Research Article

Blood
Purification Received: March 11, 2022
Blood Purif
Accepted: March 17, 2023
DOI: 10.1159/000530268 Published online: May 10, 2023

Kt/V or Bicarbonate: What Is More

Important for Growth in Pediatric
Peritoneal Dialysis Patients?

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Lucimary de Castro Sylvestre a, b Rejane de Paula Bernardes c
Débora Stremel Ribeiro d Maria Esther Díaz-González de Ferris e
Guido Filler f, g, h, i
a
Division of Pediatric Nephrology, Department of Pediatrics, Hospital Pequeno Príncipe, Curitiba, Brazil;
b
Department of Pediatrics, School of Medicine, Pontifícia Universidade Católica Do Paraná, Curitiba, Brazil;
c
Department of Pediatric Nephrology, Clinica Nefrokids, Curitiba, Brazil; dDepartment of Public Health, City Health
Department, Curitiba, Brazil; eDepartment of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill,
NC, USA; fDepartments of Paediatrics, University of Western Ontario, London, ON, Canada; gDepartment of
Medicine, University of Western Ontario, London, ON, Canada; hPathology & Laboratory Medicine, University of
Western Ontario, London, ON, Canada; iDepartment of Paediatrics, Lilibeth Caberto Kidney Clinical Research Unit,
London, ON, Canada

Keywords total infused dialysate volume was 5.26 L/m2/day (range

Peritoneal equilibration test · Kt/V · Height velocity ·
Adequacy testing · Bicarbonate
Abstract
Introduction: Growth retardation is a common problem in
pediatric patients with chronic kidney disease. It is unknown if
the growth of children on peritoneal dialysis (PD) can be
augmented by more dialysis. Methods: We studied the effect
of various peritoneal adequacy parameters on delta height
standard deviation scores (SDSs) and growth velocity z-scores
in 53 children (27 males) on PD, who underwent 2 longitu-
dinal adequacy tests at 9-month intervals. None of the
patients were on growth hormone. Intraperitoneal pressure
and standard KDOQI guidelines were compared to the out-
come measures delta height SDS and height velocity z-scores,
using univariate and multivariate tests. Results: At the time of
the second PD adequacy test, their mean age was 9.2 ± 5.3
years; mean fill volume was 961 ± 254 mL/m2; and median
2.03–15.32 L). The median total weekly Kt/V was 3.79 (range
0.9–9.5), and the median total creatinine clearance was 56.6
(range 7.6–133.48) L/week, higher than previous pediatric
studies. The delta height SDS was a median of −0.12 (range −2
to +3.95)/year. The mean height velocity z-score was −1.6 ±
4.0. The only relationships discovered were between the delta
height SDS and age, bicarbonate, and intraperitoneal pres-
sure, but not for Kt/V or creatinine clearance. Conclusion: Our
findings highlight the importance of normalization of bicar-
bonate concentrations to improve height z-score.
© 2023 S. Karger AG, Basel
Introduction
In children treated with chronic peritoneal dialysis
(PD), weekly Kt/Vurea of 1.8/week is recommended
[1–4]. While no longer part of the Kidney Disease

karger@karger.com © 2023 S. Karger AG, Basel Correspondence to:

www.karger.com/bpu Guido Filler guido.filler @ lhsc.on.ca
Outcomes Quality Initiative (KDOQI) guidelines, a
weekly creatinine clearance (CCr) of at least 60 L/
1.73 m2 was recommended [5]. In a randomized con-
trolled trial of adults, increasing the weekly total Kt/Vurea
above 1.7 failed to improve patient survival [6]. The value
of these measurements for patient survival has been
questioned, and adequate sodium removal has been
proposed to replace Kt/Vurea in both adults [7] and
pediatric patients [8]. Children have a much lower car-
diovascular risk, and these recommendations may not be
applicable [9]. Warady et al. [10, 11] and Holtta et al. [12]
demonstrated a positive relationship between growth and
total solute clearance in small pediatric studies. Gold-
stein’s review of pediatric single-center studies concluded
that clearance, while being important, is not all that
matters for patient growth, and more research is required
to provide optimal dialysis [13]. A study with 24 patients
with a much higher PD prescription than the proposed
KDOQI guidelines (mean weekly Kt/Vurea 3.45 ± 0.73)
failed to demonstrate any correlation with patients’
growth. Those studies point to the fact that optimal
growth of pediatric patients on PD depends on other
factors besides small solute clearance, so the question
remains which adequacy parameters are important. A
multisite European study suggested that a high trans-
porter state of the peritoneal membrane has a negative
effect in patients’ growth [12]. Apex time has not been
analyzed in pediatric adequacy studies, and intraperito-
neal pressure (IPP) has not been included in previous
studies [2]. Despite the recommendation of an IPP
between 5 and 15 cm H2O [4], the ideal IPP for optimal
height velocity has not been elucidated.
To address this knowledge gap, we evaluated the influ-
ence of comprehensive adequacy tests on growth and height
velocity in a large single-center retrospective study of a
prospectively applied protocol on adequacy testing of 53
pediatric PD patients. As growth velocity is age dependent,
we chose both height velocity z-score and delta height
standard deviation score (SDS) as primary outcomes.
Materials and Methods
The retrospective nature of our study did not influence patient
treatment and was considered exempt from ethics board review.
The standard of care at our institution is a consensus protocol by
the physicians in the group. Out of 73 pediatric patients who
initiated the first PD treatment after June 1997 and who underwent
adequacy testing between June 2000 and June 2005, 53 patients
were eligible for the study and had paper medical records available.
Inclusion criteria were at least two consecutive adequacy tests and
no interruption of PD treatment between the two tests.
2 Blood Purif
DOI: 10.1159/000530268
Patients slowly increased dwell volumes until they reached an
average dwell volume of 917 ± 245 mL/m2 body surface area.
Patients were either treated with continuous ambulatory PD
(CAPD, n = 25), continuous cycling PD (CCPD, n = 16), or
nocturnal intermittent PD (NIPD, n = 10). The difference between
CCPD and NIPD was the lack of a daytime dwell on NIPD.
Average duration for the cyclic nighttime PD was 9.4 ± 2.9 h. Seven
patients on CCPD had an additional daytime dwell. Ultrafiltration
targets were individually based on patient hydration status, fluid
intake requirements, and residual urinary output.
Adequacy testing was comprised of a standardized peritoneal
equilibration test (PET) with a target dwell volume of 1,000 mL/m2.
Where applicable, the PET was performed at least 1 month after
catheter insertion. Standard laboratory testing measured creatinine
(modified Jaffé), urea, calcium, phosphate, intact parathyroid hormone
(PTH), etc. Calcium carbonate was the only phosphate binder used
during the study period. Weekly Kt/Vurea determination was per-
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formed as previously described [2]. IPP was determined according to
Fischbach et al. [14]. Catheter flux was determined during filling and
draining of PD solution normalized to body surface area (mL/min/
m2). Complications included episodes of peritonitis, exit site infections,
tunnel infections, catheter blockage, hernias, leakage, constipation, and
the need for surgical intervention (i.e., catheter replacement). Standard
anthropometric data were obtained with either an upright stadiometer
for older children or a stadiometer for infants in supine position.
Weight was determined using a beam scale for older children and an
electronic scale for infants. While nutrition was not evaluated in this
study, dieticians optimized the nutrition in every patient. Six patients
had a gastrostomy tube for feedings.
Statistical analysis was performed using GraphPad Prism (Windows
version 4.01, GraphPad Software, San Diego, CA, USA). SPSS version
12.0 (SPSS Inc. Chicago, IL, USA) was used for bivariate or multivariate
analysis controlling for confounding factors such as age. We first
analyzed for normal distribution using the D’Agostino-Pearson omni-
bus test. Contiguous normally distributed data were expressed as mean ±
one standard deviation, but if not normally distrusted, we reported
median and range. Appropriate parametric statistical tests were used.
Most parameters were not normally distributed, so we used nonpara-
metric tests, with the Spearman rank test for correlation analysis, and the
Wilcoxon’s matched pairs test for paired observations or the Mann-
Whitney U test for unpaired observations comparing parameters
between groups. Unless stated otherwise, all p values are two-tailed.
Results
We enrolled 53 patients (27 males), and their charac-
teristics at the first adequacy testing are summarized in
Table 1. The median time between PD initiation and the
first test was 95 days (minimum 7 days, maximum 1,186
days). The average time between the first and the second
tests was 208 ± 73 days. Mean age at PD initiation was
8.7 ± 5.1 years. Primary diagnoses were obstructive
uropathy (n = 22, 42%), acquired glomerulopathy (n =
16, 30%), hereditary nephritis (n = 11, 21%), and vascu-
lopathies (n = 1, 2%). Three patients had an unknown
etiology of end-stage kidney disease (ESKD). Four
Sylvestre/Bernardes/Stremel Ribeiro/Díaz-
González de Ferris/Filler
Table 1. Patient characteristics at first standardized peritoneal dialysis adequacy testing

Parameter Mean or median* for not Standard deviation Minimum Maximum

normally distributed parameters

Age, years 8.6 5.3 0.2 19.9

Height, cm 113.8 28.6 53.5 167.0
Height z-score −2.29 1.59 −5.70 0.90
Weight, kg 18.85* 3.30 52.60
BMI, kg/m2 15.35* 11.53 25.19
Dwell volume, mL/kg 37.5 9.3 17.1 66.6
Total dialysis volume, L/m2/day 4.9* 1.7 21.2
Intraperitoneal pressure, cm H2O/m2 11.4* 6.0 29.1
Drain catheter flow, mL/min/m2 379 147 89 755
Potassium, mmol/L 4.2 0.8 2.4 6.3
Intact PTH, pg/mL 199* 3.5 1,827
Serum albumin, g/L 35.7* 20.0 49.0

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Hematocrit 0.316 0.060 0.201 0.456
Weekly total Kt/Vurea 3.13* 0.22 8.90
Weekly PD Kt/Vurea 2.31* 0.22 8.9
Total CCr, L/week/1.73 m2 59.3 30.3 7.6 133.5
PD CCr 36.8 19.3 6.2 85.1

Clinical data of 53 PD patients at the time of the first adequacy test. PTH, parathyroid hormone; CCr, creatinine clearance; *, not
normally distributed data, therefore expressed as median and range.

patients had infantile cystinosis and were included.
Twenty patients (38%) were anuric.
At the first testing, 30 patients were on CAPD, 10
patients on CCPD, and 13 patients on NIPD. By the
time of the second testing, 3 patients were converted
from CAPD to CCPD, 2 patients from CAPD to NIPD,
and 2 patients from NIPD to CCPD. At the time of the
second PD adequacy test, the mean age was 9.2 ± 5.3 years
old. All patients had two adequacy tests at a mean time
interval of 210 ± 75 days. As the PD prescription was altered
post-first adequacy testing, we used the prescription of the
second testing as a surrogate marker for the previous 210
days, thus responsible for the height gain of the patients.
The mean fill volume used for the first standard PET
was 969 ± 281 mL/m2 and at the second one 961 ±
254 mL/m2, not significantly different (p = 0.6880, paired
t test). The median total infused volume was 5.26 L/m2/
day (range 2.03–15.32 L), significantly higher than at the
first visit (p = 0.0445, Wilcoxon’s matched pairs test).
According to the switches outlined above, 25 patients
were on CAPD, 15 patients on CCPD, and 13 patients on
NIPD, at the time of the second testing. For the entire
cohort, the median residual urinary output was 411 mL/m2
(range 0–3,046), not significantly different from the first
visit (377, p = 0.22, Wilcoxon’s matched pairs test).
The median total weekly Kt/Vurea was 3.79 (range
0.9–9.5), significantly higher than at the first test (median
3.13, p = 0.0399, one-sided, Wilcoxon’s matched pairs
test). The patient with a Kt/Vurea of only 0.9 had a weekly
Kt/Vurea of 3.67 on his first evaluation and 3.73 on
subsequent testing, and the patient with a Kt/Vurea of
9.5 had a previous weekly Kt/Vurea of 2.88 and a sub-
sequent of 4.18. We suspect a collection or calculation
error. The second lowest Kt/Vurea was 1.29, and this
patient previously had 2.33 and subsequently 3.64. The
median PD Kt/Vurea amounted to 2.14 (range 0.41–9.5).
Similarly, the total CCr increased from 59.3 ± 30.3 to
72.7 ± 44.0 L/week and 1.73 m2 (p = 0.0258, paired t test).
The median IPP normalized to body surface area was
10.89 cm H2O/m2 (range 4.5–27.6). The average catheter
flux was 349 ± 146 mL/min/m2. The laboratory param-
eters were similar on second testing. The comparison of
the first and second test is given in Table 2.
Under these dialysis prescriptions, average height z-score
for age was −2.5 ± 1.8, independent of age. Delta height SDS
was a median of −0.12 (range −2.00 to +3.95)/year. Median
delta height SDS did not differ by dialysis modality. Average
height velocity z-score was −1.6 ± 4.0. Both the delta height
SDS (Spearman r = 0.375, p = 0.015) and the height velocity
z-score (Spearman r = 0.329, p = 0.020) showed an age
dependency, with older children having a significantly
better growth velocity than the younger ones.
Delta height z-score did not correlate with any of the
dialysis parameters above. Total Kt/Vurea, PD Kt/Vurea,

Bicarbonate and Growth of Kids on PD Blood Purif 3

DOI: 10.1159/000530268
Table 2. Comparison of total clearance, residual urine output, and key laboratory findings between the first and second testing

Parameter First visit Second visit Unit p value

Total weekly creatinine clearance 59.29±30.30 72.66±43.98 L/week/1.73 m2 0.01

Total weekly Kt/V 3.31±1.78 3.80±1.98 0.05
Ultrafiltration 661 (−1,489, 2,586) 663 (−350, 2,368) mL/24 h/m2 0.3
Residual diuresis (mean, min, max) 377 (0, 3,898) 390 (03, 046) mL/24 h/m2 0.07
Albumin 3.57±0.56 3.63±0.64 g/dL 0.21
Intact parathyroid hormone 165 (3.5, 1,827) 126 (4.8, 1,887) pg/mL 0.2
Hematocrit 31.7±6.0 34.0±7.6 % 0.02
Bicarbonate 24.59±3.92 24.49±3.91 mmol/L 0.43
Urea 104.98±40.33 97.96±35.06 mg/dL 0.14
Creatinine 5.31±2.73 5.47±2.50 mg/dL 0.19
Potassium 4,20±0.79 4.12±0.82 mmol/L 0.25
Calcium 9.92±1.20 10.03±1.09 mg/dL 0.28
CaxPO4 product 47.11±14.77 49.14±17.17 mg2/dL2 0.22

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and residual urine output had no effect on the height
velocity z-score. Median delta height SDS in the anuric
group was −0.10 (range −0.51 to +2.89), not significantly
different from the delta height SDS in those patients with
residual urine output (median 0.00, range −2.00 to +3.95,
Mann-Whitney test). Although renal osteodystrophy and
nutrition affect growth, we found no correlation between
phosphate or iPTH. One patient had a suppressed iPTH
of 3.5 pg/mL (normal 10–55) and may have had ady-
namic bone disease. Nutrition adherence was not assessed
in the study. Using univariate analysis, height velocity
z-score correlated significantly only with bicarbonate
(Spearman r = 0.327, p = 0.020). When controlling for
age, there was only a weak but nonsignificant trend
toward significance between height velocity SDS and
bicarbonate (r = 0.181, p = 0.053, one-sided). After
adjusting for age, total and PD Kt/Vurea still failed to
show a relationship with height velocity z-score. Using a
bivariate model, there was no relationship between the
Kt/Vurea and delta height SDS or height velocity z-score,
nor was there a relationship between height velocity
z-score or delta height SDS and total Kt/Vurea.
Using multivariate analysis, tendencies were found be-
tween bicarbonate and infused volume (Spearman r = 0.433,
p = 0.001) and between Schwartz eGFR and infused volume
(Spearman r = 0.490, p < 0.001). Similar relationships
existed between dwell volume and Schwartz eGFR (Spear-
man r = 0.561, p < 0.001) and IPP (Spearman r = −0.422, p =
0.02). With multivariate models, there was only a trend but
no significance between delta height SDS and total CCr
(Spearman r = 0.245, p = 0.059, one-sided) and PD CCr (r =
0.246, p = 0.058, one-sided), whereas Kt/Vurea had no effect
at all. Not surprisingly, there was a significant correlation
after adjusting for age between residual urinary output and
total CCr (r = 0.304, p = 0.027) as well as between total PD
Kt/Vurea and PD CCr and total CCr.
We then analyzed what parameters differed between
those patients who were above and below the mean height
velocity z-score. As membrane characteristics have been
associated with growth failure, we analyzed the effect of
transporter types. Twenty-six patients (49%) were high
transporters at the time of the second adequacy test. The
average height velocity z-score of −1.733 ± 3.887 in the
high transporter group was not significantly different
from the other patients (mean −1.563 ± 4.267, p =
0.8838, unpaired t test). However, there was a slight trend
toward a better delta height SDS in patients who were not
high transporters (median −0.2000 vs. 0.0750, p = 0.0346,
one-sided, Mann-Whitney U test).
We found significant differences for bicarbonate con-
centration. Median bicarbonate concentration was 23.1
(range 18.0–28.8) mmol/L in the group with poor growth,
compared to the group with good growth (median 26.1
[range 18.0–31.3] mmol/L, p = 0.039, Mann-Whitney test).
We correlated the IPP with the fill volume normalized
to body surface area. As expected, there was a weak but
significant positive correlation between the IPP and the
fill volume normalized to body surface area (r = 0.38, p =
0.0044). We correlated the IPP and body mass index
(BMI) medians. The median BMI was 15.3 kg/m2
(range 12.6–26.3). Median IPP was 11.0 cm H2O (range
7.0–20.0). We confirmed a strong relationship between
BMI and IPP (Pearson r = 0.3078, p = 0.0249). The BMI
z-score in all but 6 patients was normally distributed.
Average BMI z-score at the beginning of the study was
−1.17 ± 1.17, significantly lower than at the second
measurement (−0.99 ± 1.22, p = 0.000476, paired t test).
Delta BMI z-score was 0.11 ± 0.20, significantly greater

4 Blood Purif Sylvestre/Bernardes/Stremel Ribeiro/Díaz-

DOI: 10.1159/000530268 González de Ferris/Filler

Fig. 1. Relationship between intraperitoneal pressure versus low
and high body mass index z-score.
than zero (p = 0.0005, one-sample t test). We then
arbitrarily divided the patients into two groups, those
with a worse and those with a better BMI z-score. At
the beginning of the study, there was a significant differ-
ence between the IPP in the patients with worse and better
BMI z-score. While patients with a lower BMI z-score had
a higher intraperitoneal pressure (12.75 ± 0.5622, n = 24,
vs. 11.04 ± 0.4889, n = 23, p = 0.0272, unpaired t test,
Fig. 1), this difference was no longer evident at the second
measurement. We then calculated whether the delta BMI
SDS had an influence on the delta height SDS. There was a
weak correlation between both parameters without stat-
istical significance (p = 0.0769, Pearson correlation, Fig. 2).
Discussion
This single-center study with a large pediatric PD cohort
evaluated the feasibility of Kt/Vurea as a dialysis prescription
target on growth. Because of the first adequacy testing and
analysis of other parameters like creatinine, urea, potassium
and bicarbonate levels, ultrafiltration rate, dialysis was
intensified. However, despite the increase in dialysis pre-
scription, the average height z-score worsened from −2.3 ±
1.6 to −2.5 ± 1.8. There was some inconsistency of the urine
collections, highlighting the difficulties of obtaining accurate
Kt/V in children. The median weekly Kt/Vurea of 3.79
exceeded dialysis prescriptions in the studies by Holtta
[12] and Chadha [10], as did the average weekly CCr of
72.7 L/week and 1.73 m2. Based on our findings, growth of
Bicarbonate and Growth of Kids on PD
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Fig. 2. Relationship between delta BMI SDS and delta height SDS.
our children was independent of Kt/Vurea (both total and
PD) and total CCr. Similar to the findings provided by
Chadha et al. [10], our data suggest that total Kt/Vurea and
total CCr did not predict catch-up growth. The proportion
of anuric patients in our study was similar to the 50%
reported in the cohort from Chadha et al. [10].
Importantly, none of our patients received growth
hormone therapy, which explains why the group from
the University of Missouri experienced a catch-up growth
of 0.2 whereas our cohort experienced a −0.12 catch-
down growth. Interestingly, residual urinary output was
also not a predictor of improved height velocity or
positive delta height SDS.
Our data support the findings in Goldstein’s review
[13], namely, that increasing PD prescription above a
certain threshold failed to improve patient outcome. In
children, accurate determination of Kt/Vurea is particu-
larly difficult because of frequent urinary collection errors
[15]. We therefore question the value of weekly Kt/Vurea
determination being a gold standard evaluation for the
estimation of PD adequacy in children.
Age had the strongest effect on growth. Younger
children did worse than older children, despite a similar
PD prescription per body surface area. It is well estab-
lished that growth failure is particularly common in very
young children with ESKD [16]. Age should be consid-
ered as an important covariate in any pediatric PD
adequacy study, given the different growth velocities.
Growth also was dependent on bicarbonate concentra-
tions. Aggressive sodium bicarbonate supplementation
has been emphasized in chronic kidney disease/ESKD
[17]. A large European study suggests that 30% of
Blood Purif 5
DOI: 10.1159/000530268
children on PD require ongoing bicarbonate supplemen-
tation despite being on PD [18]. Our data suggest to
support bicarbonate normalization.
It has been shown that BMI correlates with IPP [19],
and we confirmed this relationship. In addition, we found
a trend toward better delta height SDS and delta BMI
z-score. Nutrition was not assessed in this study. How-
ever, a change in the BMI z-score reflects nutrition.
Perhaps, the marked differences with age blunted the
effects and prevented statistical significance in a two-
tailed model. However, this trend suggests that those
patients with presumed better nutrition and better delta
BMI z-score demonstrate improved height velocity.
Apart from renal acidosis, residual renal function,
nutrition, and renal osteodystrophy affect growth of
children on PD. While nutrition was optimized in every
patient through visits with our dietitians, the fact that we
did not assess adherence to diet restrictions forms a major
limitation. The assessment of residual function may have
been rather inaccurate, as timed urine collections in
children are notoriously unreliable [20]. Also, optimiza-
tion of renal osteodystrophy, renal anemia, and especially
avoidance of adynamic bone disease are important for
linear growth of children on dialysis [21]. Although the
median iPTH level in this cohort was significantly ele-
vated, only 1 patient had a suppressed iPTH, and we
therefore do not believe that adynamic bone disease had a
significant impact on our results. We did not collect
hemoglobin values in this study, given the local financial
restrictions but sub-target hemoglobin levels are common
among pediatric PD patients [22]. Furthermore, medi-
cation information was inconsistently documented in the
paper medical records, and we could not measure adher-
ence. Approximately 40% of patients had bicarbonate
prescribed. Also, 4/53 children had infantile cystinosis,
where multiple factors affect growth [23]. A potential bias
could be introduced since some of the testing occurred as
early as 7 days after initiation of PD, once a steady-state
prescription was obtained. The KDOQI guidelines sug-
gest that the first PET be performed 4–8 weeks after PD
initiation. Nonetheless, the study clearly demonstrates the
importance of normalizing renal acidosis for growth
while prescribing high urea clearance did not improve
height velocity.
In summary, Kt/Vurea and CCr failed to predict
growth in this large single-center PD adequacy study.
Given the inaccuracy of the timed urine collection, the
value of this adequacy parameter assigned a very high
importance in the KDOQI guidelines maybe questioned
for pediatric PD patients. The effect of age adjusted for
growth velocity requires further analysis, as does the
6 Blood Purif
DOI: 10.1159/000530268
question about the importance of bicarbonate concen-
trations. While the importance of Kt/Vurea remains
questionable, the measurement of IPP and its relation-
ship to BMI and nutritional assessment should probably
be included in pediatric PD adequacy studies.
Acknowledgments
The authors would like to thank the patients and caregivers for
allowing us to share this experience in the peer-reviewed literature.
Statement of Ethics
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The manuscript was prepared and conducted ethically in accord-
ance with the World Medical Association Declaration of Helsinki. As
this is a retrospective cohort study without any impact on manage-
ment, the institution advised us that ethics approval was not required.
This study protocol was reviewed, and the need for approval was
waived by the ethics board of Pontifícia Universidade Católica do
Paraná. The same institution also waived the need for consent.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
No funding was available for this study.
Author Contributions
Guido Filler, Lucimary de Castro Sylvestre, and Rejane de Paula
Bernardes conceived the original study idea and provided intel-
lectual insight. Guido Filler wrote the manuscript, obtained and
reviewed all necessary references, was responsible for all editing
and obtaining approval from all authors, and developed the figures
and table. Lucimary de Castro Sylvestre, Rejane de Paula Ber-
nardes, and Déborah Stremel Ribeiro collected the data and
provided major intellectual insight into the study as well as the
manuscript editing of each version. Maria Esther Díaz Gonzáles de
Ferris revised multiple versions of the manuscript, provided major
intellectual insight into the study, and was responsible for trim-
ming it to the allowed word count. All authors contributed to and
approved the final manuscript.
Data Availability Statement
All relevant data have been included in the manuscript. De-
tailed laboratory findings of the patient would be available from
the first author.
Sylvestre/Bernardes/Stremel Ribeiro/Díaz-
González de Ferris/Filler
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