e186 Journal of Hypertension Vol 36, e-Supplement 1, June 2018
variably sized nuclei that were massively enlarged, irregularly shaped, and abnor-
mally hyperchromatic, which findings were indicative of KIN. Approximately one
year after quitting nivolumab treatment, his renal function improved to SCr level of
1.42 mg/dL,
Results: Case 2: A 76-year old female with non-small cell lung cancer started
treatment by nivolumab. Two months later, she exhibited AKI (SCr level from 0.81
to 1.54 mg/dL). Kidney biopsy revealed tubular injury with interstitial infiltra-
tion of inflammatory cells. Of note, tubular epithelial cells were focally enlarged
with hyperchromatic nuclei, which finding was consistent with that of KIN. Since
most of the enlarged tubular epithelial cells were positive for Ki-67, karyomegalic
changes of tubular epithelia are suggested to be associated with the cell cycle
abnormalities of tubular cells. The patient was administrated high dose of cortico-
steroid, and SCr level returned to that of her baseline.
Conclusions: Conclusion: This is the first report of characteristic histological find-
ings of KIN in nivolumab-associated AIN. The association of nivolumab-induced
AIN with cell cycle derangement in our patients suggests that the activation of effec-
tor T cell by nivolumab may affect the proliferation of tubular epithelial cells, thereby
leading to karyomegalic changes. In addition to the discontinuation of nivolumab, the
administration of corticosteroid successfully improved renal function.
DEEP VENOUS THROMBOSIS AND KIDNEY DISEASE
I. Prkacin1, T. Bulum2, T. Svagusa3, A. Golub4, T. Pikivaca5, G. Cavric1. 1Merkur
University Hospital, Department of Internal Medicine, University of Zagreb,
School of Medicine, Zagreb, CROATIA, 2Merkur University Hospital, Vuk Vrho-
vac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University of
Zagreb, Zagreb, CROATIA, 3University Hospital Dubrava, Department of Inter-
nal Medicine, Zagreb, CROATIA, 4Hospital for Pulmonary Diseases and TBC
Klenovnik, Klenovnik, CROATIA, 5Health Centre Zagreb West, Zagreb, CROATIA
Objective: Deep venous thrombosis (DVT) affects 2 million people in the USA.
Usually occurs in the leg, mainly affecting the large veins in the calf and thigh
on one side. Half of patients experiencing DVT do not show symptoms. DVT is
potentially life threatening conditions that come under the category of venous
thromboembolism (VTE). Kidney disease is one of independent risk factors for
VTE/DVT. Very little has been done to study the relationship between DVT, expe-
cially distal DVT (DDVT) and kidney disease.
Design and method: Patients (p) with DDVT were consecutively enrolled in
this study from January to June 2016.
Baseline kidney function was assessed, and p were followed during 3 months.
Changes in eGFR for up to 3 months were evaluated. eGFR was calculated us-
ing the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formu-
la < 60 mlmin/1.73m2
The study was approved by local ethics committees and provided written in-
formed consent to participate.
Results: Of 3209 p in Emergency Department we identified 65 (2% of all) with
simptomatic (pain + edema) limb DVT (upper limb 3p, proximal lower limb
22p + 40 p with DDVT). The mean age was 61.5 years (27–92 years), 70%
and 32% had hypertension and diabetes mellitus. 38% atrial fibrillation and no
one known malignant disease; body mass index was 34.4 ± 5.1 kg/m2, eGFR
55 ± 21 mlmin/1.73m2. At baseline 25% had chronic kidney disease: 10% mod-
erate chronic kidney disease (stage 3 CKD) (CrCl 30–59 mL/min), 15% had mild
CKD (CrCl 60–89 mL/min). After ultrasound doppler imaging and confirmation
of DDVT with positive D-dimer test result, we put p on DOACs.The 3-month
administration of DOACs for DVT caused a nonsignificant decrease of eGFR
(declined from 55 ± 21 mlmin-11.73m2 to 54 ± 16 mlmin-11.73m2 (p = 0.01)).
Control ultrasound imaging after 3 months was associated with recanalisation of
DVT, without proximal exstension and no thromboembolic events. In 20% of p
with DDVT we found new malignant disease (lung and colon).
Conclusions: Kidney dysfunction is common among individuals with DVT. The
results of our study suggest that the treatmen of DDVT of the limbs with DOACs
in p with kidney dysfunction is safe therapy.
NEBIVOLOL AND IRBESARTAN REDUCE POST-HEMODIALYSIS
AND AMBULATORY BP IN PATIENTS WITH INTRADIALYTIC
HYPERTENSION: A RANDOMIZED CROSS-OVER STUDY
A. Bikos1, C. Loutradis1,2, E. Aggeloudi1, A. Karpetas3, V. Raptis4,
E. Ginikopoulou2, S. Panagoutsos5, P. Pasadakis5, I. Balaskas6, V. Liakopoulos6,
A. Papagianni1, P.A. Sarafidis1. 1Department of Nephrology, Hippokration
Hospital, Aristotle University of Thessaloniki, Thessaloniki, GREECE, 2Protypo
Hemodialysis Unit, Thessaloniki, GREECE, 3Therapeutiki Hemodialysis Unit, Thes-
saloniki, GREECE, 4Pieria Hemodialysis Unit, Katerini, GREECE, 5Department
of Nephrology, General Hospital of Alexandroupoli, Alexandroupoli, GREECE,
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
6Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA
Hospital, Aristotle University of Thessaloniki, Thessaloniki, GREECE
Objective: Blood pressure (BP) increase during or immediately after hemodialy-
sis is an abnormal hemodynamic response to ultrafiltration and occurs in 5–20%
of patients. Intradialytic hypertension is associated with adverse clinical outcomes
and is often poorly diagnosed and controlled. This study aimed to evaluate the
effects of nebivolol and irbesartan in 24hour ambulatory BP in hemodialysis pa-
tients with intradialytic hypertension.
Design and method: This is a randomized cross-over study in 38 hemodialy-
sis patients (age: 60.4 ± 11.1 years, male: 65.8%) with intradialytic hypertension,
defined as mean intradialytic rise > = 10 mmHg in systolic BP (SBP) over 6
consecutive hemodialysis sessions. After baseline evaluation, patients were ran-
domly assigned to nebivolol 5 mg and subsequently irbesartan 150 mg, or vice
versa. Half of the patients received a single drug-dose 1 hour before hemodialysis
(n = 19) or for a whole week, before evaluation (n = 19). A two-week wash-out
period took place before the initiation of the second drug. All subjects underwent
24hour ambulatory BP monitoring starting before a midweek session.
Results: In total, 20 (52.6%) patients received nebivolol first and 18 (47.4%) received
irbesartan first. Patients receiving a single dose of either nebivolol or irbesartan had
lower post-dialysis SBP and diastolic BP (DBP) [Baseline: 161.6 ± 16.3/95.4 ± 12.3;
Nebivolol: 146.1 ± 20.4 (p = 0.003), 84.5 ± 11.8 (p < 0.001); Irbesartan: 144.7 ± 29.9
(p = 0.003), 86.8 ± 18.0 (p = 0.047) mmHg; respectively], non-significantly
lower 24-hour SBP and lower DBP [Baseline: 147.8 ± 16.0/87.7 ± 11.9; Nebivo-
lol: 144.0 ± 19.5 (p = 0.070), 83.3 ± 11.7 (p = 0.015); Irbesartan: 143.1 ± 21.7
(p = 0.171), 84.7 ± 12.8 (p = 0.095) mmHg]. Patients on weekly administration of
either nebivolol or irbesartan had significantly lower post-dialysis SBP and DBP
(Baseline: 167.1 ± 13.6/99.8 ± 10.6 Nebivolol: 145.2 ± 16.6 (p < 0.001), 91.0 ± 11.8
(p = 0.003); Irbesartan: 147.1 ± 23.8 (p = 0.002), 87.6 ± 12.5 (p = 0.001) mmHg),
significantly lower 24-hour SBP and DBP (Baseline: 148.2 ± 12.5/91.7 ± 9.7
Nebivolol: 139.2 ± 10.4 (p < 0.001), 85.2 ± 7.7 (p = 0.001); Irbesartan: 142.9 ± 15.7
(p = 0.188), 85.5 ± 9.9 (p = 0.015) mmHg; accordingly) and significantly lower day-
time and nighttime ambulatory SBP and DBP. No significant differences in BP re-
duction between nebivolol and irbesartan were observed.
Conclusions: Both nebivolol and irbesartan reduce post-dialysis and 24-hour BP
in patients with intradialytic hypertension. Weekly administration had greater ef-
fect and nebivolol seemed numerically slightly more potent than irbesartan; perma-
nent administration of these agents may be more effective than pre-dialysis dosing.
TRANSIENT SALT LOADING CAUSES PERSISTENT HYPERTENSION
THROUGH EPIGENETIC MODIFICATION OF THE RENAL
ARTERIOLES
H. Inoue, K. Miyashita, M. Sato, A. Hagiwara, K. Fujii, M. Ryuzaki, S. Endo,
A. Uto, H. Itoh. Department of Endocrinology, Metabolism and Nephrology, Keio
University, School of Medicine, Tokyo, JAPAN
Objective: We have previously reported that the medial hypertrophy of the renal
arterioles induced by transient salt loading causes sustained elevation of blood
pressure in spontaneous hypertensive rat (SHR) even after the salt loading had
completed [Oguchi et al. Hypertension 2014]. Epigenetic modification of gene
expression has attracted attention as a possible mechanism for sustained biologi-
cal effects and onset of hypertension. The present study investigated the signifi-
cance of histone acetylation in each segment of the kidney in the induction of
hypertension after transient salt loading.
Design and method: C57bl6 mice were implanted deoxycorticosterone acetate
(DOCA) pellets and given drinking water containing 1% NaCl for 2 weeks to
induce hypertension. We evaluated blood pressure, histological findings and gene
expressions of the kidney during and after the transient salt loading. The degree
of histone acetylation was assessed by immunostaining of acetylated H3 and H4
in each segment of the kidney including renal arterioles, segmental arteries, glom-
eruli and tubules. Gene expressions were examined in each segment of the kidney
collected by laser capture microdissection (LCM).
Results: Transient salt loading caused elevation in blood pressure during and
even after stopping salt loading associated with persistent medial hypertrophy of
renal arterioles. In the media of renal arterioles, histone acetylation was enhanced
during salt loading, and the enhanced histone acetylation persisted even after stop-
ping salt loading. The gene expression of MMPs in the renal arterioles collected
by LCM increased during salt loading, and did not decline even after stopping salt
loading. On the other hand, in the segmental arteries, neither hyper-acetylation nor
hyper-expression of MMPs was observed. Also, in the tubules, enhanced histone
acetylation by the salt loading returned to the initial level after the completion.
Conclusions: The persistent medial hypertrophy along with focally sustained his-
tone hyper-acetylation and elevation in MMPs expressions in the renal arterioles