Sodium Removal per Ultrafiltration Volume in Automated Peritoneal Dialysis in Pediatric Patients

doi:10.21203/rs.3.rs-3136787/v1

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Sodium Removal per Ultrafiltration Volume in Automated Peritoneal Dialysis in Pediatric Patients

https://doi.org/10.21203/rs.3.rs-3136787/v1

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Journal Publication

published 02 May, 2024

Read the published version in Pediatric Nephrology →

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Background

The standard sodium removal in adult anuric patients on continuous ambulatory peritoneal dialysis (CAPD) is 7.5 g/L of ultrafiltration volume (UFV). Although automated PD (APD) is widely used in pediatric patients, no attempt has yet been made to estimate sodium removal in APD.

Methods

The present, retrospective cohort study included pediatric patients with APD who were managed at Tokyo Metropolitan Children’s Medical Center between July 2010 and November 2017. The patients underwent a peritoneal equilibrium test (PET) at our hospital. Sodium removal per UFV was calculated by peritoneal function and dwell time using samples from patients on APD with 1- and 2-hour dwell effluent within three months of PET and 4- and 10-hour dwell effluent at PET.

Results

In total, 217 samples from 18 patients were included, with 63, 81, and 73 of the samples corresponding to the High [H], High-average [HA], and Low-average [LA] PET category, respectively. Sodium removal per UFV (g/L in salt equivalent) for dwell times of 1-, 2-, 4-, and 10-hour was 5.2, 8.8, 8.0, and 11.5 for PET [H], 5.3, 5.8, 5.6, and 8.1 for PET [HA], and 4.6, 5.1, 5.1, and 7.1 for PET [LA], respectively.

Conclusions

Sodium removal per UFV in pediatric APD was less than the standard adult CAPD and tended to be lower with shorter dwell times, leading to sodium accumulation (Na sieving). Otherwise, salt intake should be restricted in combination with daytime CAPD, especially in anuric patients.

Automated peritoneal dialysis

sodium removal

dwell time

peritoneal equilibrium test

Na sieving

Patients on peritoneal dialysis (PD) have a tendency to fluid overload [1], which induces hypertension, a risk factor of cardiovascular disease (CVD). CVD is a common cause of death in patients on PD, including children [2]. Therefore, the management of fluid and blood pressure is important for patients on PD, as these are closely related to sodium kinetics, and it is necessary to educate the patients about their sodium intake. The standard sodium intake for adult anuric patients on PD is 7.5 g/L of ultrafiltration volume (UFV) based on the sodium removal rate in continuous ambulatory PD (CAPD) [3].

The management of fluid and blood pressure differs somewhat between pediatric patients and adults. Pediatric patients require more water and solute removal than adult patients owing to their higher water intake per body weight and need for adequate nutrition during growth and development. Automated PD (APD) at bedtime is widely used in pediatric patients to improve their quality of life, including school activities and social life. According to the International Pediatric Peritoneal Dialysis Network Registry, 75.7% of pediatric patients choose APD although there are regional and economic differences [2, 4]. In short-dwell APD, sodium tends to accumulate in the body because the sodium removal rate per UFV is low, a phenomenon known as “Na sieving” [5]. Na sieving leads to a vicious cycle of intense thirst and water intake that increases the required UFV.

Sodium removal in APD has not yet been estimated. To understand sodium kinetics in pediatric patients on APD, we investigated herein sodium removal per UFV by peritoneal function and dwell time.

Patient selection

The present, retrospective cohort study analyzed pediatric patients on PD who were managed at Tokyo Metropolitan Children’s Medical Center between July 2010 and November 2017. The patients who underwent a peritoneal equilibrium test (PET) at our hospital were included, and those with peritoneal function [Low] on PET were excluded owing to the small number of available samples. The clinical data on the eligible patients were obtained from electronic medical records. In addition to the patient's sex and primary disease, data on age at the time of PD fluid sample collection, height, weight, anuria or non-anuria, peritoneal function on PET within three months, dialysis prescription, and serum sodium level were collected.

PD fluid samples

Samples obtained from eligible patients at regular outpatient visits and at admission for PET were analyzed. Samples obtained within three months after peritoneal manipulation surgery or peritonitis were excluded because of the possibility of increased peritoneal permeability or peritoneal leakage. Samples obtained within three months of PD induction were also excluded because the dialysis prescriptions were often not consistent.

Data on PD injection volume, sodium concentration in dialysis fluid, PD effluent volume, and sodium concentration in the PD effluent were obtained for 1- and 2-hour dwell effluent in APD within three months of PET and 4- and 10-hour dwell effluent at PET. For APD samples, net APD effluent volume divided by the number of APD cycles was used in the calculation.

Eligible samples were divided into 12 groups by peritoneal function on PET (High [H], High Average [HA], Low Average [LA]) and dwell time (1-, 2-, 4-, 10-hour). UFV was calculated as follows: (PD effluent volume) - (PD injection volume). Sodium removal was calculated as follows: (sodium concentration in PD effluent) x (PD effluent volume) - (sodium concentration in dialysis fluid) x (PD injection volume). The sodium concentrations in the dialysis fluids of Baxter Inc. and Terumo Corp. were determined as 132 and 135 mmol/L from the accompanying documents. UFV and Sodium removal were converted per body surface area (/m²) of the patient at the time of sample collection, respectively. Samples with extremely low or negative UFV were excluded as ultrafiltration failure. To avoid a significant decrease in the number of samples, the cutoff for ultrafiltration failure was defined as ≤ 50 mL/m² for PET [HA] and [LA], < 0 mL/m² for PET [H].

Statistical analyses

Box-and-whisker plots were made for sodium removal per UFV for each group. The median of sodium removal per UFV for each group was compared by Mann-Whitney's U test. To adjust the dialysis conditions, sub-analyses were performed only on samples using dialysate with a sugar concentration of 2.5%, using dialysate from Baxter Inc. or using dialysate from Terumo Corp., respectively. All p-values were two-sided and were considered to indicate statistical significance if < 0.05. All analyses were performed using IBM SPSS 24.0 Statistics software package (IBM Corp., Armonk, NY).

Ethical considerations

The present study was conducted in accordance with the ethical principles set out in the Declarations of Helsinki and with the ethical guidelines for Medical and Health Research Involving Human Subjects issued by the Ministry of Health, Labour and Welfare of Japan. The study was approved by a central ethics board (Tokyo Metropolitan Children’s Medical Center; approval number 2020b-118) before commencement. Because all the data were reported retrospectively using the patient’s medical records, informed consent was waived in accordance with the above guidelines. The study protocol was displayed publicly on the Tokyo Metropolitan Children’s Medical Center website pursuant to the guidelines.

Patients and samples

Patient and sample characteristics are shown in Table 1. Eighteen patients were included, and the male-to-female ratio was 6:12. The primary diseases were congenital nephrotic syndrome (n = 6), hypoplastic-dysplastic kidney (n = 5), nephronophthisis (n = 2), and others (polycystic kidney disease, antineutrophil cytoplasmic antibody associated nephritis, ischemic kidney disease) (n = 5). Each patient underwent PET approximately every six months at our hospital.

Table 1

Patient and sample characteristics
peritoneal function	dwell time	patient	sample	Age* Median (IQR) (years)		Male: Female	anuria: non-anuria*	Baxter: Terumo	primary disease
PET [H]	1-hour	4	32	2.3	(1.0–8.3)	7:25	23:9	21:11	CNS(14), PKD(9), HDK(9)
	2-hour	2	5	1.5	(0.5–1.6)	0:5	0:5	5:0	HDK(5)
	4-hour	5	18	2.6	(1.7–3.5)	5:13	16:2	7:11	HDK(8), PKD(8), CNS(2)
	10-hour	5	8	3.5	(2.2–4.0)	2:6	7:1	4:4	HDK(6), PKD(1), CNS(1)
	total	6	63	2.4	(1.2–4.1)	14:49	46:17	37:26	HDK(28), CNS(17), PKD(18)
PET [HA]	1-hour	7	42	6.2	(1.4–7.8)	3:39	41:1	22:20	CNS(29), HDK(9), IKD(3), PKD(1)
	2-hour	2	8	2.9	(1.0–3.1)	0:8	0:8	5:3	CNS(5), HDK(3)
	4-hour	10	19	4.4	(1.7–6.0)	3:16	12:7	12:7	CNS(11), HDK(4), IKD(3), PKD(1)
	10-hour	6	12	3.9	(2.0–5.3)	3:9	7:5	10:2	CNS(8), IKD(3), HDK(1)
	total	11	81	4.4	(1.4–6.8)	9:72	60:21	49:32	CNS(53), HDK(17), IKD(9), PKD(2)
PET [LA]	1-hour	4	12	1.3	(1.1–2.1)	10:2	11:1	3:9	CNS(11), IKD(1)
	2-hour	5	29	7.0	(2.8–12.8)	2:27	0:29	13:16	ANCA(13), CNS(11), NPH(3), HDK(1), IKD(1)
	4-hour	11	21	4.5	(3.2–12.1)	8:13	5:16	10:11	CNS(6), ANCA(5), IKD(4), HDK(3), NPH(3)
	10-hour	8	11	4.7	(3.3–11.9)	5:6	2:9	7:4	IKD(4), ANCA(2), CNS(2), NPH(2), HDK(1)
	total	12	73	4.5	(2.6–12.2)	25:48	18:55	33:40	CNS(30), ANCA(20), IKD(10), NPH(8), HDK(5)
total		18	217	3.6	(1.5–7.2)	48:169	124:93	119:98	CNS(100), HDK(50), PKD(20), ANCA(20), IKD(19), NPH(8)
PET; peritoneal equilibrium test, [H]; High, [HA]; High Average, [LA]; Low Average, IQR; interquartile range, CNS; congenital nephrotic syndrome, HDK; hypoplastic-dysplastic kidney, PKD; polycystic kidney disease, ANCA; antineutrophil cytoplasmic antibody associated nephritis, IKD; ischemic kidney disease, NPH; nephronophthisis
*at time of sample collection

The total number of samples from the eligible patients was 217. The median age was 3.6 years (interquartile range (IQR): 1 year 6 months to 7 years 2months) at the time of sample collection, and the ratio of anuria to non-anuria cases was 124:93, and the ratio of Baxter Inc. to Terumo Corp. dialysate used was 119:98. The number of samples was 63, 81, and 73 at PET [H], [HA], and [LA] and 86, 42, 58, and 31 at a dwell time of 1-, 2-, 4-, and 10-hour, respectively. The median serum sodium level at the time of sample collection was Na 139.0 (IQR: 137.0 to 141.0) mmol/L. UFV and sodium removal per body surface area of the patient at the time of sample collection were calculated for all 217 samples and divided into 12 groups according to peritoneal function and dwell time (Table 2).

Table 2

Ultrafiltration volume and sodium removal in 12 groups by peritoneal function and dwell time
peritoneal function	dwell time	sample	serum Sodium level* Median (IQR) (mmol/L)		Ultrafiltration volume Median (IQR) (mL/cycle/m²)		Sodium removal Median (IQR) (mmol/cycle/m²)		Sodium removal per Ultrafiltration volume Median (IQR) (mmol/L)
PET [H]	1-hour	32	138.0	(135.8–139.0)	59.0	(50.8–84.9)	5.4	(4.3–7.1)	87.7	(74.2–97.6)
	2-hour	5	138.0	(138.0–139.0)	21.9	(21.0–100.9)	3.4	(3.3–15.8)	149.7	(143.2–156.3)
	4-hour	18	140.5	(137.0–142.0)	165.2	(125.7–182.0)	10.9	(5.8–17.8)	135.5	(105.2–179.9)
	10-hour	8	141.0	(138.8–142.3)	83.8	(67.4–161.3)	16.8	(15.2–26.2)	195.0	(147.1–209.7)
PET [HA]	1-hour	42	138.0	(136.0–141.0)	82.2	(67.8–92.4)	6.8	(5.7–8.4)	89.8	(70.6–102.1)
	2-hour	8	139.5	(138.8–141.0)	89.2	(80.3–93.7)	9.4	(6.5–11.0)	99.1	(85.3–114.9)
	4-hour	19	139.0	(137.0–141.0)	195.0	(103.2–259.2)	20.4	(10.3–29.3)	94.4	(86.8–116.5)
	10-hour	12	139.0	(137.8–141.0)	209.3	(133.9–259.5)	21.1	(15.6–34.1)	137.4	(107.0–145.2)
PET [LA]	1-hour	12	138.0	(136.0–140.0)	66.6	(60.4–80.5)	5.4	(3.6–6.6)	78.1	(59.3–82.7)
	2-hour	29	140.0	(139.0–141.0)	75.8	(62.4–91.6)	6.6	(4.8–8.6)	85.8	(64.9–107.9)
	4-hour	21	139.0	(137.0–140.0)	267.6	(236.0–380.9)	25.3	(20.1–32.2)	86.2	(78.3–93.3)
	10-hour	11	140.0	(139.0–140.0)	202.2	(164.7–310.3)	23.5	(21.9–25.2)	120.8	(96.7–127.3)
PET, peritoneal equilibrium test; [H]: high; [HA], high average; [LA], low average; IQR, interquartile range
*at time of sample collection

Sodium removal per Ultrafiltration volume

Box-and-whisker plots were made for sodium removal per UFV for their total and each groups, and their medians were compared by Mann-Whitney's U test (Fig. 1). In all groups, sodium removal per UFV tended to be lowest at 1-hour of dwell time. Sodium removal per UFV in the group with a dwell time of one hour was 4.6–5.3 g/L in salt equivalent, or up to 2.9 g/L less than the value of 7.5 g/L reported in adult patients on CAPD. Sodium removal per UFV (g/L in salt equivalent) for dwell times of 1-, 2-, 4-, and 10-hour was 5.2, 8.8, 8.0, and 11.5 for PET [H], 5.3, 5.8, 5.6, and 8.1 for PET [HA], and 4.6, 5.1, 5.1, and 7.1 for PET [LA], respectively. To achieve the adult CAPD standard of 7.5 g/L (127.5 mmol/L in sodium equivalent), it took more than 2 hours for PET [H], and PET [HA] and [LA] could not achieve it with APD alone.

To adjust the dialysis conditions, sub-analyses were performed only on samples using dialysate with a sugar concentration of 2.5% (Supplemental Fig. 1). Since the number of samples was significantly reduced to 121, sub-analysis was performed at 1, 4, and 10 hours of dwell time. As in the original study, sodium removal per UFV tended to decrease with shorter dwell times. Similarly, dialysate from Baxter Inc. and Terumo Corp. with different sodium concentrations (132 and 135 mmol/L) were also analyzed, and the same trend as in the original analysis was observed (data not shown).

In our study, sodium removal per UFV tended to be lowest at 1-hour of dwell time. In particular, in PET [H], sodium removal per UFV in the group with a dwell time of one hour was significantly lower than those with dwell time longer than two hours. To achieve the adult CAPD standard of 7.5 g/L, it took more than 2 hours for PET [H], and PET [HA] and [LA] could not achieve it with APD alone. [3].

The 3-pore model proposed by Rippe [6] may be used to estimate water and solute transport in PD. The smallest pores, which are selectively permeable only to free water, corresponds to a channel called aquaporin in the peritoneal cell membrane. The small pores are permeable to electrolytes as well as water while the large pores are permeable to proteins. Heimbürger et al. reported trends in solutes and solution in dialysate during a 6-hour dwell in 41 studies of 33 adult patients on CAPD [7]. In this report, the sodium concentration in the dialysate decreased from the start to a dwell time of 30–90 minutes mainly because of the movement of free water from the intravascular to the intraperitoneal space via aquaporins. At this time, sodium was accumulating because its removal per UFV was low, in a phenomenon known as Na sieving. After a dwell time of 60–90 minutes, the sodium concentration in the dialysate began to increase, indicating the movement of water, including electrolytes, via the small pores. Subsequently, the sodium concentration in the dialysate continued to increase slowly until 360 minutes. However, as the dialysate began to be absorbed into the lymphatic lumen, the UFV peaked at 120–240 minutes and began to decrease, as did the net sodium removal. Our results are consistent with these findings, showing that sodium removal per UFV is low in short-dwell APD and results in Na sieving.

In pediatric maintenance PD, 75.7% of patients chose APD for its relatively greater compatibility with school life and caregiver support while 23.5% chose CAPD [2, 4]. Although PD generally allows a milder restriction of salt intake than HD, it is important to keep in mind that APD may not be as efficient as CAPD at removing salt because of Na sieving. Our results also showed that sodium removal per UFV was lowest in one hour of dwell time in all groups. Especially in PET [H], the difference between one and two hours of dwell time was significantly larger, 61.9 mmol/L (3.6 g/L salt equivalent). Therefore, to reduce Na sieving in APD, dwell times less than one hour should be avoided if possible. However, in actual clinical practice, especially in the management of anuric infants on APD, it may be difficult to achieve a dwell time of more than two hours because of the high UFV requirement per body size. And in such cases, Na sieving becomes a more pressing concern. Na sieving causes hypernatremia, which often leads to increased water intake due to severe thirst, hypertension, and an increased UFV requirement, resulting in a vicious cycle. Thus, in patients who require management with short-dwell APD, the risk of Na sieving should be borne in mind, and a combination of a long daytime dwell for sodium removal as well as restriction of sodium intake should be considered.

The limitations of this study are that it is a single-center, retrospective study; it is an exploratory study and was not corrected for multiplicity; and that urine sodium excretion was not examined in patients with residual kidney function. Because hypoplastic-dysplastic kidney is common primary disease in chronic kidney failure in children and salt-losing kidney failure is common, some non-anuric patients on APD have no problem with their total sodium excretion. Furthermore, since the volume of dialysate per body surface area and the concentrations of sugar and sodium are not standardized, a prospective cohort study with standardized parameters can provide more accurate results. Also, by calculating the dwell time precisely, it may be possible to determine the shortest dwell time at which sodium removal per UFV equilibrates per peritoneal function.

Sodium removal per UFV in pediatric APD was less than the standard adult CAPD and tended to be lower with shorter dwell times, up to 2.9 g/L less than the value of 7.5 g/L reported in adult patients on CAPD and led to Na sieving. If a short-dwell APD cannot be avoided, especially in anuric patients, the risk of Na sieving should be considered, and salt intake should be restricted in combination with daytime CAPD.

Funding:

The authors did not receive support from any organization for the submitted work.

Conflicts of interests:

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval:

This study was approved by the Ethics Committee of Tokyo Metropolitan Children’s Medical Center (approval number 2020b-118).

Consent:

All the data were reported retrospectively using the patient's medical records. The requirement for informed consent was waived according to the relevant guidelines.

Author contribution statements:

All the authors contributed to the study’s conception and design. Material preparation and analysis were performed by T. Tokunaga, R. Hamada, and H. Hataya. T. Inoguchi, N. Mikami, C. Terano, R. Harada, Y. Hamasaki, K. Ishikura, and H. Hataya managed the patients and collected the data. The first draft of the manuscript was written by T. Tokunaga, and all the authors commented on previous versions of the manuscript. All the authors have read and approved the final version of the manuscript.

Nakayama M (2002) Water and Electrolyte Balance (WEB) Study Group in CAPD. Multicenter survey on hydration status and control of blood pressure in Japanese CAPD patients. Perit Dial Int May-Jun 22(3):411–414. https://doi.org/10.1177%2F089686080202200318
van Amstel SP, Noordzij M, Borzych-Duzalka D, Chesnaye NC, Xu H, Rees L, Ha I-S, Zenaida L, Antonio N, Hooman W, Wong K, Vondrak YC, Yap H, Patel M, Szczepanska S, Testa M, Galanti, Jameela A, Kari C, Samaille SA, Bakkaloglu (2021 Sep) Wai-Ming Lai, Luisa Fernanda Rojas, Mabel Sandoval Diaz, Biswanath Basu, Alicia Neu, Bradley A Warady, Kitty J Jager, Franz Schaefer. Mortality in Children Treated With Maintenance Peritoneal Dialysis: Findings From the International Pediatric Peritoneal Dialysis Network Registry. Am J Kidney Dis 78(3):380–390. https://doi.org/10.1053/j.ajkd.2020.11.031
Yasuhiko Ito M, Ryuzaki H, Sugiyama T, Tomo AC, Yamashita Y, Ishikawa A, Ueda Y, Kanazawa Y, Kanno N, Itami M, Ito H, Kawanishi (2021) Masaaki Nakayama, Kazuhiko Tsuruya, Hideki Yokoi, Mizuya Fukasawa, Hiroyuki Terawaki, Kei Nishiyama, Hiroshi Hataya, Kenichiro Miura, Riku Hamada, Hyogo Nakakura, Motoshi Hattori, Hidemichi Yuasa, Hidetomo Nakamoto. Peritoneal Dialysis Guidelines 2019 Part 1. Ren Replace Ther 7:40. Position paper of Japanese Society of Dialysis Therapyhttps://doi.org/10.1186/s41100-021-00348-6
Azocar FSchaeferDBorzych-DuzalkaM, Munarriz RL, Sever L, Aksu N, Lorena Sànchez Barbosa, Yajaira Silva Galan, Xu H, Coccia PA, Szabo A, Wong W, Salim R, Vidal E, Pottoore S, Bradley A, Warady IPPN (2012) investigators. Impact of global economic disparities on practices and outcomes of chronic peritoneal dialysis in children: insights from the International Pediatric Peritoneal Dialysis Network Registry. Perit Dial Int. Jul-Aug ;32(4):399–409. https://doi.org/10.3747/pdi.2012.00126
Krediet RT, Lindholm B, Rippe B (2000) Pathophysiology of peritoneal membrane failure. Perit Dial Int 20(Suppl 4):S22–42. https://doi.org/10.1177%2F089686080002004S03
Rippe B (1993) A three-pore model of peritoneal transport. Perit Dial Int 13(Suppl 2):S35–S38. https://doi.org/10.1177%2F089686089301302S09
Heimbürger O, Waniewski J, Werynski A, Lindholm B (1992 May) A quantitative description of solute and fluid transport during peritoneal dialysis. Kidney Int 41(5):1320–1332 https://doi.org/10.1038/ki.1992.196

SupFig1230701.pptx
Supplemental Figure 1. Sodium removal per liter of Ultrafiltration volume by peritoneal function and dwell time (Only samples with dialysate of 2.5% sugar concentration) SupFig 1. pptx UFV; Ultrafiltration volume, PET; peritoneal equilibrium test, [H]; High, [HA]; High Average, [LA]; Low Average Asterisk indicates a significant difference (* p < 0.05, ** p < 0.01).

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Editorial decision: Major Revisions Needed
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You are reading this latest preprint version

Sodium Removal per Ultrafiltration Volume in Automated Peritoneal Dialysis in Pediatric Patients

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

INTRODUCTION

METHODS

Patient selection

PD fluid samples

Statistical analyses

Ethical considerations

RESULTS

Patients and samples

Sodium removal per Ultrafiltration volume

DISCUSSION

CONCLUSION

Declarations

References

Supplementary Files

Status:

Journal Publication

Version 1