Version May 2024
INTRODUCTION — Pediatric chronic kidney disease (CKD) is a chronic, progressive disorder. As the estimated glomerular filtration rate (GFR) declines to less than 30 mL/min per 1.73 m2 (CKD stage 4), preparations for kidney replacement therapy (KRT) are needed [1]. The family/caregiver and, if appropriate, the child should be provided with information related to options for KRT. These include preemptive kidney transplantation, peritoneal dialysis (PD), and hemodialysis (HD).
KRT options and timing of KRT for children with CKD are reviewed here.
Topic reviews that include more comprehensive descriptions of the different forms of KRT for pediatric CKD, including complications and outcome, are discussed separately. (See "Hemodialysis for children with chronic kidney disease" and "Chronic peritoneal dialysis in children" and "Kidney transplantation in children: General principles" and "Kidney transplantation in children: Complications".)
STAGING CHRONIC KIDNEY DISEASE — Assessing kidney function is dependent on the age of the child, as follows:
●Children two years of age and older – For children two years of age and older, the severity of CKD is categorized into stages based on estimated glomerular filtration rate (GFR) (table 1A) [2]. End-stage kidney disease (ESKD) is categorized as stage G5 with a GFR below 15 mL/min per 1.73 m2. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Staging: Risk stratification'.)
●Children under two years of age – Children under two years of age do not fit within the above classification system, because they normally have a low GFR even when corrected for body surface area. In these patients, estimated GFR based upon serum creatinine can be compared with normative age-appropriate values to detect kidney impairment (table 1B). A GFR value >1 standard deviation below the mean should raise concern and prompt more intensive monitoring [2]. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Estimated glomerular filtration rate'.)
In children, the level of proteinuria and eGFR have been used to characterize the timeline of CKD progression [3]. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Evaluation of proteinuria'.)
Classification of CKD in children, including calculation of GFR and evaluation of proteinuria, is discussed in detail separately. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course".)
EPIDEMIOLOGY
Chronic kidney disease stage 5 (end-stage kidney disease) — In well-resourced countries, KRT is typically initiated in children with CKD stage 5 (also referred to as end-stage kidney disease [ESKD]). Although ESKD is relatively uncommon among children around the world, reported incidence rates vary depending on the country, from 1.9 to 18 per million childhood population. [4,5]. This variability is primarily due to global differences in the ability to diagnosis and manage children with significant kidney impairment in various parts of the world, as well as genetic and environmental factors [4]. Resource-abundant countries are more likely to possess the necessary resources for the detection and treatment of ESKD. The incidence of ESKD increases with age, with the highest incidence in adolescence [5,6].
The epidemiology of ESKD in children is discussed in detail separately. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Epidemiology'.)
Kidney replacment therapy
●Incidence – Globally, most children receiving KRT live in Europe, the United States, Australia/New Zealand and Japan [7]. The incidence of KRT initiation for ESKD is reported for the following regions:
•United States – In the United States, the incidence of starting KRT for pediatric ESKD is approximately 12 patients per million children, which represented 912 new patients 0 to 17 years old in 2020 [6].
•Europe – In Europe in 2011, the incidence was 28 per 1 million age-related population [8]. In the United Kingdom, the number of children starting KRT has been stable with an incidence of new patients between 9 and 10 per million children [9,10].
●Prevalence – The overall worldwide prevalence of KRT has increased due to improved survival with reported ranges from 18 to 100 per 1 million age-related population [4].
●Use of KRT modalities – KRT modalities for children with CKD include kidney transplantation, hemodialysis (HD), and peritoneal dialysis (PD).
The choice of KRT varies, particularly with age and resources. Data worldwide has shown that PD is the most common initial KRT therapy in children nine years and younger, and HD for patients aged 10 years and older [6,8,11,12]. In the United States, PD is the most common initial dialysis modality for children younger than five years. However, over time, kidney transplantation becomes the preferred choice of KRT as children transition from initial dialysis to transplantation [6,9,13].
Details of the different KRT modalities are discussed separately. (See "Kidney transplantation in children: General principles" and "Hemodialysis for children with chronic kidney disease" and "Chronic peritoneal dialysis in children".)
ETIOLOGY — The most common cause of pediatric end-stage kidney disease (ESKD) requiring KRT is congenital anomalies of the kidney and urinary tract (CAKUT). The proportion of cases with CAKUT decreases with increasing age due to the increased incidence of acquired glomerular disease (figure 1) [14-16]. The etiology of CKD and CAKUT are discussed in greater detail separately. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Etiology' and "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)
WHEN TO PREPARE FOR KIDNEY REPLACEMENT THERAPY — We start preparing the child and the family for KRT as the estimated glomerular filtration rate (GFR) declines to <30 mL/min per 1.73 m2 (CKD stage 4) [1]. Preparation includes educating the family/caregivers and child regarding KRT options (preemptive kidney transplantation, peritoneal dialysis [PD], and hemodialysis [HD]). (See "Chronic kidney disease in children: Overview of management", section on 'Preparation for kidney failure'.)
PREEMPTIVE TRANSPLANTATION AS PREFERRED KIDNEY REPLACEMENT THERAPY MODALITY
Benefits of transplantation over dialysis — For children with ESRD requiring KRT, we prefer kidney transplantation to any form of dialysis due to multiple factors, including:
●Decreased mortality rates – Globally, all-cause mortality rates for children who have received a transplant are significantly lower than for those on dialysis. As an example, a study from the Australia and New Zealand Dialysis and Transplant registry of patients receiving KRT revealed mortality rates of 4.8, 5.9, and 1.1 per 100 patient years for children receiving hemodialysis (HD), peritoneal dialysis (PD), and a functioning transplant, respectively [17].
Additionally, a study from a large national database of children with end-stage kidney disease (ESKD), the United States Renal Data System (USRDS), reported first-year mortality rates per 1000 person-years of 30.2, 34.2, and 17.3 for PD, HD, and transplant patients, respectively [6]. Survival probability at five years was calculated as 81, 86, and 96 percent for HD, PD, and transplant patients, respectively. The expected remaining lifetime for males and females (ages 0 to 14 years) was estimated to be 18.8 years for dialysis patients versus 62.2 for transplant recipients and 72.8 years for the general population.
●Better outcomes for kidney transplantation – Kidney transplantation is associated with better outcomes in health-related quality of life measures, growth, and development than either HD or PD [18]. Transplantation is less disruptive to family lifestyle, schooling, and social interactions than dialysis. In addition, transplantation avoids the dietary and fluid restrictions necessary while on dialysis and preserves vascular and peritoneal access sites for future use if the transplant should fail.
●Increased risks of dialysis – Dialysis is associated with an increased risk of cardiovascular disease (eg, ischemic heart disease, cerebrovascular disease, heart failure, cardiac arrest/arrhythmias, cardiomyopathy) [19] and vascular calcification, which occur at a proportionately earlier age. (See "Vascular calcification in chronic kidney disease".)
Timing of transplantation — We prefer transplantation performed prior to the need for dialysis because mortality is lower in patients who receive preemptive transplantation than in those undergoing chronic dialysis [18,19]. We start preparing the patient and family/caregivers for transplant as the glomerular filtration rate (GFR) declines to <30 mL/min per 1.73 m2 (CKD stage 4). However, the exact timing for transplant varies depending on individual patient factors.
Limited data also suggest that renal allograft survival is better for children who received a pre-emptive transplant as initial KRT versus dialysis. In a retrospective study from the United Kingdom Transplant Registry of 2038 pediatric kidney transplant recipients, the five-year allograft survival was 91, 87, and 86 percent for the pre-emptively transplanted, initial PD, and initial HD groups, respectively [20].
Preemptive transplantation is more easily accomplished in children than in adults because of the availability of parental donors in many cases who are a haplotype match, are relatively young and healthy, and are frequently willing to donate a kidney. In addition, because pediatric nephrologists generally follow their patients from the early stages of CKD, they can more easily prepare the patient and their family for transplantation and avoid initiating dialysis. If a living related donor is not available, many countries prioritize children on the deceased donor transplant waiting list.
Despite these advantages, preemptive transplantation is still not achieved in the majority of children with ESKD, because they may present in CKD stage 5 with insufficient preparatory time required for transplantation prior to the need for dialysis or because transplantation is not possible or advisable due to small size, comorbidity, nonadherence to medical therapy, family instability, or other factors.
Preemptive transplantation has increasingly become the initial choice of treatment for pediatric ESKD.
●Europe – Preemptive transplantation has increased from 12 percent of European children who received KRT to 20 percent in 2016 [5,21]. In the United Kingdom, rates of preemptive kidney transplantation have increased to 36 percent [5,8,9].
●Australia and New Zealand – Up to 22 percent of children in Australia and New Zealand receive a preemptive transplant [12,22].
●North America – In North America, the rate was 14.38 percent in 2020 compared with 17.4 percent in 2019, based on data from the USRDS 2022 Annual Data Report [6]. The lower rate that year may be the result of disruptions in care during the COVID-19 pandemic.
DIALYSIS AS AN ALTERNATIVE KIDNEY REPLACEMENT THERAPY MODALITY
Choosing a dialysis modality — When preemptive transplantation is not an option, we choose between hemodialysis (HD) and peritoneal dialysis (PD). To make this choice, we use a multiprofessional team to carefully evaluate the family’s social, psychological, and economic background. Ideally this team includes the family physician, nephrologist, dialysis nurse, psychologist, and a social worker [23-25]. We base our decision on the following factors:
●Patient age and size – In infants and young children, we prefer PD because it is technically easier to perform than HD, does not require a vascular access or venipuncture, and allows for a more liberal fluid intake [26,27]. In school-age children, home dialysis therapies, such as PD with the use of an automated PD cycling device, also facilitates regular school attendance. (See "Hemodialysis for children with chronic kidney disease" and "Chronic peritoneal dialysis in children", section on 'Peritoneal dialysis versus hemodialysis'.)
●Comorbidities – We prefer PD over HD when there are contraindications to the use of anticoagulation and in children who have cardiovascular instability.
The only absolute contraindications to PD include conditions that affect the integrity of the abdominal cavity and peritoneum (ie, omphalocele, gastroschisis, obliterated peritoneal cavity) (table 2). (See "Chronic peritoneal dialysis in children", section on 'Contraindications to CPD'.)
●Technical, social, and compliance issues – We often prefer home dialysis (PD or HD) over dialysis at a medical center, as it has less impact on time away from family, school and friends. However, home dialysis may not be possible if the family is unable to provide adequate care. In these families, choice is dictated by the dialytic modality available for children at a nearby center. We also consider proximity to a pediatric HD center, as well as the ability to achieve and maintain suitable vascular access, when counselling families about different dialysis modalities available. For those who live a long distance from a HD center, home dialysis means that the family does not need to travel to the unit three or more times per week for treatments. (See "Home hemodialysis (HHD): Establishment of a program" and "Hemodialysis for children with chronic kidney disease", section on 'Home hemodialysis'.)
We recognize the tremendous burden of care that families experience with home-based dialysis therapy. In addition to the burden associated with the dialysis procedure itself, for those patients who receive PD there is the burden associated with decisions regarding the type of PD solution daily, concern about complications particularly peritonitis and drain pain, and safely managing machine errors [28,29]. Families must be made fully aware of the burden of care involved with performing PD as part of the modality selection process so that appropriate support systems may be put in place.
●Patient and parent/caregiver preference – We discuss the selection of a dialysis modality with the child and their parents/caregivers, and we respect the child and parents/caregivers’ choice as long as there are no clear drawbacks.
●Preservation of dialysis access – We always consider the importance of preserving dialysis access (the PD catheter for the PD patient and either the HD catheter or fistula for the HD patient) when selecting the optimal dialysis modality for a child.
The choice between the two modalities varies worldwide, as limited data suggests similar five-year mortality between the two modalities in children [30,31]. In a study of data from the Italian Registry of Pediatric Chronic Dialysis, outcomes were compared between 310 children on PD or HD who were propensity-matched based on gender, age, primary cause of end-stage kidney disease (ESKD) and comorbidities [31]. Mortality rates at two-year follow-up and rates of transplantation three years after dialysis initiation were similar between groups. Although there was a lower mortality rate for patients on HD at five-year follow-up, the very low event rate and potential for selection bias limit confidence in this finding. In this cohort, patients who were initiated on PD compared with those on HD were more likely to be younger, have a diagnosis of a congenital anomalies of the kidney and urinary tract (CAKUT), and have a higher urinary output. Further data are needed to determine if the choice of modality affects long-term outcome.
There are also no studies to suggest that either PD or HD is otherwise superior in children with ESKD [32]. International registries suggest that PD is the preferred and most widely used modality in younger children (in those less than five years in the United Kingdom renal replacement registry, European Society for Pediatric Nephrology registry, and United States Renal Data System [USRDS] registry). Data from the USRDS demonstrates that between 2016 to 2020, 50 percent of patients aged one to five years received PD as their initial renal replacement therapy, in contrast with only 30.7 percent of those aged 6 to 12 years [6]. The use of PD has increased in lower- and middle-income countries, both in children and adults [33].
Planning for dialysis — Planning for initiation of dialysis is dependent upon the chosen modality.
Hemodialysis — Children who are to receive HD need evaluation for vascular access. Vascular access options include arteriovenous (AV) fistula or a central venous tunneled catheter. AV fistulae require time to mature prior to use, which may be several weeks to months. As a result, if an AV fistula is chosen, it ideally needs to be established several weeks to months prior to the initiation of dialysis. As in adults, the "fistula first" policy applies to children as well, as AV fistulae are associated with a lower incidence of complications compared with catheters [34,35]. The use of a central venous catheter, which is associated with a greater rate of infectious complications when compared with AV fistulae, should ideally be reserved for patients too small to permit surgical construction of a fistula or when there is an expectation for expeditious (<1 year) kidney transplantation [36,37]. The need for increased attention to advanced proactive planning for placement and maturation of an AV fistula (optimal vascular access) is reflected by the finding that most pediatric patients (81 percent) in the United States initiate HD with a central venous catheter [38]. (See "Hemodialysis for children with chronic kidney disease", section on 'Vascular access'.)
Peritoneal dialysis — Children who are to initiate PD need to undergo abdominal surgery for placement of a PD catheter. Use of a double cuff catheter and perioperative antibiotic prophylaxis within 60 minutes prior to the incision for catheter placement has been associated with fewer infectious complications of PD [39,40]. Ideally, there should be ample time for the abdominal wound to heal prior to the initiation of dialysis, thereby avoiding complications of leaking and infection. The minimum timeframe for healing is approximately two weeks. Absolute and relative contraindications to PD are included in the related table (table 2). (See "Chronic peritoneal dialysis in children".)
Timing of dialysis initiation — The timing of dialysis initiation is a complex decision that should take into account the estimated glomerular filtration rate (GFR) as well as signs and symptoms of uremia. We initiate some form of KRT in children when the GFR falls below 15 mL/min per 1.73 m2 (CKD stage 5) (table 1A). At that level of kidney function or below, the classical clinical indications for dialysis (ie, uremic symptoms) present, including:
●Fluid overload (ie, inability to maintain euvolemia with development of hypertension and/or significant peripheral edema)
●Deterioration in nutritional status and/or growth failure with declining weight and/or height percentiles
●Uncontrolled metabolic abnormalities (eg, hyperkalemia, hyperphosphatemia, acidosis)
●Subjective complaints of the patient (eg, loss of appetite, nausea, fatigue, inability to concentrate, perceived poor quality of life)
We make the decision to start dialysis as part of a discussion between the patient (if age appropriate), their parents/caregivers, and their healthcare providers. We only start dialysis once we’ve determined that these conditions are persistent and refractory to medication and/or dietary management. The duration of uremic symptoms before we decide dialysis is necessary depends on their severity as well as the distress they are causing the child. In general, we prioritize the severity of uremic symptoms and the distress they are causing the child over the GFR.
In Europe, the United States, and Canada, the average GFR at the time of commencement of KRT is 8 to 9 mL/min/1.73 m2, although there is a wide variation between centers [8,41,42]. A randomized controlled trial in adults has shown that starting dialysis at higher levels of GFR is associated with worse outcomes, and there is evidence that this is the case in children too [43-46]. Methods of estimating GFR, including circumstances in which the estimated GFR may be inaccurate, are discussed separately. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Glomerular filtration rate'.)
KRT may be initiated earlier in children with CKD at a higher GFR primarily to permit the provision of the nutritional needs necessary to maintain normal (or near normal) growth. As noted above, preemptive kidney transplantation is the preferred modality, as it is the intervention that provides the best outcomes regarding growth, development, quality of life, and patient survival. On the other hand, some children with continued good urine volumes can be maintained off dialysis for a substantial period of time with very low GFRs if strict attention is paid to growth, nutrition, and therapeutic control of metabolic abnormalities. There is no evidence that either approach is better. (See 'Preemptive transplantation as preferred kidney replacement therapy modality' above.)
For patients who undergo dialysis as the initial KRT, earlier indications for intervention prior to CKD stage 5 may include:
●Children with nephrotic syndrome requiring bilateral nephrectomies pretransplant.
●Correction of metabolic abnormalities that fail medical management including hyperkalemia, hyperphosphatemia, and metabolic acidosis. (See "Chronic kidney disease in children: Complications", section on 'Hyperkalemia' and "Chronic kidney disease in children: Complications", section on 'Metabolic acidosis'.)
●Inadequate nutrition because of fluid limitations. This is especially an issue with infants who are maintained on a completely liquid diet (ie, formula or breast milk). In these patients, dialysis is instituted to allow the required volume of feeds to maintain adequate growth.
●Hypertension that is refractory to dietary sodium restriction and medications.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in children".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology – In well-resourced countries, kidney replacement therapy (KRT) is typically initiated in children with chronic kidney disease (CKD) stage 5 glomerular filtration rate (GFR; below 15 mL/min per 1.73 m2) (table 1A), also referred to as end-stage kidney disease (ESKD). Globally, the reported incidence for ESKD ranges from 4 to 18 per million children worldwide. This variability is thought to be due to global differences in the ability to detect ESKD and the resources to provide KRT, as well as genetic and environmental factors. (See 'Epidemiology' above.)
●Etiology – The most common cause of pediatric ESKD is congenital anomalies of the kidney and urinary tract (CAKUT). The proportion of cases with CAKUT decreases with increasing age due to the increasing incidence of acquired glomerular disease (figure 1). (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Etiology' and "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)
●When to prepare for KRT – For children with CKD, we start preparing for KRT when their GFR falls below 30 mL/min per 1.73 m2 (CKD stage 4 (table 1A-B)). This includes educating the family/caregivers and child regarding KRT options (preemptive kidney transplantation, peritoneal dialysis [PD], and hemodialysis [HD]).
●Preemptive kidney transplantation as preferred KRT modality – We prefer transplantation performed prior to the need for dialysis because long-term outcomes (eg, growth, development, quality of life, and mortality) in patients who receive preemptive transplantation are better than in those undergoing chronic dialysis. (See 'Preemptive transplantation as preferred kidney replacement therapy modality' above.)
●Dialysis as an alternative KRT modality – When preemptive transplantation is not an option, we choose between HD and PD. We make this choice with a multiprofessional team in consultation with the patient and family/caregivers. It is based on multiple factors, including technical, social, and compliance issues, and family preference. (See 'Dialysis as an alternative kidney replacement therapy modality' above.)
•Timing of dialysis initiation – In some children, we occasionally initiate dialysis before GFR falls below 15 mL/min per 1.73 m2 (CKD stage 5), primarily to maintain normal growth and to manage metabolic abnormalities that are unresponsive to other medical interventions. However, some children, and in particular, infants, with maintained urine output may continue without dialysis for years if attention is paid to their nutritional and therapeutic management. (See 'Timing of dialysis initiation' above.)
ACKNOWLEDGMENT — We are saddened by the death of Lesley Rees, MD, FRCPCH, who passed away in May 2022. UpToDate acknowledges Dr. Rees's past work as an author for this topic.
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