confirm
(n.15) or PLD (n.10). and gait speed, the Timed-Up and Go (TUG) test, and the Short Physical Performance
Basal characteristics and cytokine levels were not significantly different between the Battery (SPPB) for severity. Functionality scales of malnutrition inflammation (MIS),
two groups. All over the study, no significant modifications of circulating cytokine comorbility of Charlson, dependence of Barthel, fragility by FRAIL index2 and
levels were observed. Similarly, no significant differences were found between patients Physical Activity Scale for the Elderly (PASE) were conducted.
on HDx or PLD evaluated at different time points. After a single HD treatment, IL-8 RESULTS: Sixty patients were involved in the study. Sixty-eight percent (41) were
showed a significant reduction compared to pre-dialysis levels in both groups. IL-8 men, with a mean age of 81.8565.58 years and length of stay in HD 49.88640.29
reduction rate resulted significantly correlated with IL-8 pre-dialysis levels. Finally, months. The sequential four steps resulted in a prevalence of confirmed sarcopenia of
there were no correlations between cytokine levels and clinical characteristics and 20% and of severe sarcopenia of 20%. Correlation of the different variables defined by
outcomes. the EWGSOP2 with the scales of MIS, Barthel, Frail, Charlson and PASE was analyzed.
CONCLUSION: In maintenance HD patients, COVID-19 is not related to a sustained It is observed that the SARC-F but not BIA correlates with the functionality tests. The
inflammatory response. Modulation of the inflammation is not a suitable therapeutic GFD is the test that correlates with more variables, both functional and
target in this specific population. Other mechanisms could be involved in the anthropometric. Of the severity measurement scales, the SPPB is the one that correlates
pathogenesis of COVID-19 in HD patients. with the greatest number of variables.
CONCLUSION: These findings question the four-step EWGSOP2 assessment for very
elderly hemodialysis patients and suggest that 20% had confirmed severe sarcopenia.
Functionality scales correlated better with GFD and SPPB.

i496 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO907 ASSOCIATION OF ADIPOSITY AND SARCOPENIA WITH MO908 UNCORRECT NUTRITIONAL MANAGEMENT AND LOW
CARDIAC VALVE CALCIFICATION IN PATIENTS ON QUALITY OF LIFE IN HEMODIALIZED PATIENTS:
MAINTENANCE HEMODIALYSIS. A CROSS-SECTIONAL MULTICENTRIC STUDY
STUDY
Ersilia Satta1, Carmine Romano2, Tersa Della Corte3, Carmelo Alfarone3,
Petrini Plyntzanopoulou1, Marios Papasotiriou2, Athina Drakou3, Guido Gembillo4, Sandro Gentile5
Panagiotis Politis4, Christos Andriopoulos4, Evangelos Papachristou2, 1
Nefrocenter research srl, and Nyx Sturtup, Via xxIV May Cava dei Tirreni, Naples , Italy,
Theodora Papachrysanthou4 2
Nefrocenter research srl, and Nyx Sturtup, Naples, Italy, 3Nefrocenter research srl, and
1
Konstantopouleio General Hospital, Department of Nutrition and Diet, Athens, Greece, Nyx Sturtup, Via xxIV May Cava dei Tirreni, Naples, Italy, 4Unit of Nephrology and
2
University Hospital of Patras, Department of Nephrology, Patras, Greece, 3Henry Dialysis, Department of Clinical and Experimental Medicine, Department of Clinical
Dunant Hospital Athens, Department of Nephrology, Athens, Greece and 4Nephroiatriki and Experimental Medicine, Messina, Italy and 5Department of Internal Medicine,
Dialysis Unit, Department of Nephrology, Athens, Greece University Campania L Vanvitelli, Naples, Italy

BACKGROUND AND AIMS: Cardiac valve calcification (CVC) is a common BACKGROUND AND AIMS: In patients with kidney impairment, the progression to
disorder in patients with end stage kidney disease (ESKD) and is a predictor of end-stage renal diseases (ESRD) can lead to a gradual loss of independence with
cardiovascular disease and all-cause mortality. Several risk factors are related to CVC worsening quality of life. Proper nutritional management and daily exercise can help
in patients with ESKD which include higher age, dyslipidemia, hypertension and patients live with their condition in a more propositive way.
diabetes as well as inflammation, bone mineral disease and malnutrition. Moreover, METHOD: We performed a multicentric study on the habits of 222 hemodialyzed
visceral adiposity is associated with disturbed lipid metabolism and proinflammatory patients, belonging to 4 different dialysis centers. Through self-administered
activity which could predispose for CVC. Furthermore, sarcopenia and dynapenia is a questionnaires, we collected information about patients attitudes and behavior that
state common in patients with ESKD. Thus, the aim of this cross-sectional study is to affect their daily activities and self-care.
investigate the relationship of adiposity, components of sarcopenia and malnutrition RESULTS: Through the use of the Council for Nutritional Appetite Questionnaire, we
with cardiac valves calcification in patients on chronic hemodialysis. assessed that 60,81% of patients had a risk of weight loss of 5% in the next six months
METHOD: Adult patients that were on maintenance hemodialysis were eligible for (Table 1 Baseline Characteristics). The Malnutrition Inflammation Score indicated that
entering the study. Recruitment took place from March 2019 to September 2020. 39,63% had a mild malnutrition and 12,16% a severe malnutrition; the serum albumin
Exclusion criteria included, patients with less than 6 months on hemodialysis, patients was between 3-5 and 3,9 g/dL in 42,79% of patients, 3,0 – 3,4 g/dL in 18,01% of
with cancer, inflammatory bowel disease, severe infection, cardiac valve disease prior to patients, <3 g/dL in 3,15% of the whole cohort. For the bioimpedance analysis (BIA)
dialysis initiation, history of parathyroidectomy and intravenous albumin the Body Cells Mass Index (BCMI) values were indicative in 60% of patients of a
administration 3 months prior to nutritional assessment. Calcification of heart valves normal nutritional status (Figure 1), parameters that remained superimposable in the
and systolic and diastolic function was assessed by using two-dimensional pre and post-dialysis BIA. The ECM/BCM ratio indicated in pre-dialysis that 27% of
echocardiography. Nutritional assessment was made using the Geriatric Nutritional patients present a state of dehydration and, on the contrary, 73% an edematous state,
Risk Index. Conicity Index, Waist to Height Ratio, the Visceral Adiposity Index, the vice-versa in the post-dialysis the dehydration status rises to 48% and the edematous
Lipid Accumulation Product, the Height to Waist Phenotype were also calculated. state falls to 52% (Figure 2). For the BIA a phase angle of less than 4  was found in
Waist, calf and mid arm circumference measurement was performed in the end of a 18% of patients, a critical value linked to a higher mortality risk. 56% of patients
midweek dialysis session. Muscle strength was based on a measurement of hand grip showed a value between 4  -5  while 26% values between 6  and 10  .
strength using a hydraulic hand dynamometer in the non-fistula hand prior to dialysis
session. Dynapenia was considered for values < 16 kg in females and < 27kg in males.
Serum biochemistry parameters such as total protein, albumin, calcium, phosphate,
total cholesterol, triglycerides, HDL, LDL, CRP and iPTH were also measured.
RESULTS: Overall, 130 patients were included in the study with a mean age of
66612.47 years (68.5% males) and an average dialysis duration of 4.3764.95 years. No
cardiac valve calcification was found in 34.6%, while both aortic and mitral valve
calcification was found in 41.5% of patients. Calcification only of the aortic (AVC) or
mitral (MVC) valve was found in 14.6% and 9.2% respectively. Compared to non AVC
group, AVC group had significantly higher age, higher prevalence of diastolic
dysfunction, CRP values and CRP/albumin ratio and lower albumin to total proteins
ratio. Patients with MVC showed significantly higher prevalence of diastolic
dysfunction, higher levels of iPTH, CRP/albumin ratio and lower albumin to total
proteins ratio. Adiposity, nutritional, anthropometric indices and sarcopenia
parameters such as creatinine index, muscle power and physical performance status
did not show any difference between all CVC groups. Increased age [OR (95%CI):1.06
(1.00-1.12) p=0.05], diastolic dysfunction [OR (95%CI): 3.07 (1.05-8.92); p=0.04],
CRP/albumin ratio were associated with increased risk of AVC, whereas the CRP/
albumin ratio appeared as the most powerful risk factor for mitral and for any CVC
[OR (95%CI): 3.41 (1.40-8.28); p=0.007, OR (95%CI): 7.98 (2.62-24.98) p<0.001,
respectively]. ROC analysis indicated that increased values of CRP/albumin ratio are
strong positive predictors of AVC [AUC, 95%CI 0.66 (0.56-0.75) p=0.002], MVC
[AUC, 95%CI 0.642 (0.545-0.74) p=0.005] and calcification of any valve [AUC, 95%CI
0.71 (0.615-0.806) p<0.001].
CONCLUSION: Adiposity, nutritional, anthropometric indices and sarcopenia did
not show to correlate with CVC in patients with ESKD on hemodialysis. Factors, such
as diastolic dysfunction and notably increased CRP/albumin ratio were strong
predictors of CVC.
MO908 Figure 1: Body Cell Mass Index (BCMI) bioimpedentiometry of the total
patients

10.1093/ndt/gfab102 | i497
Abstracts Nephrology Dialysis Transplantation

percentage according to the one used.


AIM: To assess prevalence of malnutrition-inflammation by MIS scale (malnutrition-
inflammation-score) in HD or PD patients of Spanish dialysis units.
METHOD: We evaluated 2937 patients on dialysis (HDþPD) in Spain were evaluated
on the MIS scale strata (Kalantar-Zadeh 1999) also analyzing:
Common data: Age, sex, dialysis time, Charlson-I., RRF, albumin,prealbumin,Kt/V
transferrin, CRP, DM, Specific-HD: HD type, AVF or Catheter, Specific-PD:PD-type,
transport type.
Statistical analysis with SPSS.23 software, using parametric and non-parametric test.
RESULTS: We evaluate 2748 HD patients, median age 71 (RIC20), 65.90% male,
median MIS 6 (RIC4), DM 36.91%, T in HD 36m (RIC54), FRR 35.44% , Charlson
Index 7 (RIC4) and 186 in PD (62.96% men), median
-age 62 (RIC 24), median-MIS 4 (RIC 2), T in PD of 18.5 m (RIC 23.5),DM 30.77%,
FRR 79.89%, I Charlson 5 (RIC 4), In PDA 99pac-52.38%.
Prevalence of global malnutrition (MIS>2) was 89% considering HD1DP and 50%
when MIS>5 (table 1)

MO909 Table 1. Prevalence of malnutrition in HD and PD

Total 2937 HD 2748 DP 189


Well-nourished (0-2) 343 (11%) 303 (11.0%) 40 (21.2%)
Mild-malnourished (Risk ) (3-5) 1158 (39%) 1053 (38.3%) 105 (55.6%)
Moderate-malnourished (6-7) 588 (20%) 564 (20,5%) 24 (12.9%)
Severe malnourished (8-10) 523 (17%) 512 (18.6%) 11(5.8%)
Extreme malnourished (>10) 325 (13%) 316(11.5%) 9 (4.8%)
In PD the higher normonutrides greater Kt/V in manual vs automatic not the
malnourished ones. FRR significantly in greater % in normonutrides. No differences in
malnutrition depending on carrier type. CRP sig major in MIS>2 and >5
In HD, Normo versus malnourished and with MIS>5 significant difference: HD type,
CRP, HD Type, AVF vs catheter, age,sex.
The prescription for Oral supplement was low and higher in HD 12.4% vs DP 6.3%.
CONCLUSIONS: 1.- There is a high prevalence of malnutrition on dialysis being
higher in HD. 2.- In PD, FRR major and CRP minor in well-nourished versus
malnourished. 3.- In HD: Normo versus malnourished and with MIS>5 significant
difference: HD type, CRP,Charlson I. AVF vs catheter, age,sex. 4.- There is a
percentage of malnourished patients with very low percentage of oral supplement.

MO910 CHANGE IN BODY COMPOSITION MEASURED BY


MO908 Figure 2:Bioimpedentiometry ratio between Extra Cellular Mass and Body BIOIMPEDANCE SPECTROSCOPY AFTER COVID19
Cell Mass Index (ECM / BCM) of the total number of patients in the pre-dialysis and LOCKDOWN IN HAEMODIALYSIS PATIENTS
post-dialysis times (30 minutes from the end of dialysis).
Lucia Aubert1, Marıa Fernandez-Vidal1, Paula Jara Caro Espada1, Sara Afonso1,
Justo Sandino Pérez1, Evangelina Mérida1, Elena Gutiérrez1, Claudia Yuste1
1
CONCLUSION: In conclusion, the data from this study show that inappetence and Hospital Universitario 12 de Octubre, Nephrology, Madrid, Spain
single alterations indicative of risk of malnutrition are frequent in Hemodialysis
patients, but a clear diagnosis of malnutrition is relatively rare. A large percentage of BACKGROUND AND AIMS: Changes on body composition have an impact on the
patients are overweight, with increased abdominal adiposity but with reduced cell mass survival of haemodialysis (HD) patients. The aim of the study was to determine the
and with a protein intake lower than recommended levels. The results underline that impact of the reduction of physical activity due to COVID19 lockdown on body
malnutrition risk leading to a lower quality of life are still major problems in composition in HD patients.
Hemodialysis patients. Bioimpedance analysis and PhA analysis represents a useful METHOD: Retrospective and observational study including 149 HD patients.
tool in the clinical management of hemodialized patients. Nutritional and Bioimpedance spectroscopy (BIS) data were recorded before and after
COVID19 lockdown (mean of 148 6 20 days between determinations).
RESULTS: Over the 49 days of COVID19 lockdown, we observed a decrease in
normohydrated weight (NHW) of 1.01 6 3.59 kg mainly secondary to a reduction on
total body water (TBW) 0.95 6 3.78 L (extracellular water 0.45 6 1.58 L and
intracellular water 0.41 6 2.36 L). There was also a small loss on lean tissue index (LTI)
MO909 MULTICENTER EPIDEMIOLOGICAL STUDY OF of 0.28 6 2.42 kg/m2, with an increase of fat tissue index (FTI) 0f 0.02 6 2.82 kg/m2.
MALNUTRITION INFLAMATION IN DIALYSIS “EMID” IN Twenty-three patients presented COVID19 infection, of which 21 required admission
SPANISH DIALYSIS CENTERS (median of 10 [4-16] days). Patients who presented COVID19 were older (70.7 6 12.0
vs 64.9 6 16.6 years, NS) with higher Charlson index (7.48 6 2.77 vs 6.33 6 2.65, p =

Guillermina Barril1, Angel Nogueira1,2, Secundino Cigarran3, Juan Latorre4, 0.07). Patients with COVID19 infection presented a greater loss on LTI (-1.18 6 3.15
Rosa Sanchez5, Antonio De Santos6, Fernando Hadad-Arrascue7, bs -0.16 6 2.30 kg/m2; p = 0.22), FTI (-0.41 6 3.38 vs 0.06 6 2.74 kg/m2; p = 0.54);
Igor Romaniouk8, Gloria Anton-Perez9, Israel Thuissard10 BMI (-1.49 6 2.14 vs -0.25 6 0.96 kg/m2; p = < 0.01) and NHW (-4.00 6 6.33 vs -0.62
1 6 2.90 kg; p = < 0.01) compared to patients without COVID19 infection. The length
Hospital Universitario de la Princesa, Nefrology, Madrid, Spain, 2Hospital Universitario of hospitalization was associated with greater loss of BMI and NHW, resulting,
de la Princesa, Nephrology, Madrid, Spain, 3Hospital de la mari~na, Nephrology, Burela, therefore, in overhydration. There also had lower serum phosphorus (3.6 6 0.8 vs 5.2
Spain, 4hospital de la mari~na, Nephrology, Burela, Spain, 5Hospital General de Villalba, 6 0.8 mg/dl; p = 0.01) and serum albumin (3.5 6 0.4 vs 4.0 6 0.1 g/dl; p = 0.01). Seven
6
Nephrology, Villalba, Spain, Hospital General de Villaba, Nephrology, Villaba, Spain, patients died during hospitalization. Deceased patients were older (78.4 6 6.6 vs 67.4
7
Clinica RTS Baxter, Hmodialysis, Murcia, Spain, 8Hospital de la Ribera, Nephrology, 6 12.4 years; p = 0.01), presented higher comorbidity (estimated by Charlson index
Alzira- Valencia, Spain, 9Avericum, Hemodialysis, Las Palmas , Spain and 10Universidad 10.0 [8.0-11.0] vs 6.5 [4.3-8.0]; p = 0.02) and were more overhydrated (3.4 6 3.6 vs 1.9
Europea, Facultad de Ciencias biomédicas, Villavicioa de Od on- Madrid, Spain 6 1.9; p = 0.34). Although not statistically different, they had lower LTI (10.4 6 2.1 vs
12.0 6 3.4 kg/m2; p = 0.18) and lower serum albumin (3.4 6 0.6 vs 3.9 6 0.4 g/dl; p =
BACKGROUND AND AIMS: There is a high prevalence of malnutrition (PEW) in 0.08) compared to survivors. Patients who survived COVID19 infection had longer
patients on dialysis (HD-PD). There is no single tool to diagnose it, varying the hospitalization (57% were discharged between twelfth and forty third day; mean

i498 | Abstracts
Nephrology Dialysis Transplantation Abstracts
hospitalization 14.6 6 11.5 days). Deceased patients died within the first 12 days of MO912 INMUNE STATUS ON HAEMODIALYSIS PATTIENTS
hospitalization (6.8 6 4.1 days). AFFECTED WITH COVID19 INFECTION
CONCLUSION: COVID19 lockdown induced a weight reduction on HD patients due
to decrease in total body water. COVID19 infection increased this reduction, inducing Justo Sandino Pérez1, Alberto Utrero-Rico2, Claudia Yuste1,
greater loss on lean and fat tissue composition. Moreover, COVID19 impact on body Elena Gutierrez-Solis1, Enrique Morales1, Evangelina Mérida1,
composition was magnified with the length of hospitalization. Cecilia Gonzalez-Cuadrado2, Marta Chivite-Lacaba2, Esther Mancebo2,
Estela Paz-Artal2, Paula Jara Caro Espada3
1
Hospital 12 De Octubre, Nephrology, Madrid, Spain, 2Hospital 12 De Octubre,
Immunology department (Instituto de investigaci
on Hospital 12 de Octubre), Madrid,
Spain and 3Hospital 12 De Octubre, Nephrology (Instituto de investigaci
on Hospital 12
de Octubre), Madrid, Spain
MO911 ALTERED CIRCULATING OMENTIN-1 LEVELS REFLECT
IRON DEFICIENCY IN CHRONIC HEMODIALYSIS PATIENTS BACKGROUND AND AIMS: End-stage renal disease patients on haemodialysis
(HD) seem more likely to develop severe COVID19 disease. Over the course of COVID
Davide Bolignano1, Pierangela Presta1, Giuseppina Crugliano1, Marta Greco2, disease, we observed a poor tolerance to HD sessions with a marked tendency of
Francesco Dragone2, Daniela Foti2, Michele Andreucci1, Giuseppe Coppolino1 clinical deterioration over them.
1 The objective is to evaluate changes on immunological system over HD session on
Magna Græcia University, Nephrology and Dialysis Unit, Catanzaro, Italy and 2Magna
patients affected with COVID19 compared with patients without COVID19.
Græcia University, Pathology Lab, Catanzaro, Italy
METHOD: Fourteen HD patients were studied including 9 confirmed COVID19
infection and 5 healthy controls. Predialysis and postdialysis blood samples were
BACKGROUND AND AIMS: Iron deficiency is pervasive among hemodialysis (HD) compared to study alterations on immune status. We identified cytoKines by Luminex
patients; however, although transferrin saturation (TSAT) of <20% and/or serum (CCL2, CXCL10, IL1Ra, IL10, IL12p70, TNFa, IL17Ra, IL6, IL7) and adaptive
ferritin of <200 ng/mL should express iron scarcity, in HD patients high ferritin levels lymphocyte subsets (CD4/CD8 naı̈ve, CD4/CD8 MC, CD4/CD8 MP, CD19, CD56).
could be related to inflammation rather than reflecting optimal iron stores. Omentin-1 Monocyte subsets (CD14þCD16-, CD14þCD16þ, CD14-CD16þ) were detected
is an anti-inflammatory adipokine that is also involved in regulation of iron from peripheral blood mononuclear cells (PBMC), as well as immune activation
metabolism through binding with lactoferrin. In this pilot study, we aimed at (CD11b, HLA-DR, CD86) and migration factors (CCR2, CCR5). The supernatant of
evaluating serum levels of Omentin-1 in a small HD population, in order to determine isolated CD14þ cells after 4-hour stimulation with LPS where analysed by Luminex to
its possible relationships with iron status. measure cytokines (CCL2, CXCL10, GM-CSF, IL10, IL12p70, IL17Ra, IL6, IL7, TNFa).
METHOD: Omentin-1 was measured by ELISA in serum samples of 33 chronic HD RESULTS: Patients with COVID19 presented predialysis: (1) higher plasmatic levels of
patients before a single mid-week HD session and at 1h, 2h and 3h after dialysis start. IL12p70, TNFa e IL7, (2) lymphopenia and neutrophilia, (3) higher percentage of
Common biochemical and clinical parameters were also recorded. intermediate monocytes and lower of non-classical, (4) lower membrane expression of
RESULTS: Serum omentin-1 levels were statistically higher in HD patients than in CCR2, HLA-DR y CD86 over Cd14þ cells, and (5) higher production of CCL2, GM-
matched healthy controls (763 [367-1423] vs. 371 [228-868] ng/mL; p=0.03). CSF, IL10, IL12p70 y IL17Ra by LPS stimulated monocytes compared with patients
Omentin-1 levels were broken down after the first hour of HD (reduction ratio: without COVID19. When analysed the fold-change between pre and postdialysis
4565%) and tended to get back to baseline after the third hour (p=0.04). Correlation values, patients with COVID19 infection present a: (a) higher plasmatic levels of IL6,
analyses showed omentin-1 levels to be directly associated with serum iron (R=0.380; IL1Ra, CCL2 e CXCL10, (b) reductions of total lymphocites, (c) higher membrane
p=0.03), ferritin (R=0.843; p<0.001), TSAT (R=0.661; p<0.001), serum amylase expression of CCR2, CD33 y CD86 on CD14þ cells, and (d) higher production of
(R=0.454; p=0.01), ALT (R=0.380; p=0.03) and inversely with serum phosphate (R=- TNFa, GM-CSF, IL10, IL17, IL6 e IL7 by LPS stimulated monocytes compared with
0.403; p=0.02), troponin (R=-0.443; p=0.01) and transferrin (R=-0.390;p=0.04). At patients without COVID19. No differences on lymphocite subset were found.
ROC analyses, Omentin-1 levels showed a remarkable capacity to discriminate HD CONCLUSION: The clinical deterioration on COVID19 infected patients over HD
patients with iron deficiency (TSAT<20%) with an AUC of 0.830 (95%CI 0.658 to session could be related with monocyte activation and pro-inflammatory cytokines
1.000; p=0.002. best cut-off value: 478.8 ng/mL; sens. 75%; spec. 85%). Of note, such secretion.
discriminatory capacity was even better than that of serum ferritin (AUC 0.739; 95%CI
0.528 to 0.950; p for differences between AUCs=0.04; Figure 1)
CONCLUSION: Findings from this pilot study demonstrate that HD patients have
altered Omentin-1 values probably because this protein is involved in the maintenance
of iron equilibrium. Larger studies are needed to confirm whether Omentin-1 might be
proposed as a new tool in the assessment of iron deficiency and in the management of
iron therapy for HD patients. MO913 BODY COMPOSITION EVALUATED BY BIOIMPEDANCE IN
FRAIL PATIENTS ON HEMODIALYSIS


Alvaro 
Alvarez Lopez1, Barbara Cancho Castellano1, Cristina Lo pez Arnaldo1,
Rosa Maria Diaz Campillejo1, Elena Garcia de Vinuesa Palo1, Rafael Arago n Lara2,
Jorge Alberto Rodriguez Sabillon1, Julia n Valladares Alcobendas1, Isis Cerezo
Arias1, Marıa Victoria Martın Hidalgo Barquero1, Rosa Marıa Ruiz Calero
Cendrero1, Nicolas-Roberto Robles Perez-Monteoliva1
1
Badajoz University Hospital, Nephrology, Badajoz, Spain and 2Badajoz University
Hospital, Internal Medicine, Badajoz, Spain

BACKGROUND AND AIMS: Frailty is known as a biological syndrome of decreased


reserves and resistance to stress, with a decline of multiple physiological systems,
causing vulnerability. Its prevalence ranges from 10-80 %. The etiopathogenesis is
multifactorial, based on the loss of muscle mass associated with aging or sarcopenia.
Chronic Kidney Disease (CKD) is a model of accelerated aging, with impaired physical
function, frailty and cognitive decline.
The main theorical frameworks on frailty are the one advocated by Linda Fried, in
which she develops a phenotype as a risk situation for developing disability and one
advocated by Kennet Rockwood which establishes that frailty consists of addition of
various health conditions including comorbidity and disability. Our objective was to
evaluate frailty in stage 5 CKD in haemodialysis, measured by clinical scale and to
relate it to the body composition measured by bioimpedance.
METHOD: Cross-sectional study in 40 subjects with CKD in hospital haemodialysis,
70.5613.03 years, 62.5% male. 40% Diabetic Nephropathy, 10% Glomerulopathies,
7.5% Nephroangiosclerosis, 2.5% Chronic Tubule-Interstitial Nephropathies, 32.5%
Unknow, 2.5% Others. 35% arteriovenous fistula, 10% arteriovenous graft, 55% central
venous catheter. Hemodialysis type: 40% High Flux, 45% Online postdilutional
Haemodiafiltration, 10% Acetate Free Biofiltration. Fragility was measured by the
Rockwood clinical scale: not fragile (1-4), moderately fragile (5-6) and severely fragile
(7-9). Body composition was estimated by monofrequency bioimpedance
measurement. Chi-Cuadrado was used to study differences between dichotomous
variables and ANOVA for continuous variables. Spearman correlations was used to
examinate the intensity of association between two quantitative variables. Statistical
analysis was performed with SPSS 13.0.

10.1093/ndt/gfab102 | i499
Abstracts Nephrology Dialysis Transplantation

Not fragile Moderately fragile Severely fragile Sig.


Age 67613,18 76,3369,56 76,27612,25 p=0,08
Male 15 (37.5%) 6 (15%) 4 (10%) p=0.032
Female 8 (20%) 0 7 (17.5%)
Diabetes Mellitus 12 54.5% 4 18.2% 6 27.3% p=0.82
Time HD months 74,65689,49 49,67641,13 46,91635,51 P=0,52
Charlson Comorbidity Index 7,0962,4 9,6762,42 7,7362,42 p=0,073
Speed of the march m/s 0,8360,22 0,3560,29 0,2560,36 p=0,001
Plasma Creatinine mg/dL 9,0962,19 7,1961,81 7,4662,26 p=0,055
Albumin g/dL 3,9360,58 3,8860,19 3,7460,43 p=0,583
Cholesterolmg/dl 141,0636,33 169,67628,92 126,55622,19 p=0,04
C reactive protein mg/dl 3,4064,04 6,4268,64 5,9468,04 p=0,413
KT/V 1,4660,27 1,5960,18 1,6060,27 p=0,24
Phase angle 4,5660,91 3,2260,76 3,5560,96 P=0,001
Exchange Na/K 1,2360,25 1,8360,84 1,5560,66 p=0,024
Total body water % 51,8868,01 56,40611,52 50,2566,95 p=0,350
Extracelular water EW% 53,9465,43 63,9667,05 61,3668,02 p=0,001
Intracelular water IW% 46,0465,43 36,0467,05 38,6168,01 p=0,001
EW/IW 1.260.26 1.960.69 1.7060.81 p=0.007
• Fat free mass 48,0866,58 49,469,08 36,564,88 p<0.001
• FFM kg
• Muscle mass 27,5764,53 24,0164,9 18,5463,18 P<0.001
• MM kg
• Fat mass 26,26612,6 21,57612,82 21,469,84 P=0,493
• FM kg
• BCMI 7,9261,64 6,6761,37 5,8961,08 P=0,002
• Body cell mass index

RESULTS: 42.5% of the subjects presented a degree of fragility 5, severely fragile MO914 INTRADIALYTIC RESISTANCE TRAINING HAS POSITIVE
27.5%. EFFECT ON SURVIVAL IN HEMODIALYSIS PATIENTS
The results are shown in the Tables 1 and 2. INDEPENDENTLY OF THEIR NUTRITION STATUS
MEASURED BY BODY COMPOSITION MONITORING

Marek Hudacek1, Aurel Zelko2,3, Jaroslav Rosenberger1,2,3,4,5


1
Fresenius Medical Care - Dialysis Services, Slovakia, 2Graduate School Kosice Institute
rs Sig. for Society and Health, Faculty of Medicine, Pavol Jozef Safarik University, Kosice,
Slovakia, 3Department of Health Psychology and Research Methodology, Faculty of
Phase angle -0.59 0.0001
Medicine, Pavol Jozef Safarik University, Kosice, Slovakia, 4Olomouc University Society
Exchange Na/K 0.3 0.06 and Health Institute, Palacky University Olomouc, Olomouc, Czech Republic and 52nd
Total body water -0.43 0.0059 Department of Internal Medicine, Faculty of Medicine, Pavol Jozef Safarik University,
Kosice, Slovakia
EW 0.59 0.0001
IW -0.59 0.0001 BACKGROUND AND AIMS: Malnutrition is considered to be an independent
EW/IW 0.59 0.0000 predictor of mortality in hemodialysis population. Physical inactivity is also connected
FFM -0.52 0.0007 to worse outcomes, and patients are recommended to comply with at least some
physical excercise.
MM -0.72 0.0000 The aim of this study was to evaluate the survival of hemodialysed patients, taking into
FM 0.22 0.17 account the nutritional status, assessed by Body Composition Monitor. In addition,
analysed the impact of three months intradialytic resistatance training.
BCMI -0.63 0.0000 METHOD: It was a prospective study of patients undergoing hemodialysis from three
hemodialysis departments. Patients from two departments underwent three months
CONCLUSION: The degree of frailty is greater in the elderly. Measurement of body intradialytic resistance training while those from the third department served as
composition by bioimpedance can be useful to indirectly asses frailty. The phase angle controls. Cox multivariate regression analysis was used to analyse patient survival
could be an indicator of fragility, since in more fragile subjects its value decreases, its depending on performing intradialytic resistance training and their nutritional status.
physiological role remains to be elucidated. There is a positive trend to an increase in RESULTS: The group of 90 patients included 35 women, 55 men (61%) with a mean
extracellular water in more fragile subjects, keeping the subjects in their dry weight, so age of 62.6 years, and a mean dialysis program duration of 49.1 months. 31 patients
it will be necessary to evaluate what is due. completed whole three months interdialytic training. In total, 80% of participants
survived the follow-up period of two years. Cox regression analysis showed a
statistically significant effect of the intervention: the patients who had been training
had a benefit in survival (HR 4.4; 95%CI 1.003;19.267; p=0,05). The stratification by
nutritional status did not change this model, it was always crucial whether patients
exercised or not. Malnourished patients had also a better survival when they were
training.
CONCLUSION: Malnourished hemodialysed patients have higher mortality
compared to well-nourished patients. Intradialytic resistance training brings survival
benefit and might reduce the adverse effects of malnutrition. Therefore we recommend
this intervention even in malnourished hemodialysed patients.

i500 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO915 DIETARY ADVICE IN HEMODIALYSIS PATIENTS: IMPACT OF non-randomised trials. All studies investigated nocturnal haemodialysis (one with the
A TELEHEALTH APPROACH DURING THE COVID-19 additional of short daily), three were in-centre and two were at home. Range of
PANDEMIC duration for the included studies was 2-18 months. Outcomes of interest measured
included lean body mass, protein and carbohydrate intake, body mass index, dry lean
Ana Valente1, Joana Jesus1, Ana Dinis1, Andre Correia1, Joana Breda1, mass and water soluble vitamin levels. Of these trials, only one reported a statistically
Joana Godinho1, Telma Oliveira1, Cristina Garagarza1 significant increase in an outcome of interest (lean body mass). One study also
1
Nephrocare Portugal, Nutrition Department, Lisboa, Portugal reported cross-sectional data highlighting Vitamin-C deficiency in half of their
nocturnal haemodialysis population.
BACKGROUND AND AIMS: Telehealth technologies are being implemented widely CONCLUSION: There is insufficient high-quality evidence assessing the effect of
and can be used to provide education and self-management support to help and sustain extended haemodialysis on nutritional parameters. Further research is required to
lifestyle changes, namely in patients with chronic diseases. The purpose of this study understand the impact of novel dialysis prescriptions on these clinical parameters.
was to assess the effect of a telehealth-delivered nutritional intervention, via the
telephone, in maintenance hemodialysis (HD) patients during the coronavirus
outbreak. MO917 INFLAMMATORY PARAMETERS IMPROVEMENT WITH
METHOD: This was a multicenter observational prospective longitudinal study of a CITRATE COMPARED TO ACETATE DIALYSATE
cohort of 156 patients in maintenance HD from 15 dialysis units conducted during the
COVID-19 pandemic. We assigned patients to receive dietary counselling, through a Jose Jesus Broseta Monzo1, Luis Carlos Lo pez Romero2, Diana Rodrıguez1,
phone call, according to their biochemical and nutritional parameters (potassium Elena Guillen Olmos1, Pilar Sa nchez-Pérez2, Julio Hernandez Jaras2
>5.5mEq/L; phosphorus >5.5mg/dL or <3.5mg/dL; interdialytic weight gain 1
percentage (%IDWG) >4.5%). Dry weight, %IDWG, body mass index, potassium, Hospital Clınic of Barcelona, Department of Nephrology and Renal Transplantation,
phosphorus, calcium, calcium/phosphorus product, normalized protein catabolic rate, Barcelona, Spain and 2Hospital Universitari i Politècnic La Fe, Department of
albumin and hemoglobin were recorded at baseline and 1 month after the nutrition Nephrology, València, Spain
counselling. A p-value < 0.05 was considered statistical significant.
RESULTS: The prevalence of patients with hyperkaliemia and hyperphosphatemia BACKGROUND AND AIMS: The relation between inflammation and cardiovascular
decreased significantly after the dietary advice (50% vs. 34.6% and 36.5% vs. 19.2%, disease is well established. Dialysis patients are at a higher risk of cardiovascular death,
respectively). A statistical significant reduction in serum potassium (mEq/L) [median: mostly attributed to cardiovascular disease. This study evaluated the potential benefits
6.2 (IQ:6.0-6.5) vs. 5.7 (IQR:5.3-6.1)] and phosphorus (mg/dL) [median: 6.5 (IQR: 6.1- of citrate (CD) vs. acetate dialysate (AD) regarding the patients’ inflammatory status.
7.2) vs. 5.5 (4.7-6.1)] was observed in patients receiving counselling for hyperkalemia METHOD: Single-center, cross-over, prospective study, with a follow-up of a total of
and hyperphosphatemia. In addition, there was a statistical significant decrease in the 24 dialysis sessions, 12 with each dialysate. Blood samples were taken on the twelfth
prevalence of patients with hypophosphatemia (28.8% vs. 18.6%). There was also a dialysis session with each type of dialysate. Every patient acted as its own control. The
significant decrease in the %IDWG [(median: 4.8% (IQR: 4.2-6.8) vs. 4.4% (IQR: 3.8- pre-dialysis parameters analyzed were procalcitonin (PCT), high-sensitivity C-reactive
6.2)], although no statistically significant differences were observed in the prevalence of protein (hsCRP) and interleukin-6 (IL-6).
patients with high %IDWG. Regarding the person contacted by telephone, data showed RESULTS: Pre-dialysis hsRCP [AD: 4,32 (1,27 – 12,16) vs. CD: 4,08 (0,98 – 8,65) mg/
statistically significant differences in potassium (mEq/L) [patient – median: 6.2 L, p = 0,031], PCT [AD: 0,44 (0,28 – 0,74) vs. CD: 0,38 (0,29 – 0,44) ng/mL, p = 0,037],
(IQR:6.1-6.4) vs. 5.7 (IQR: 5.4-6.0); caregiver – mean: 6.3 6 0.3 vs. 5.7 6 0.7] and and IL-6 [AD: 13,7 (7,85 – 29,03) vs. CD: 11,8 (5 – 27,13) pg/mL, p = 0,029] are
phosphorus (mg/dL) [patient –median: 6.5 (6.1-7.2) vs. 5.6 (4.9-6.1); caregiver – mean: significativly higher after twelve dialysis sessions with AD vs. CD.
6.760.8 vs. 5.161.5] values when the contact was with the patient or the caregiver. In CONCLUSION: Even in the medium term, the use of citrate instead of acetate as the
relation to hypophosphatemia (mg/dL) (mean: 2.460.7 vs. 3.060.9) and %IDWG dialysate acidifier, reduces the measured inflammatory parameters and could therefore
[median: 4.6% (IQR: 4.1-7.1) vs. 4.1% (IQR: 3.5-6.6)], the main statistically significant be considered a more biocompatible dialysate option.
differences were only observed when the contact was done directly with the patient. No
differences were seen whenever the contact was with the nursing homes.
CONCLUSION: Our results suggest that telehealth-delivered dietary interventions can MO918 INFECTIOUS COMPLICATIONS IN HEMODIALYSIS:
improve clinical and nutritional parameters in HD patients. Therefore, it may be an INTERSET OF NEUTROPHIL TO LYMPHOCYTE AND
effective strategy to promote a continuous nutritional monitoring in these patients, at PLATELETS TO LYMPHOCYTE RATIOS
least, when or where the face-to-face option is a critical factor.
Rania Lahouimel1,2, Toumi Salma1,2, Hanen Abid1,2, Emna Kharrat1,2,
Amira Saai1,2, Ikram Agerbi1,2, Najla Dammak1,2, Hanen Chaker1,2,
MO916 THE EFFECT OF EXTENDED HAEMODIALYSIS ON Khaoula Kammoun1,2, Soumaya Yaich1,2, Mohammed Benhmida1,2
1
NUTRITIONAL PARAMETERS: A SYSTEMATIC REVIEW university hospital centre hédi chaker, nephrology, Tunisia and 2sfax faculty of medi-
cine, renal pathology research laboratory UR12ES14
Alireza Majlessi1, Daniel March1, James Burton1
1
University of Leicester, Cardiovascular Sciences, Leicester, United Kingdom BACKGROUND AND AIMS: Infectious complications represent the leading cause of
death among the dialysis population, prompting early diagnosis and increased
BACKGROUND AND AIMS: Individuals who receive haemodialysis have a high vigilance. Neutrophil-to-lymphocyte and platelets-to-lymphocyte ratios are newly
mortality rate, up to 20% within one year of starting dialysis and just under 50% at 5 emerging as more accessible and simple markers for the detection of the onset of
years. One of the risk factors that contributes to this high mortality rate is the infections. The objective of our study is to prove the value of these markers in the
nutritional status of haemodialysis patients; improving this will be a key element of risk diagnosis of infections in hemodialysis patients.
mitigation. Extended haemodialysis may improve nutritional outcomes through better METHOD: This is a cross-sectional study spread over one year including 85 chronic
clearance and reduced dietary restrictions and medications. The aim of this systematic hemodialysis patients with duration of at least 6 months. patients with hemopathies,
review is to provide an up to date assessment of trials of extended haemodialysis tumors, or with a history of hospitalization during the 3 months before the study were
reporting the following nutritional outcomes: Lean body mass, body mass index, excluded. CRP was used as a biomarker of infections and N / L; P / L ratios were
protein intake and energy intake, nutritional status assessed by the subjective global calculated to study the correlation between the two biomarkers. Based on the literature
assessment and PEW scores, and circulating markers of appetite. reviews, the threshold of the N / L ratio and the P / L ratio admitted for our stydy were
METHOD: No limits on language were set, and databases were searched from respectively : > = 2.5 and > = 150.
inception to December 2020 using a predefined search strategy. Inclusion criteria were; RESULTS: The mean age of our patients was 49 6 19 years with a predominance of
randomised and non-randomised trials of extended haemodialysis (defined by >15 women (55%) .The average duration in hemodialysis was 67.2 months. An infectious
hours per week of total haemodialysis time), with a comparator group which received complication was noted in 22% of our patients whose distribution was as follow: 4% as
conventional in-centre haemodialysis (usually <=12 hours per week of hemodialysis a pulmonary infection with 3 coronavirus cases, 6% a sepsis, one case of abscess of the
time). The following databases were searched: Medline, EMBASE, CINAHL, Cochrane nephrectomy compartment.The median value of the CRP was 37610mg/l We found a
Controlled Register of Trials (CENTRAL), the Web of Science Core positive correlation between the 2 ratios associated (RNL and RPL) and infection with
Collection,PROSPERO, Clinicaltrials.gov, the ISCRTN Registry and Conference (p = 0.03) . We noted throw this study that patients with both high ratios RPL> 150
Proceeding Citation Index, National Health Service Centre for Reviews and and RNL> 2.5 have significantly elevated values of CRP.
Dissemination: Health Technology Assessment (HTA), and Database of Abstracts of CONCLUSION: N/L and P/L ratios are easy-to-calculate markers that are of great
Reviews of Effects (DARE). Additional internet searches (i.e Google Scholar) were also benefit to the hemodialysis population. We have shown through this study the
conducted. Search results were compiled in Endnote and studies were screened for title existence of a positive correlation between the N/L and P/L ratios and the occurrence
and abstract. of infections in hemodialysis patients. We therefore encourage the use of this ratios to
RESULTS: Searches identified 9251 records. After removing duplicates 6190 records be included as markers to detect infections occurence.
were screened for title and abstract against inclusion criteria, leaving 22 papers for full
text screening. A further 17 records were removed following full text screening. Of the
remaining 5 papers, one was a randomised controlled trial and four were prospective,

10.1093/ndt/gfab102 | i501
Nephrology Dialysis Transplantation 36 (Supplement 1): i502–i503, 2021
10.1093/ndt/gfab112

RENAL TRANSPLANTATION. EXPERIMENTAL,


IMMUNE-TOLERANCE OF ALLOGENIC AND
XENOGENIC TRANSPLANTS

MO919 THE INTERPLAY BETWEEN IL-6 AND IL-17 MIGHT PLAY A


SIGNIFICANT ROLE IN CHRONIC ANTIBODY MEDIATED
REJECTION IN RENAL ALLOGRAFT RECIPIENTS

Mantabya Singh1, Narayan Prasad1, Mohit Rai3, Akhilesh Kumar Jaiswal1,


Manas Ranjan Behera1, Vikas Agarwal3, Durga P Misra3
1
Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Nephrology,
Lucknow, India and 3Sanjay Gandhi Post Graduate Institute of Medical Sciences Gene expression analysis of IL-6, MCP1 and CCL20 was significant higher (p<0.001)
(SGPGIMS), Clinical Immunology, Lucknow, India with synergistic activation of IL-6 and IL-17 as compared to either IL-6 or IL-17 alone,
while SOCS3 gene expression was downregulated. (Fig 3) There was significant
BACKGROUND AND AIMS: Chronic antibody-mediated rejection (CABMR) plays reduction in IL-6 concentration in culture supernatant with IL-6 and IL-17 inhibitor
a critical role in kidney allograft loss and consider among one of the most important together (Fig 4) and m-RNA expression of IL-6 and MCP-1 was significantly reduced.
barriers that is responsible for late term graft loss. Previously we believed that (Fig 5)
alloreactive T-cell and de-novo DSA responsible for late term graft loss but recent
study suggested that not only immune cell, non-immune cells like fibroblast also plays
important role in chronic inflammation and allograft rejection via IL-6 amplifier loop
(IL-6þIL-17). The interaction between non-immune tissues/cells and the immune
system plays a critical role in chronic inflammation and late graft rejection. In chronic
inflammation IL-6 enhance the production of acute phase proteins, T cell Subset
differentiation, Maturation of Plasma cells, Generation of cellular and humoral
immune responses and Control the transition from acute to chronic inflammation by
changing the nature of leucocyte infiltration (from neutrophils to monocyte).
We sought to see whether IL-6 and IL-17A mediated synergistic activation of
inflammation amplifier is operational in CABMR.
METHOD: Recruitment of patients according to Banff 2017criteria and biopsy was
taken from consented patients and establishment of fibroblast culture from renal
biopsy of patients with CABMR.
Fibroblast culture from CABMR patients were cultured to purity and pre stimulated
with IL-6 (20ng/ ml), IL-17(50ng/ ml), IL-6 plus IL-17 for 24 hours and culture
supernatant were collected for IL-6 ELISA to see synergistic activation.
Serum IL-6, MCP1 and CCL20 levels of Healthy control (HC), CABMR and Non-
CABMR patients and MCP1, CCL20 level in culture supernatant were measured by
ELISA. m-RNA expression of IL-6, MCP1, CCL20 and SOCS3 gene were measured by
real time PCR (Syber-green method)
One-way ANOVA and Non-parametric Student t tests (two-tailed) were used for the
statistical analysis of differences between groups.
RESULTS: In comparison to IL-6 and IL-17 alone these cytokines synergistically
induced more IL-6 production from renal fibroblasts. (Fig 1) also, we found that
concentrations of effectors of inflammation amplifiers like IL-6, CCL-20 & MCP-1 in
sera were significantly higher in CABMR patients compared to Non rejection patients,
while their concentration in culture supernatant was higher when fibroblast cell
stimulated with IL-6 and IL-17 together as compared either IL-6 or IL-17 alone. (Fig 2)

CONCLUSION: CABMR is perpetuated by inflammation amplifier loop or synergistic


induction of IL-6 and IL-17. Inhibition of IL-6 with Anti-IL-6 (Tocilizumab) and IL-17
with Anti-IL-17 reduces the tissue injury marker (IL-6, MCP1, CCL20) and allograft
rejection.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
MO920 TRANSITION FROM GENERIC TO BRAND TACROLIMUS IN MO921 PROGNOSTIC OUTCOMES OF TRANSPLANTED KIDNEY
TUNISIAN RENAL TRANSPLANT RECIPIENTS USING SOLUBLE CD30 AND B2- MICROGLOBULIN

Dorra Amor1, Sahtout Wissal2, A Ellouz1, Ameni Abderrahman1, Awatef Azzabi2, Ahmed Abo omar1, Gamal Saadi2
Mayssa HadjBrahim2, Sanda Mrabet2, Asma Fradi2, Narjes Ben Aicha2, 1
Faculty of medicine, Tanta university, Nephrology unit, internal medicine department,
Dorsaf Zallema2, Ferdaous Sabri2, Asma Omezzine1, Yosra Guedri2, tanta, Egypt and 2cairo universty, Nephrology unit, internal medicine department, cairo,
Abdeltif Achour2 Egypt
1
Sahloul Hospital Sousse, Biochemestry Laboratory, Sousse, Tunisia and 2Sahloul
Hospital Sousse, Nephrology, Sousse, Tunisia BACKGROUND AND AIMS: Transplantation is the first successful modality of renal
replacement therapy (RRT) for irreversible chronic kidney disease (CKD; stage 5).
BACKGROUND AND AIMS: Due to unavailability of the generic tacrolimus, Identifying additional factors associated with poor long-term prognosis after
commonly used in renal transplant patients in Tunisia, all renal transplant switched to transplantation may provide clues regarding the pathophysiological mechanisms
the Brand. No previous studies have assessed the pharmacokinetic differences of this involved in allograft failure and identify high-risk patients who may benefit from
generic tacrolimus compared to the brand. The aim of the present study was to additional monitoring or interventions. Successful kidney transplantation results in a
evaluate the effect of this switch on the tacrolimus dose (D) and on the dose-adjusted substantial decrease in b2M levels, but a delayed decrease or increasing levels after
tacrolimus trough blood concentrations (C0/D) in Tunisian renal transplant recipients. transplantation may serve as a marker of acute rejection or inflammation. Several
METHOD: For the 255 renal transplant monitored in biochemestry department of reports show that elevated sCD30 levels, pre and post transplantation are associated
Sahloul University hospital, 808tacrolimus trough concentration (C0) were collected with a poor prognosis for long term kidney graft survival. These studies found higher
from october 2018 to February 2020 and were divided to 406 C0 determination before CD30 levels in allograft recipients and a good predictor of impending acute rejection.
switch and 402 after switch. The dose and the post-transplantation period was The aim of the work is to study the prognostic outcomes of transplanted kidney using
recorded for each C0. CD30 and b2-Microglobulin
RESULTS: The generic tacrolimus doses used were significantly higher compared to METHOD: prospective study was conducted in nephrology unit –internal medicine
the brand: 0,12 mg/kg [0,02-0,6] vs 0,11 mg/kg [0,02-0,22] p<0,001 and this was department at Tanta and Kasr El Ainy university ,over 1 year.20 patients subjected to
reported in different post graft periods: 0,17 [0,03-0,22] vs 0,13 [0,06-0,22] p<0,001in primary Tx.participated in this study.Cd30 and b2M.at day -1,2weeks and 3
the 3 first months after the transplantation and 0,11 [0,02-0,48] vs 0,08 [0,02-0,22] months,with clinical follow up after 1 year to detect graft survival
p<0,001 above.The C0/D were significantly lowe runder the the generic tacrolimus RESULTS: At day -1,level of cd30 was higher in rejection group than the other patient
compared to the brand 48,34ng/ml per mg/kg/day [11,58-210,00] vs77,35ng/ml per group.2 weeks post transplantation ,level of cd30 was higher in rejection group than the
mg/kg/day[19,38-221,67]; p<0,001 and this was reported in different post graft other patient group and at 3 monthes post transplantation level of cd30 was higher in
periods: 71,12ng/ml per mg/kg/day [6,80, 451,56] vs80,9750ng/ml per mg/kg/day rejection group than the other patient group,and these differences are statistically
[17,33-458,80] p=0,017 in the 3 first months after the transplantation and 71,12ng/ml highly significant.(p values :0.003 ,0.005 and 0.002 respectively)
per mg/kg/day [6,80, 451,56] vs80,9750ng/ml per mg/kg/day [17,33-458,80] p=0,017 Successful transplantation leads to significant decrease in serum cd30 at 2 weeks post
above. Dose needed to reach target tacrolimus C0 seems to be higher with the generic tx.(P1 <0.005) and at 3 monthes post tx. (P1<0.001) although in rejection group,
tacrolimus compared to the brand. significant decrease in cd30 was at 2 weeks post tx.only(P1<0.005) and at 3 monthes
CONCLUSION: Approval of a generic is dependent on bioequivalence testing in serum cd30 began to rise again with( P1 0.157). At day -1,level of b2microglobulin was
healthy adult volunteers after a single dose, however studies on renal graft recipient higher in rejection group than the other patient groupwith statistically significant
populations after chronic use are needed to assed bioequivalence in this special difference (p. 0.01).2 weeks post transplantation ,level of b2microglobulin was higher
population. in rejection group than the other patient groupbut statistically not significant(p. 0.18 )
and at 3 monthes post transplantation level of b2microglobulin was higher in rejection
group than the other patient group but statistically non significant(p. 0.18 ).
Successful transplantation leads to significant decrease in serum b2microglobulin at 2
weeks post tx.(P1 <0.002) and at 3 monthes post tx. (P1<0.001) although in rejection
group ,significant decrease in b2microglobulin was at 3 monthes post
tx.only(P1<0.005) and at 2 weeks no significant decrease(p1 0.15)
CONCLUSION: pre transplantation high Cd30 and b2M is associated with poor
outcome.failure of decrease of cd30 and b2M post Tx. also associated with poor
outcome or infection. Successful transplantation leads to significant decrease in serum
cd30 and b2M. which can be used as predictors of graft survival with better sensitivity
and specificity than serum creatinin.

10.1093/ndt/gfab112 | i503
Nephrology Dialysis Transplantation 36 (Supplement 1): i504–i530, 2021
10.1093/ndt/gfab110

MO923 PREDICTING POST-TRANSPLANT HRQOL TO OPTIMIZE


RENAL TRANSPLANTATION. EPIDEMIOLOGY AND OUTCOMES IN OLDER KIDNEY TRANSPLANT RECIPIENTS
OUTCOME Vasiliki Tsarpali1,2, Karsten Midtvedt3, Kjersti Lønning3, Tomm Bernklev2,4,
Nanna Von der Lippe5, Anna Varberg Reisater3, Kristian Heldal1,3
1
Telemark Hospital Trust, Clinic of Internal Medicine, Skien, Norway, 2University of Oslo,
MO922 CASUAL FACTORS AND CLINICAL IMPACT OF URINARY Institute of Clinical Medicine, Oslo, Norway, 3Oslo University Hospital, Department of
TRACT INFECTIONS IN RENAL TRANSPLANTED PATIENTS: Transplantation Medicine, Section of Nephrology, Oslo, Norway, 4Vestfold Hospital
AN OBSERVATIONAL RETROSPECTIVE STUDY* Trust, Department of Research and Innovation, Tønsberg, Norway and 5Oslo University
Hospital, Department of Medicine, Section of Nephrology, Oslo, Norway
Federica Tripodi1, Carlo Maria Alfieri1,2, Marianna Tangredi1, Donata Cresseri1,
Maria Rosaria Campise1, Maria Teresa Gandolfo1, Anna Regalia1, Evaldo Favi2,3, BACKGROUND AND AIMS: Kidney transplantation (KT) is the optimal treatment
Piergiorgio Messa1,2 for older patients in need for kidney replacement therapy, with favorable outcomes
1
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan Italy, Nephrology, both on survival, and health-related quality of life (HRQoL). Given the current organ
dialysis and renal transplantation, Italy, 2University of Milan, Department of Clinical scarcity, allocation of transplants should prioritize patients who are expected to benefit
Sciences and Community Health, Italy and 3Fondazione IRCCS Ca’ Granda Ospedale most from KT and identifying reliable predictors of post-transplant HRQoL outcomes
Maggiore Policlinico, Milan Italy, Renal Transplantation Unit, Italy is essential to optimize the selection process.
METHOD: Patients  65 years, who were enlisted for KT between January 2013 and
BACKGROUND AND AIMS: Urinary tract infections (UTIs) are the most common November 2016 at the Norwegian national transplant center, were asked to participate.
infectious disease in kidney transplanted patients (KTxps), especially during the first Self-reported HRQoL was assessed using the Kidney-Disease Quality of Life Short
year of kidney transplantation (KTx). This study aims to examine the etiology of UTIs Form version 1.3 (KDQOL-SF) survey. Pre-transplant comorbidity was assessed by the
in a large cohort of KTxps, trying to identify their potential predisposing factors both Liu comorbidity index (LCI). Linear mixed-effect models were used to detect HRQoL
during the first year and in the global follow-up (FU) of KTx. The impact of UTIs on changes over time (pre-KT, at -6, -12 and -36 months post-KT), and to identify pre-
KTx and patient’s survival in the long term will also be analyzed. transplant predictors of post-transplant outcomes.
METHOD: In our study 585 KTxps (M 343; median age 49 years), out of the 616 RESULTS: By November 2020, 220 (76%) out of 289 enrolled participants, were
KTxps transplanted in our Department between 2004 and 2016, were studied and transplanted. The mean age at KT was 71.8 (4.1) years, 154 (70%) were males, 57 (26%)
followed up for a median time of 8 years. Clinical and biochemical data about the 1st were transplanted pre-emptively and 30 (13.6%) received a transplant from a living
(T1) and the 12th month (T12) of KTx were collected. Parameters related to UTIs, donor.
defined by a positive urine culture associated with urinary sediment suggestive of UTI, Longer dialysis vintage was independently associated with impaired physical function
regardless of clinical symptoms, were considered in the global FU. A number of UTIs post-transplantion (Figure 1). Pre-transplant LCI score  7 consistently predicted
3 was considered significant during the 1st year of KTx and in the overall FU. The poorer HRQoL outcomes at baseline and after 3-years, compared with LCI score < 7
reduction of the eGFR/year of FU, the loss of graft and the death of KTxps with a (Figure 2). At 3- years post-transplant, increasing LCI score was lineary associated with
functioning graft were evaluated as outcome. decreasing SF-36 scores. Recipients on dialysis for  1 year with LCI  7 experienced
RESULTS: The cohort had a slight prevalence of males (59%) and a median age of 49 the worst outcomes, with a marked and sustained post-transplant physical
years. At the time of KTx, JJ ureteral stent (JJ) was placed in 38% of KTxps, with a deterioration (Figure 3).
median stay time of 47 days. During the FU, 1700 UTIs were found in 458 KTxp, 550
UTIs during the first year of KTx. The pathogens most responsible for UTIs in the
global FU were Escherichia coli (61%), Enterococcus (12%) and Klebsiella (8%).
According to the number of UTIs found during the 1st year of KTx, KTxp were
categorized in: UTI13 (N=139) and UTI1<3 (N=446). UTI13 were more
frequently female and older than UTI1<3, had more prevalence of JJ and ATG
induction therapy, and had lower hemoglobin and serum albumin at both T1 and T12.
The presence of JJ, belonging to the female gender and induction therapy with ATG
were the factors most correlated with IVU13 (OR 1.9, 5.3 and 2.1).
The studied cohort was also categorized according to the number of UTIs during the
global FU in UTItot 3 (N=168) and UTItot<3 (N=417). UTI tot 3 were more
frequently females, older, had a longer dialysis vintage and higher prevalence of JJ
placement than UTI tot<3. Furthermore, they had significantly lower hemoglobin and
serum albumin values, both at T1 and T12. The presence of JJ, the female gender and
age at KTx were the factors most related to UTItot 3 (OR 1.8, 5.9 and 1.0).
During the FU, the median absolute reduction in eGFR was found to be -0.6[-2.0;
þ0.9](mL/min)/years. Despite a greater reduction in glomerular filtrate rate in UTI
tot3 group, the graft loss and the death with functioning graft had no correlation with
either UTI13 (7 and 5 patients, respectively) or UTItot3 (12 and 8 patients,
respectively).
Graft loss was observed in 51 KTxps. The number of infections/follow-up time of these
KTxps was comparable to that found in those who had a still functioning transplant at
the end of observation, and no statistical differences were found in survival analysis
according to IVU tot3 category.
During the global FU, 40 KTxp died with functioning graft. Also with regard to this
outcome, no significant correlations were observed with the number of UTIs/follow-up
time and in the survival analysis.
CONCLUSION: Our data confirm that UTIs are frequent in KTxps. Some factors,
such as induction therapy and JJ use, certainly have a favoring effect in UTIs
development. Despite the relation observed between UTIs and eGFR reduction, UTIs
had no significant impact on graft loss. Beyond prevention through the improvement
of lifestyles and various behavioral aspects, the implementation of personalized
immunosuppressive protocols associated with a careful management of JJ are desirable
interventions in order to prevent the development of UTIs in KTxps.

C The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved
V
Nephrology Dialysis Transplantation Abstracts
cTNI and GDF-15 were measured on stored serum samples obtained pretransplant.
Information about patients was extracted from the prospectively maintained database
of renal transplant recipients at our center.
RESULTS: Receptors had a median age of 54.1 and were 67.4% male. 22% were
diabetic before the transplant, whereas 9.5% and 8.1% had prior history of coronary
and peripheral artery disease. 16.5% transplants were performed preemptively. Median
GDF-15 was 5346.4 (IQR= 4071.83-6786.32) pg/ml and median cTNI was 5.6 (IQR=
3.11-10.67) ng/l. After follow up, 77 (21.45%) patients died. During this period,
incidence of cerebrovascular accident, acute coronary syndrome and mayor adverse
cardiovascular events (MACE) was 6.38%, 12.68% and 20.56% respectively. Patients
were stratified in tertiles according to GDF-15 and cTNT levels. In the univariate
analysis, higher levels of GDF-15 significantly related to overall mortality,
cardiovascular mortality, cerebrovascular accident, acute coronary syndrome and
major adverse cardiovascular events. Higher cTNI related to cardiovascular mortality,
acute coronary syndrome and MACE, but not overall mortality (Log Rank p=0.4).
(Fig 1).

By multivariate cox regression analysis, including both biomarkers and clinical


characteristics (age, diabetes, prior coronary and peripheral artery disease and
pretransplant renal replacement therapy), the relation between overall survival and
GDF-15 remained significant for the highest tertile (HR 2.2 CI95% (1.2-4.1), p = 0.01).
Similarly, GDF-15 relation with cerebrovascular accidents and MACE remained
significant after the adjustment by these characteristics [HR 9.7 CI95% (2.2-43.1), p =
0.003 and HR 2.7 CI95% (1.4-5.1), p = 0.002] for the highest risk tertile. On the
contrary, posttransplant acute coronary syndrome was only related to cTNI tertiles and
previous coronary artery disease in the multivariate model [HR 3.2 CI95% (1.5-7.3), p
= 0.003 for the highest cTNI tertile].
CONCLUSION: Our study highlights the potential utility of GDF-15 as a predictor of
mortality and cardiovascular events after kidney transplant and its superiority
compared to cTNI. In our study, cardiac troponin showed a stronger relation with
acute coronary events, probably due to its specific production in myocardial tissue.
Altogether, these two molecules could be used in conjunction with clinical
characteristics to create prognostic models to better stratify patient’s risk prior organ
CONCLUSION: Older wait-listed candidates either on dialysis for >1 year or with
allocation, predict mortality and cardiovascular adverse events after transplant and
elevated pre-transplant LCI are at high risk for impaired HRQoL post-transplant
ideally find strategies to minimize them. Large-scale, multicenter validation using these
outcomes and should be re-evaluated with respect to transplantability on a regular
biomarkers would be the next step to prove its utility among kidney transplant
basis. The identification of criteria to optimize the selection of older transplant
candidates.
candidates should be the scope of future studies

MO925 VALVULAR HEART DISEASE EVOLUTION IN KIDNEY


MO924 GROWTH DIFFERENTIATION FACTOR 15 PREDICTOR
TRANSPLANT RECIPIENTS AND RELATED RISK FACTORS
VALUE IS SUPERIOR TO TROPONIN I IN THE EVALUATION
OF KIDNEY TRANSPLANT CANDIDATES
Isabel Galceran1, M. Dolores Redondo Pacho n1, Marıa José Pérez S
aez1,
Carlos Arias Cabrales1, Carla Burballa Tarrega1, Anna Buxeda1, Marta Crespo
Marina De Cos Gomez1, Maria Teresa Garcia Unzueta2, Adalberto Benito
Barrio1, Julio Pascual Santos1
Hernandez1, Mario Perez Arnedo1, Alejandro Aguilera Fernandez1, 1
Marina Serrano Fern andez3, Lara Belmar Vega1, Rosalıa Valero San Cecilio1, Juan Hospital del Mar, Nephrology, Barcelona, Spain
Carlos Ruiz San Milla n1, Emilio Rodrigo1
1
University Hospital Marques de Valdecilla-IDIVAL, Nephrology, Santander, Spain, BACKGROUND AND AIMS: Cardiovascular diseases remains the leading cause of
2
University Hospital Marques de Valdecilla-IDIVAL, Clinical Analysis, Santander, Spain death in recipients of kidney transplantation (KT). Valvular heart disease (VHD) is not
and 3University Hospital Marques de Valdecilla-IDIVAL, Oncology, Santander, Spain an exclusion criteria for KT, however it’s repercussion on KT follow-up has been less
studied. Our objective was to analyse the impact of VHD in KT recipients and related
risk factors of VHD progression (VHDp).
BACKGROUND AND AIMS: Elevation of cardiac troponin has been shown to be a
METHOD: Observational retrospective cohort study of all patients who underwent KT
marker of myocardial ischemia and other cardiovascular pathologies frequently
at Hospital del Mar (Barcelona, Spain) between January 1980 and December 2018.
present in patients with CKD. Pretransplant cardiac troponin I (cTNI) has
VHD was defined as presence of aortic stenosis (AS), aortic regurgitation, mitral
demonstrated its predictor value of survival after kidney transplant in previous studies.
stenosis, mitral regurgitation, tricuspid stenosis, tricuspid regurgitation or double valve
Growth differentiation factor 15 (GDF-15) is a biomarker induced by oxidative stress
injury of any degree diagnosed by echocardiography. We analysed the VHDp, defined
currently studied as a predictor of mortality and cardiovascular events (CVE) in
as worsening of the initial valvular degree on heart ultrasound after KT, risk factors
multiple scenarios, including patients with chronic kidney disease. The aim of this
related with VHDp, recipients and graft survival.
study is to compare the utility of cTNI and GDF-15 to predict posttransplant mortality
RESULTS: During the study period, 1422 patient underwent KT and 48 of them
and CVE in a cohort of kidney transplant recipients.
(3.4%) had VHD diagnosed prior to KT. In the median time of follow-up of 56.3
METHOD: We included 359 kidney transplants performed between 2005 and 2015.
months (IQR25-75 17.7-119 month), 17 patients (35.4%) presented VHDp and 31

10.1093/ndt/gfab110 | i505
Abstracts Nephrology Dialysis Transplantation

patients did not (64.6%). Figure 1 shows the primary outcome in the different types of median patient survival after late re-transplantation was 32 years. There were fewer
VHD, AS was the valve with more VHDp after KT. deaths after rapid re-transplantation than late re-transplantation, but given the small
Statistical evaluation revealed that recipients with VHDp had a higher body mass index number of cases in the former, this difference did not reach statistical significance (p =
(BMI) (27.4 6 6.3 vs 24.3 6 3.8 kg/m2, p=0.04) and worse PTH control (427.0 6 309.3 0.3). There was no association between the timing of re-transplantation and an
vs 186.2 6 140.6 pg/ml, p=0.02) at the moment of the KT. Also, patients with VHDp increased risk of graft failure (HR 0.30 [0.04 – 2.2]). While four rapid re-transplants
reached a worse nadir glomerular filtration rate (GFR) (44.1 6 17.5 vs 56.0 6 13.9 ml/ did not share any incompatibilities between donors, four did share at least one HLA
min/1.73m2, p=0.01) during the follow-up, needed more time to reach their nadir GFR type I incompatibility, and one shared an incompatibility of HLA class I and class II.
(4 [2-13] vs 1.2 [1.0-4.7] months, p<0.001) and required more furosemide dose at that There were no T-cell mediated rejections (TCMR), and there was only one AMR in the
time (72.7 6 21.7 vs 15.8 6 5.6 mg/day, p=0.02). rapid rapid re-transplantation group, whereas there were six TCMRs and fifteen AMRs
At the end of follow-up, 213 KT recipients had died, 16 with preKT-VHD (33.3% of all in the late re-transplantation group (p = 0.03 and p = 0.4, respectively).
patients with VHD) and 197 without preKT-VHD (14.3% of all cases without VHD). CONCLUSION: Rapid re-transplantation appears to be safe and does not entail
There was a statistical significant association between preKT-VHD status and all-cause increased rejection risk, nor it diminishes long-term graft survival when compared to
mortality after KT (log rank < 0.001). However, there wasn’t statistical association late re-transplantation.
between preKT-VHD status and death-censored graft survival (log rank = 0.2).
CONCLUSION: VHD has a significant impact on increased pos-KT mortality but it is
not associated with graft survival. More than one third of recipients with preKT-VHD
presented deterioration after KT. We found that increased preKT BMI and PTH, nadir
GFR after KT, time to reach this nadir GFR and diuretic dose at that time are related
with VHD progression.
MO927 IMPACT OF DONOR AGE ON LIVING DONOR KIDNEY
TRANSPLANTATION

Takahisa Hiramitsu1, Kiyomi Ohara1, Toshihide Tomosugi1, Kenta Futamura1,


Manabu Okada1, Goto Norihiko1, Toshihiro Ichimori1, Shunji Narumi1,
Yoshihiko Watarai1
1
Nagoya Daini Red Cross Hospital, Transplant and Endocrine Surgery, Myokencho
Showaku, Japan

BACKGROUND AND AIMS: Although elderly living donors are recognized as a


marginal donor for kidney transplantation, the number of elderly living donors are
increasing because of insufficiency. We investigated the impact of donor age on living
donor kidney transplantation.
METHOD: A total 858 adult living donor kidney transplantation (LDKT) between
Valvular heart disease progression after kidney transplant. January 2008 and December 2018 was included in this study and followed up until
AS: aortic stenosis. MR: mitral regurgitation. TR: tricuspid regurgitation. KT: kidney September 2020. LDKTs were stratified into 3 groups according to the donor age; 157
transplant. Severe-Sx: severe valvulopathy that needed heart valvular replacement LDKTs from donors aged 30 – 49, 592 LDKTs from donors aged 50 – 69, and 109
surgery before kidney transplant. LDKTs from donors aged 70 – 89. To investigate the impact of donor age on living
donors, postoperative estimated glomerular filtration rates (eGFR), mortality rate and
incidence of end stage renal disease were compared between 3 donor age groups. To
investigate the impact of donor age on recipients, postoperative eGFR was compared
between 3 donor age groups and the risk factors of graft loss were analyzed using Cox
MO926 RAPID VS. LATE RE-TRANSPLANTATION FOR EARLY regression hazard model.
KIDNEY GRAFT LOSS RESULTS: The eGFRs of donors demonstrated a decline with increased donor age and
significant differences at all time points among 3 donor age groups. (Figure 1)
Diana Rodrıguez Espinosa1, Jose Jesus Broseta Monzo1, Evelyn Hermida-Lama1, Mortality rate and incidence of end stage renal disease of donors were similar among 3
Elena Cuadrado1, Jimena Del Risco1, Joaquim Casals1, Elena Guillen Olmos1, donor age groups. (Figure 2) The eGFRs of recipients demonstrated a decline with
Enrique Montagud-Marrahi1, Fritz Diekmann1 increased donor age and significant differences at all time points among 3 donor age
1 groups. (Figure 3) Multivariate analysis using Cox regression hazard model
Hospital Clınic of Barcelona, Nephrology and Kidney Transplant, Barcelona, Spain
demonstrated donor aged 70 – 89 as a significant risk of graft loss (P = 0.024, hazard
ratio 3.053, 95% confidence interval 1.160 – 8.040).
BACKGROUND AND AIMS: Early graft failure (EGL) is a devastating complication
of kidney transplantation. Patients with EGL have an increased risk of mortality of up
to twelve times compared to patients who received grafts that survive beyond 30 days.
Moreover, they may have become sensitized to antigens from the failed graft and that
human leukocyte antigen antibodies (anti-HLA), identified on single antigen bead
assays, may not be reliable until several weeks after transplantation. Thus, if rapid re-
transplantation occurs, there is no certainty regarding the recipient’s immunological
status. Hence, there could be an increased immunological risk with the consequent
disturbance of the new graft’s survival.
METHOD: We performed a retrospective single-center observational study in re-
transplanted patients with EGL (defined as graft loss before 30 days from transplant)
between January 1977 and November 2019 from our center to analyze the outcomes of
rapid re-transplantation (occurred within 30 days of EGL) vs late re-transplantation
(occurred beyond those 30 days).
RESULTS: T: here were 82 re-transplants after EGL. The median overall patient
survival after re-transplantation was 32 years. Eight patients died within the first year.
Among the mortality causes, there were four septic shocks, one cardiogenic shock, one
massive pulmonary thromboembolism, one myocardial infarction, and one unknown
cause. When analyzed for periods, death censored graft survival was 89% at one and
five years after re-transplantation. One graft was lost at eight days due to antibody-
mediated rejection (AMR), while there was one death with a functioning graft three
months after re-transplantation secondary to a pulmonary embolism. Seventy-three
late re-transplants occurred. When analyzed for periods, death censored graft survival
was 81% and 69% at one and five years after re-transplantation, respectively. The

i506 | Abstracts
Nephrology Dialysis Transplantation Abstracts
METHOD: Clinical, laboratory and dietary data from the TransplantLines Biobank
and Cohort Study (NCT03272841), comprising 424 KTR were analyzed. Exhaled H2
concentration was measured using a model DP Quintron Gas Chromatograph.
Diarrhea was classified according to the Bristol Stool Form Scale (BSFS) and stool
water content was measured using a freeze-drying method. Dietary intake was assessed
using a validated self-administered food frequency questionnaire (FFQ). Possible
determinants of exhaled H2, such as sex, age, eGFR, mycophenolate mofetil and
tacrolimus use, and several other clinical, biochemical and nutritional factors, were
studied using univariable linear regression. All variables with a p<0.05 were included
in a multivariable linear regression model run backward to identify the determinants of
exhaled H2 production.
RESULTS: KTR (55.4613.2 years, 60.8% male, mean eGFR 49.8619.1 mL/min/1,73
m2) were divided into three groups according to median exhaled H2 concentration
(G1, 1.0-6.9 ppm, n=151; G2, 7.0-19.9 ppm, n=139; G3, 20.0 ppm, n=134). Hence,
signs of small intestinal bacterial overgrowth (exhaled H2 20 ppm) were identified in
31.6% of KTR. Seventy-six patients (33.0%) had diarrhea according to BSFS. Exhaled
H2 correlated with stool water content (r=0.24, p=0.04) and increased risk of diarrhea
(OR = 6.03, 95% CI 1.6-22.1, p<0.01). In multivariable linear regression analyses,
polysaccharide intake was independently associated with exhaled H2 (std. b=0.24,
p=0.01), whereas the other factors were not significant.
CONCLUSION: These findings suggest that higher fasting exhaled H2 is associated
with increased risk of diarrhea in KTR with polysaccharide intake as an independent
determinant of exhaled H2. The present results suggest that diarrhea in KTR may
reflect an altered small bowel gut microbial composition, at least partly under dietary
influence.

MO929 KIDNEY TRANSPLANTATION IN MONOCLONAL


IMMUNOGLOBULIN DEPOSITION DISEASE: A REPORT OF 6
CASES

Elena Cuadrado Pay an1, Alicia Molina-Andujar1, Natalia Tovar2, Natalia Castrejo n
de Anta3, Ignacio Revuelta1, David Cucchiari1, Federico Cofan Pujol1,
1 2 2 2
Nuria Esforzado , M.Teresa Cibeira , Laura Rosin ~ol , Joan Bladé ,
Fritz Diekmann1, Carlos Fern andez de Larrea2, Luis F. Quintana3
1
Hospital Clınic Barcelona, Nephrology and Kidney Transplantation, Barcelona, Spain,
2
Hospital Clınic Barcelona, Hematology, Barcelona, Spain and 3Hospital Clınic
Barcelona, Pathological anatomy, Barcelona, Spain

BACKGROUND AND AIMS: Monoclonal immunoglobulin deposition disease


(MIDD) is a systemic rare condition that usually leads to end stage renal disease.
Treatment of patients with a bortezomib-based regimen followed by autologous stem
cell transplantation (ASCT) has been increasingly used, with improvements in the
CONCLUSION: The prognosis of living donors after donation were not affected by response rates and the renal graft outcomes in kidney transplant recipients
the donor age except for the lower eGFR with increased donor age. The eGFRs of METHOD: Retrospective study of 6 patients diagnosed of MIDD with complete
recipients and graft loss rates were the worst in the recipients transplanted from donors response but not renal response after hematologic treatment that underwent kidney
aged 70 – 89. transplant in our institution between 2010 and 2019.
RESULTS: A total of 6 patients (5 women) were analyzed, with mean age at diagnosis
of 47 years (range 40-53). At presentation their mean eGFR was 18 mL/minute (range
9-25) and mean proteinuria of 5.5 g (range 0.290-12.5). The deposit was kappa type
except in 1 case (heavy and light lambda type chains). In all of them there was an
absence of monoclonal component in blood and urine but positive immunofixation in
MO928 EXHALED HYDROGEN AS A MARKER OF INTESTINAL 5 cases (2 only in urine). 3 started chronic hemodialysis during admission and the
FERMENTATION IS ASSOCIATED WITH DIARRHEA IN others at 3, 5 and 44 months after diagnosis. As hematological treatment, all received
KIDNEY TRANSPLANT RECIPIENTS bortezomib followed by ASCT, being under complete hematological response at the
time of kidney transplant. It was performed at 28 months on average from ASCT
Fernanda Guedes Rodrigues1,2, Johann Casper Swarte1,3, Rianne M. Douwes1, (range 11-42), with mean kappa/lambda ratio of 2.6 (range 1.33-3.75). 3 patients
Tim J. Knobbe1, Ita Pfeferman Heilberg2,4, Stephan Bakker1, Martin De Borst1 received induction with thymoglobulin and 3 with basiliximab, followed by triple
1 therapy with tacrolimus þ prednisone þ mTOR inhibitor (4 patients) or
University Medical Center Groningen, University of Groningen, Department of mycophenolate (2 patients). During a median follow-up of 20,5 months from kidney
Nephrology, Groningen, The Netherlands, 2Universidade Federal de S~ ao Paulo, Nutrition transplant and 54 months from ASCT, 1 patient experienced hematologic relapse and 2
Post-Graduation Program, S~ ao Paulo, Brazil, 3University Medical Center Groningen, had hematologic progression (one of them with MIDD relapse in the allograft)
University of Groningen, Department of Gastroenterology and Hepatology, Groningen, requiring treatment. The patient with organ relapse received Daratumumab
The Netherlands and 4Universidade Federal de S~ ao Paulo, Department of Nephrology, monotherapy achieving complete hematologic response but graft failure. The other 5
S~ao Paulo, Brazil patients had functional graft with median serum creatinine 1.68 mg/dl.
CONCLUSION: In patients with MIDD and sustained complete hematologic
BACKGROUND AND AIMS: Diarrhea is a common gastrointestinal (GI) complaint response, a kidney transplant can be considered. The optimal approach to treatment of
among kidney transplant recipients (KTR). Exhaled hydrogen (H2) is a surrogate hematologic relapse or recurrence of MIDD after kidney transplant remains to be
marker of small intestinal bacterial overgrowth, which has been proposed to drive GI determined
symptoms such as diarrhea. In a large cohort of KTR, we assessed the amount of
exhaled H2 to evaluate its association with diarrhea and potential clinical and dietary
determinants.

10.1093/ndt/gfab110 | i507
Abstracts Nephrology Dialysis Transplantation

MO931 PRETRANSPLANT ANGIOTENSIN II TYPE 1 RECEPTOR


ANTIBODIES INFLUENCE GRAFT FUNCTION BUT NOT
GRAFT SURVIVAL AT 1 YEAR AFTER KIDNEY
TRANSPLANTATION IN A LOW IMMUNOLOGICAL RISK
COHORT

MO930 BURDEN OF DISEASE IN INCIDENT DIALYSIS PATIENTS Bogdan Marian Sorohan1,2, Andreea Ioana Berechet1, Bogdan Obrisca1,2,
WAIT LISTED FOR KIDNEY TRANSPLANTATION 2008 – 2016 Ileana Constantinescu2,3, Ionut Maruntelu3, Dorina Tacu4, Catalin Baston2,4,
IN GERMANY Ioanel Sinescu2,4, Gener Ismail1,2
1
Fundeni Clinical Institute, Nephrology, Bucharest, Romania, 2Carol Davila University of
Martin Wagner1,2, Wolfgang Arns3, Katherine Rascher4, Heyke Cramer1, Medicine and Pharmacy, General Medicine, Bucharest, Romania, 3Fundeni Clinical
Mathias Schaller4, Dieter Bach1, Gero Von Gersdorff4 Institute, Immunogenetics, Bucharest, Romania and 4Fundeni Clinical Institute, Center
1
KfH-Board of Trustees for Dialysis and Kidney Transplantation, Neu-Isenburg, Germany, of Uronephrology and Renal Transplantation, Bucharest, Romania
2
University Hospital Würzburg, Department of Medicine I - Nephrology, Würzburg,
Germany, 3Cologne Merheim Medical Center, Department of Nephrology and BACKGROUND AND AIMS: Angiotensin II type 1 receptor antibodies (AT1R-Ab)
Transplantation, Cologne, Germany and 4University of Cologne, Faculty of Medicine are associated with graft rejection and poor graft outcomes in kidney transplantation
and University Hospital Cologne, Internal Medicine II - QiN-group, Cologne, Germany (KT). It has been shown that AT1R-Ab have a negative impact on both short-term and
long-term graft function, even in the absence of rejection, but this has not been
BACKGROUND AND AIMS: Only a subset of all patients on dialysis is eligible for confirmed by other studies. Our aim was to assess the frequency of pretransplant
kidney transplantation (KTx) due to the large variation of mortality risk. It has been AT1R-Ab and to determine their influence on graft function and survival at 1 year
shown that the burden of disease is increasing over the last years in patients at dialysis after KT.
inception. Moreover, the number of available kidney grafts is decreasing, resulting in a METHOD: We performed a prospective, observational cohort study in 67 adult KT
prolonged time on the waiting list. In our study we describe the burden of disease and recipients, transplanted between October 2018 and October 2019. Clinical, biological
3-year mortality in a sample of incident dialysis patients in Germany, stratified by KTx and immunological data of the recipients, age, gender and type of donor, transplant
status, including trends over time. and immunosuppression parameters were collected at the moment of transplantation.
METHOD: The QiN (Quality in Nephrology) dataset is a registry-based observational A cut-off > 10 U/mL was used for AT1R-Ab detection.
study in which >90% of all patients treated in dialysis centers of the non-profit kidney RESULTS: Among the 67 recipients mean age was 41.3 6 10.3 years, male gender was
care provider KfH are enrolled. In our analyses we included all adult patients beginning predominant (59.7%) and the main known cause of end-stage renal disease was
dialysis treatment between 2008 and 2016. Primary outcome was 3-year all-cause death glomerular disease. Six patients out of 67 (9%) had a previous kidney transplant. The
up until Dec 31, 2019. Patients were stratified by last available KTx- status: (a) KTx donor mean age was 50 6 15.5 years and 65.7% of patients received the kidney graft
within 3 years, (b) on dialysis - on waiting list, (c) on dialysis - in evaluation for KTx, from a cadaveric donor. Pretransplant AT1R-Ab were detected in 7 out of 67 patients
(d) on dialysis - KTx never planned, (e) on dialysis - KTx status missing. The burden of (10.4%) and none of the patients had specific antibodies against human leucocyte
disease was assessed by the AROii score (Floege et al. 2015), a predictive model antigen. After 1 year of follow-up, median estimated glomerular filtration rate (eGFR)
including patient characteristics, laboratory variables and dialysis parameters. of the recipients was 54 ml/min/1.73 m2 (40.6 – 65.9), 10.4% of patients developed
RESULTS: Of a total of n=25987 incident patients analyzed, 3.2% underwent KTx delayed graft function, 7.5% had graft failure and no cases of biopsy proven graft
within 3 years, 10.6% were listed for KTx, and 13.4% were in evaluation. In 49.5% KTx rejection or death was reported. Patients with pretransplant AT1R-Ab had a significant
was never planned and in 23.3% KTx status was missing. These groups differed reduced graft function at 1 year after KT compared to those without antibodies [35
significantly in median AROii score, reflecting their burden of disease at dialysis (29.8- 55.2) vs 56.1 (41.3 – 66.5) ml/min, p=0.02]. After multivariate linear regression
inception: KTx never planned or missing (AROii score 10) as compared to KTx (AROii analysis, pretransplant AT1R-Ab were an independent determinant of eGFR at 1 year
score 1), listed (AROii score 3) and in evaluation (AROii score 4) (p<0.001). after KT (b: -14.066; 95% CI: -27.44 - -0.68; p=0.04). Cox regression analysis was used
Similarly, 3-year observed mortality (n=8059 [31%]) differed widely across KTx strata to assess the association of AT1R-Ab along with other clinical, biological and
(log rank p<0.001), ranging from 11% in listed patients to 44% (HR 5,982; [5.335; immunological parameters with graft failure. Neither the univariate (HR= 2.07, 95%
6.707]) in those with missing KTx status (figure). In the period 2008-2019 the number CI: 0.23-18.52, p=0.51) nor the multivariate (HR= 1.36, 95% CI: 0.10-14.09, p=0.80)
of KTx within 3 years decreased, but the proportion of patients on the waiting list and Cox regression models showed that pretransplant AT1R-Ab were an independent
the proportion of patients in evaluation increased. In all patients on dialysis the burden predictor for graft loss.
of disease at dialysis inception increased over time across KTx strata (p<0.05). CONCLUSION: We showed that pretransplant AT1R-Ab are an independent
CONCLUSION: About three quarters of patients started dialysis with a very high determinant of graft function but do not influence the graft survival at 1 year after
mortality risk and at least half of them were considered ineligible for KTx. Patients transplantation in a prospective low immunological risk cohort of kidney transplant
listed or in evaluation for KTx in Germany have become sicker over the last decade. recipients.
With decreasing numbers of KTx in Germany the time on the waiting list is prolonged.
Longer waiting times and the increasing burden of disease result in advanced risk at the
time of transplantation.

i508 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO932 POPULATION DENSITY AND U.S. KIDNEY reduce the high incidence of PTDM by influencing just modifiable risk factors,
TRANSPLANTATION DURING THE FIRST YEAR COVID-19 including obesity and the associated IR. The aim of this work is to determine the effect
PANDEMIC of precisely determined physical activity and lifestyle changes on IR and other risk
factors for PTDM in patients after KT.
Ekamol Tantisattamo1,2, Natnicha Leelaviwat3, Natchaya Polpichai4, METHOD: This is a prospective controlled analysis, which included 44 patients after
Natsuki Eguchi1,5, Natsumon Udomkittivorakul6, Hwakyung Seo1,7, primary KT in the Martin Transplant Center. Half consisted of a study group (n = 22)
Chawit Lopimpisuth6, Busara Songtanin6, Sakditad Saowapa3, whose patients were assigned to perform regular physical activity. The primary goal
Possawat Vutthikraivit8 was to complete at least 150 minutes of moderate intensity physical exertion per week.
1
Division of Nephrology, Hypertension and Kidney Transplantation, Department of They performed an aerobic or combined (aerobic þ anaerobic) type of sports activity.
Medicine, University of California Irvine School of Medicine, Orange, California, United Monitoring was provided by a sports tracker (Xiaomi Mi Band 3 compatible with Mi
States of America, 2Multi-Organ Transplant Center, Section of Nephrology, Department Fit mobile application). The other half was made up of a control group. The exclusion
of Internal Medicine, William Beaumont Hospital, Oakland University William criterion at that time was already diagnosed with diabetes mellitus or a pre-diabetic
Beaumont School of Medicine, Royal Oak, Michigan, United States of America, 3Faculty condition. IR was assessed using the HOMA-IR (Homeostatic Model Assessment for
of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 4Faculty of Insulin Resistance) index from fasting blood glucose and insulinemia values. Each
Medicine Songklanagarin Hospital, Prince of Songkla University, Songkhla, Thailand, patient underwent an oral glucose tolerance test (oGTT) at the end of follow-up.
5
Division of Kidney and Pancreas Transplantation, Department of Surgery, University of Patients in both groups have the same immunosuppressive protocol. The duration of
California Irvine School of Medicine, Orange, California, United States of America, follow-up was 6 months.
6
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 7School of RESULTS: In the observed group we univariately found in the 3rd and 6th month of
Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, monitoring significantly lower waist circumference (P = 0.0437, P = 0.0372), better
California, United States of America and 8Phramongkutklao College of Medicine, graft function (P = 0.0036, P = 0.0137), lower value glycemia (P = 0.0016, P = 0.0003),
Mahidol University, Bangkok, Thailand C-peptide (P = 0.0447, P = 0014) and lower low-density lipoprotein (LDL) at 6 months
(P = 0.0444) compared to the control group. We confirmed a statistically significantly
BACKGROUND AND AIMS: Coronavirus disease 19 (COVID-19) pandemic leads lower IR at 6 months (P = 0.0202) and fasting blood glucose at 3 and 6 months (P =
to poorer health outcomes and more utilizing of healthcare resources. Kidney 0.0227) by multivariate analysis in the observed group. After the end of the follow-up,
transplant (KT) can lead to worsening transplant outcomes with COVID-19 and trend we identified statistically significantly fewer patients with a negative oGTT result in the
of KT in the United States decreases. Given a highly contagious disease, high control group (P < 0.0001), significantly more patients with impaired glucose
population density may contribute to not only higher rate of the disease, but also lower tolerance, fasting hyperglycemia (P = 0.0078) and diagnosed with PTDM (P = 0.0212).
rate of KT. We aim to examine the association of the number of COVID-19 cases and In the control group, we found a statistically significant increase in glycemia at 30 (P =
change in the number of KT with the interaction of population density in the United 0.0034) as well as at 120 minutes (P = 0.0011) during oGTT compared to the observed
States. group.
METHOD: A cross-sectional study was conducted by using publicly available data of CONCLUSION: In our study, we confirmed a significant effect of regular physical
COVID-19 cases and KT in the United States were retrieved from the Centers of activity in preventing the development of IR and associated pre-diabetic conditions
Disease Control and Prevention (CDC) and the Organ Procurement and and PTDM.
Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR),
respectively. The association of the cumulative COVID-19 cases of 47 states in the
United States where KT occurred between January 1, 20202 and January 6, 2021 with
difference in the number of KT between year 2019 and 2020 (DKT) was examined by
using multiple linear regression.
RESULTS: During the study period, a total of 20,136,895 COVID-19 cases were
detected in the United States and 326,535 patients died. From all 47 states, 23,002 and
20,554 adult KT were performed in 2019 and 2020, respectively. Mean COVID-19
cases and deaths were 428,4456457,344 and 6,9486 6,911, respectively among the 47
states. Mean DKT2019 - 2020 were 526 81. Every 10,000 COVID-19 cases was associated
with a decrease in 1.06 KT in year 2020 compared to year 2019 (bcoeff 0.00011, p
<0.0001, 95% CI 0.00006, 0.00015). However, after adjusted for the number of KT in
2019, COVID-19 cases (< or  median cases of 317,545), population density (< or 
median density of 114 people/mile2), and the interaction term between COVID-19
cases and population density, the states with high rate of COVID-19 (317,545 cases/
year) and high population density (114 people/mile2) had a decrease in 12.4 KT;
whereas, there was 4.5 KT decrease in states with low COVID-19 rate and low
population density (bcoeff 0.1024705, p 0.000, 95%CI 0.066272, 0.1386691, p interaction -
0.686).
CONCLUSION: The number of KT in 2020 has decreased independent to the number
of 2019 KT and population density. However, a decrease in the number of KT was MO933 Figure 1: Development of HOMA-IR index during the study period.
lower in the states with low COVID-19 rate and low population density compared to HOMA-IR: Homeostatic Model Assessment for Insulin Resistance; M: Month
those with high COVID-19 rate and high population density. Distribution of
healthcare resources and utilization including KT in the states with low COVID-19
cases and low population density may be one of the strategies to continue KT, which is
life-saving therapy and better survival benefit compared to being on dialysis in end-
stage kidney disease population with a high mortality risk.

MO933 EFFECT OF PHYSICAL ACTIVITY AND LIFESTYLE CHANGES


ON INSULIN RESISTANCE IN PATIENTS AFTER KIDNEY
TRANSPLANTATION

Karol Gran k1, Vnucak Matej1, Petra Sk


a a1, Margaréta Pytliakov
alov a2,
L’udovıt Laca1, Maria n Moka 3, Ivana Dedinska1
n
1
University Hospital in Martin and Jessenius Medical Faculty of the Comenius
University, Martin, Slovak Republic, Surgery Clinic and Transplantation Center, Martin,
Slovakia, 2University Hospital in Martin and Jessenius Medical Faculty of the Comenius
University, Martin, Slovak Republic, Clinic of Anesthesiology and Intensive Medicine,
Martin, and 3University Hospital in Martin and Jessenius Medical Faculty of the
Comenius University, Martin, Slovak Republic, Clinic of Internal Medicine I., Martin, MO933 Figure 2: Comparison of oGTT results at the end of the follow-up.
Slovakia oGTT: oral glucose tolerance test; IFG: impaired fasting glucose; IGT: impaired glucose
tolerance;
PTDM: post-transplant diabetes mellitus
BACKGROUND AND AIMS: The incidence of post-transplant diabetes mellitus
(PTDM) after kidney transplantation (KT) is high and ranges from 15-30%. Insulin
resistance (IR) at the time of KT is the most significant risk factor for the development
of PTDM in patients after KT, as demonstrated by several analyzes. It is possible to

10.1093/ndt/gfab110 | i509
Abstracts Nephrology Dialysis Transplantation

(74.1 6 68.4 mg/L vs 160.7 6 74.4 mg/L, p <0.0001), D-dimer (967.3 6 949.0 lg/L vs
2810.1 6 1807.7 lg/L, p <0.0001) and the frequency of procalcitonin increase (29.5 vs
86.4%, p <0.001). The independent factors of adverse outcome (Cox model) were high
levels of comorbidity index (p <0.006) and procalcitonin (p <0.006), as well as the
IMV use (p <0.0001). It was not possible to establish differences in Groups 1 and 2
depending on the use of individual drugs (Corticosteroids, Baricitinib, Monoclonal Ab
IL-6/IL-17/IL-1b, antiCOVID plasma) as well as their combinations.
CONCLUSION: The frequency of SARS-CoV-2 infection in RTR was more than 2
times lower in summer compared to spring and autumn, which suggests a seasonal
nature of this infection. The course of the disease was characterized by high hospital
and general mortality. High values of the comorbidity index, procalcitonin and the
IMV use were independent predictors of the fatal outcome.

MO935 HEALTH RELATED QUALITY OF LIFE AFTER KIDNEY


TRANSPLANTATION: A SYSTEMATIC REVIEW

Yiman Wang1, Marc Hemmelder2, Willem Jan W. Bos3,4, Jaap-Jan Snoep5,


Aiko De Vries4,6, Friedo W. Dekker1, Yvette Meuleman1
1
Leiden University Medical Center, Department of Clinical Epidemiology, The
Netherlands, 2 Maastricht University Medical Centre, Department of Internal Medicine,
The Netherlands, 3St Antonius Hospital, Department of Internal Medicine, The
Netherlands, 4Leiden University Medical Center, Department of Internal Medicine,
Division of Nephrology, The Netherlands, 5Tergooi, Hilversum, Department of Internal
Medicine, The Netherlands and 6Leiden University Medical Center, Transplant Center,
The Netherlands
MO933 Figure 3: Comparison of glycemia during oGTT.
oGTT: oral glucose tolerance test BACKGROUND AND AIMS: Health-related quality of life (HRQOL) is becoming an
increasingly important outcome in kidney transplantation besides graft function and
patient survival. It is of clinical interest to understand whether kidney transplant
recipients (KTRs) experience better HRQOL after the invasive procedure and to what
extent they can restore HRQOL. To the best of our knowledge, the last relevant
MO934 COVID-19 IN RENAL TRANSPLANT RECIPIENTS (RTR) systematic review and meta-analysis, which compared HRQOL in KTRs to patients on
dialysis, only included eligible publications before 2005. With the considerable
improvement in nephrology care and the exponential increase in studies focusing on
Irina Kim1,2, Nadiya Frolova3, Lyudmila Artyukhina1, Ekaterina Ivanova1, HRQOL in the past two decades, an updated overview of the current literature is
Vitaly Berdinsky1, Irina Ostrovskaya1, Vladimir Vinogradov1, Andrey Frolov1, needed. Moreover, to gain a comprehensive picture of HRQOL in KTRs, it is also
Tatiana Buruleva1, Maria Maltseva1, Olesya Ruseykina2, Irina Skryabina1, necessary to include relevant comparison groups such as the general population and
Elizaveta Volodina2, Natalja Tomilina1,4, Mikhail Zubkin1,2,5 healthy controls to understand to which extent HRQOL can be restored to a “pre-
1
State Budgetary Healthcare Institution “Moscow City Clinical Hospital No.52 of CKD” level. To describe HRQOL in KTRs, this systematic review summarizes the
Moscow Healthcare Department”, Nephrology, Moscow, Russia, 2Gabrichevsky Moscow published literature to date that compared HRQOL of KTRs with other relevant
Research Institute of Epidemiology and Microbiology, Nephrology, Moscow, Russia, populations (i.e. patients receiving dialysis, patients on the waiting list for kidney
3
State Budgetary Healthcare Institution “Moscow City Clinical Hospital No.52 of transplantation, patients with chronic kidney disease [CKD] not receiving dialysis, the
Moscow Healthcare Department”, Nephrology, Moscow , Russia, 4Evdokimov Moscow general population, and healthy controls) and themselves before kidney
State University of Medicine and Dentistry, Nephrology, Moscow, Russia and 5Kirov transplantation. To avoid potential bias, we include studies using different HRQOL
Military Medical Academy, Nephrology, Saint Petersburg, Russia questionnaires.
METHOD: A thorough literature search was conducted in PubMed, EMBASE, Web of
BACKGROUND AND AIMS: SARS-CoV-2 infection has a severe course in Science, and COCHRANE Library. Studies were included when published between
immunocompromised (RTR) patients. The aim is to study the clinical course and risk January 2000 and October 2020, and when comparing HRQOL in adult KTRs to the
factors for adverse outcomes and results of COVID-19 treatment in RTR. relevant populations. The quality of included studies was assessed using the Risk Of
METHOD: At the beginning of the study there were 2580 RTR observed at Moscow Bias Assessment tool for Non-randomized Studies (RoBANS). Prespecified study
Nephrology Center, by the end of it there were 2776 RTR. A retrospective uncontrolled characteristics and HRQOL scores were extracted. Due to substantial clinical and
observational study included 279 RTR (M: 172/F: 107, aged 49.9610.9 yrs.), infected methodological heterogeneity, results were summarized in a narrative manner without
with SARS-CoV-2 from April 1 to November 30, 2020. The period after kidney pooled estimates.
transplantation before the onset of the disease was 54,0 months (14.0;108.0). After RESULTS: 44 studies comprising 6929 KTRs were included in this systematic review.
confirmation of COVID-19 by PCR and chest  MMF/ffza were canceled, CNI dose The mean age of KTRs in all studies ranged from 29 to 72 years old, and only two
was minimized (target blood level was CyA 30-50 ng/ml, ac 1,5-3 ng/ml), a CS dose studies were conducted in an elderly cohort ( 65 years). The majority of studies (93%)
was increased to 10-15 ng/day. Observation endpoints: discharge/recovery or death. reported a higher percentage of male KTRs (median 62%; range 43% to 86%). The
RESULTS: The number of RTR infected with SARS-CoV-2 from April 1 to May 31, average time of HRQOL-measurements after kidney transplantation ranged from 1 to
2020 was 108; there were 42 RTR from June 1 to August 31, 2020; and 129 RTR - from 234 months after the operation. 50% of the studies had a cross-sectional design; 32%
September 1 to November 30, 2020. 59 RTR (21,1%) had a mild course of COVID-19. had a prospective, and 18% had a retrospective design; and 55% of the studies were
Patients with moderate and severe course (220/78.9%) were treated in the hospital. The single-center studies. While taken into account study heterogeneity, KTRs reported a
period from the onset of the disease to the hospitalization was 7.1 6 5.1 days. Severe higher HRQOL after kidney transplantation compared to pre-transplantation and
lung damage (> 50%) occurred in 97 of 220 (44.1%); decrease in SpO2 <95% was seen compared to patients receiving dialysis with or without being on the waiting list,
in 128 of 220 (58.2%); 31 patients died. Thus, hospital mortality was 14.1%, overall especially in disease-specific domains (i.e. burden of kidney disease, effect of kidney
mortality was 11.1%. Scr during the course increased from 160.9 6 68.2 lmol/l to disease, and symptoms). Additionally, KTRs had comparable to marginally higher
185.4 6 130.9 lmol/l (p <0.01) with no signs of acute rejection; and after the recovery, HRQOL compared to patients with CKD stage 3-5. When compared to healthy
it decreased to 158.1 6 63.2 lmol/l (p <0.01). Risk factors associated with fatal controls or the general population, KTRs reported similar HRQOL in the first one or
outcome were analyzed among the survivors (group 1; n-189) and the deceased (group two years after kidney transplantation, and lower physical HRQOL and lower to
2; n-31). Groups 1 and 2 differed in the frequency of severe lung damage (69/36.9% vs comparable mental HRQOL with an average post-transplant time longer than two
24/77.4%, p <0.001); the Charlson comorbidity index (4.4 6 1.7 vs 6.1 6 2.5, p years.
<0.001); the frequency of IMV use (0 vs 23, p <0.0001), Scr upon admission (160.3 6 CONCLUSION: Patients generally report better HRQOL after successful kidney
67.1 mmol/l vs 208.9 6 99.4 mmol/l, p <0.03), Hb levels (116.3 6 21.8 g/l vs 91.7 6 transplantation compared to themselves before the operation and patients receiving
23.9 g/l, p <0.001), white blood cell count (11.1 6 4.8  109/L vs 18.1 6 7.5  109/L, dialysis with or without waiting for kidney transplantation, but HRQOL of KTRs does
p <0.001), lymphocyte count (0.7 6 0.4  109/l vs 0.4 6 0.4  109/L, p <0.02), not return to “pre-CKD” HRQOL levels. Future studies investigating risk factors for
albumin (32.4 6 4.1 g/l vs 25.8 6 2.8 g/l, p <0.001), glucose (6.1 6 1.9 mmol/l vs 7.8 6 impaired HRQOL are needed to maximize the long-term benefit of kidney
2.8 mmol/l, p <0.001), LDG (305.6 6 135.6 U/l vs 800.8 6 313.8 U/l, p <0.0001), CRP transplantation.

i510 | Abstracts
Nephrology Dialysis Transplantation Abstracts
MO936 KIDNEY RE-TRANSPLANTATION: NOT TOO OLD FOR A Melek E et al have shown that doppler ultrasound is a non-invasive study that, through
SECOND CHANCE the resistance index (RI), has traditionally been used for the early diagnosis of acute
graft rejection (AR); however, it is influenced by extrarenal systemic factors. Naesens et
Clara Pardinhas1, Rita Leal1,2, Francisco Caramelo3, Teofilo Yan4, al published that in 321 kidney transplant recipients, RI wasnt associated with
Carolina Figueiredo1, Luıs Rodrigues1,2, Maria Guedes Marques1,2, histological findings of AR in protocol biopsies.
Catarina Roma ~ozinho1,2, Lidia Santos1,2, Arnaldo Figueiredo5, Rui Alves1,2 Elastography is another ultrasonographic modality for the evaluation of the kidney
1
Coimbra University and Hospital Center, Nephrology, Portugal, 2Faculty of Medicine, graft, which measures the stiffness/elasticity of the tissue expressed in Kpa
University of Coimbra, Nephrology Universitary Clinic, Portugal, 3Faculty of Medicine, (kilopascals).
University of Coimbra, Biostatistical lab and medical informatics, Portugal, 4Hospital Stock in 2011 and Kim BJ in 2018 published studies where they showed that increased
Amato Lusitano, Nephrology , Portugal and 5Coimbra University and Hospital Center, stiffness was correlated with the diagnosis of kidney graft rejection.
Urology The aim of this study was to describe the association between elastography with
microvascular inflammation determined by Banff for diagnosis of renal allograft
subclinical rejection.
BACKGROUND AND AIMS: A growing number of end-stage renal disease patients
METHOD: Observational, analytical and cross-sectional study that included kidney
waiting for a kidney transplant (KT) are older than 50 years old. Consequently, many
transplant patients who underwent protocol biopsy and renal elastography at the
kidney transplant recipients will be in need of dialysis or re-transplantation at an older
Central Military Hospital in Mexico City between January 2018 and December 2020.
age. For young patients, re-transplantation offers an advantage over dialysis but in the
The demographic and biochemical characteristics, degree elastography stiffness and
elderly these benefits are not well established. For selected older recipients, with
Banff 2017 lesions were determined. The sample calculation, determination of
rigorous cardiovascular and neoplastic evaluation, immunosenescence might actually
correlation degree and ROC curve elaboration were performed.
provide an advantage in graft outcomes. Our aim was to compare major clinical
RESULTS: We included 146 patients. 56.8% were men; the most common causes of
outcomes between patients older and younger than 60 years old at re-transplantation,
CKD were undetermined and chronic glomerulonephritis with 52.7% and 17.1%
and between first and second KT for recipients older than 60 years old.
respectively. 47.3% were hypertensive at biopsy time and 1.4% had chronic heart
METHOD: We performed a retrospective, longitudinal study, that included all
failure. The most common immunosuppression schemes were FK/MPA/steroid and
patients submitted to a second KT between January 2008 and December 2019,
FK/mTOR-i/steroid with 60.3% and 13%, respectively. The mean GFR was 65.31 ml/
excluding patients with more than 2 grafts or multi-organ transplant. We defined two
min which shows graft good function. The mean stiffness in the elastography was 15.73
groups according to recipient’s age at re-transplant, older and younger than 60 years-
Kpa. The rest of baseline data are shown in Table 1.
old, and compared major clinical outcomes such as biopsy proven acute rejection,
death-censored graft survival and patients’ survival. Afterwards, we selected KT
patients older than 60 years, and compared the same outcomes for patients with first
and second KT. Follow-up time was defined at 1st June 2020 for functioning grafts or
at graft failure (including death with a functioning graft).
MO937 Table 1. Baseline demographic data of study population.
RESULTS: We included 109 patients with a second KT, 13 (12%) older than 60-years-
old (group 1), with a mean age of 62.85 6 2.9 years, and 96 (88%) younger than 60-
years-old (group 2), with a mean age of 40.4 6 10.6 years. Group 1 recipients were all n Mean Standard deviation
male (100% vs 59.4%; p=0.004) and had higher body mass index (2562.8 vs 22.563.6
kg/m2, p=0.016). Recipients from the group 1, waited less time for their second KT (SD)
(37.7621.8 vs 64.8658.8 months; p=0.003), but had older donors (59.5613.5 vs Age (years) 146 37.08 12.628
45.9611.5 years old; p<0.001), and significantly more expanded-criteria donors
(76.9% vs 26%; p<0.001). HLA mismatch and PRA (%) were similar for both groups.
Body Mass Index (BMI) 146 25.70 3.715
Regarding biopsy proven acute rejection, there were no events for older patients Postransplant time (months) 146 55.18 59.380
compared to 21 patients (22%) for the younger group (p<0.05). Death censored graft Tacrolimus level (ng/mL) 109 6.16 2.797
survival was similar for both groups (logrank test p=0.124) with similar 1 year and 5
years graft survival (group 1: 91.7%, 82.5% versus group 2: 90.1%, 85.2% p=0.944). We Everolimus level (ng/mL) 36 3.66 2.024
found no difference in patients’ mortality at follow up between both groups (logrank Cyclosporine level (ng/mL) 19 81.50 41.362
test p=0.0124). Focusing on differences between re-transplantation (group 1, N=13) Proteinuria (mg/day) 146 636.66 1707.071
and first kidney transplant (group 2, N=390) in patients older than 60-year-old, there
were more males in group one, but we found no other differences in recipient and Creatinine to biopsy (mg/dL) 146 1.50 1.634
donor demographic characteristics, or waiting time for kidney graft (38622 versus GFR at biopsy (ml/m2SC) 146 65.31 23.980
47625 months, p=0.17). As expected, PRA was significantly higher in group 1 (25
629% vs 3.7611%, p=0.018) but there were no differences in HLA matching. At
Elastography stiffness (Kpa) 146 15.73 6.874
follow-up, the mean time post-transplant for group 1 was 47639.68 and for group 2 Banff IFTA (%) 146 19.58 14.815
was 63 639.9 months (p=0.144). There were no differences regarding acute rejection
episodes (0% vs 3.1%; p=0.521) or death censored graft survival was similar at 1 and 5 Had rejection 36.3% of the biopsies, the most frequent chronic AMR C4d- with 15.1%
years (group 1: 91.7%, 82.5% versus group 2: 93.4%, 86.3% p=0.983). and active AMR C4d- 8.9%.
CONCLUSION: In carefully selected patients, advanced age should not be a When analyzing the ROC curves, the Banff 2017 lesions AUC values that correlated
contraindication to kidney re-transplantation. Immunosenescense might lead to lower better with graft stiffness were: v=0.607, i=0.594, g=0.578, C4d deposit=0.519,
acute rejection rates and older donors might be used with less restrictions. In our study, ptc=0.498. Figure 1.
major clinical outcomes were comparable to their younger counterparts with a second
graft and to older patients with a first graft.

MO937 ASSOCIATION OF RENAL ELASTOGRAPHY WITH BANFF


MICROVASCULAR INFLAMMATION IN PROTOCOL BIOPSIES
FOR SUBCLINICAL RENAL GRAFT REJECTION DIAGNOSIS

Lucino Bahena Carrera1, Javier Bastida Alquicira2


1
Central Military Hospital, Nephrology and Transplantation, Mexico, Mexico and
2
Central Military Hospital, Radiology Department at, Mexico, Mexico

BACKGROUND AND AIMS: The most common cause of renal graft failure is
chronic dysfunction in 24.7% and the most common etiology of this is clinical or
subclinical rejection. The incidence of subclinical rejection varies from 15 to 50% (25%
in protocol biopsies in the first year after transplantation and 35% after two years). CONCLUSION: Intimal arteritis, inflammation, and glomerulitis are the Banff lesions
best associated with elastography graft stiffness in protocol biopsies. Prospective
studies are recommended in patients with acute graft dysfunction to find an adequate
elastography cut-off value that allows another tool for fast and non-invasive diagnosis
of renal graft rejection.

10.1093/ndt/gfab110 | i511
MO938 PATIENT SURVIVAL AFTER LIVING DONOR KIDNEY Belgium, Division of Intensive care, Brussels, Belgium, 9Cliniques Universitaires Saint-Luc,
DONATION Brussels, Belgium, Institut de Recherche Expérimentale et Clinique, Brussels, Belgium
and 10Cliniques Universitaires Saint-Luc, Brussels, Belgium, Department of Abdominal
Marcel Naik1, Kayo Sakurayama1, Lukas Lehner1, Klemens Budde1, Surgery and Transplantation, Brussels, Belgium
Fabian Halleck1
1 BACKGROUND AND AIMS: Recurrence of anti-glomerular basement membrane
Charité, Medical Department, Division of Nephrology and Internal Intensive Care
Medicine, Berlin, Germany (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited
case reports and registry analysis. The aim of this study was to evaluate in a large
BACKGROUND AND AIMS: Living donor kidney transplantation [LDKT] is cohort of patients with detailed data collection and long follow-up the risk of
associated with best patient survival and life quality among kidney replacement recurrence of anti-GBM disease and graft loss caused by recurrence, the risk factors
therapies in case of chronic kidney disease. Yet, numerous previous studies have associated with clinical recurrence and the long-term patient and graft survival.
reported inconsistent results. The aim of this study was to investigate the influence of METHOD: Multicenter retrospective study. Inclusion criteria: patients with anti-GBM
recipient and donor characteristics on LDKT recipients in our center. glomerulonephritis transplanted with a kidney between 1977 and 2015. Exclusion
METHOD: All LDKT recipients from 01.01.1997 to 18.03.2020 were analyzed criteria: systemic vasculitis (except ANCA), lupus erythematosus and
retrospectively. Based on the biological relationship between recipient and donor, cryoglobulinemia. Clinical recurrence was defined as reappearance of signs of
recipients were grouped into “related” (biologically related) and “unrelated” (not glomerulonephritis along with histological signs of proliferative glomerulonephritis
related). Endpoints of this study were patient survival, death-censored graft survival and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies.
and graft survival including death analyzed by Kaplan-Meier method and log-rank test. RESULTS: Fifty-three patients were included. Clinical recurrence in a first kidney
Independent risk factors were estimated with Cox-regression. transplant occurred in only one patient five years after transplantation -a prevalence
RESULTS: Among 946 LDKT recipients we identified n=548 related and n=398 rate of 1.9%- in the context of cessation of immunosuppressive drugs. The graft was
unrelated recipients. Over a median observation time of 6.3 years 9.1% (86) of grafts lost due to recurrence. Histological recurrence with linear IgG staining on kidney
failed and 10.8% (102) of recipients died. Rates of graft failure and deaths were 8.8% biopsy in the absence of histologic signs of proliferative glomerulonephritis was
and 7.1% in related recipients and 9.5% and 15.8% in unrelated recipients, respectively. observed in four patients, in the context of cellular rejection. Two patients lost their
Kaplan-Meier-analysis showed 5, 10 and 15 year overall patient survival of 93.8%, kidney graft from severe acute rejection; the others fully recovered. Patient survival was
85.6% and 76.0%; death-censored graft survival of 94.7%, and 87.3% and 79.8%; graft 100%, 94% and 89% at 5, 10 and 15 years, respectively. Overall, death-censored first
survival including death were 89.8%, 76.3% and 62.7%. There was a significant graft survival rates were 88%, 83% and 79% at 5, 10 and 15 years, respectively.
difference between subgroups in patient survival (p<0.001) and graft survival CONCLUSION: Recurrence rate of anti-GBM glomerulonephritis after
including death (p<0.001) but not in death-censored graft survival (p=0.280). (figure transplantation is very low, and associated with graft loss. The long-term patient and
1, 2, 3) In the multivariate analysis we observed recipient age in years (Hazard Ratio graft survival rates are excellent.
[HR]:1.08; p<0.001) and donor age in years (HR:0.97; p=0.008) to be independent risk
factors for patient mortality. The occurrence of a delayed graft function (HR:2.52;
p<0.001) as well as recipient age in years (HR:1.04; p<0.001) were risk factors for graft
survival including death, while delayed graft function (HR:4.05; p<0.001) was the only
independent risk factor for death-censored graft survival.
CONCLUSION: LDKT recipients without a biological relationship to their donors
have an inferior patient survival and graft survival including death. The donor
relationship as well as delayed graft function, recipient age and donor age should be
taken into account during patient evaluation. Recipients subjected to these
characteristics should be informed about their individual risks and carefully monitored
long term. Further evaluations are needed particularly including the effects of
immunosuppressive medication.

MO939 RECURRENCE AND OUTCOME OF ANTI-GLOMERULAR


BASEMENT MEMBRANE GLOMERULONEPHRITIS AFTER
KIDNEY TRANSPLANTATION: A BELGIAN MULTICENTER MO939 Figure 1: Kaplan-Meier curve. Patient survival and death-censored first graft
STUDY survival after kidney transplantation for anti-GBM glomerulonephritis.

Sophie Coche1, Ben Sprangers2,3, Steven Van Laecke4, Laurent Weekers5,


Vicky De Meyer6, Rachel Hellemans7, Diego Castanares8, Heleen Ameye2, Eric
Jean Goffin1,9, Nathalie Demoulin1,9, Valentine Gillion1,9, Michel Mourad9,10,
Tom Darius9,10, Buemi Antoine10, Devresse Arnaud1,9, Nada Kanaan1,9
1
Cliniques Universitaires Saint-Luc, Brussels, Belgium, Division of Nephrology, Brussels,
Belgium, 2Katholieke Universiteit Leuven, Division of Nephrology, Leuven, Belgium,
3
Katholieke Universiteit Leuven, Department of Microbiology, Immunology and
Transplantation, Laboratory of Molecular Immunology, Rega Institute, Leuven, Belgium,
4
Ghent University Hospital, Division of Nephrology, Ghent, Belgium, 5Centre Hospitalier
Universitaire Sart-Tilman, Division of Nephrology, Liège, Belgium, 6Vrije Universiteit
Brussel, Division of Nephrology, Ixelles, Belgium, 7Universitair Ziekenhuis Antwerpen,
Division of Nephrology, Edegem, Belgium, 8Cliniques Universitaires Saint-Luc, Brussels,

i512 | Abstracts
Nephrology Dialysis Transplantation Abstracts
ACUTE REJECTION (N=20, 18,.%) NO REJECTION (N=89, 81.7%) p
RISK FACTORS RELATED TO SECOND KIDNEY TRANSPLANT
Receptor age (years) (mean 6 sd) 36.2 6 12 44,7 6 11 <0.01
cPRA (%) (mean 6 sd) 38.6 6 27 20.9 6 24 <0.05
HLA mismatch (mean 6 sd) 3.5 6 1.2 3.7 6 1.4 0.499
RISK FACTORS RELATED DO FIRST KIDNEY TRANSPLANT
First graft acute rejection (N,%) 11, 56% 19, 21% <0.01
OR 4.7, 95%CI [1.5 - 14.7]
First graft nephrectomy (N,%) 12, 60% 29, 33% <0.05
OR 3.1, 95%CI [1.1 - 8.4]
First graft survival(months) (mean, 95%CI) 44.7 [22.4-66.5] 81.9 [62.5-101] <0.01
Primary dysfunction (N,%) 3, 17% 8 ,11% <0.05
HLA mismatch (mean 6 sd) 3.4 6 0.9 3.5 60.9 0.88

MO940 ACUTE REJECTION IN KIDNEY RETRANSPLANTATION: RISK MO941 CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION
FACTORS AND IMPACT IN GRAFT SURVIVAL

Rita Leal1,2, Clara Pardinhas1, Luıs Rodrigues1,2, Maria Guedes Marques1,2,


Clara Pardinhas1, Rita Leal1,2, Francisco Caramelo3, Teofilo Yan4,
Lidia Santos1,2, Catarina Roma ~ozinho1,2, Francisco Caramelo3, Helena Sa 1,2,
Carolina Figueiredo1, Rui Nogueira1, Luıs Rodrigues1,2, Maria Guedes
Arnaldo Figueiredo4,5, Rui Alves1,2
1
Marques1,2, Catarina Rom~ aozinho1,2, Lidia Santos1,2, Arnaldo Figueiredo5,
ario de Coimbra, Nephrology, Portugal, 2Faculdade de
Centro Hospitalar e Universit Rui Alves1,2
Medicina da Universidade de Coimbra, Nephrology Universitary Clinic, Portugal, 1
3 Coimbra University and Hospital Center, Nephrology, Portugal, 2Faculty of Medicine,
Faculdade de Medicina da Universidade de Coimbra, Biostatistical lab and medical
University of Coimbra, Nephrology Universitary Clinic, Portugal, 3Faculty of Medicine,
informatics, Portugal, 4Centro Hospitalar e Universit
ario de Coimbra, Urology and
University of Coimbra, Biostatistical lab and medical informatics, Portugal, 4Hospital
Kidney Transplantation Unit, Portugal and 5Faculdade de Medicina da Universidade de
Amato Lusitano, Nephrology, Portugal and 5Coimbra University and Hospital Center,
Coimbra, Portugal
Urology, Portugal

BACKGROUND AND AIMS: Kidney retransplantation confers a robust survival


BACKGROUND AND AIMS: As kidney transplants are growing in absolute
benefit over dialysis in selected patients and recent data has shown second graft
numbers, so are patients with failed allografts and thus potential candidates for re-
outcomes similar to those of a first graft. However, the management of these patients is
transplantation. Re-transplantation is challenging due to immunological barriers,
challenging, particularly due to allosensitization and an increased risk of acute
surgical difficulties and clinical complexities but it has been proven that successful
rejection, which are related with poorer graft survival. The recognition of risk factors to
second transplantation improves life expectancy over dialysis. It is important to
acute rejection, dependent on the first and second graft, might help us to personalize
evaluate re-transplantation outcomes since 20% of patients on the waiting list are
standard care and achieve similar graft survival rates to patients with a first transplant.
waiting for a second graft. Our aim was to compare major clinical outcomes such as
Our aim was to identify risk factors to second graft acute rejection, and the impact of
acute rejection, graft and patient survival, between patients receiving a first or a second
acute rejection in graft failure.
kidney transplant.
METHOD: We performed a retrospective, longitudinal study including all patients
METHOD: We performed a retrospective study, that included 1552 patients submitted
submitted to a second kidney transplant between January 2008 and December 2019,
to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January
excluding patients with more than 2 grafts or multi-organ transplant. Demographic,
2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant
clinical and histocompatibility data from the donor and receptor were collected from
were excluded. Demographic, clinical and histocompatibility characteristics of both
our unit database. Delayed graft function was defined as the need of dialysis in the first
groups were registered from our unit database and compared. Delayed graft function
week post-transplant. All acute rejection episodes were biopsy proven, according to
was defined has the need of dialysis in the first week post-transplant. All acute rejection
Banff 2017 criteria. Follow-up was defined at 1st June 2020 for functioning grafts or at
episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was
graft failure, with a mean time of 94642 months.
defined at 1st June 2020 for functioning grafts or at graft failure (including death with a
RESULTS: We included 109 patients of which 70 males (64%), mostly Caucasian
functioning graft).
(97%), with a mean age of 43612 years at second kidney transplant. The main causes
RESULTS: Recipients of a second graft were significantly younger (43 612 vs 50 6 13
of end stage renal disease were glomerular disease (37%), undetermined cause (34%),
years old, p<0.001) and there were significantly fewer expanded-criteria donors in the
and urological pathology (15%). First kidney transplant was performed before the year
second transplant group (31.5% vs 57.5%, p<0.001). The waiting time for a second
2010 in 95 patients (87%). The median time of first graft survival was 75 months (IQR
graft was longer (63650 vs 48629 months, p=0.011). HLA mismatch was similar for
58.5-91.4) and the main causes of first graft loss were chronic allograft nephropathy
both groups but PRA was significantly higher for second KT patients (21.6625%
(N=62, 70.5%) and 11 patients (12.5%) presented primary disfunction due to surgical/
versus 369%; p<0.001). All patients submitted to a second KT had thymoglobulin as
vascular complications. During follow-up, 20 patients (18%) presented biopsy proven
induction therapy compared to 16% of the first KT group (p<0.001). We found no
acute rejection: 3 patients borderline changes, 10 patients T cell mediated and 7
difference in primary dysfunction or delayed graft function between groups. Acute
patients antibody mediated, the majority during the first-year post-transplant (N=17,
rejection was significantly more frequent in second kidney transplant recipients (19%
85%). The risk factors for second graft rejection are summarized in table 1. First year
vs 5%, p<0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3
graft survival of the second transplant was 90% and survival at follow up was 72.5%
were borderline changes. For the majority of the patients (85%), acute rejection
(N=79). Acute rejection was an important risk factor for graft loss (OR 6.548
occurred in the first-year post-transplant. Death censored graft failure occurred in 236
(95%CI[2.292 - 18.703]), p<0.01).
(16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft,
CONCLUSION: Worst outcomes in first kidney transplant, such as acute rejection,
p=0.08. Survival analysis showed similar graft survival for both groups (log-rank
primary dysfunction and lower graft survival were related with an increased risk of
p=0.392). We found no difference in patients’ mortality at follow up for both groups.
acute rejection in second graft outcomes, and consequently a higher risk of graft failure.
CONCLUSION: Although second graft patients presented more episodes of biopsy
proven acute rejection, especially at the first-year post-transplant, we found no
differences in death censored graft survival or patients’ mortality for patients with a
second kidney transplant. Second transplants should be offered to patients whenever
feasible.

10.1093/ndt/gfab110 | i513
Abstracts Nephrology Dialysis Transplantation

decades (1: 1989-1998; 2: 1999-2008; 3: 2009-2018). Data regarding donor and


recipient demographics, time on dialysis, immunization, cold ischemia time,
hemodynamic parameters and immunosuppression were collected from our
prospectively maintained data base.
RESULTS: Main donor, recipient and perioperative characteristics are summarized in
table 1. There were clear differences in these characteristics between the decades,
standing out more adverse features from both recipients and donors.
Overall incidence rate of DGF was 16% (n=493): 14% in decade 1; 19.3% in decade 2
and 15% in decade 3.
On univariate analysis, most studied variables included in table 1 were statistically
significant as predictors of DGF. However, on multivariate analysis, we found that in
the first decade the predominant risk factors for DGF were pre-transplant dialysis time
and cold-ischemia time, whilst in the following decades donor characteristics, as well as
recipient’s weight became more relevant (table 2).
CONCLUSION: The observed shift from donor-unrelated variables in the first decade
into donor-related variables in the second and third decades as the main determinants
of DGF highlights the impact of expanding donor’s acceptance criteria. Nevertheless,
the increase in expanded criteria donors did not translate into poorer overall results,
probable contributors being shorter cold-ischemia times and stronger
immunosuppression.

MO942 PREDICTORS OF DELAYED GRAFT FUNCTION IN KIDNEY


TRANSPLANT RECIPIENTS THROUGHOUT 3 DECADES: A
SINGLE-CENTER EXPERIENCE
MO943 IMPACT OF NON-ACTIVE HEPATITIS B ON PATIENT
Carolina Figueiredo1,2, Mariana Fernandes3, Filipe Mira1,2, Clara Pardinhas1, SURVIVAL AFTER RENAL TRANSPLANTATION
Rita Leal1,2, Luıs Rodrigues1,2, Maria Guedes Marques1, Lidia Santos1,
Catarina Roma ~ozinho1,2, Carlos Alberto Bastos4, Helena S a1,2, Anissa Paschereit1, Klemens Budde1, Michael Dürr1, Marcel Naik1
Arnaldo Figueiredo2,4, Rui Alves1,2 1
1
Charité Universit€
atsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Nephrologie
Coimbra Hospital and University Center, Nephrology, Portugal, 2University of Coimbra, und Internistische Intensivmedizin, Berlin, Germany
Faculty of Medicine, Portugal, 3University of Aveiro, Mathematics, Portugal and
4
Coimbra Hospital and University Center, Urology and Kidney Transplantation, Portugal
BACKGROUND AND AIMS: Dialysis patients (pts) have an increased risk for
hepatitis B (HB) infection and impaired response to HB vaccine compared to the
BACKGROUND AND AIMS: Delayed graft function (DGF), defined as the need for general population. As shown in other studies, patient and graft survival in pts with
dialysis within one week post-transplantation, is associated with poorer kidney graft chronic HB is worse. This study assesses the outcome of HBc-positive patients after
survival. We aimed to identify risk factors for DGF throughout 3 decades and evaluate kidney transplantation (KTx).
their effect on graft survival. METHOD: In our retrospective analysis we included all patients >18 years old, who
METHOD: Retrospective study including 3081 kidney transplants performed at our underwent kidney transplantation from 01.01.1990 to 31.08.2019 in our center.
transplantation unit between January 1st, 1989 and December 31st, 2018, split in 3 Patients were grouped by their serostatus prior to kidney transplantation into

MO942 Table 1: Recipient, donor and perioperative characteristics. HLA: human leukocyte antigen; SAP: systolic arterial pressure; DAP: diastolic arterial pres-
sure. Quantitative variables are displayed in mean6std (Kruskal-Wallis test); qualitative variables in n (%) (Pearson X2 test).

1st decade (n=724) 2nd decade (n=972) 3rd decade (n=1385) p-value
Recipient characteristics Age (years) 41.3614.0 44.0613.6 49.8613.2 <0.001
Weight (kg) 62.2612.7 64.5613.0 70.2613.6 <0.001
Pre-transplant dialysis time (m) 39.0639.1 50.7645.2 48.7630.8 <0.001
HLA compatibility 2.561.0 2.661.2 2.261.3 <0.001
Donor characteristics Age (years) 31.0613.8 40.2616.5 52.0614.1 <0.001
Weight (kg) 52.4623.7 71.6613.1 74.2614.3 <0.001
Expanded criteria donor 115 (15.9) 434 (44.7) 1052 (76.0) <0.001
Creatinine (mg/dl) 1.260.5 1.060.4 0.960.4 <0.001
Perioperative characteristics Cold ischemia time (h) 21.466.4 14.367.4 14.966.4 <0.001
Reperfusion SAP (mmHg) 136.8617.1 127.0619.6 120.6618.8 <0.001
Reperfusion DAP (mmHg) 79.869.9 75.8613.3 70.0614.1 <0.001

MO942 Table 2: Multivariate analysis including the variables statistically significant on the univariate analysis (binary logistic regression). Statistically signifi-
cant results (p<0.05) are highlighted in yellow.

1st decade 2nd decade 3rd decade


OR 95%CI OR 95%CI OR 95%CI
Recipient characteristics Recipient weight (kg) 1.01 0.99–1.03 - - 1.02 1.01-1.04
Pre-transplant dialysis time (m) 1.00 1.00-1.01 1.01 1.00–1.01 1.00 0.99–1.01
Donor characteristics Donor age (years) 1.00 0.99–1.02 1.02 1.00-1.03 1.01 0.99–1.02
Donor weight (kg) - - 1.02 1.00-1.04 1.01 1.00-1.03
Donor creatinine (mg/dl) - - 2.02 1.29-3.18 2.71 1.80-4.11
Perioperative characteristics Cold ischemia time (h) 1.06 1.02-1.10 - - - -

i514 | Abstracts
Nephrology Dialysis Transplantation Abstracts
“A: naı̈ve” (HB negative), “B: HBc-positive” (non-active HB) and “C: HBsAg-positive”
(chronic HB). Primary endpoints included patient and graft survival analyzed with
Kaplan-Meier and log-rank test. Regression analysis was applied to determine
independent risk factors for the occurrence of primary endpoints.
RESULTS: In 2487 kidney transplant patients, serologic markers were retrievable. We
identified n=2198 HB naı̈ve, n=218 non-active HB and n=75 chronic HB pts. Overall
29.1% (A:27.7%, B:37.6%, C:45.3%) pts died and 20.3% (A:19.1%, B:27.5%, C:37.3%)
pts suffered from graft failure. The 5-year pts survival (Fig. 1) was A: 87.0%, B: 82.8%,
C: 82.2%. The 10-year pts survival was A: 71.7%, B: 61.1%, C: 64.5% and the 20-year
pts survival was A: 43.1%, B: 26.1%, C: 40.9% (p=0.01). Kaplan-Meier-analysis showed
a 5-year graft survival (Fig. 2) of 87.7% in the naı̈ve, 86.1% in non-active HB and 84.3%
in chronic HB group. The 10-year graft survival was A: 77.3%, B: 64.9%, C: 76% and
the 20-year graft survival was A: 59.7%, B: 52.2%, C: 33.4% (p<0.001). The overall 5-
year pts and graft survival (Fig. 3) was A: 78.7%, B: 74.2%, C: 68.6%. The 10-year pts
and graft survival was A: 59.8%, B: 46.4%, C: 51.8%. The 20-year overall rate was A:
30.8%, B: 26.4%, C: 14.9% (p<0.001).

MO943 Figure 3: Patient and graft survival plots (p<0,001) and number of patients at
risk (at 0, 1825, 3650, 5475, 7300 days) in each HB group

Regression analysis (Table 1) showed that anti-HBs positivity (100 IE/l) was a
protective factor for graft failure and death (p<0.001).

MO943 Table 1: Multivariate regression analysis of variables associated with graft


failure and patient deathAbbreviations: CI, confidence interval; HCV AB, hepatitis C
antibodies; CMV Ab, cytomegalovirus antibodies; MM broad, broad antigen HLA
mismatches; Anti-HBs, antibody titer against hepatitis B surface antigen

variable Exp (B) 95% CI p


Recipient age 1,02 1,03 1,03 <0,001
Donor age 1,01 1,01 1,02 <0,001
Cold ischemia time 1,00 1,02 1,03 0,01
CMV Ab 0,85 0,99 1,14 0,83
MO943 Figure 1: Patient survival plots (p=0.001) and number of patients at risk (at 0,
1825, 3650, 5475, 7300 days) in each HB group HCV Ab 1,38 1,82 2,40 <0,001
Donor type
Living donor reference
Cadaver donor 1,13 1,58 2,20 0,01
HepB-Status
naı̈ve reference
Non-active HB 0,97 1,22 1,53 0,09
Chronic HB 0,98 1,47 2,22 0,06
MM broad
0 reference
1 1,05 1,50 2,13 0,03
2 1,16 1,50 1,96 0,002
3 1,34 1,72 2,22 <0,001
4 1,23 1,62 2,13 0,001
5 1,34 1,81 2,45 <0,001
6 2,70 2,45 3,54 <0,001
Anti-HBs
negative reference
10 IE/l 0,74 0,89 1,08 0,23
100 IE/l 0,58 0,69 0,83 <0,001
1000 IE/l 0,46 0,61 0,81 0,001

CONCLUSION: HB leads to earlier graft loss and inferior patient survival. Beside the
already known negative effect of chronic HB infection, also in patients with non-active
HB infection overall survival was significant worse to HB naı̈ve patients. Thus, non-
MO943 Figure 2: Graft survival plots (p<0.001) and number of patients at risk (at 0,
1825, 3650, 5475, 7300 days) in each HB group

10.1093/ndt/gfab110 | i515
Abstracts Nephrology Dialysis Transplantation

active HB status is an important risk factor for overall transplant outcome. Next, MO945 SERUM AND URINE LEUCINE RICH ALPHA-2-
influence of antiviral and immunosuppressive regimens and incidence of HB- GLYCOPROTEIN-1 IS ASSOCIATED WITH KIDNEY
reactivation are to be analyzed. TRANSPLANT INJURY AND FAILURE

Aiga Vasiļvolfa1, Juta Kroic a2, Anna Popova3, Ka rlis Ra 


cenis3, Baiba Slisere 3
,
Ieva Ziedina3, Inese Folkmane4, Aivars Lejnieks5, Harijs Cernevskis3,
3 3
Aivars Petersons , Viktorija Kuzema
1
Rı̄ga Stradiņs University; University of Latvia, Pauls Stradiņs Clinical University Hospital,
Riga, Latvia, 2Rı̄ga Stradiņs University, Riga, Latvia, 3Rı̄ga Stradiņs University, Pauls
MO944 BONE DISEASE AFTER KIDNEY TRANSPLANTATION - Stradiņs Clinical University Hospital, Riga, Latvia, 4University of Latvia, Pauls Stradiņs
(SUBTOTAL) PARATHYROIDECTOMY REDUCES FRACTURE Clinical University Hospital, Riga, Latvia and 5Rı̄ga Stradiņs University, Riga East Clinical
RISK University Hospital, Riga, Latvia
Ulrich Jehn1, Anja Kortenhorn1, Katharina Schütte-Nütgen1, Markus Strauss2,
Hermann Josef Pavensta €dt1, Barbara Suwelack1, Stefan Reuter1 BACKGROUND AND AIMS: Kidney transplantation is the treatment of choice for
1 most of the patients with end stage chronic kidney disease. To improve patient and
Universit€atsklinikum Münster - UKM, Nephrology, Münster, Germany and graft survival, early diagnostics and discovery of specific biomarkers is important.
2
Universit€atsklinikum Münster - UKM, Cardiology, Münster, Germany Leucine rich alpha-2-glycoprotein-1 (LRG-1) is an innovative, non-invasive biomarker

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