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
Classifcation — A staging schema for CKD in children is based upon the level of kidney function (defined by glomerular filtration rate [GFR]) as follows (table 1) [2]:
●G1 – Normal or high GFR (≥90 mL/min per 1.73 m2)
●G2 – Mildly decreased GFR between 60 and 89 mL/min per 1.73 m2
●G3a – Mildly to moderately decreased GFR between 45 and 59 mL/min per 1.73 m2
●G3b – Moderately to severely decreased GFR between 30 and 44 mL/min per 1.73 m2
●G4 – Severely decreased GFR between 15 and 29 mL/min per 1.73 m2
●G5 – Kidney failure GFR of less than 15 mL/min per 1.73 m2 (end-stage kidney disease [ESKD])
Estimated GFR — The definition of a normal GFR (G1) is extracted from adult outcome studies and the value in children is not known. GFR increases with maturation from infancy and approaches adult mean values by two years of age. Children under two years of age, therefore, do not fit within the above classification system because they normally have a low GFR even when corrected for body surface area. For this reason, an improvement in GFR can be seen at this age range in CKD as well. In these patients, calculated GFR based upon serum creatinine can be compared with normative age-appropriate values to detect kidney impairment. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Definitions and diagnosis' and "Chronic kidney disease in children: Clinical manifestations and evaluation", section on 'Serum creatinine and GFR'.)
The GFR can be estimated by using the Schwartz formula, which is based upon serum creatinine, age, height, and in adolescents, the gender of the patient (calculator 1).
GFR = k X Height (cm) / Screat
Height represents the body height measured in centimeters, and Screat is the serum creatinine. The constant k is directly proportional to the muscle component of the body, and varies with age (in the original equation). The estimated GFR also depends on the laboratory assay used to measure serum creatinine [3].
●When serum creatinine is measured by the Jaffe method, the value for k is 0.33 mg/dL (29.2 mcmol/L) in preterm infants through the first year of life, 0.45 mg/dL (39.8 mcmol/L) for term infants through the first year of life, 0.55 mg/dL (48.6 mcmol/L) in children and adolescent girls, and 0.7 mg/dL (61.9 mcmol/L) in adolescent boys.
●When serum creatinine is determined using enzymatic methodology, the value for k is 0.413 when the creatinine is measured in mg/dL (36.5 when the creatinine is measured in mcmol/L) for all children with CKD between ages 1 and 16 years [4].
Additional approaches to estimating GFR for children and young adults up to 25 years of age include the use of serum cystatin C. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Estimated glomerular filtration rate'.)
Albuminuria — The severity of albuminuria (as measured by urinary albumin-to-creatinine ratio) is also an indication of the potential for progression of CKD and is staged as below [2] (see "Definition and staging of chronic kidney disease in adults", section on 'Albuminuria'):
●A1 – Normal to mildly increased; <30 mg/g, <3 mg/mmol
●A2 – Moderately increased; 30 to 299 mg/g, 3 to 29 mg/mmol
●A3 – Severely increased; ≥300 mg/g, ≥30 mg/mmol
In children, the level of proteinuria and eGFR has also been used to characterize the timeline of CKD progression [5]. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Evaluation of proteinuria'.)
EPIDEMIOLOGY OF CKD STAGE 5 (END-STAGE KIDNEY DISEASE) AND KRT
CKD stage 5 (end-stage kidney disease [ESKD]) — In well-resourced countries, KRT is typically initiated in children with CKD stage 5 (also referred to as end-stage kidney disease [ESKD]). However, data from national major registries indicate CKD stage 5 (ESKD) is uncommon as illustrated by the following:
●New Zealand – The highest estimated incidence of ESKD in children was reported in New Zealand with an annual rate of 18 per million children [6]. The incidence has remained stable from 2012 to 2019 [7].
●United States – In the United States, the incidence of ESKD peaked at 17.5 per million population in 2004 and decreased to 11.5 per million in children 0 to 17 years old in 2018 [8].
●Japan – A low annual incidence of ESKD has been reported in Japan with a rate of 4 per million children at or below 19 years of age in 2012 [9].
●Europe – In a report from a population-based registry that includes data from 22 European countries, the overall incidence ranged between 5.5 and 6.6 per million children, which was stable during the study period from 2007 to 2016 [10]. There were significant differences in incidence amongst countries with the lowest reported rate of 1.9 per million children in Estonia and Moldova, and the highest of 11.9 per million children in Ireland. However, this inconsistency may be due to parts of Europe where children are undiagnosed and/or undertreated for CKD.
The incidence of ESKD increases with age, with the highest incidence occurring in adolescence [8,10].
Variability in the reported incidence of ESKD is primarily due to differences globally 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 [6]. Resource-rich countries are more likely to possess the necessary resources for the detection and treatment of ESKD.
Kidney replacment therapy (KRT) — Globally, most children receiving KRT live in Europe, the United States, Australia/New Zealand and Japan [11]. 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 [6].
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 11.5 patients per million children, which represented 838 new patients 0 to 17 years old in 2018 [8].
●Europe – In Europe in 2011, the incidence was 28 per 1 million age-related population [12]. 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 [13,14].
KRT modality choice — KRT choices in 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 [8,12,15,16]. However, overtime, kidney transplantation becomes the preferred choice of KRT as children transition from initial dialysis to transplantation [8,13,17]
ETIOLOGY — The most common cause of pediatric 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) [18-20]. 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)".)
KRT OPTIONS
Transplantation: Preferred KRT modality based on lower mortality — Globally, all-cause mortality rates for children on dialysis are significantly higher than what is experienced by the transplant population. As a result, transplantation is the preferred KRT modality.
●Australia and New Zealand – Data for patients receiving KRT between 1963 and 2002 from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry revealed mortality rates of 4.8, 5.9, and 1.1 per 100 patient years for children receiving HD, PD, and recipients of a functioning transplant, respectively [21].
●United States – In the United States, the one-year adjusted all-cause mortality rate decreased from 43.5 per 1000 person-years in 2001 to 2003 to 23.8 per 1000 person-years in 2016 to 2018 [8]. The following results were reported in the USRDS 2020 annual report based on data for children (age 0 to 17 years) who received KRT between 2016 and 2018:
•First year mortality rates per 1000 person-years were 33.4, 21.4, and 18 for PD, HD, and transplant patients, respectively.
•Survival probability at five years was calculated as 83, 86, and 99 percent for HD, PD, and transplant patients, respectively.
•The expected remaining lifetime for males and females (ages 0 to 14 years) was estimated to only be 18.8 years for dialysis patients versus 62.2 for transplant recipients and 72.8 years for the general population based on 2018 data.
Other factors that have been shown to influence patient survival include age at onset of ESKD, presence of comorbidities, access to transplantation, macroeconomics, and sex [22,23].
Mortality is higher for girls than boys. Adjusted analysis of data from the USRDS of children between 2 and 19 years of age who initiated KRT (transplantation or dialysis) between 1995 and 2012 showed that death was more likely in girls than boys (hazard ratio [HR] 1.36, 95% CI 1.25-1.50). However, access to transplantation was lower for girls than boys, but this did not fully attenuate the difference in mortality. This discrepancy in mortality may be attributed to differences in the underlying cause of ESKD, as girls are more likely to have underlying systemic diseases (eg, systemic lupus erythematous), which contribute to increased mortality.
Preemptive renal transplantation — Preemptive transplantation is the preferred KRT options. It is performed prior to the need for dialysis, because [24]:
●Kidney transplantation is associated with better outcomes in health-related quality of life measures, growth, and development than either PD or HD.
●Mortality is higher in patients undergoing chronic dialysis compared with those with preemptive transplantation [25].
●Limited data 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 HD groups, respectively [26].
●Dialysis is more disruptive to family lifestyle, schooling, and social interactions.
●Avoidance of dialysis preserves vascular and peritoneal access sites for future use (ie, lifetime for a child) if the transplant should fail.
●Dietary and fluid restrictions are necessary on dialysis.
●Dialysis is associated with an increased risk of cardiovascular disease (eg, ischemic heart disease, cerebrovascular disease, heart failure, cardiac arrest/arrhythmias, cardiomyopathy) [25] and vascular calcification, which occur at a proportionately earlier age. (See "Vascular calcification in chronic kidney disease".)
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, non-adherence 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 [10,27]. In the United Kingdom, rates of preemptive kidney transplantation have increased to 36 percent [10,12,13].
●Australia and New Zealand – Up to 22 percent of children in Australia and New Zealand receive a preemptive transplant [16,28].
●North America – In North America, the rate is 20 percent based on data from the USRDS 2020 Annual Data Report [8].
Dialysis options — When preemptive transplantation is not an option, the choice between the two forms of dialysis (hemodialysis [HD] and peritoneal dialysis [PD]) is generally dictated by patient age, technical, social, and compliance issues, and family/caregiver preference. The choice between the two modalities varies worldwide and limited data suggests similar 5-year mortality between the two modalities in children [29,30].
In a study from the Italian Registry of Pediatric Chronic Dialysis of children receiving dialysis, a propensity-matched analysis of 310 patients based on gender, age, primary cause of ESKD and comorbidities showed similar mortality rates at two-year follow-up and rates of transplantation three years after dialysis initiation [30]. However, there was a lower mortality rate for patients on HD compared with PD at five-year follow-up. Of note, in this cohort, patients who were initiated on PD compared with those on HD were more likely to be younger, had a diagnosis of a congenital anomalies of the kidney and urinary tract (CAKUT), and had a higher urinary output. However, further data are needed to determine if the choice of modality affects long-term outcome.
In general, the following factors are used to choose dialysis modality:
●In infants and young children, PD is preferred because it is technically easier to perform than HD, as it does not require a vascular access or venipuncture, and it allows for a more liberal fluid intake [31,32]. In the United States, PD is the most common initial dialysis modality for children less than nine years, and HD is most common for children age 6 years and older. (See "Hemodialysis for children with chronic kidney disease" and "Chronic peritoneal dialysis in children", section on 'Peritoneal dialysis versus hemodialysis'.)
●PD may be precluded in children with intra-abdominal pathology. (See "Chronic peritoneal dialysis in children", section on 'Contraindications to CPD'.)
●Home dialysis (PD or HD) is often preferred as it has less impact on time away from family, school and friends. However, it may be precluded by the inability of the family to provide adequate care. In these families, choice is dictated by the dialytic modality available for children at a nearby center. (See "Home hemodialysis (HHD): Establishment of a program" and "Hemodialysis for children with chronic kidney disease", section on 'Home HD'.)
TIMING OF RRT — As in adults, some form of KRT is needed in children when the glomerular filtration rate (GFR) falls below 15 mL/min per 1.73 m2 (chronic kidney disease [CKD] stage 5). At that level of kidney function, the classical clinical indications for dialysis present and include fluid overload, uremic symptoms, and uncontrolled metabolic abnormalities (eg, hyperkalemia, hyperphosphatemia). In Europe, US 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 amongst centers [12,33,34]. 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 [35-38].
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 renal transplantation' 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.
Planning for initiation of dialysis is dependent upon the chosen modality:
●Hemodialysis (HD) – Children who are to receive HD will 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 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 [39,40]. 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 [41,42]. The need for increased attention for 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 [43]. (See "Hemodialysis for children with chronic kidney disease", section on 'Vascular access'.)
●Peritoneal dialysis (PD) – 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 [44,45]. 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. (See "Chronic peritoneal dialysis in children".)
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
●Introduction – For children with chronic kidney disease (CKD), preparations for kidney replacement therapy (KRT) are needed when their glomerular filtration rate (GFR) falls below 30 mL/min per 1.73 m2 (CKD stage 4 (table 1)). This includes educating the family/caregivers and child regarding KRT options (preemptive kidney transplantation, peritoneal dialysis [PD], and hemodialysis [HD]).
●Epidemiology – In well-resourced countries, KRT is typically initiated in children with CKD stage 5 (GFR below 15 mL/min per 1.73 m2), 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 of CKD stage 5 (end-stage kidney disease) and KRT' 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. (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)".)
●KRT options – The choices of KRT in children with CKD include kidney transplantation, hemodialysis (HD), and peritoneal dialysis (PD). (See 'KRT options' above.)
•Preemptive transplantation is the preferred KRT, because it is associated with better long-term outcomes (eg, growth, development, quality of life, and mortality). (See 'Transplantation: Preferred KRT modality based on lower mortality' above and 'Preemptive renal transplantation' above.)
•When preemptive transplantation is not an option, the choice between the two forms of dialysis for ESKD is generally dictated by technical, social, and compliance issues, and family preference. (See 'Dialysis options' above.)
●Timing of KRT – As in adults, some form of KRT is generally needed in children when the GFR falls below 15 mL/min per 1.73 m2 (CKD stage 5). KRT may be occasionally initiated earlier in children, 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 RRT' above and "Chronic kidney disease in children: Complications".)
