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Epidemiology of Pediatric Chronic Kidney Disease and Pediatric kidney Failure: what we Learn from the Studies

Review Article | DOI: https://doi.org/10.31579/2834-5142/068

Epidemiology of Pediatric Chronic Kidney Disease and Pediatric kidney Failure: what we Learn from the Studies

  • Celina de Faria Rezende 1*
  • Sérgio Veloso Brant Pinheiro 2,3
  • Mariangela Leal Cherchiglia 4
  • Maria Goretti Moreira Guimarães Penido 1,2
  • Hugo André da Rocha 4

1 Santa Casa de Belo Horizonte, Unidade de Nefrologia Pediátrica do Centro de Nefrologia, Belo Horizonte, Minas Gerais, Brazil.

2 Universidade Federal de Minas Gerais, Departamento de Pediatria, Faculdade de Medicina Belo Horizonte, Minas Gerais, Brazil.

3 Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

4 Universidade Federal de Minas Gerais, Departamento de Medicina Social e Preventiva, Faculdade de Medicina, Belo Horizonte, Minas Gerais, Brazil.

*Corresponding Author: Celina de Faria Rezende, Santa Casa de Belo Horizonte, Unidade de Nefrologia Pediátrica do Centro de Nefrologia, Belo Horizonte, Minas Gerais, Brazil.

Citation: Celina de Faria Rezende, Sérgio Veloso Brant Pinheiro, Mariangela Leal Cherchiglia ,Maria Goretti Moreira Guimarães Penido, Hugo André da Rocha (2023) Epidemiology of pediatric chronic kidney disease and pediatric kidney failure: what we learn from the studies, International Journal of Clinical Nephrology. 5(4); DOI:10.31579/2834-5142/068

Copyright: © 2023, Celina de Faria Rezende. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 02 August 2023 | Accepted: 24 August 2023 | Published: 08 September 2023

Keywords: children; adolescents; epidemiology; incidence, survival; chronic kidney disease

Abstract

CKD (chronic kidney disease) has become a growing concern worldwide, with its rates showing a significant increase in recent years. Data on the prevalence and incidence of CKD in the pediatric population are limited. It is estimated that CKD affects approximately 1 to 3% of the global pediatric population, with regional variations. The prevalence ranges from 56 to 74.7 cases per million of the age-related population (pmarp). This increasing prevalence is reflected in the higher risk of various causes of mortality, progression to advanced stages, and the emergence of cardiovascular disease. 

The most common cause of CKD among children is congenital anomalies of the kidney and urinary tract (CAKUT). With progressing CKD, various complications occur, and end-stage renal disease (ESRD) can develop.

The epidemiology of CKD in children and adolescents also encompasses issues related to access to proper medical care, early diagnosis, and effective treatment. Identifying at-risk groups and implementing screening programs can play an important role in reducing the incidence and morbidity of CKD in this population.

Furthermore, epidemiological research aims to gain a better understanding of the ethnic, socioeconomic, and geographic disparities associated with CKD in children and adolescents, allowing for more targeted prevention and intervention strategies.

In conclusion, the epidemiology of chronic kidney disease in children and adolescents is an evolving field, essential for guiding public health policies and clinical practices aimed at preventing, early diagnosing, and treating this complex disease, thereby promoting renal health and overall well-being among this vulnerable population.

1.Introduction

The kidneys are fundamental organs for maintaining the homeostasis of the human body. The decline in the function of these organs can occur abruptly, classified as acute kidney injury, or progressive, with variable time during its evolution, characterizing chronic kidney disease (CKD) and end-stage renal disease (ESRD) when the loss of function is permanent [1,2].

CKD affects both the structure and function of the kidneys, with multiple causes and prognostic factors. In this condition, there is a progressive decline in glomerular filtration rate, loss of regulatory, excretory and endocrine functions, which can affect other organs in the individual. Several factors can be associated with both the etiology and progression of kidney function loss such as hypertention, proteinuria, anemia, dyslipidemia, metabolic acidosis, prematurity, low birth weight, small for gestational age, lower socioeconomic status, inadequate parental health literacy, etc [3]. Therefore, it is important to recognize individuals who are at risk of developing CKD through early diagnosis and identify factors associated with a worse prognosis, defined as those factors related to a faster progression of renal function loss [4].

CKD is defined as persistent renal structural or functional abnormalities for a greater period than or equal to three months and with health implications, such as glomerular filtration rate (GFR) less than 60mL/min/1.73m2, urinary sediment alterations, tubular disorders, and abnormalities in imaging or histology of the renal parenchyma, regardless of the cause or specific clinical presentation [5,6].

The individual in an advanced stage of CKD has a reduced life expectancy and increased risks of cardiovascular disease. They face significant dietary restrictions and should take use a large number of medications, which dramatically worsens their quality of life. The repercussions of the disease also extend to the patient’s mental and behavioral health, impacting the family, particularly in low socioeconomic populations with diverse cultural backgrounds, who receive treatment subsidized by the Brazilian Unified Health System (SUS), which covers 85% to 90% of patients on Renal Replacement Therapy (RRT) [7-9].

The available modalities for RRT are hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (Tx). Ideally, family physicians, pediatricians and other pediatric specialists would be aware of the epidemiology of CKD before the need for RRT in order to provide effective guidelines for preventing or delaying the progression of the disease. This would facilitate better adherence in any RRT modality. Preparation before and after the start of treatment is also important, with multidisciplinary follow-up essential to help the patient and his family understand and accept the treatment, as this is the only guarantee of survival [8].

Patients with CKD have a high mortality rate that can be influenced by individual factors such as age, primary cause of CKD, comorbidities, and even factors related to healthcare utilization. Additionally, individuals on RRT have lower survival rates compared to the general population [7].

The patient should be referred to a nephrologist or pediatric nephrologist as soon as possible for follow-up, with the aim of delaying the initiation of RRT, having permanent vascular access, and avoiding urgent dialysis treatment [8-10]. Early diagnosis and referral to a nephrologist are essential steps in managing these patients, enabling a focus on pre-RRT education and implementing preventive measures to slow down the progression to more advanced stages of CKD, as well as reducing morbidity and mortality [10].

CKD is recognized as one of the main public health priorities worldwide. Its global prevalence is estimated at ~ 10% of the general population, affecting > 800 million adults worldwide, of which approximately 4 million require RRT [11,12]. This global increase in CKD is due to the increased prevalence of diabetes, hypertension, obesity and aging. In addition to being a significant clinical problem, CKD also raises economic and organizational concerns, as RRT consumes a substantial proportion of healthcare resources [12]. 

In Brazil, RRT has been performed since the 1970s, but it was only in 2004 that the Ministry of Health established a Public Policy for the Care of Patients with CKD, following the principles of the Brazilian Unified Health System (SUS) [13]. This public policy defines care strategies that aim at providing equitable and quality care for patients at all stages of CKD through the integration of various levels of  health care, with a focus on prevention, treatment and rehabilitation [14].

As mentioned above, the progressive growth in the incidence and prevalence of patients requiring RRT is considered a major global public health problem [15]. According to the Brazilian Institute of Geography and Statistics (IBGE), the Brazilian population in March 2023 was 189,4 million people, with over 92% of the Brazilian population being registered [16]. In 2022, the Brazilian Society of Nephrology (SBN) census found that there were 872 registered dialysis units in Brazil. The SBN sent questionnaires to all units, but unfortunately, only 243 RRT clinics answered. Due to the low answer’s rate, the SBN estimates that there are currently 153,831 people with some degree of CKD in Brazil, with a calculated prevalence of approximately 716 per 1,000 inhabitants [17]. The annual SBN census presents an approximate overview of dialysis treatment in Brazil, providing data and analyzes that will contribute to the direction of public policies and strategies aimed at improving RRT in the country [17,18].

2. Pediatric Chronic Kidney Disease and Renal Failure

Although the concept of CKD in children and adolescents is similar to that of adults, this pediatric disease presents some peculiarities. There is little evidence and many factors involved are not yet known.  It brings serious consequences associated with significant impairment of growth and development in these individuals, resulting in a significant reduction in life expectancy at birth [19].

To date, there is limited data on the epidemiology of this condition in the pediatric population. Unfortunately, most of this data is still underestimated because registration is only done when the individual already requires dialytic treatment. These epidemiological data are mainly concentrated on patients undergoing RRT, which represents only a portion of the pediatric population with CKD during childhood. A considerable number of children will progress to ESRD only in adulthood [12,19].

One of the main characteristics of pediatric CKD is that the underlying disease is different from that in adults. As mentioned before, there are specific severe complications such as growth and developmental disorders and urological problems [19,20]. Once the patient reaches renal failure, they will require a long-term RRT, including kidney transplantation. Therefore, long-term prognosis after transitioning to RRT is extremely important, considering that patient and graft survival rates are the primary goals in children and adolescents.

These studies on epidemiological data of pediatric CKD and pediatric renal failure are important for better management of these patients. In recent years, pediatric cases of CKD or records of renal failure, as well as cohort studies, have been reported worldwide (Table 1) [21-47].

2.1 Diagnosis of pediatric CKD

The diagnosis CKD in adults is performed by estimating the glomerular filtration rate (eGFR) from a filtration marker, such as serum creatinine or cystatin C, using formulas, or by testing urine for the presence of protein or albumin. However, there is no ideal method to accurately estimate GFR in children, considering that it varies with age, sex, race, ethnicity and size, which pose challenges in developing precise eGFR equations for children, especially in the early stages of the disease. Another limitation is the diversity of laboratory methods for measuring serum creatinine or cystatin C, and currently, the revised Schwartz and CKiD formulas are used [48,49].

CKD was first defined by the KDOQI guidelines in 2002 and endorsed in KDIGO 2012 [50,51]. These classifications have shown limitations as the classification of CKD is based on arbitrary eGFR cutoffs, ignoring age and sex-related changes. They only apply to children over two years old and give more importance to albuminuria, while most of these children have non-glomerular diseases. Stages 1-2 would be better defined by associated abnormalities rather than being classified as pediatric CKD [52-55]. 

Pediatric studies evaluating the prevalence of CKD in the last 10 years have followed CKD guidelines using only eGFR to report the incidence and prevalence of CKD stages 3-5. However, none of them combined the presence of albuminuria and reduced eGFR to report CKD in stages 1-5. Thus, to differentiate CKD from transient fluctuations in renal function or acute kidney injury, the definition of CKD includes a criterion of chronicity, meaning a low eGFR or high albuminuria that must be observed for at least three months, requiring repeated assessments over time [12].

CKD is also defined as the presence of renal structural alterations [51]. These alterations have been defined as pathological abnormalities (markers of renal damage: albuminuria), abnormalities in the urinary sediment, tubular disorders, histological abnormalities, history of kidney transplant, or structural abnormalities in imaging exams, with implications for health. However, not all abnormalities are related to prognosis [56].

2.2 Classification

CKD is classified into five stages (Table 1) according to the National Kidney Foundation Outcomes Quality Initiative (NKF-K / DOQI), with stage 1 being the mild form of the disease and stage 5 representing ESKD [51,56].

Table 1: Glomerular Filtration Rate and Classification of CKD

Modified from Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease, 2013 [51].
There is also a recommendation for the classification of CKD based on urinary albumin loss [51,57]. It is believed that this new classification, which includes albuminuria, may better characterize the prognosis of patients (Table 2).

Table 2 : Categories of albuminuria in CKD

Modified from Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease, 2013 [51].

2.3 Incidence and prevalence

Considering that CKD is often asymptomatic in its early stages, obtaining reliable data about the initial stages of this disease in the pediatric population is challenging. Unfortunately, these data are underestimated because registration is only done when the individual already requires RRT [12,20]. Although some reports of pediatric CKD are emerging in the literature, only a few reports on its epidemiology in stages 2 to 5 are available, especially in developing countries. For these countries, most data are obtained from reports of tertiary care referral centers. However, the quality of these data varies [20,30,36].

The European societies of pediatric nephrology have provided data on the all stages of CKD [30-32,34-36]. The incidence was 11 to 12 per million of the population of the same age (pmpa) for CKD stages 3 to 5, and 8 pmpa for CKD stages 4 to 5. While an increase in incidence has been observed in France since the 1970s, this was not found in Sweden [30,58]. The prevalence of pediatric CKD in stages 2-5 was estimated to be between 30 and 100 per million of the population related to age per year (pmpay) [12].

A low prevalence of CKD stages 3-5, 30 pmpay, was found in Japan. However, this was a survey sent to all institutions in the country, and reports of pediatric CKD cases < 15>

One factor that affects the epidemiology of CKD in the pediatric population is race [19]. In North America, the incidence of this disease is two to three times higher in African-American children, compared to Caucasian children, regardless of gender [24].

A study conducted in Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, Uruguai and Venezuela) showed a wide variation in the incidence of pediatric CKD, ranging from 2.8 to 15.8 new cases per million of the population per year (pmpy) [62]. A national survey in Chile estimated an incidence of 5.7 pmpy and a prevalence of 42.5 pmpy in children under 18 years old [63]. Half of these patients were receiving conservative treatment, and the rest were undergoing RRT. In the Middle East and Southeast Asia, an average incidence of CKD in children and adolescents aged 0 to 15 years old was found to be 38 pmpy in a referral center in Kuwait. The prevalence increased from 188 in 1996 to 329 pmpya in 2003 [64]. In children from Jordan, an incidence of 11 pmpy and a prevalence of 51 pmpya were reported [65]. Two reports from Vietnam showed an annual incidence of hospitalization due to CKD in children of 5 pmpy, and most of the patients had already reached ESRD [66,67].A study conducted in a single center in Africa identified a very low incidence of CKD, estimated at 3 pmpy in Nigeria and 1 to 2 pmpy in South Africa [68,69]. Peco-Antic’ et al., described the results of the Serbian Pediatric Registry of Chronic Kidney Disease (SPRECKID). The authors found that the annual median incidence of pediatric CKD in stages 2 to 5 was 14.3 per million of the population in the same age group (pmpy), while CKD in stages 2 to 4 or CKD stage 5 were 9.1 and 5.7 pmpy, respectively. The median prevalence of CKD in stages 2 to 5 was 96.1 pmpy, 52.8 pmpy for CKD in stages 2 to 4, and 62.2 pmpy for CKD stage 5 [33]. In 2021, Masalskienė et al., reported that the prevalence of pediatric CKD in stages 2 to 5 was 48.0 per million of the population in 1997; 88.7 in 2006; and 132.1 in 2017 [70]. Numerous risk factors (prematurity or low birth weight, obesity, smoking, hyperuricemia, acute kidney injury) have contributed to this increase, as observed in several other countries [71-73].

Regarding ESRD, the data on its incidence and prevalence in the pediatric population vary across different countries. Approximately 80% of patients on RRT worldwide live in Europe, Japan, or North America, where all pediatric patients with this condition have access to RRT. On the other hand, in developing countries, limited human resources, lack of training, and limited healthcare for patients with CKD and ESRD result in rationing or even lack of RRT [55].

Studies have shown that in 2008, the median incidence of RRT in children under 20 years of age was 9 per million population per year (pmpy), ranging from less than 4 in Russia to 18 pmpy in New Zealand. The incidence of RRT was 9.5 pmpy in 11 countries in Western Europe and Australia, compared to 15.5 pmpy in the United States [74-76]. In all registries, the incidence was higher in adolescents. This incidence was twice as high in the United States as in Western Europe for patients aged 15 to 19 years old (30.6 vs. 15.3) and was also higher in the age group of 0 to 14 years old (10.5 vs. 6.5). This difference can be partially explained by the timing of RRT initiation (mean GFR of 10.4 ml / min / 1,73 m2 in Europe vs. mean GFR of 11.3 to 13.6 ml / min / 1,73 m2 in the United States [77,78]. The incidence in Malaysia was comparable to Europe, suggesting good access to RRT, despite being a country with a public and government-funded dialysis program [79]. Previous reports from countries offering RRT showed that the incidence rates ranged from 6.5 pmpy in Brazil in the late 1980s to 17 pmpy in Kuwait in the period 1995-2002 [80,81].

In 2015, Konstantyner et al., showed that the incidence of CKD in children and adolescentes undergoing dialysis treatment in Brazil was 6.6 cases per million population per year (pmpy) in 2012. The Southern region showed the highest rate of new pediatric cases under this therapy: 11.0 cases pmpy, while the northeastern region had the lowest rate: 3.8 pmpy [81]. The authors concluded that the incidence of pediatric ESRD in dialysis treatment in Brazil was similar to those lower incidences reported in the literature and related this finding to the significant socioeconomic diversity and the level of human development index in the different regions of the country, which may favor the underdiagnosis of CKD and ESRD [81]. In developing countries where RRT is not accessible to all, the incidence rates are extremely low (<1>

As already known, incidence and prevalence of ESRD also differ according to race [74]. The US Renal Data System (USRDS) in 2010 showed that African-American children had an incidence almost twice as high as white children [74]. In Australia and New Zealand, renal disease is more common in Maori, Pacific Islander, and indigenous Australian populations than in non-indigenous populations, although the difference in ESRD incidence is mainly among those aged over 15 years old [47,75]. In the UK in 2008, the prevalence and incidence of RRT in children from the South Asian population were 2.5 and 1.5 times higher than those in the white population aged 0 to 15 years old [82]. 

As mentioned above, the incidence and prevalence of ESRD vary worldwide in children [83-87]. The United States Renal Data System (USRDS), the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used to compare the incidence and prevalence among children and adolescents. All rates were expressed as per million population related to age (pmpy) [26,47,87]. The incidence of pediatric ESRD has been decreasing according to the USRDS registry and remains constant according to the ANZDATA and ERA-EDTA registries. Consistent trends were observed in all age groups except for American children under 5 years old. Unlike the overall decreasing trend in the United States, the incidence rate has been increasing in this specific population [19].

The prevalence rates have slightly increased according to the USRDS and ANZDATA registries, while in Europe they have been decreasing over time. When stratified by age, there was an increase among children under 5 years old in Australia, New Zealand and the United States [19]. These rates were higher in the United States (incidence: 13 pmpy; prevalence: 77 pmpy [ages 0-17 years old between 2005 and 2017]) than in Australia and New Zealand (incidence: 9 pmpy; prevalence: 55 pmpy [ages 0-17 years old between 2007 and 2018]) and Europe (incidence: 9 pmpy; prevalence: 60 pmpy [ages 0-19 years old between 2005 and 2017]) [19].

A study from the ERA-EDTA registry demonstrated a small reduction of 2.5% per year in the incidence of European patients <19>

According to Geylis et al., studies found in the literature suggest that up to one in 10,000 children may have CKD [92]. However, all studies conducted in hospitals underestimate the prevalence, as only patients with manifest CKD, followed in pediatric nephrology centers, are evaluated in these studies [92]. As previously mentioned, there are only a limited number of studies in the general pediatric population, and they present a very different reality from that suggested by current hospital-based studies. In fact, a much higher prevalence of undiagnosed pediatric CKD in stages 2-5 (around 1%) has been reported in cross-sectional studies in Turkey, Iran and China, suggesting a possibly 100 times higher prevalence of pediatric CKD than estimated in hospital-based studies [93-95].

In addition to national health surveys, another approach to estimate the prevalence of evident chronic conditions is to identify cases from administrative data sources, such as health insurance records. Based on data from a single health insurance company in the US, including nearly two million individuals in the pediatric age group (< 21>

In a recent issue of the Pediatric Nephrology Journal, the population prevalence of CKD in Southern Israel was estimated using hospital data and laboratory data [92]. The strength of the aforementioned study was to use all serum creatinine measurements available after two years of age in the electronic medical records to define CKD as ≥ 2 eGFR values below 60 ml/min/1.73 m2 at least three months apart, thus including the criterion of chronicity which was overlooked by other studies [92]. The estimated prevalence of children meeting these criteria in 2019 was 1,033 per million population (pmp) (0.1%). The prevalence of children still classified as having CKD at the last follow-up was slightly lower (882pmp) and may be overestimated. Another interesting finding of this study is that a reduction of -1 ml/min/1.73 m2  in eGFR per year could suggest that it might take decades before these children with mild to moderate CKD (average age of 12 years old and eGFR of 50 ml/min/ 1.73 m2 ) reach advanced CKD or kidney failure [92]. 

According to hospital-based studies on the prevalence of pediatric CKD (ranging from 0.3 to 1 per 10,000 children) and the results of the few population-based studies suggesting a much higher prevalence (from 1 to 10 per 1,000 children), the current total number of children and adolescents in stages 2-5 of CKD worldwide can be extrapolated to two million cases of CKD in a population of two billion children [12]. This is concerning because pediatric CKD falls within the same range as the estimated number of children with cancers, the estimated number of children with type 1 diabetes, and is 10 times higher than the number of children affected by cystic fibrosis [12]. 

Thus, CKD is one of the most non-communicable pediatric diseases. However, unlike the aforementioned illnesses, public awareness, political attention, and the necessary investment for pediatric CKD are still very poor. This is partly due to the complexity of pediatric CKD, which encompasses many etiologies and a wide spectrum of presentations, ranging from a silent disease in its early stages to its devastating impact on quality of life and life expectancy [12]. As a result, the understanding of pediatric CKD among the public, physicians and health authorities is very low. The lack of awareness among policymakers about pediatric kidney diseases and the consequences of delays in diagnosis and appropriate treatment are major contributors to alarming situations [12]. For example, the rate of late presentation of pediatric CKD, defined as the first visit to pediatric nephrology with complete loss of kidney function, is unacceptably high (> 40%), especially in low-and middle-income countries, reflecting the lack of timely diagnosis and referral to pediatric renal care [97]. Another long-term concern is the demand for better prevention and treatment by pediatric nephrologists [98]. Finally, it has been demonstrated that public investment in specialized and multidisciplinary pediatric renal care is cost-effective in optimizing outcomes such as access to the best treatment and survival [99,100].

Interestingly, pediatric CKD and ESRD in developing countries are lower than in developed countries. However, this may be related to underdiagnosis of the causes of CKD, differences in access to healthcare and regional socioeconomic inequalities. That is the most likely explanation on the differences in prevalence and incidence rates of CKD and ESRD among developed and developing countries. Thus, the importance of pediatric CKD prevention policies is highlighted [81].

2.4 Gender and age

Data from the literature showed that the average age of children with CKD was 10 years old with a predominance of males. The male-to-female ratio ranged from 1:1.05 to 1:1.31), which is also consistent with literature findings. This occurrence is due to the fact that the main cause of CKD was congenital abnormalities of the kidneys and urinary tract (CAKUT), and it was identified more frequently among boys [20,33,70].

A study conducted with 82 children and adolescents undergoing RRT, at a single center in southeastern Brazil (Belo Horizonte) showed a predominance of males, and the average age of the patients was 9.25 years old at the beginning of RRT [54]. This finding is very close to those described in studies on RRT in Serbia [33](9.8 years old), Korea [101] (9.7 years old), and also in another part of Brazil (12.5 years old) [80]. It can be observed that these are developing countries. Reports from developed countries showed a lower average age at the start of RRT, such as in Italy (6.9 years old) and Spain (3.9 years old) [31,36]. This is likely because in these countries there is greater accessibility to diagnosis, and the main causes of CKD are CAKUT and hereditary diseases, which are diagnosed earlier [31,36].

2.5 Causes and initial modality of RRT

In the three largest registries (USRDS, ANZDATA, ERA-EDTA), the main cause of complete loss of renal function is CAKUT (30%), followed by glomerulonephritis (15-30%). The proportion of CAKUT decreases with advancing age, while glomerulonephritis increases [19]. Similar results have been reported in Japan [19]. However, a systematic review of children requiring dialysis in sub-Saharan Africa demonstrated that primary glomerulonephritis was the main cause (50%) of renal function loss [102]. A similar finding was also reported by Rezende et al., in Belo Horizonte, MG, southeastern Brazil. The authors found that 36.6% of the patients had glomerulonephritis as the cause of renal function loss [54].

Among children and adolescents, the proportion of those who initiated RRT with HD represented approximately half of all incident patients, according to the three major registries (USRDS, ANZDATA, ERA-EDTA) [19]. However, PD was the predominant initial modality of RRT in Japan. When data were stratified by age, PD was prevalent among children under five years old, and HD was more prevalent among the ones aged 15 years old or older [19]. Interestingly, the proportion of HD has decreased in Australia, New Zealand and the United States over time among those aged 15 years old or older, while PD has increased. However, the percentage of HD has increased among children under five years old in all three registries (USRDS, ANZDATA, ERA-EDTA) [19]. The reason for the increasing trends of HD among children under five years old is not clear, and PD remains preferrable to HD in this population.

Regarding preemptive kidney transplantation, its proportion has remained unchanged in the last decade. This type of transplant seems to be more common in Europe than in the other two regions, accounting for approximately 25%. However, its proportion varies within European countries, and the rate of preemptive transplantation was 17

2.7 Conclusions

Pediatric CKD has distinct characteristics from the disease in adults and can lead to severe and specific complications. It can be caused by urological problems such as CAKUT or non-CAKUT-related issues, followed by hereditary diseases like glomerulopathies, which may vary with age and be more common in older age groups. Several risk factors for CKD and ESRD can be identified. Among the modifiable factors are metabolic acidosis, proteinuria, arterial hypertension, and underlying urological abnormalities; among the non-modifiable factors are age, sex, racial and genetic factors, low birth weight, prematurity, and socioeconomic status.

The average age of pediatric CKD is around 10 years with a predominance of males (the male-to-female ratio ranging from 1:1.05 to 1:1.32). Children and adolescents with ESRD are exposed to 30 to 60 times higher risk of mortality compared to their healthy peers, but the survival rate has improved over time in many countries.

Considering hospital-based studies examining the prevalence of pediatric CKD (0.3 to 1 per 10,000 children) and the limited population-based studies suggesting a much higher prevalence (1 to 10 per 1,000 children), the current total number of children and adolescents affected by stages 2-5 of CKD worldwide can be extrapolated to over two million cases of CKD in a population of two billion children.

Public awareness, political attention and the necessary investment for pediatric CKD and ESRD are still very poor. This is partly due to the complexity of these conditions, which encompass many etiologies (often rare diseases) and involve a wide spectrum of presentations, often starting as a silent disease. However, it can progress with devastating impact on quality and life expectancy. Lack of public awareness, lack of awareness among policy makers about pediatric kidney disease and the consequences of delays in diagnosis and appropriate treatment are major contributors to the current alarming situation. The rate of late presentation of pediatric CKD, defined as the first consultation with a pediatric nephrologist already with some loss of renal function, is unacceptably high (> 40%), especially in low and middle-income countries, reflecting the lack of timely diagnosis and referral to pediatric renal care. Another concerning long-term situation is the association of clinically evident but mild CKD in pediatric patients with an increased risk of kidney failure in young adults. This fact further highlights the demand for better prevention and treatment by pediatric nephrologists.

Therefore, there is a need to raise awareness about pediatric CKD to improve health outcomes. This requires collecting more population-based data, registries, and cohorts that include not only ESRD but also the early stages of CKD where kidney failure can be delayed or prevented, evaluating the impact of population screening interventions in children with CKD risk factors. The implementation and execution of CKD prevention programs are essential in primary care. Identifying individuals with CKD risk factors and referring them for evaluation by a pediatric nephrologist who will provide conservative treatment along with a multidisciplinary team will delay disease progression and, consequently, the need for ESRD treatment.

Given the information presented about CKD and ESRD in children and adolescents, their therapeutic modalities, the increasing incidence and prevalence of the disease in both adult and pediatric populations, and the possibilities of prevention and delaying the progression of CKD to ESRD, it is crucially relevant to understand the detailed profile of the pediatric population on ESRD treatment to obtain important and necessary data for the adjustment of healthcare policies.

Declaration of conflict of interest:

There are no conflicts of interest.

Funding agency name:

None

Indication of authors' contribution:

Celina de Faria Rezende 1; Sérgio Veloso Brant Pinheiro 2,3; Mariangela Leal Cherchiglia 4; Maria Goretti Moreira Guimarães Penido 1,2; Hugo André da Rocha4 were responsible for the research idea, data acquisition, and supervision or mentorship.

References

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