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Groothoff Introduction In some cases, dialysis is required for a longer time, either before initial transplantation or folIn developed countries, chronic dialysis and kid- lowing the loss of an initial transplant when reney transplantation in children have become stan- transplantation is much more difficult to dard approaches to end-stage kidney disease accomplish As a result, patients with childhood(ESKD) care since the early 1970s Contrary to onset ESKD have most often experienced one or the situation in adults, few patients with childhood- more courses of short-term dialysis and a long onset ESKD have experienced a long course of period with a functioning graft Data on the longdialysis Kidney transplantation, preferably pre- term effects of dialysis during childhood are emptive without prior dialysis, is widely accepted therefore scarce; however, variable access to kidas the optimal mode of chronic renal replacement ney transplantation, even within developed countherapy (RRT) for children who have ESKD. Yet, tries, has provided important insights into the in practice, most children with ESKD have initi- consequences of long-term dialysis in children ated RRT management with dialysis while awaitIn this chapter, we review existing data on the ing the availability of a kidney to be transplanted long-term outcome of RRT in children, focusing on the role of dialysis and its associated potential long-term hazards We pay special attention to one of the most life-threatening late technical complications of peritoneal dialysis (PD), encapsulating peritoneal sclerosis (EPS) Most of the data included in the chapter come from registry M Honda (*) studies, all of which have the important limitation Department of Clinical Research Support Center, of incomplete and unverified data Another limiMetropolitan Children’s Medical Center, tation is that almost all of the data come from Tokyo, Japan e-mail: mhond@fol.hi-ho.ne.jp developed countries, with only a few reports from other countries that account for a large part C Terano · T Inoguchi · K Kikunaga · R Harada Department of Nephrology, Tokyo Metropolitan of the world Children’s Medical Center, Tokyo, Japan e-mail: chikako_terano@tmhp.jp; tomohiroinoguch@kuh.biglobe.ne.jp; ryouko_harada@tmhp.jp J W Groothoff Pediatric Nephrology Department, Amsterdam UMC/ Emma Children’s Hospital, Amsterdam, Netherlands e-mail: j.w.groothoff@amsterdamumc.nl © Springer Nature Switzerland AG 2021 B A Warady et al (eds.), Pediatric Dialysis, https://doi.org/10.1007/978-3-030-66861-7_39 745 746 Epidemiology Worldwide and Nationwide Registries While there is little information on long-term outcomes in children receiving dialysis, some worldwide, nationwide, and regional registries provide valuable data Prominent national and international registries consulted here include the following: the United States Renal Data System (USRDS), which is a compulsory registration system that includes children under 21 years of age in the USA; the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS), which contains voluntary data reporting derived from children under 21 years of age in North America; the United Network for Organ Sharing (UNOS), which collects data on all patients who are registered for kidney transplantation in the USA; the European Society for Paediatric Nephrology, the European Renal Association, and the European Dialysis and Transplant Association (ESPN/ERA-EDTA), which is a voluntary organization that coordinates an international European RRT registry for all patients; and the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry, which is a comprehensive, compulsory database which includes information from children and adolescents with chronic kidney disease (CKD) who initiate RRT at up to 20 years of age in Australia and New Zealand Additional national registries which include limited long-term data pertaining to dialysis in children include the following: United Kingdom Renal Registry, National Dutch Registry (RENINE/LERIC study), Italian Registry (Italian Registry of Pediatric Chronic Peritoneal Dialysis), Polish Registry, Canadian Organ Replacement Register (CORR), Registry of Taiwan, and the Japanese Registry (Japanese Study Group of Pediatric Peritoneal Dialysis [JSPPD]) [1–18] M Honda et al ge, Modality, and Primary Kidney A Disease at the Start of Dialysis When preemptive transplantation is not feasible for the pediatric patient who develops ESKD, PD and hemodialysis (HD) are the only available options The initial dialysis modality chosen for pediatric patients might be a factor that influences long-term outcomes HD is most often used as the initial treatment modality for ESKD in adults [10], while HD and PD are chosen with near-equal frequency in children However, the dialysis modality at RRT initiation varies greatly by country The initial treatment modality by country based on registry data is shown in Table 39.1 Overall, dialysis is chosen for approximately 75–80% of pediatric patients as the first treatment modality for management of ESKD. Whereas in the ESPN/ERA-EDTA, ERA-EDTA, and USRDS registries HD was recorded as the initial treatment prescribed for 40–55% of patients [8–12], HD was the initial modality for only 15–35% of patients in the ANZDATA, Polish, Canadian, UK, and Japanese Registries [13–18] (Table 39.1) When the initial dialysis modality was examined by era using data from the ERA-EDTA and the ANZDATA registries, there was no difference in the choice of the first treatment regimen [12, 16] However, when the relationship between age at the start of dialysis and modality was analyzed, the proportion of patients prescribed PD was higher for younger children with ESKD, and the proportion of patients initially prescribed HD gradually increased with age, as shown in Fig. 39.1 [10] In the 2018 USRDS report, PD was the most common initial ESKD treatment modality for children aged 9 years and younger, and HD was the most common initial modality for patients aged 10 years and older Based on data from other registries as well, HD was used more often in older children, while PD was the preferred therapy in children less than 5 years of age (Table 39.2) In 39 Long-Term Outcome of Chronic Dialysis in Children the Italian Registry, the median age at the start of dialysis in 295 PD patients was 7.7 ± 4.8 years, whereas the median age of the 1163 HD patients was 11.4 ± 3.1 years; 102 PD patients (34%) and only three HD patients were less than 5 years of age at the initiation of dialysis [19] The primary kidney disease in patients with ESKD also varies by age and country (Table 39.3) Congenital anomalies of the kidney and urinary tract (CAKUT) are the main causes of ESKD across all age groups worldwide Hereditary nephropathies are common in the youngest group of patients, while focal segmental glomerulosclerosis (FSGS) and glomerulonephritis have been found to be less common in the youngest age groups, especially those less than 5 years of age Thus, the primary potential confounding factors in any analysis of initial dialysis modality in children are patient age at initiation and the country in which the child was being treated ong-Term Dialysis in Pediatric L Patients Even among children for whom dialysis was chosen as the first RRT modality, most have received a kidney transplant within a few years The time to transplant has become shorter over time, and thus the dialysis duration has also become shorter As a result, unlike in adults, there is little information on children who undergo long-term dialysis awaiting kidney transplantation 747 The Polish Registry has reported a median duration of dialysis in children of 1.83 years (range, 0.2–16.3 years), while the CORR Registry revealed a median duration of dialysis of 559.5 days in 2004 and 388 days in 2012 [17, 20] Over 50% of patients in the ANZDATA Registry who received RRT between 1963 and 2002 received their first kidney transplant within 1 year of starting dialysis, and over 90% received a kidney transplant within 3 years [16] Since 2005, the median time from dialysis initiation to initial transplant in the USA has continued to decrease, and it was at its lowest in 2015, at 12.9 months in the USRDS Registry In 2015, the median time to transplant was shorter for HD patients (12.1 months) compared with PD patients (13.6 months; Fig. 39.2) [10] The Dutch late outcome cohort study, Late Effects of Renal Insufficiency in Children (LERIC), of 249 children with an onset of RRT at age 0–15y between 1972 and 1992 reported a mean dialysis time of survivors of 4.7 years (HD 2.3 years; PD 2.4 years) and 19.7 transplant years after a mean follow-up of 25.5 RRT years [5] In 2010, five and 33 out of 249 patients had received PD and HD for more than 10 years, respectively [21] In the ESPN/ERA-EDTA Registry, Kaplan- Meier survival curve analysis showed that among the 500 and 2591 patients who started HD before and after 5 years of age, respectively, there were 14.7% and 18.4% patients who continued HD 3 years later These figures were 12.0% and 22.1%, respectively, for the 1498 and 1884 Table 39.1 Initial treatment modality for ESKD Registry ERA-EDTA ESPN/ERA-EDTA USRDS ANZDATA Poland Japan Canada UK Age (years) 0–19 0–14 0–21 0–18 0–18 0–19 0–19 0–15 PD (%) 25 38 25.7 48.3 61.5 60.6 50.2 45 HD (%) 53 41.4 51.2 33.9 32.3 15.7 27.1 35 PD peritoneal dialysis, HD hemodialysis, RTX renal transplantation RTX (%) 23 20.3 20.0 17.7 6.2 21.9 22.7 22 Reference [8, 12] [11] [9, 10] [16] [13] [14] [17] [15] M Honda et al 748 patients who initiated PD before and after 5 years of age [22] In the USRDS Registry, among the 845 and 5103 patients who started dialysis before and after 5 years of age, there were 8.2% and 22.1% patients, respectively, who continued dialysis 5 years later [23] Based on these data, most children with ESKD who have received dialysis as their initial RRT modality received a kidney transplant within a few years, and the times to transplant and dialysis duration have decreased over time However, there seems to be a subset of patients in whom dialysis has been continued for more than to 10 years, especially in children over 5 years of age who are undergoing PD. Since there is a widely dispersed experience with patients undergoing long-term dialysis (e.g., for or 10 years), these data have only rarely been analyzed or reported Patient Survival The patient survival following dialysis initiation in those who received PD or HD is shown in Table 39.4 The survival rate at 5 years on PD TX transplantation, PD peritonela dialysis, HD hemodialysis Fig 39.1 Renal replacement therapy modality at initiation by patient age from USRDS (Modified from Ref [10]) Table 39.2 Initial treatment modality for ESKD by age Age PD HD RTX Japan [14] (2006–2011) 0–4 y 5–9 y 10–14 y 87.3% 55.0% 54.9% 8.2% 11.0% 14.6% 2.5% 32.0% 28.7% 15–19 y 37.3% 31.4% 29.7% ANZDATA [16] (2012–2017) 0–9 y 10–17 y 58.0% 42.0% 28.0% 38.0% 15.0% 20.0% PD peritoneal dialysis, HD hemodialysis, RTX renal transplantation ERA-EDTA [12] (2011–2016) 0–4 y 5–9 y 10–14 y 58.8% 23.2% 16.9% 29.4% 42.7% 50.2% 11.8% 34.1% 32.9% 15–19 y 13.4% 64.8% 21.8% ... between 1963 and 2002 received their first kidney transplant within 1 year of starting dialysis, and over 90% received a kidney transplant within 3 years [16] Since 2005, the median time from dialysis... consequences of long-term dialysis in children ated RRT management with dialysis while awaitIn this chapter, we review existing data on the ing the availability of a kidney to be transplanted... urinary tract (CAKUT) are the main causes of ESKD across all age groups worldwide Hereditary nephropathies are common in the youngest group of patients, while focal segmental glomerulosclerosis (FSGS)