Regional variation of underlying kidney diseases in children undergoing chronic kidney replacement therapy around the globe

Regional variation of underlying kidney diseases in children undergoing chronic kidney replacement therapy around the globe | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Regional variation of underlying kidney diseases in children undergoing chronic kidney replacement therapy around the globe Dagmara Borzych-Dużałka, Marjolein Bonthuis, Uma Ali, Yap Yok Chin, and 20 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7393084/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Dec, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Background There is a scarcity of demographic information regarding the distribution of the diseases leading to kidney failure (KF) in children living in the emerging world. We used data from international, regional and national registries to provide a global overview of the underlying disease spectrum in children commencing kidney replacement therapy (KRT). Methods We analyzed KF causes among 23,620 children and adolescents commencing maintenance KRT in 80 countries, using data from the IPNA Global KRT Registry (including ESPN/ERA Registry), the International Pediatric Dialysis Network (IPDN), the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The analysis considered geographic region, country-level gross national income (GNI), average annual temperature, and patient age. Results Marked regional differences were observed in the distribution of KF causes. Immune-mediated glomerulopathies (GP) were most common in Southeast Asia, hereditary nephropathies in the Middle East, Africa, and Europe, and systemic GP in Northeast Asia and Latin America. In 14% of cases the cause of KF was unknown, with the highest proportion in Northeast Asia. Disease patterns were also influenced by the countries’ GNI and average yearly temperature; immune-mediated GP accounted for 43% of diagnoses in low-income countries and were more frequent in warmer climates. Among younger children, congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies were the predominant cause of KF, whereas adolescents more commonly presented with immune-mediated GP. Conclusion There is significant global variability in the spectrum of diseases leading to pediatric KF, which is partially attributable to genetic, environmental, and macroeconomic factors. Primary Kidney Disease Kidney Failure children regional variation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The etiologies of pediatric kidney failure (KF) have been extensively studied in high-income regions, particularly in North America, Europe, Japan, and Australia/New Zealand. In these regions, congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of KF, accounting for 30–60% of cases, followed by glomerular diseases (mainly focal segmental glomerulosclerosis (FSGS)), hereditary diseases including ciliopathies, and systemic conditions like lupus nephritis [ 1 , 2 ]. Much less is known about the etiologies of KF in children living in low- and middle-income countries (LMIC). Literature is largely limited to single-center or regional reports, which may not be generalizable [ 3 – 5 ]. Some evidence suggests that children in emerging countries may face a higher prevalence of infectious and environmental etiologies, including various forms of post-infectious glomerulonephritis, systemic vasculitis and hemolytic uremic syndrome. Also, congenital obstructive uropathies may go undiagnosed or untreated due to limited access to prenatal imaging and perinatal care [ 6 , 7 ]. The lack of systematic data collection is a major barrier to epidemiological research in low- and middle-income countries. According to a worldwide survey performed by IPNA in 2017, national registries for both dialysis and kidney transplantation in children were established in only 51 countries, covering just one third of the global child population [ 8 ]. The lack of systematic monitoring of a large part of the global pediatric population hampers quantitative assessment of the causes of KF, treatment access, management practices and clinical outcomes and slows the development of lifesaving, cost-efficient kidney replacement therapy (KRT) programs in many parts of the globe. To address this critical knowledge gap, the International Pediatric Nephrology Association Kidney Replacement Therapy (IPNA KRT) Registry was established in 2018 as a global registry collecting prospective population-based data on the demographics and etiologies of KF, KRT modality choices and patient and technique outcomes in children. [ 9 ]. The aim of the current analysis, combining data from the IPNA KRT Registry, the ESPN/ERA Registry, the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), was to examine and compare the underlying causes of KF in children across diverse global regions. This comparative approach is hoped to enable a better understanding of regional differences in maintenance KRT, highlight disparities in diagnostic patterns and healthcare infrastructure, and inform global strategies for prevention, early detection and management of pediatric KF. Methods Data sources Data were extracted from the International Pediatric Nephrology Association Kidney Replacement Therapy (IPNA KRT) Registry including ESPN/ERA Registry data (80 countries), the International Pediatric Dialysis Network (IPDN) (7 countries), published information from the United States Renal Data System (USRDS), and the Australian and New Zealand Dialysis and Transplant (ANZDATA) annual reports [ 9 , 11 – 13 ]. The global IPNA KRT registry collects population-based national data on children receiving either hemodialysis, peritoneal dialysis, or a kidney transplant. Data excerpts are provided by existing national and regional registries. In countries without established registries pediatric KRT centers use an online data entry platform ( www.ipna-registry.org ) [ 9 ]. For the analysis presented here, 38 countries without established national registries used the online data entry system, 29 countries provided data via the ESPN/ERA Registry and 3 extracted data from national registry databases. Primary kidney diseases (PKD) were classified using the ERA-EDTA PKD coding system (Supplemental Table 1) [ 10 ]. The International Pediatric Dialysis Network (IPDN) Registry collects prospectively clinical data from children commencing maintenance hemodialysis or peritoneal dialysis [ 11 ]. The IPDN disease classification system is presented in Supplemental Table 1. For the IPNA and IPDN registries, the registry protocols were approved by the relevant institutional review boards at each participating center and/or country, in accordance with local requirements. The ESPN/ERA Registry provided data based on a trilateral agreement involving the IPNA registry, the ESPN/ERA Registry, and participating country. Written informed consent from parents or guardians, and patient assent when applicable, were obtained. For pediatric patients with KF receiving KRT in the United States data were extracted from the USRDS report [ 12 ]. In the US, pediatric nephrologists are required to complete a Centers for Medicare & Medicaid (CMS) Medical Evidence Report containing initial demographic data and follow-up data. The United Network for Organ Sharing (UNOS) collects data on kidney transplantation and is reported in the USRDS database as well. The USRDS kidney diagnoses classification is depicted in Supplemental Table 1. ANZDATA is a voluntary database to which patients who reside in Australia or New Zealand and receive chronic KRT are reported through a Web portal [ 13 ]. The ANZDATA kidney disease classification system is shown in Supplemental Table 1. Categorization of disease etiologies For this study, PKD were classified into six main disease categories of interest and 10 subcategories: 1 ) Congenital Anomalies of the Kidney and Urinary Tract including kidney dysplasia, obstructive uropathy, reflux nephropathy and other CAKUT; 2) Immune-mediated glomerulopathies including primary and secondary glomerulopathies; 3) Hereditary/familial nephropathies including ciliopathies, familiar and syndromic glomerulopathies, hereditary tubulopathies and not further specified familial diseases; 4) post-AKI CKD including thrombotic microangiopathies; 5) other including tubulointerstitial nephritis, hematologic-oncologic and post-traumatic disease; 6) unknown . For a complete list of diseases under each category, please see Supplemental Table 1. Regional and GNI categorization Geographic regions were defined in accordance with the regional boards of the International Society of Nephrology: Africa, Central Europe, Latin America, Middle East, Russia and Newly Independent States (NIS), North America and the Caribbean, South Asia, Northeast Asia, Southeast Asia, and Western Europe (Table 1 ). Countries were classified as low, low-middle, upper-middle, and high-income countries based on World Word Bank data ( https://data.worldbank.org ) using quartiles of Gross National Income (GNI) in the calendar year of KRT initiation [ 14 ]. Table 1 Countries by geographic region and number of patients 0–17 at KRT start per country (N = 80) and region (N = 10) Africa (n = 7) Latin America (n = 12) Western Europe (n = 14) Eastern and Central Europe (n = 17) Russia and Newly Independent States (n = 5) Middle East (n = 7) Northeast Asia (n = 3) South Asia (n = 4) South-East Asia & Oceania (n = 8) North America And Caribbean (n = 3) No. of patients by region N = 240 N = 1,201 N = 6,033 N = 3,455 N = 1,929 N = 1,170 N = 1,086 N = 1710 N = 1,571 N = 5,227 No. of patients per country Burkina Faso (7) Egipt (1) Marocco (140) Nigeria (4) Tunisia (81) Uganda (1) Zambia (6) Argentina (209) Bolivia (16) Brazil (171) Chile (235) Colombia (43) Guatemala (79) Haiti (11) Mexico (27) Nicaragua (25) Peru (342) Paraguay (18) Uruguay (25) Austria (269) Denmark (207) Finland (215) France (2210) Germany (415) Greece (63) Israel (125) Italy (222) Malta (6) Norway (186) Portugal (285) Spain (1218) Switzerland (231) UK (382) Albania (33) Bosnia & Herzegovina (58) Croatia (112) Bulgaria (77) Cyprus (17) Czech Rep (104) Estonia (10) Hungary (49) Latvia (14) Lithuania (53) Macedonia (18) Poland (1111) Romania (317) Serbia (126) Slovenia (42) Slovakia (107) Turkey (1207) Armenia (14) Belarus (139) Georgia (24) Russia (1411) Ukraine (341) Jordan (123) Syria (214) Iran (622) Lebanon (2) Oman (14) Saudi Arabia (66) United Arab Emirates (129) China (849) Hong Kong (70) South Korea (167) Bangladesh (107) India (1230) Sri Lanka (55) Pakistan (317) Indonesia (57) Laos (11) Malaysia (989) Philippines (133) Singapore (61) Vietnam (8) Australia/New Zealand (312)** USA (4162)* Canada (1038) Puerto Rico (27) *USRDS data, **ANZDATA Average yearly temperature was calculated by averaging the minimum and maximum daily temperatures in the country, averaged for the years 1991–2020, from World Bank Group, derived from raw gridded climatologies of the Climatic Research Unit [ 15 ]. Analysis dataset All reported patients with KF who commenced chronic kidney replacement therapy (KRT) at 0 to 17 years of age were included in the present analysis. Patient-level data on date of birth, start date of KRT and PKD were extracted from the IPNA and IPDN registries, while age category and PKD were available from the USRDS and ANZDATA reports. The IPNA KRT Registry included incident patients who initiated kidney replacement therapy (KRT) between 1997 and 2025, whereas the IPDN dataset comprised patients who began KRT between 2007 and 2025. The USRDS report included incident KRT patients from 2018 to 2022, while the ANZDATA report covered the period from 2017 to 2022. For a complete list of date of enrolment by region and country, please see Supplemental Table 2. Statistical Analysis Descriptive statistics were used to summarize results as median (interquartile range) for continuous variables and number (%) for categorical variables and analyzed using SAS 9.4. Chi-square tests were used to compare categorical variables such as etiology frequencies across different regions, countries and income groups. Non-linear regression analysis was utilized to evaluate relationships between continuous variables like gross national income per capita, average yearly temperature, and the proportion of specific KF etiologies. Data were analyzed on regional and country-level. For the latter analyses countries with at least 6 patients in a particular category were included. Statistical significance was set at p < 0.05. Results Regional Distribution of Kidney Failure Etiologies KF etiology was extracted from data of 23,620 children and adolescents aged 0–17 at KRT initiation, across 80 countries and 10 world regions (Table 2 ). Table 2 Subjects receiving KRT by diagnostic category and geographic region. Total Africa Latin America Western Europe Central/ Eastern Europe Russia/NIS Middle East Northeast Asia South Asia Southast Asia, Australia, Oceania North America P Total N 23,620 240 1,201 6,033 3,455 1,929 1,170 1,086 1,709 1,570 5,227 CAKUT 8,250 (35) 97 (41) 541 (45) 2,167 (36) 1,249 (36) 899 (47) 418 (36) 202 (19) 749 (44) 401 (25) 1,527 (30) < 0.0001 Kidney dysplasia 4,089 (50) 35 (36) 301 (55) 1,283 (59) 418 (33) 420 (47) 162 (39) 160 (79) 320 (43) 205(51) 782 (51) < 0.0001 Obstructive uropathy 2,241 (27) 20 (21) 128 (24) 518 (24) 399 (32) 284 (31) 66 (16) 13 (6) 209 (28) 95 (24) 509 (33) < 0.0001 Reflux nephropathy 1,208 (15) 29 (30) 60 (11) 280 (13) 262 (21) 143 (16) 82 (20) 28 (14) 117 (16) 61 (15) 146 (9) < 0.0001 Other CAKUT 715 (8) 13 (13) 52 (10) 86 (4) 170 (14) 52 (6) 108 (26) 1 (1) 103 (14) 40 (10) 90 (6) < 0.0001 Familial/hereditary NP 4,785 (20) 60 (25) 124 (10) 1,653 (27) 941 (27) 426 (22) 353 (30) 175 (16) 276 (16) 159 (10) 618 (12) < 0.0001 Cystic kidney disease 2,107 (44) 25 (42) 63 (51) 691 (42) 392 (42) 215 (50) 147 (42) 79 (45) 149 (54) 58 (36) 288 (47) < 0.0001 Hereditary and syndromic GP 1,565 (32) 9 (15) 47 (38) 411 (25) 362 (38) 161 (38) 122 (35) 76 (43) 69 (25) 81 (51) 227 (37) < 0.0001 Tubulopathies 577 (12) 23 (38) 14 (11) 169 (10) 95 (10) 32 (8) 79 (22) 18 (11) 55 (20) 12 (7) 80 (13) Familial unspecified 536 (11) 3 (5) 0 382 (23) 92 (10) 18 (4) 5 (1) 2 (1) 3 (1) 8 (5) 23 (4) Immune-mediated GP Primary Systemic 4,705 (20) 3,644 (77) 974 (13) 30 (13) 24 (80) 6 (20) 257 (21) 184 (72) 73 (28) 927 (15) 743 (80) 184 (20) 402 (12) 312 (78) 90 (22) 257 (13) 218 (85) 39 (15) 178 (15) 153 (86) 25 (14) 274 (25) 197 (61) 77 (28) 361 (21) 313 (87) 48 (13) 684 (43) 496 (83) 101 (17) 1,335 (26) 1004 (75) 331 (25) < 0.0001 Post-AKI (TTP, toxic, Infectious) TTP 1,283 (5) 833 (64) 10 (4) 3 (33) 68 (6) 58 (85) 425 (7) 270 (63) 159 (5) 108 (67) 176 (9) 150 (85) 76 (6) 53 (69) 38 (4) 24 (63) 75 (4) 44 (59) 38 (2) 20 (52) 219 (4) 103 (47) < 0.0001 Other (tubulointerstitial, trauma, oncologic, surgical loss) 1,302 (6) 4 (2) 29 (2) 156 (2) 79 (2) 70 (4) 30 (2) 20 (2) 57 (3) 28 (2) 829 (17) Unknown/uncertain 3,294 (14) 39 (16) 182 (15) 705 (12) 625 (18) 101 (5) 115 (10) 377 (35) 191 (11) 260 (17) 699 (12) < 0.0001 Globally, the predominant underlying etiologies of KF were congenital anomalies of the kidney and urinary tract (CAKUT) (35%), hereditary nephropathies (20%), and immune-mediated glomerulopathies (20%) (Table 2 , Fig. 1 ). In 14% of cases, the cause of KF was reported as unknown. Significant regional variation was noted in the relative frequency of acquired glomerulopathies and hereditary disorders. Immune-mediated glomerulopathies were most prevalent in Southeast Asia, accounting for 43% of pediatric KF cases, in contrast to 12–15% reported in Europe, Russia/Newly Independent States (NIS), the Middle East, and Africa (p < 0.001; Fig. 1 , Table 2 ). The highest national proportions of glomerular diseases were observed in the Philippines, Laos, and South Korea (Fig. 2 a). FSGS was the leading glomerular cause of KF, representing 34% of immune-mediated glomerulopathies globally, followed by vasculitis (8.3%) and SLE nephritis (7.7%). The distribution of both primary and secondary glomerular disorders varied notably across regions. While FSGS was the predominant immune-mediated cause of KF in the Middle East (55%), South Asia (47%), North America (39%), and Northeast Asia (38%), its prevalence was considerably lower in Central Europe (14%). Lupus nephritis contributed most significantly to KF in Latin America (14%) and Southeast Asia (10%). IgA nephropathy accounted for 8% of KF cases in Western Europe, compared to only 2–4% in other regions (p < 0.001). A notably high proportion of cases (25%) were classified as unspecified primary glomerulopathies, with regional variation ranging from 8% in the Middle East to 44% in Russia/NIS (p < 0.001) (Fig. 3 ). Familial and hereditary kidney disorders (depicted by green shades in Fig. 1 ) were most common in the Middle East (30%), Africa (25%), and Europe (27%), and were least frequent in the Americas and Southeast Asia (10–12%). Finland, Saudi Arabia and Oman reported the highest fractions of hereditary disorders leading to KF (Fig. 2 b). Across all regions cystic kidney diseases represented the leading hereditary cause of KF (44%), followed by hereditary and syndromic glomerulopathies. Hereditary tubulopathies were notably more prevalent in Africa (38%) and the Middle East (22%); they constituted the most common hereditary disorders in Tunisia (47%) and Pakistan (41%). Primary hyperoxaluria emerged as the predominant hereditary disorder leading to KF in these countries, accounting for 8 out of 9 cases in Tunisia and 72% of hereditary disorders in Pakistan. CAKUT disorders were the leading cause of KF in all regions except in North and Southeast Asia, where they accounted for only 19% and 25% of cases, respectively. Isolated kidney dysplasia was consistently reported as the most frequent form of CAKUT, comprising 35–60% of cases in most regions, and reaching up to 80% in Northeast Asia. In this latter region, obstructive uropathy was notably less common (6%) than in other areas (16–33%). Considerable variation was also observed in the proportion of KF cases with unknown etiology , which constituted 14% overall. This category was more prevalent in Northeast Asia, driven primarily by a high fraction of unexplained cases in China (41%). In Latin America, Guatemala stood out with 73% and Nicaragua with 56% unexplained cases. Factors associated with Primary Kidney Disease (PKD) distribution Gross National Income Of the total cohort, 476 patients (2%) originated from low-income countries (LIC), 2,597 (11%) from low-middle-income countries (LMIC), 7,086 (30%) from high-middle-income countries (HMIC), and 13,461 (57%) from high-income countries (HIC). Significant differences were observed in the relative frequency of acquired immune-mediated glomerulopathies, which accounted for 43% of diagnoses in LIC as compared to 15% in countries with higher national incomes (p < 0.0001). Country-based comparison revealed a negative correlation between the fraction of immune-mediated glomerulopathies relative to all diagnoses and gross national income per capita (Fig. 3 ). Average yearly temperature The reporting countries represented all climate zones with average yearly temperatures ranging from − 4.0°C in Canada to 30.4°C in Burkina Faso. The average temperature was positively correlated with the fraction of immune-mediated glomerulopathies among all reported diagnoses per country (Fig. 3 ), whereas the frequency of IgA nephropathy was inversely correlated with temperature. None of the other diagnosis groups showed associations with ambient temperature. Patient age The distribution of KF etiologies by age group largely reflected the manifestation age and natural history of the diseases. CAKUT and hereditary nephropathies predominated among younger children, whereas immune-mediated glomerulopathies were more common in adolescents (Fig. 5 ). Post-ischemic CKD was observed to be twice as prevalent in children under five years of age compared to their older counterparts. “Unknown” and “other” causes of KF were most frequently reported in adolescent patients. DISCUSSION This study presents the first global, population-based comparative analysis of the disease spectrum leading to KF in childhood, leveraging registry data from multiple countries across all continents. Our investigation revealed substantial regional heterogeneity in disease distribution. The most pronounced variation in disease occurrence was identified for immune-mediated glomerulopathies , which was a much less frequent cause of KF in Europe and Africa than in Asia and the Americas. The observed regional variation of glomerular disease etiologies is in keeping with findings of the International Kidney Biopsy Survey [ 16 ]. In an analysis of more than 42,000 mostly adult cases, FSGS predominated in North America, SLE nephritis in Asia and Latin America, and IgA nephropathy in Europe and Asia. The high proportion of glomerular disorders particularly in Southeast Asia and parts of Latin America may be attributable to both genetic and environmental conditions. Genetic susceptibility to autoimmune conditions is known to vary by ethnicity. HLA variants enhancing autoantibody activity are more prevalent among Hispanic and Asian populations, which may exacerbate disease severity and accelerate progression to KF [ 17 ]. In addition, the high burden of bacterial, viral, and parasitic infections in regions characterized by hot and humid climatic conditions may trigger autoimmune disorders independently of genetic predisposition [ 18 ]. Indeed, we observed a significant association of the country-specific fraction of pediatric KF cases caused by primary glomerulonephritis with the average annual temperature. Furthermore, limited healthcare resources may impact the risk of progression to KF of patients with treatable acquired glomerular conditions more than those with congenital and hereditary kidney disorders. In line with this notion, glomerular diseases were found to be 2.5-fold overrepresented as KF causes in low-income as compared to high- and upper-middle-income countries. Poor access to specialized care and effective treatment may contribute to this association, although confounding by correlated environmental conditions is likely. Notably, the highest prevalence of FSGS was reported in the Middle East. This finding is in keeping with a biopsy study in 376 Saudi Arabian children, where FSGS accounted for 32% of cases [ 19 ]. Given the high incidence of hereditary diseases in this region, it is likely that a major proportion of FSGS cases were not related to immune pathology but represented undiagnosed genetic podocytopathies. Likewise, the high FSGS prevalence reported for North America is likely due to African American patients who frequently harbor high-risk APOL1 gene variants predisposing to FSGS and accelerated decline of kidney function [ 20 ]. The proportion of patients with KF due to IgA nephropathy was higher in Europe than East Asia, even though individuals of both East Asian and European descent are susceptible to IgA nephropathy. This discrepancy may reflect the widespread implementation of urinary screening programs in Eastern Asia, which has been demonstrated to cost-effectively reduce the incidence of KF among patients with IgA nephropathy [ 21 , 22 ]. Hereditary, familial, and syndromic kidney diseases of genetic origin were most prevalent in the Middle East and North Africa, most likely reflecting cultural factors such as high rates of parental consanguinity common within Islamic societies. The relatively elevated frequency of genetic disorders reported by European centers may be attributed to broad access to advanced genetic diagnostics as well as the presence of large migrant populations, particularly from North Africa and the Middle East. While CAKUT was the leading cause of pediatric KF globally, its relative prevalence exhibited marked regional variation, ranging from 18% in Northeast Asia to 46–47% in Latin America and Russia/NIS. Stratification by income level indicates that CAKUT is the predominant diagnosis in low-middle-income countries (LMICs), accounting for 55% of KF cases, compared to 45% in higher-income settings. Early diagnosis of CAKUT allows effective renoprotective management including prompt urological intervention, adequate fluid intake, prevention of urinary tract infections, and pharmacological RAS blockade. Data from high-income European countries indicate that 50% of children diagnosed with CAKUT do not require KRT within the first 30 years of life [ 23 ]. In contrast, access to early diagnosis and therapeutic interventions may be more limited in LMICs, resulting in faster progression and a higher fraction of children on KRT in these countries. The relatively low proportion of CAKUT cases reported in the lowest income group may reflect elevated mortality rates associated with missed or late diagnosis. Additionally, limited healthcare infrastructure, insufficient government policies, and shortages of pediatric nephrologists substantially restrict access to KRT in low-income settings particularly for infants, resulting in markedly reduced treatment rates [ 24 ]. In a recent study, the proportion of infants initiating KRT ranged from 1–2% in Asia and Africa to 12% in Western Europe [ 25 ]. Notably, a considerable proportion of KF cases across all regions and national income levels were of unknown etiology . High rates of KF patients with unidentified etiology likely reflect the often asymptomatic progression of CKD to advanced stages, compounded by global inequities in nephrology care and delayed referrals to specialized care [ 26 ]. The observation also may indicate significant gaps in current diagnostic capabilities and variability in the extent of diagnostic workup across countries. Several measures could be cost-efficient in improving the timely detection of CKD in children. The existence of fetal and neonatal ultrasound programs is key to the early detection of CAKUT cases [ 27 ]. Routine implementation of genetic testing has been shown to clarify the underlying disease in up to 40% of pediatric KF cases and enhance clinical management [ 28 ]. Urine dipstick screening is an inexpensive and efficient tool for early detection of glomerular disorders which, given the availability of effective therapies, may justify the introduction of national screening programs in countries with a high incidence of glomerular diseases leading to KF [ 29 ]. In some circumstances, regional clustering of kidney failure from unknown etiology might be related to unidentified environmental factors. This is exemplified by the high proportion of patients with unknown etiology reported for Guatemala and Nicaragua, countries that represent a hotspot of Mesoamerican Endemic Nephropathy, a condition assumed to be related to an unidentified environmental toxin or infectious agent [ 26 , 30 ].` Several limitations inherent to this study warrant consideration. Data collection methodologies varied, with some regions contributing data from national registries and others from individual centers. Participation in the IPDN registry and the web-based part of the IPNA registry is voluntary, introducing potential selection bias. Globally, regions lacking resources for registry documentation are underrepresented in this analysis. Also, the classification of regions according to the ISN regional boards may have oversimplified the ethnic composition and macroeconomic conditions within specific geographic areas. Furthermore, regional differences in kidney biopsy indication policies might have biased the reported disease etiologies. Finally, access to KRT may vary by age and underlying disease, particularly in low-resource environments. Consequently, the underlying diseases of neonates, young infants and patients with severe syndromic disorders who were not accepted for KRT may have been regionally underrepresented as causes of KF. Variable representation of the youngest, CAKUT-predominant age group would impact reciprocally on the calculated regional proportions of underlying kidney diseases. Despite these limitations, this study provides valuable insights that may inform future CKD screening programs, guide national healthcare resource allocation and disease management and help prioritize target regions for clinical trials. The study’s strengths include its large, diverse dataset encompassing multiple countries and regions. Future enhancements to the registry could incorporate detailed biopsy data, biomarker analyses, genetic testing results, and comprehensive individual-level socioeconomic and healthcare access information. In conclusion, significant global variation exists in the etiologies of pediatric KF, influenced by geographic, ethnic, genetic, and socioeconomic factors. A substantial proportion of KF cases remain unexplained, even in high-income countries, underscoring persistent gaps in early detection of pediatric kidney disease worldwide. The IPNA pediatric KRT registry establishes a foundation for life-course epidemiological studies aimed at identifying at-risk populations and enhancing early diagnosis and management strategies. Declarations Acknowledgements We would like to thank the patients, their parents, and the staff of all the dialysis and transplant units who have contributed data via their national registries and contact persons, who are listed as Collaborators. Collaborators IPNA Registry Participants: Hazem Awad, Loai Akram Eid, Eihab Al Khasawneh, Gurinder Kumar, Watfa Shahwan Al Dhaheri, Helen Nazaryan, Maria Laura Beaudoin, Saimul Haque, Azmeri Sultana, Gerard Coulibaly, Claudia Gorena, Reyna Callisaya, Clotilde Garcia, Oreste Ferra Neto, Francisco Cano, Hong Xu, Shenqian Jing, Yihui Zhai, Eugene Chan, Richard Baquero Rodriguez, Hesham Safouh, Tinatin Davitaia, Maria Lipka, Cristina Zelaya, Judith Exantus, Henny Adriani Puspitasari, Choni Rinat, Vardit Peles, Aditi Sinha, Alpana Ohri, Kumar Manish, Manoj Matnani, Saumil Gaur, Sushmita Banerji, Jyoti Sharma, Suprita Kalra, Susan Uthup, Nivedita Kamath, Uma Ali, Amol Mbdave, Swati Bhardwaj, Neha Agarwal, Mehul Shah, Puneet Singh, Aliza Mittal, Sukanya Govindan, Pankaj Deshpande, Indira Agarwal, Vaibhav Keskar, Sudha Ekambaram, Sukanya Govindan, Satya Prasad VVR, Koushal Kumar Khajuria, Kinnari Vala, Kalaivani Ganesan, Kalaivani Ganesan, Subal Pradhan, Nakysa Hooman, Afshin Safaie Asl, Hamidreza Badeli, Hadi Sorkhi, Hamid Mohamadjafari, Ahmadali Nikibakhsh, Ali Derakhshan, Mitra Basiratnia, Masoumeh Mohkam, Mostafa Sharifian Dorcheh, Nasrin Esfandiar, Seyyed Mohammad Taghi Hosseini Tabatabaei, Daryoush Fahimi, Fahimeh Askarian, Mastaneh Moghtaderi, Neamatollah Ataei, Seyed Taher Esfahani, Nahid Mamizadeh, Parsa Yousefichaijan, Rama Naghshizadian, Anoush Azarfar, Fatemeh Ghane Sharbaf, Saeideh Parvaresh, Ehsan Valavi, Mojgan Mazaheri, Mohammad Reza Razavi, Mohsen Akhavan Sepahi, Hossein Emad Momtaz, Abolhassan Seyedzadeh, Simin Sadeghi Bojd, Maryam Esteghamati, Banafsheh Arad, Mahmood Maleknejad, Masoudeh Sabzechian, Alaleh Gheissari, Zahra Noparast, Reham Al Mardini, Ghazi Mohamad Al-Salaita, Hee Gyung Kang, Philavanh Kedsadtha, Aoun Bilal, Sami Sanjad, Umeshi Karu, Kenza Soulami, Yap Yok Chin, Adebowale Ademola, Mohamed Alriyami, Reyner Loza, Marbella Angeles, Alona R. Arias-Briones, Madiha Aziz, Seema Hashmi, Khem Chand Moorani, Naureen Akhtar, Muhammad Imran, Farhana Amanullah, Iftikhar Ijaz, Ahad Qayyum, Marta Suarez, Marlene Martinez Pico, Mohammed Shalaby, Nada Kalakattawi, Najlaa Alotaibi, Osama Safder, Sherif Mohamed ElDesoky, Layla Abdullah Basheer, Jameela Abdulaziz Kari, Mya Than, Ng Kar Hui, Bassam Saeed, Hala Wannous, Huda Mazloum, Ghalia Sawaf, Sameh Mabrouk, Anthony Batte, Anthony Batte, Anabella Rebori, Claudia Vieira, Vu Huy Tru, Chisambo Mwaba Collaborative ESPN/ERA Registry and IPNA Registry Participants: D Shtiza, G Mayer, J Kerschbaum, L Buchwinkler, D Kaiser-Feistmantl, S Baiko, O Raikevic-Liachovskaya, A Dudarevich, D Pokrajac, D Roussinov, I Kos, I Jakopcic, J Ivancic, M Ban, Matkovic, M Davidovic, L Lamot, K Vrljičak, A Elia, K Vondrak, K Hommel, Ü Toots, J Helve, P Finne, C Couchoud, M Lassalle, J Hogan, K Krupka, B Höcker, L Pape, B Tönshoff, T Davitaia, G Moustakas, G Reusz, O Horváth, Cs Berecki, A Szabó, T Szabó, O Lakatos, B Gianoglio, I Guzzo, E la Porta, F Paglialonga, C Corrado, E Vidal, E Verrina, A Popova, S Derkevica, V Kuzema, A Jankauskiene, S Rudaitis, V Said-Conti, N Abazi, A Åsberg, AV Reisæter, A Bjerre, A Zurowska, I Zagozdzon, C Mota, JE Esteves, M Abranches, C Gomes, G Mircescu, L Garneata, E Podgoreanu, EA Molchanova, EV Zakharova, AM Andrusev, M Kostić, B Spasojević, M Cvetković, I Gojković, D Paripović, G Miloševski-Lomić, L Podracka, G Kolvek, N Battelino, G Novljan, J Buturovic-Ponikvar, A Alonso Melgar and the Spanish Paediatric Registry, E Maurer, GF Laube, CE Kuehni, P Parvex, S Tschumi, L Mader, S Bakkaloglu, SP Fomina, All the staff of the UK Renal Registry and of the renal units submitting data, and All of the Scottish Renal Registry team. IPDN Registry Participants: Laura Alconcher, Patricia G Vallés , Monica Grossman, Paula Alejandra Coccia, Rosana Salim, Sara Testa, Enrico Verrina, Karel Vondrack, Lorena Sànchez Barbosa, Nikoleta Printza, Constantinos J. Stefanidis, Attila Szabo, Rukshana Shroff, Amrit Kaur, Judith Hayes, Chris Reid, Claus Peter Schmitt, Susanne Schaefer, Julia Thumfart, Lars Pape, Marcus Kemper, Günter Klaus, Rainer Buescher, Sandra Habbig. Funding This study was made possible by a grant provided by IPNA. The ESPN/ERA Registry, providing data from European countries to the IPNA KRT registry, is funded by the European Society of Pediatric Nephrology (ESPN) and the European Renal Association (ERA). Support was also received from ERKNet, the European Reference Network for Rare Kidney Diseases. ERKNet is funded by the European Union within the framework of the EU4Health program (101085068). References Harambat J, van Stralen KJ, Kim JJ, Tizard EJ (2012) Epidemiology of chronic kidney disease in children. Pediatr Nephrol 27(3):363–373 Becherucci F, Roperto RM, Materassi M, Romagnani P (2016) Chronic kidney disease in children. Clin Kidney J 9(4):583–591 Sacca E, Hazza I (2006) Pediatric end-stage renal disease: Single center analysis. Saudi J Kidney Dis Transpl 17(4):581–585 Mong Hiep TT, Janssen F, Ismaili K, Khai Minh D, Vuong Kiet D, Robert A (2008) Etiology and outcome of chronic renal failure in hospitalized children in Ho Chi Minh City, Vietnam. Pediatr Nephrol 23(6):965–970 Asinobi AO, Ademola AD, Ogunkunle OO, Mott SA (2014) Paediatric end-stage renal disease in a tertiary hospital in South West Nigeria. BMC Nephrol 15:25 Warady BA, Chadha V (2007) Chronic kidney disease in children: The global perspective. Pediatr Nephrol 22(12):1999–2009 Ingelfinger JR, Kalantar-Zadeh K, Schaefer F, World Kidney Day Steering Committee (2016) Averting the legacy of kidney disease: Focus on childhood. Indian J Nephrol 26(2):71–76 van Ploos S, Noordzij M, Warady BA, Cano F, Craig JC, Groothoff JW et al (2018) Renal replacement therapy for children throughout the world: The need for a global registry. Pediatr Nephrol 33(5):863–871 International Pediatric Nephrology Association Registry. www.ipna-registry.org [Accessed July 2025] ERA Registry PRD codes. https://www.era-edta-reg.org/en/registry/ [Accessed July 2025] International Pediatric Dialysis Network Registry www.pedpd.org [Accessed July 2025] United States Renal Data System (USRDS) (2018) USRDS annual data report: Volume 2: End-stage renal disease, Chap. 7 Australia and New Zealand Dialysis and Transplant Registry https://www.anzdata.org.au/anzdata / [Accessed July 2025] World Health Organization Indicator Metadata Registry List https://www.who.int/data/metadata [Accessed July 2025] Climate (2024) Change Knowledge Portal. climateknowledgeportal.worldbank.org. World Bank Group. Retrieved 7 May Haas M, Meehan SM, Kagen R, Chang A (2018) Changing etiologies of glomerular disease in the United States: A 10-year review of native kidney biopsies. Nephrol Dial Transpl 33(1):55–63 Larsen CP, Butnor KJ, Ylaya K, Racusen LC (2013) The role of HLA and autoantibodies in the pathogenesis of glomerulonephritis. Nat Rev Nephrol 9(7):395–405 Davidson A, Diamond B (2001) Autoimmune diseases. N Engl J Med 345(5):340–350 Al Sabban E (1997) Spectrum of glomerular disease among children in Saudi Arabia. Saudi J Kidney Dis Transpl 8(3):285–288 Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI et al (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329(5993):841–845 Zhai YH, Xu H, Zhu GH, Wei MJ, Hua BC, Shen Q et al (2007) Efficacy of urine screening at school: Experience in Shanghai, China. Pediatr Nephrol 22(12):2073–2079 Honda K, Akune Y, Goto R (2024) Cost-effectiveness of school urinary screening for early detection of IgA nephropathy in Japan. JAMA Netw Open 7(2):e2356412 Wühl E, van Stralen KJ, Verrina E, Bjerre A, Wanner C, Heaf JG et al (2013) Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract. Clin J Am Soc Nephrol 8(1):67–74 Erickson RL, Kamath N, Iyengar A, Ademola A, Esezobor C, Lalji R et al (2024) Disparities in kidney care in vulnerable populations: A multinational study from the ISN-GKHA. PLOS Glob Public Health 4(12):e0002885 Kamath N, Erickson RL, Hingorani S, Bresolin N, Duzova A, Lungu A et al (2024) Structures, organization, and delivery of kidney care to children living in low-resource settings. Kidney Int Rep 9(7):2084–2095 Cerón A, Fort MP, Morine CM, Lou-Meda R (2014) Chronic kidney disease among children in Guatemala. Rev Panam Salud Publica Dec. 36(6):376–382 Richter-Rodier M, Lange AE, Hinken B, Hofmann M, Stenger RD, Hoffmann W et al (2012) Ultrasound screening strategies for the diagnosis of congenital anomalies of the kidney and urinary tract. Ultraschall Med 33(7):617–623 Schaefer F, Schramm T, Amann K (2018) Genetic testing in pediatric nephrology: When, how, and why? Pediatr Nephrol 33(3):403–412 Krogsbøll LT, Jørgensen KJ, Gøtzsche PC (2015) Screening with urinary dipsticks for reducing morbidity and mortality. Cochrane Database Syst Rev. ;(1):CD010321 Lou-Meda R, Alvarez-Elías AC, Bonilla-Félix M (2022) Mesoamerican Endemic Nephropathy (MeN): A Disease Reported in Adults That May Start Since Childhood? Semin Nephrol 42(5):151337 Supplementary Files SupplementalMaterial.docx Cite Share Download PDF Status: Published Journal Publication published 08 Dec, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Minor Revisions Needed 24 Oct, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviewers invited by journal 20 Aug, 2025 Editor assigned by journal 20 Aug, 2025 First submitted to journal 17 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7393084","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":503152080,"identity":"feb45aa2-1ed9-46e8-ad47-33c05e6f912a","order_by":0,"name":"Dagmara Borzych-Dużałka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYDCCAwwMzAwVYKYBAwMbkGInSssZZC3MxGhhbCNFC9/x4xc/F86rTVzb3ryB4UPZYQZzQlokz+QUS8/cdjxx25ljBYwzzh1msGwmoMXgQE6CNO+2Y4nbbuQYMPO2HWYwOExIy/k3yb955wC13H9jwPyXKC030o9J8zbUAG3hMQCGAxFaJG+8YbOeceyA8bYzaQUHe86l8xD0C9/59Me3C2rqZLcdP7zxwY8yazlz9gYCehh4gNHBAHHMARiXAGB/ACTqEHwitIyCUTAKRsEIAwBfYkxQe6DRLAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-9058-2782","institution":"Department of Pediatrics, Nephrology and Hypertension, Medical University of Gdansk","correspondingAuthor":true,"prefix":"","firstName":"Dagmara","middleName":"","lastName":"Borzych-Dużałka","suffix":""},{"id":503152081,"identity":"9099d23f-d19f-412b-9d56-d953dbca72f5","order_by":1,"name":"Marjolein Bonthuis","email":"","orcid":"","institution":"ERA/EDTA Registry, Department ofMedical Informatics","correspondingAuthor":false,"prefix":"","firstName":"Marjolein","middleName":"","lastName":"Bonthuis","suffix":""},{"id":503152082,"identity":"3f72bda1-fb2a-44b5-8c62-76c17f2823ed","order_by":2,"name":"Uma Ali","email":"","orcid":"","institution":"Lilavati Hospital and Research Centre, Mumbai","correspondingAuthor":false,"prefix":"","firstName":"Uma","middleName":"","lastName":"Ali","suffix":""},{"id":503152083,"identity":"d59260d1-7270-4fad-95ee-856eeae89427","order_by":3,"name":"Yap Yok Chin","email":"","orcid":"","institution":"Hospital Tunku Azizah, Kuala Lumpur","correspondingAuthor":false,"prefix":"","firstName":"Yap","middleName":"Yok","lastName":"Chin","suffix":""},{"id":503152084,"identity":"7ed02ddb-8fff-4e2b-b640-de9f04981791","order_by":4,"name":"Michael Manno","email":"","orcid":"","institution":"Canadian Institution for Health Information (CIHI), Toronto","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Manno","suffix":""},{"id":503152085,"identity":"f1a34062-5bca-46cf-a703-715f9166e465","order_by":5,"name":"Yihui Zhai","email":"","orcid":"","institution":"Children's Hospital of Fudan University, Shanghai","correspondingAuthor":false,"prefix":"","firstName":"Yihui","middleName":"","lastName":"Zhai","suffix":""},{"id":503152086,"identity":"33f670fe-308c-4b0c-b167-962ec1e25887","order_by":6,"name":"Reyner Loza","email":"","orcid":"","institution":"Cayetano Heredia Hospital, Lima","correspondingAuthor":false,"prefix":"","firstName":"Reyner","middleName":"","lastName":"Loza","suffix":""},{"id":503152087,"identity":"c2fd39ea-32bd-404e-b3d4-bc3068971001","order_by":7,"name":"Seema Hashmi","email":"","orcid":"","institution":"Sindh Institute of Urology and Transplantation (SIUT), Karachi","correspondingAuthor":false,"prefix":"","firstName":"Seema","middleName":"","lastName":"Hashmi","suffix":""},{"id":503152088,"identity":"234b97f0-2ff6-40cf-a297-210c7a390362","order_by":8,"name":"Naye Choi","email":"","orcid":"","institution":"Seoul National University College of Medicine, Seoul National University","correspondingAuthor":false,"prefix":"","firstName":"Naye","middleName":"","lastName":"Choi","suffix":""},{"id":503152089,"identity":"ff149db6-d516-4062-b538-3a407e0dcad6","order_by":9,"name":"Kenza Soulami","email":"","orcid":"","institution":"Pediatric Nephrology, Casablanca","correspondingAuthor":false,"prefix":"","firstName":"Kenza","middleName":"","lastName":"Soulami","suffix":""},{"id":503152090,"identity":"0132c589-0ad7-44f5-b656-afdbf5425eb4","order_by":10,"name":"Judith Exantus","email":"","orcid":"","institution":"Faculty of Medicine and Pharmacy, State University of Haiti, Port-Au-Prince","correspondingAuthor":false,"prefix":"","firstName":"Judith","middleName":"","lastName":"Exantus","suffix":""},{"id":503152091,"identity":"34e9ca53-630e-4f3c-83a3-c291dc2e869c","order_by":11,"name":"Mohamed S. Al Riyami","email":"","orcid":"","institution":"The Royal Hospital, Muscat","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"S. Al","lastName":"Riyami","suffix":""},{"id":503152092,"identity":"c9b49c9c-4e32-436a-83f3-564a079c730a","order_by":12,"name":"Sameh Mabrouk","email":"","orcid":"","institution":"Faculty of Medicine Ibn El Jazzar, University of Sousse","correspondingAuthor":false,"prefix":"","firstName":"Sameh","middleName":"","lastName":"Mabrouk","suffix":""},{"id":503152093,"identity":"593ca56e-9ab0-4707-9171-3af365e34592","order_by":13,"name":"Marbella Ma Angeles","email":"","orcid":"","institution":"National Kidney and Transplant Institute","correspondingAuthor":false,"prefix":"","firstName":"Marbella","middleName":"Ma","lastName":"Angeles","suffix":""},{"id":503152094,"identity":"e64e1e10-e235-4112-9c23-a39edba4049b","order_by":14,"name":"Cristina Zelaya-Camacho","email":"","orcid":"","institution":"FUNDANIER - Foundation for Children with Kidney Diseases","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Zelaya-Camacho","suffix":""},{"id":503152095,"identity":"9ba5f34e-0ae8-4d3d-a147-9daee7ba26dd","order_by":15,"name":"Henny Adriani Puspitasari","email":"","orcid":"","institution":"Dr Cipto Mangunkusumo General Hospital, Jakarta","correspondingAuthor":false,"prefix":"","firstName":"Henny","middleName":"Adriani","lastName":"Puspitasari","suffix":""},{"id":503152096,"identity":"2fb77dc1-e3d0-4600-9e32-a87d71008746","order_by":16,"name":"Syed Saimul Huque","email":"","orcid":"","institution":"Bangladesh Medical University, Dhaka","correspondingAuthor":false,"prefix":"","firstName":"Syed","middleName":"Saimul","lastName":"Huque","suffix":""},{"id":503152097,"identity":"37c7b7e7-79cb-407f-848b-42d582b0ac0b","order_by":17,"name":"Francisco Cano","email":"","orcid":"","institution":"Luis Calvo Mackenna Children's Hospital, Santiago","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"","lastName":"Cano","suffix":""},{"id":503152098,"identity":"3eb8aed8-223e-4ef4-a1ec-619d954db5e6","order_by":18,"name":"Kar Hui Ng","email":"","orcid":"","institution":"Yong Loo Lin School of Medicine: National University of Singapore Yong Loo Lin School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kar","middleName":"Hui","lastName":"Ng","suffix":""},{"id":503152099,"identity":"1bfc260c-9b96-4e36-856b-ba52c5a170e6","order_by":19,"name":"Sevcan A Bakkaloglu","email":"","orcid":"","institution":"Gazi University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sevcan","middleName":"A","lastName":"Bakkaloglu","suffix":""},{"id":503152100,"identity":"5adc71a7-da36-439c-b653-35611013d673","order_by":20,"name":"Jerome Harambat","email":"","orcid":"","institution":"Bordeaux University Hospital, Pediatric Nephrology","correspondingAuthor":false,"prefix":"","firstName":"Jerome","middleName":"","lastName":"Harambat","suffix":""},{"id":503152101,"identity":"7b2e0499-0dcf-4053-9000-cd1618e68623","order_by":21,"name":"Kitty J. Jager","email":"","orcid":"","institution":"ESPN/ERA Registry, Department of Medical Informatics, Amsterdam","correspondingAuthor":false,"prefix":"","firstName":"Kitty","middleName":"J.","lastName":"Jager","suffix":""},{"id":503152102,"identity":"7369afba-a57b-4423-b941-2ab0fff74f2d","order_by":22,"name":"Bradley A Warady","email":"","orcid":"","institution":"Children's Mercy: Children's Mercy Kansas City","correspondingAuthor":false,"prefix":"","firstName":"Bradley","middleName":"A","lastName":"Warady","suffix":""},{"id":503152103,"identity":"29a2d73d-4cad-4204-add8-c3b160147c88","order_by":23,"name":"Franz Schaefer","email":"","orcid":"","institution":"Center for Pediatric and Adolescent Medicine, Heidelberg","correspondingAuthor":false,"prefix":"","firstName":"Franz","middleName":"","lastName":"Schaefer","suffix":""}],"badges":[],"createdAt":"2025-08-17 14:53:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7393084/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7393084/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-07096-3","type":"published","date":"2025-12-08T15:58:23+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90542062,"identity":"9027f2da-3179-49ff-a31d-42b3f20d0cb3","added_by":"auto","created_at":"2025-09-03 23:59:44","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":259742,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of primary kidney diseases causing kidney failure by global regions.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/d921a758430a45b2ab7fc13f.jpg"},{"id":90540572,"identity":"8f7a48e5-7259-4075-ab70-59c56b835f85","added_by":"auto","created_at":"2025-09-03 23:51:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":106499,"visible":true,"origin":"","legend":"\u003cp\u003eRelative proportion of glomerular (2a) and hereditary (2b) disorders causing KRT in childhood by country.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/3ed70b92ae49300ac75ca6eb.jpg"},{"id":90540577,"identity":"6af82e01-9803-4fa4-9154-8f7272c55524","added_by":"auto","created_at":"2025-09-03 23:51:44","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":224196,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of glomerular diseases leading to kidney failure by global region.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/a80ee67d3fa62587d8d69425.jpg"},{"id":90540573,"identity":"404c8aeb-a890-474c-9620-8c963f0b94f4","added_by":"auto","created_at":"2025-09-03 23:51:44","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":28897,"visible":true,"origin":"","legend":"\u003cp\u003eFactors associated with proportion of KF primary glomerular diseases as cause of kidney failure per country. \u003cem\u003eLeft panel\u003c/em\u003e: Gross national income (in US$, adjusted per purchasing power parity). \u003cem\u003eRight panel\u003c/em\u003e: Average yearly temperature ((in °C).\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/c65e75b5b32dcf807f068781.jpg"},{"id":90542065,"identity":"9b7694e4-2049-4ccf-a6f9-04414d329343","added_by":"auto","created_at":"2025-09-03 23:59:44","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":133951,"visible":true,"origin":"","legend":"\u003cp\u003ePrimary kidney disease distribution by patient age.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/02118978e7376b9556ab99f3.jpg"},{"id":98243838,"identity":"4e4abcfa-602e-4207-8966-e33546b5bccf","added_by":"auto","created_at":"2025-12-15 16:10:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2232529,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/7f656fd4-30cf-4bb4-830a-e045192cb6ac.pdf"},{"id":90540580,"identity":"96a821aa-2b0f-473e-bbed-e535fdb21340","added_by":"auto","created_at":"2025-09-03 23:51:44","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":30925,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7393084/v1/8aacec5cd38145acbd94a9ed.docx"}],"financialInterests":"","formattedTitle":"Regional variation of underlying kidney diseases in children undergoing chronic kidney replacement therapy around the globe","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe etiologies of pediatric kidney failure (KF) have been extensively studied in high-income regions, particularly in North America, Europe, Japan, and Australia/New Zealand. In these regions, congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of KF, accounting for 30\u0026ndash;60% of cases, followed by glomerular diseases (mainly focal segmental glomerulosclerosis (FSGS)), hereditary diseases including ciliopathies, and systemic conditions like lupus nephritis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMuch less is known about the etiologies of KF in children living in low- and middle-income countries (LMIC). Literature is largely limited to single-center or regional reports, which may not be generalizable [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Some evidence suggests that children in emerging countries may face a higher prevalence of infectious and environmental etiologies, including various forms of post-infectious glomerulonephritis, systemic vasculitis and hemolytic uremic syndrome. Also, congenital obstructive uropathies may go undiagnosed or untreated due to limited access to prenatal imaging and perinatal care [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe lack of systematic data collection is a major barrier to epidemiological research in low- and middle-income countries. According to a worldwide survey performed by IPNA in 2017, national registries for both dialysis and kidney transplantation in children were established in only 51 countries, covering just one third of the global child population [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The lack of systematic monitoring of a large part of the global pediatric population hampers quantitative assessment of the causes of KF, treatment access, management practices and clinical outcomes and slows the development of lifesaving, cost-efficient kidney replacement therapy (KRT) programs in many parts of the globe. To address this critical knowledge gap, the International Pediatric Nephrology Association Kidney Replacement Therapy (IPNA KRT) Registry was established in 2018 as a global registry collecting prospective population-based data on the demographics and etiologies of KF, KRT modality choices and patient and technique outcomes in children. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe aim of the current analysis, combining data from the IPNA KRT Registry, the ESPN/ERA Registry, the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), was to examine and compare the underlying causes of KF in children across diverse global regions. This comparative approach is hoped to enable a better understanding of regional differences in maintenance KRT, highlight disparities in diagnostic patterns and healthcare infrastructure, and inform global strategies for prevention, early detection and management of pediatric KF.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData sources\u003c/h2\u003e\u003cp\u003eData were extracted from the International Pediatric Nephrology Association Kidney Replacement Therapy (IPNA KRT) Registry including ESPN/ERA Registry data (80 countries), the International Pediatric Dialysis Network (IPDN) (7 countries), published information from the United States Renal Data System (USRDS), and the Australian and New Zealand Dialysis and Transplant (ANZDATA) annual reports [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe global IPNA KRT registry collects population-based national data on children receiving either hemodialysis, peritoneal dialysis, or a kidney transplant. Data excerpts are provided by existing national and regional registries. In countries without established registries pediatric KRT centers use an online data entry platform (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.ipna-registry.org\" target=\"_blank\"\u003ewww.ipna-registry.org\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.ipna-registry.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. For the analysis presented here, 38 countries without established national registries used the online data entry system, 29 countries provided data via the ESPN/ERA Registry and 3 extracted data from national registry databases. Primary kidney diseases (PKD) were classified using the ERA-EDTA PKD coding system (Supplemental Table\u0026nbsp;1) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe International Pediatric Dialysis Network (IPDN) Registry collects prospectively clinical data from children commencing maintenance hemodialysis or peritoneal dialysis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The IPDN disease classification system is presented in Supplemental Table\u0026nbsp;1.\u003c/p\u003e\u003cp\u003eFor the IPNA and IPDN registries, the registry protocols were approved by the relevant institutional review boards at each participating center and/or country, in accordance with local requirements. The ESPN/ERA Registry provided data based on a trilateral agreement involving the IPNA registry, the ESPN/ERA Registry, and participating country. Written informed consent from parents or guardians, and patient assent when applicable, were obtained.\u003c/p\u003e\u003cp\u003eFor pediatric patients with KF receiving KRT in the United States data were extracted from the USRDS report [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the US, pediatric nephrologists are required to complete a Centers for Medicare \u0026amp; Medicaid (CMS) Medical Evidence Report containing initial demographic data and follow-up data. The United Network for Organ Sharing (UNOS) collects data on kidney transplantation and is reported in the USRDS database as well. The USRDS kidney diagnoses classification is depicted in Supplemental Table\u0026nbsp;1.\u003c/p\u003e\u003cp\u003eANZDATA is a voluntary database to which patients who reside in Australia or New Zealand and receive chronic KRT are reported through a Web portal [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The ANZDATA kidney disease classification system is shown in Supplemental Table\u0026nbsp;1.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCategorization of disease etiologies\u003c/h3\u003e\n\u003cp\u003eFor this study, PKD were classified into six main disease categories of interest and 10 subcategories: 1\u003cb\u003e) Congenital Anomalies of the Kidney and Urinary Tract\u003c/b\u003e including kidney dysplasia, obstructive uropathy, reflux nephropathy and other CAKUT; \u003cb\u003e2) Immune-mediated glomerulopathies\u003c/b\u003e including primary and secondary glomerulopathies; \u003cb\u003e3) Hereditary/familial nephropathies\u003c/b\u003e including ciliopathies, familiar and syndromic glomerulopathies, hereditary tubulopathies and not further specified familial diseases; \u003cb\u003e4) post-AKI CKD\u003c/b\u003e including thrombotic microangiopathies; \u003cb\u003e5) other\u003c/b\u003e including tubulointerstitial nephritis, hematologic-oncologic and post-traumatic disease; \u003cb\u003e6) unknown\u003c/b\u003e. For a complete list of diseases under each category, please see Supplemental Table\u0026nbsp;1.\u003c/p\u003e\n\u003ch3\u003eRegional and GNI categorization\u003c/h3\u003e\n\u003cp\u003eGeographic regions were defined in accordance with the regional boards of the International Society of Nephrology: Africa, Central Europe, Latin America, Middle East, Russia and Newly Independent States (NIS), North America and the Caribbean, South Asia, Northeast Asia, Southeast Asia, and Western Europe (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Countries were classified as low, low-middle, upper-middle, and high-income countries based on World Word Bank data (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://data.worldbank.org\u003c/span\u003e\u003cspan address=\"https://data.worldbank.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) using quartiles of Gross National Income (GNI) in the calendar year of KRT initiation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCountries by geographic region and number of patients 0\u0026ndash;17 at KRT start per country (N\u0026thinsp;=\u0026thinsp;80) and region (N\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAfrica\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLatin America\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWestern Europe\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEastern and Central Europe\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRussia and Newly Independent States\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eMiddle East\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNortheast Asia\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eSouth Asia\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eSouth-East Asia \u0026amp; Oceania\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003cp\u003eAnd Caribbean\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNo. of patients by region\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;1,201\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;6,033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;3,455\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;1,929\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;1,170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;1,086\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;1710\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;1,571\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;5,227\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNo. of patients per country\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBurkina Faso (7)\u003c/p\u003e\u003cp\u003eEgipt (1)\u003c/p\u003e\u003cp\u003eMarocco (140)\u003c/p\u003e\u003cp\u003eNigeria (4)\u003c/p\u003e\u003cp\u003eTunisia (81)\u003c/p\u003e\u003cp\u003eUganda (1)\u003c/p\u003e\u003cp\u003eZambia (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eArgentina (209)\u003c/p\u003e\u003cp\u003eBolivia (16)\u003c/p\u003e\u003cp\u003eBrazil (171)\u003c/p\u003e\u003cp\u003eChile (235)\u003c/p\u003e\u003cp\u003eColombia (43)\u003c/p\u003e\u003cp\u003eGuatemala (79)\u003c/p\u003e\u003cp\u003eHaiti (11)\u003c/p\u003e\u003cp\u003eMexico (27)\u003c/p\u003e\u003cp\u003eNicaragua (25)\u003c/p\u003e\u003cp\u003ePeru (342)\u003c/p\u003e\u003cp\u003eParaguay (18)\u003c/p\u003e\u003cp\u003eUruguay (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAustria (269)\u003c/p\u003e\u003cp\u003eDenmark (207)\u003c/p\u003e\u003cp\u003eFinland (215)\u003c/p\u003e\u003cp\u003eFrance (2210)\u003c/p\u003e\u003cp\u003eGermany (415)\u003c/p\u003e\u003cp\u003eGreece (63)\u003c/p\u003e\u003cp\u003eIsrael (125)\u003c/p\u003e\u003cp\u003eItaly (222)\u003c/p\u003e\u003cp\u003eMalta (6)\u003c/p\u003e\u003cp\u003eNorway (186)\u003c/p\u003e\u003cp\u003ePortugal (285)\u003c/p\u003e\u003cp\u003eSpain (1218)\u003c/p\u003e\u003cp\u003eSwitzerland (231)\u003c/p\u003e\u003cp\u003eUK (382)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAlbania (33)\u003c/p\u003e\u003cp\u003eBosnia \u0026amp;\u003c/p\u003e\u003cp\u003eHerzegovina (58)\u003c/p\u003e\u003cp\u003eCroatia (112)\u003c/p\u003e\u003cp\u003eBulgaria (77)\u003c/p\u003e\u003cp\u003eCyprus (17)\u003c/p\u003e\u003cp\u003eCzech Rep (104)\u003c/p\u003e\u003cp\u003eEstonia (10)\u003c/p\u003e\u003cp\u003eHungary (49)\u003c/p\u003e\u003cp\u003eLatvia (14)\u003c/p\u003e\u003cp\u003eLithuania (53)\u003c/p\u003e\u003cp\u003eMacedonia (18)\u003c/p\u003e\u003cp\u003ePoland (1111)\u003c/p\u003e\u003cp\u003eRomania (317)\u003c/p\u003e\u003cp\u003eSerbia (126)\u003c/p\u003e\u003cp\u003eSlovenia (42)\u003c/p\u003e\u003cp\u003eSlovakia (107)\u003c/p\u003e\u003cp\u003eTurkey (1207)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eArmenia (14)\u003c/p\u003e\u003cp\u003eBelarus (139)\u003c/p\u003e\u003cp\u003eGeorgia (24)\u003c/p\u003e\u003cp\u003eRussia (1411)\u003c/p\u003e\u003cp\u003eUkraine (341)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eJordan (123)\u003c/p\u003e\u003cp\u003eSyria (214)\u003c/p\u003e\u003cp\u003eIran (622)\u003c/p\u003e\u003cp\u003eLebanon (2)\u003c/p\u003e\u003cp\u003eOman (14)\u003c/p\u003e\u003cp\u003eSaudi Arabia (66)\u003c/p\u003e\u003cp\u003eUnited Arab Emirates (129)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eChina (849)\u003c/p\u003e\u003cp\u003eHong Kong (70)\u003c/p\u003e\u003cp\u003eSouth Korea (167)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eBangladesh (107)\u003c/p\u003e\u003cp\u003eIndia (1230)\u003c/p\u003e\u003cp\u003eSri Lanka (55)\u003c/p\u003e\u003cp\u003ePakistan (317)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eIndonesia (57)\u003c/p\u003e\u003cp\u003eLaos (11)\u003c/p\u003e\u003cp\u003eMalaysia (989)\u003c/p\u003e\u003cp\u003ePhilippines (133)\u003c/p\u003e\u003cp\u003eSingapore (61)\u003c/p\u003e\u003cp\u003eVietnam (8)\u003c/p\u003e\u003cp\u003eAustralia/New Zealand (312)**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eUSA (4162)*\u003c/p\u003e\u003cp\u003eCanada (1038)\u003c/p\u003e\u003cp\u003ePuerto Rico (27)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"11\"\u003e*USRDS data, **ANZDATA\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAverage yearly temperature was calculated by averaging the minimum and maximum daily temperatures in the country, averaged for the years 1991\u0026ndash;2020, from World Bank Group, derived from raw gridded climatologies of the Climatic Research Unit [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eAnalysis dataset\u003c/h3\u003e\n\u003cp\u003eAll reported patients with KF who commenced chronic kidney replacement therapy (KRT) at 0 to 17 years of age were included in the present analysis.\u003c/p\u003e\u003cp\u003ePatient-level data on date of birth, start date of KRT and PKD were extracted from the IPNA and IPDN registries, while age category and PKD were available from the USRDS and ANZDATA reports. The IPNA KRT Registry included incident patients who initiated kidney replacement therapy (KRT) between 1997 and 2025, whereas the IPDN dataset comprised patients who began KRT between 2007 and 2025. The USRDS report included incident KRT patients from 2018 to 2022, while the ANZDATA report covered the period from 2017 to 2022. For a complete list of date of enrolment by region and country, please see Supplemental Table\u0026nbsp;2.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics were used to summarize results as median (interquartile range) for continuous variables and number (%) for categorical variables and analyzed using SAS 9.4. Chi-square tests were used to compare categorical variables such as etiology frequencies across different regions, countries and income groups. Non-linear regression analysis was utilized to evaluate relationships between continuous variables like gross national income per capita, average yearly temperature, and the proportion of specific KF etiologies.\u003c/p\u003e\u003cp\u003eData were analyzed on regional and country-level. For the latter analyses countries with at least 6 patients in a particular category were included. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eRegional Distribution of Kidney Failure Etiologies\u003c/h2\u003e\u003cp\u003eKF etiology was extracted from data of 23,620 children and adolescents aged 0\u0026ndash;17 at KRT initiation, across 80 countries and 10 world regions (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSubjects receiving KRT by diagnostic category and geographic region.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"13\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAfrica\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLatin America\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eWestern Europe\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCentral/ Eastern Europe\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRussia/NIS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMiddle East\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNortheast Asia\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eSouth Asia\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eSouthast Asia, Australia, Oceania\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNorth America\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal N\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cem\u003e23,620\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003e240\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003e1,201\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003e6,033\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003e3,455\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cem\u003e1,929\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cem\u003e1,170\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cem\u003e1,086\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cem\u003e1,709\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cem\u003e1,570\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cem\u003e5,227\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCAKUT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8,250 (35)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e97 (41)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e541 (45)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2,167 (36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1,249 (36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e899 (47)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e418 (36)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e202 (19)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e749 (44)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e401 (25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1,527 (30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKidney dysplasia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e4,089 (50)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e301 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1,283 (59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e418 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e420 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e162 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e160 (79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e320 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e205(51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e782 (51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObstructive uropathy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e2,241 (27)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e128 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e518 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e399 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e284 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e66 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e13 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e209 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e95 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e509 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReflux nephropathy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e1,208 (15)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e280 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e262 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e143 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e82 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e28 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e117 (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e61 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e146 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther CAKUT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e715 (8)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e86 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e170 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e52 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e108 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e103 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e40 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e90 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFamilial/hereditary NP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e4,785 (20)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e60 (25)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e124 (10)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e1,653 (27)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e941 (27)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e426 (22)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e353 (30)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e175 (16)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e276 (16)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e159 (10)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003e618 (12)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCystic kidney disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e2,107 (44)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e63 (51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e691 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e392 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e215 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e147 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e79 (45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e149 (54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e58 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e288 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHereditary and syndromic GP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e1,565 (32)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e411 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e362 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e161 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e122 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e76 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e69 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e81 (51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e227 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTubulopathies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e577 (12)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e169 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e32 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e79 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e18 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e55 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e12 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e80 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamilial unspecified\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e536 (11)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e382 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e92 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e18 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e3 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e8 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e23 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eImmune-mediated GP\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003cp\u003eSystemic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e4,705 (20)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e3,644 (77)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e974 (13)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e30 (13)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e24 (80)\u003c/p\u003e\u003cp\u003e6 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e257 (21)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e184 (72)\u003c/p\u003e\u003cp\u003e73 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e927 (15)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e743 (80)\u003c/p\u003e\u003cp\u003e184 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e402 (12)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e312 (78)\u003c/p\u003e\u003cp\u003e90 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e257 (13)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e218 (85)\u003c/p\u003e\u003cp\u003e39 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e178 (15)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e153 (86)\u003c/p\u003e\u003cp\u003e25 (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e274 (25)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e197 (61)\u003c/p\u003e\u003cp\u003e77 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e361 (21)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e313 (87)\u003c/p\u003e\u003cp\u003e48 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e684 (43)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e496 (83)\u003c/p\u003e\u003cp\u003e101 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003e1,335 (26)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e1004 (75)\u003c/p\u003e\u003cp\u003e331 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePost-AKI (TTP, toxic, Infectious)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTTP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e1,283 (5)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e833 (64)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e10 (4)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e3 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e68 (6)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e58 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e425 (7)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e270 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e159 (5)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e108 (67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e176 (9)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e150 (85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e76 (6)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e53 (69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e38 (4)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e24 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e75 (4)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e44 (59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e38 (2)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e20 (52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003e219 (4)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e103 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOther\u003c/b\u003e (tubulointerstitial, trauma, oncologic, surgical loss)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e1,302 (6)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e4 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e29 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e156 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e79 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e70 (4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e30 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e20 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e57 (3)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e28 (2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003e829 (17)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUnknown/uncertain\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e3,294 (14)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e39 (16)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e182 (15)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e705 (12)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e625 (18)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e101 (5)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003e115 (10)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003e377 (35)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003e191 (11)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003e260 (17)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u003cb\u003e699 (12)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eGlobally, the predominant underlying etiologies of KF were congenital anomalies of the kidney and urinary tract (CAKUT) (35%), hereditary nephropathies (20%), and immune-mediated glomerulopathies (20%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 14% of cases, the cause of KF was reported as unknown.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSignificant regional variation was noted in the relative frequency of acquired glomerulopathies and hereditary disorders. \u003cb\u003eImmune-mediated glomerulopathies\u003c/b\u003e were most prevalent in Southeast Asia, accounting for 43% of pediatric KF cases, in contrast to 12\u0026ndash;15% reported in Europe, Russia/Newly Independent States (NIS), the Middle East, and Africa (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The highest national proportions of glomerular diseases were observed in the Philippines, Laos, and South Korea (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFSGS was the leading glomerular cause of KF, representing 34% of immune-mediated glomerulopathies globally, followed by vasculitis (8.3%) and SLE nephritis (7.7%). The distribution of both primary and secondary glomerular disorders varied notably across regions. While FSGS was the predominant immune-mediated cause of KF in the Middle East (55%), South Asia (47%), North America (39%), and Northeast Asia (38%), its prevalence was considerably lower in Central Europe (14%). Lupus nephritis contributed most significantly to KF in Latin America (14%) and Southeast Asia (10%). IgA nephropathy accounted for 8% of KF cases in Western Europe, compared to only 2\u0026ndash;4% in other regions (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A notably high proportion of cases (25%) were classified as unspecified primary glomerulopathies, with regional variation ranging from 8% in the Middle East to 44% in Russia/NIS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eFamilial and hereditary kidney disorders\u003c/b\u003e (depicted by green shades in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) were most common in the Middle East (30%), Africa (25%), and Europe (27%), and were least frequent in the Americas and Southeast Asia (10\u0026ndash;12%). Finland, Saudi Arabia and Oman reported the highest fractions of hereditary disorders leading to KF (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Across all regions cystic kidney diseases represented the leading hereditary cause of KF (44%), followed by hereditary and syndromic glomerulopathies. Hereditary tubulopathies were notably more prevalent in Africa (38%) and the Middle East (22%); they constituted the most common hereditary disorders in Tunisia (47%) and Pakistan (41%). Primary hyperoxaluria emerged as the predominant hereditary disorder leading to KF in these countries, accounting for 8 out of 9 cases in Tunisia and 72% of hereditary disorders in Pakistan.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCAKUT\u003c/b\u003e disorders were the leading cause of KF in all regions except in North and Southeast Asia, where they accounted for only 19% and 25% of cases, respectively. Isolated kidney dysplasia was consistently reported as the most frequent form of CAKUT, comprising 35\u0026ndash;60% of cases in most regions, and reaching up to 80% in Northeast Asia. In this latter region, obstructive uropathy was notably less common (6%) than in other areas (16\u0026ndash;33%).\u003c/p\u003e\u003cp\u003eConsiderable variation was also observed in the proportion of KF cases with \u003cb\u003eunknown etiology\u003c/b\u003e, which constituted 14% overall. This category was more prevalent in Northeast Asia, driven primarily by a high fraction of unexplained cases in China (41%). In Latin America, Guatemala stood out with 73% and Nicaragua with 56% unexplained cases.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eFactors associated with Primary Kidney Disease (PKD) distribution\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eGross National Income\u003c/h2\u003e\u003cp\u003eOf the total cohort, 476 patients (2%) originated from low-income countries (LIC), 2,597 (11%) from low-middle-income countries (LMIC), 7,086 (30%) from high-middle-income countries (HMIC), and 13,461 (57%) from high-income countries (HIC). Significant differences were observed in the relative frequency of acquired immune-mediated glomerulopathies, which accounted for 43% of diagnoses in LIC as compared to 15% in countries with higher national incomes (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Country-based comparison revealed a negative correlation between the fraction of immune-mediated glomerulopathies relative to all diagnoses and gross national income per capita (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eAverage yearly temperature\u003c/h2\u003e\u003cp\u003eThe reporting countries represented all climate zones with average yearly temperatures ranging from \u0026minus;\u0026thinsp;4.0\u0026deg;C in Canada to 30.4\u0026deg;C in Burkina Faso. The average temperature was positively correlated with the fraction of immune-mediated glomerulopathies among all reported diagnoses per country (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), whereas the frequency of IgA nephropathy was inversely correlated with temperature. None of the other diagnosis groups showed associations with ambient temperature.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003ePatient age\u003c/h2\u003e\u003cp\u003eThe distribution of KF etiologies by age group largely reflected the manifestation age and natural history of the diseases. CAKUT and hereditary nephropathies predominated among younger children, whereas immune-mediated glomerulopathies were more common in adolescents (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Post-ischemic CKD was observed to be twice as prevalent in children under five years of age compared to their older counterparts. \u0026ldquo;Unknown\u0026rdquo; and \u0026ldquo;other\u0026rdquo; causes of KF were most frequently reported in adolescent patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study presents the first global, population-based comparative analysis of the disease spectrum leading to KF in childhood, leveraging registry data from multiple countries across all continents. Our investigation revealed substantial regional heterogeneity in disease distribution.\u003c/p\u003e\u003cp\u003eThe most pronounced variation in disease occurrence was identified for \u003cb\u003eimmune-mediated glomerulopathies\u003c/b\u003e, which was a much less frequent cause of KF in Europe and Africa than in Asia and the Americas. The observed regional variation of glomerular disease etiologies is in keeping with findings of the International Kidney Biopsy Survey [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In an analysis of more than 42,000 mostly adult cases, FSGS predominated in North America, SLE nephritis in Asia and Latin America, and IgA nephropathy in Europe and Asia.\u003c/p\u003e\u003cp\u003eThe high proportion of glomerular disorders particularly in Southeast Asia and parts of Latin America may be attributable to both genetic and environmental conditions. Genetic susceptibility to autoimmune conditions is known to vary by ethnicity. HLA variants enhancing autoantibody activity are more prevalent among Hispanic and Asian populations, which may exacerbate disease severity and accelerate progression to KF [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In addition, the high burden of bacterial, viral, and parasitic infections in regions characterized by hot and humid climatic conditions may trigger autoimmune disorders independently of genetic predisposition [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Indeed, we observed a significant association of the country-specific fraction of pediatric KF cases caused by primary glomerulonephritis with the average annual temperature.\u003c/p\u003e\u003cp\u003eFurthermore, limited healthcare resources may impact the risk of progression to KF of patients with treatable acquired glomerular conditions more than those with congenital and hereditary kidney disorders. In line with this notion, glomerular diseases were found to be 2.5-fold overrepresented as KF causes in low-income as compared to high- and upper-middle-income countries. Poor access to specialized care and effective treatment may contribute to this association, although confounding by correlated environmental conditions is likely.\u003c/p\u003e\u003cp\u003eNotably, the highest prevalence of \u003cb\u003eFSGS\u003c/b\u003e was reported in the Middle East. This finding is in keeping with a biopsy study in 376 Saudi Arabian children, where FSGS accounted for 32% of cases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Given the high incidence of hereditary diseases in this region, it is likely that a major proportion of FSGS cases were not related to immune pathology but represented undiagnosed genetic podocytopathies. Likewise, the high FSGS prevalence reported for North America is likely due to African American patients who frequently harbor high-risk APOL1 gene variants predisposing to FSGS and accelerated decline of kidney function [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe proportion of patients with KF due to \u003cb\u003eIgA nephropathy\u003c/b\u003e was higher in Europe than East Asia, even though individuals of both East Asian and European descent are susceptible to IgA nephropathy. This discrepancy may reflect the widespread implementation of urinary screening programs in Eastern Asia, which has been demonstrated to cost-effectively reduce the incidence of KF among patients with IgA nephropathy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHereditary, familial, and syndromic \u003cb\u003ekidney diseases of genetic origin\u003c/b\u003e were most prevalent in the Middle East and North Africa, most likely reflecting cultural factors such as high rates of parental consanguinity common within Islamic societies. The relatively elevated frequency of genetic disorders reported by European centers may be attributed to broad access to advanced genetic diagnostics as well as the presence of large migrant populations, particularly from North Africa and the Middle East.\u003c/p\u003e\u003cp\u003eWhile \u003cb\u003eCAKUT\u003c/b\u003e was the leading cause of pediatric KF globally, its relative prevalence exhibited marked regional variation, ranging from 18% in Northeast Asia to 46\u0026ndash;47% in Latin America and Russia/NIS. Stratification by income level indicates that CAKUT is the predominant diagnosis in low-middle-income countries (LMICs), accounting for 55% of KF cases, compared to 45% in higher-income settings. Early diagnosis of CAKUT allows effective renoprotective management including prompt urological intervention, adequate fluid intake, prevention of urinary tract infections, and pharmacological RAS blockade. Data from high-income European countries indicate that 50% of children diagnosed with CAKUT do not require KRT within the first 30 years of life [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In contrast, access to early diagnosis and therapeutic interventions may be more limited in LMICs, resulting in faster progression and a higher fraction of children on KRT in these countries. The relatively low proportion of CAKUT cases reported in the lowest income group may reflect elevated mortality rates associated with missed or late diagnosis. Additionally, limited healthcare infrastructure, insufficient government policies, and shortages of pediatric nephrologists substantially restrict access to KRT in low-income settings particularly for infants, resulting in markedly reduced treatment rates [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In a recent study, the proportion of infants initiating KRT ranged from 1\u0026ndash;2% in Asia and Africa to 12% in Western Europe [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNotably, a considerable proportion of KF cases across all regions and national income levels were of \u003cb\u003eunknown etiology\u003c/b\u003e. High rates of KF patients with unidentified etiology likely reflect the often asymptomatic progression of CKD to advanced stages, compounded by global inequities in nephrology care and delayed referrals to specialized care [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The observation also may indicate significant gaps in current diagnostic capabilities and variability in the extent of diagnostic workup across countries. Several measures could be cost-efficient in improving the timely detection of CKD in children. The existence of fetal and neonatal ultrasound programs is key to the early detection of CAKUT cases [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Routine implementation of genetic testing has been shown to clarify the underlying disease in up to 40% of pediatric KF cases and enhance clinical management [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Urine dipstick screening is an inexpensive and efficient tool for early detection of glomerular disorders which, given the availability of effective therapies, may justify the introduction of national screening programs in countries with a high incidence of glomerular diseases leading to KF [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In some circumstances, regional clustering of kidney failure from unknown etiology might be related to unidentified environmental factors. This is exemplified by the high proportion of patients with unknown etiology reported for Guatemala and Nicaragua, countries that represent a hotspot of Mesoamerican Endemic Nephropathy, a condition assumed to be related to an unidentified environmental toxin or infectious agent [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].`\u003c/p\u003e\u003cp\u003eSeveral limitations inherent to this study warrant consideration. Data collection methodologies varied, with some regions contributing data from national registries and others from individual centers. Participation in the IPDN registry and the web-based part of the IPNA registry is voluntary, introducing potential selection bias. Globally, regions lacking resources for registry documentation are underrepresented in this analysis. Also, the classification of regions according to the ISN regional boards may have oversimplified the ethnic composition and macroeconomic conditions within specific geographic areas. Furthermore, regional differences in kidney biopsy indication policies might have biased the reported disease etiologies. Finally, access to KRT may vary by age and underlying disease, particularly in low-resource environments. Consequently, the underlying diseases of neonates, young infants and patients with severe syndromic disorders who were not accepted for KRT may have been regionally underrepresented as causes of KF. Variable representation of the youngest, CAKUT-predominant age group would impact reciprocally on the calculated regional proportions of underlying kidney diseases.\u003c/p\u003e\u003cp\u003eDespite these limitations, this study provides valuable insights that may inform future CKD screening programs, guide national healthcare resource allocation and disease management and help prioritize target regions for clinical trials. The study\u0026rsquo;s strengths include its large, diverse dataset encompassing multiple countries and regions. Future enhancements to the registry could incorporate detailed biopsy data, biomarker analyses, genetic testing results, and comprehensive individual-level socioeconomic and healthcare access information.\u003c/p\u003e\u003cp\u003eIn conclusion, significant global variation exists in the etiologies of pediatric KF, influenced by geographic, ethnic, genetic, and socioeconomic factors. A substantial proportion of KF cases remain unexplained, even in high-income countries, underscoring persistent gaps in early detection of pediatric kidney disease worldwide. The IPNA pediatric KRT registry establishes a foundation for life-course epidemiological studies aimed at identifying at-risk populations and enhancing early diagnosis and management strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the patients, their parents, and the staff of all the dialysis and transplant units who have contributed data via their national registries and contact persons, who are listed as Collaborators.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCollaborators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIPNA Registry Participants:\u003c/em\u003e Hazem Awad, Loai Akram Eid, Eihab Al Khasawneh, Gurinder Kumar, Watfa Shahwan Al Dhaheri, Helen Nazaryan, Maria Laura Beaudoin, Saimul Haque, Azmeri Sultana, Gerard Coulibaly, Claudia Gorena, Reyna Callisaya, Clotilde Garcia, Oreste Ferra Neto, Francisco Cano, Hong Xu, Shenqian Jing, Yihui Zhai, Eugene Chan, Richard Baquero Rodriguez, Hesham Safouh, Tinatin Davitaia, Maria Lipka, Cristina Zelaya, Judith Exantus, Henny Adriani Puspitasari, Choni Rinat, Vardit Peles, Aditi Sinha, Alpana Ohri, Kumar Manish, Manoj Matnani, Saumil \u0026nbsp; Gaur, Sushmita Banerji, Jyoti Sharma, Suprita Kalra, Susan Uthup, Nivedita Kamath, Uma Ali, Amol Mbdave, Swati Bhardwaj, Neha Agarwal, Mehul Shah, Puneet Singh, Aliza Mittal, Sukanya Govindan, Pankaj Deshpande, Indira Agarwal, Vaibhav Keskar, Sudha Ekambaram, Sukanya Govindan, Satya Prasad VVR, \u0026nbsp;Koushal Kumar Khajuria, Kinnari Vala, Kalaivani Ganesan, Kalaivani Ganesan, Subal Pradhan, Nakysa Hooman, Afshin Safaie Asl, Hamidreza Badeli, Hadi Sorkhi, Hamid Mohamadjafari, Ahmadali Nikibakhsh, Ali Derakhshan, Mitra Basiratnia, Masoumeh Mohkam, Mostafa Sharifian Dorcheh, Nasrin Esfandiar, Seyyed Mohammad Taghi Hosseini Tabatabaei, Daryoush Fahimi, Fahimeh Askarian, Mastaneh Moghtaderi, Neamatollah Ataei, Seyed Taher Esfahani, Nahid Mamizadeh, Parsa Yousefichaijan, Rama Naghshizadian, Anoush Azarfar, Fatemeh Ghane Sharbaf, Saeideh Parvaresh, Ehsan Valavi, Mojgan Mazaheri, Mohammad Reza Razavi, Mohsen Akhavan Sepahi, Hossein Emad Momtaz, Abolhassan Seyedzadeh, Simin Sadeghi Bojd, Maryam Esteghamati, Banafsheh Arad, Mahmood Maleknejad, Masoudeh Sabzechian, Alaleh Gheissari, Zahra Noparast, Reham Al Mardini, Ghazi Mohamad Al-Salaita, Hee Gyung Kang, Philavanh Kedsadtha, Aoun Bilal, Sami Sanjad, Umeshi Karu, Kenza Soulami, Yap Yok Chin, Adebowale Ademola, Mohamed Alriyami, Reyner Loza, Marbella Angeles, Alona R. Arias-Briones, Madiha Aziz, Seema Hashmi, Khem Chand Moorani, Naureen Akhtar, Muhammad Imran, Farhana Amanullah, \u0026nbsp; Iftikhar Ijaz, Ahad Qayyum, \u0026nbsp;Marta Suarez, Marlene Martinez Pico, Mohammed Shalaby, Nada Kalakattawi, Najlaa Alotaibi, Osama Safder, Sherif Mohamed ElDesoky, Layla Abdullah Basheer, Jameela Abdulaziz Kari, Mya Than, Ng Kar Hui, Bassam Saeed, Hala Wannous, Huda Mazloum, Ghalia Sawaf, Sameh Mabrouk, Anthony Batte, Anthony Batte, Anabella Rebori, Claudia Vieira, Vu Huy Tru, Chisambo Mwaba\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCollaborative ESPN/ERA Registry and IPNA Registry Participants:\u003c/em\u003eD Shtiza, G Mayer, J Kerschbaum, L Buchwinkler, D Kaiser-Feistmantl, S Baiko, O Raikevic-Liachovskaya, A Dudarevich, D Pokrajac, D Roussinov, I Kos, I Jakopcic, J Ivancic, M Ban, Matkovic, M Davidovic, L Lamot, K Vrljičak, A Elia, K Vondrak, K Hommel, Ü Toots, J Helve, P Finne, C Couchoud, M Lassalle, J Hogan, K Krupka, B Höcker, L Pape, B Tönshoff, T Davitaia, G Moustakas, G Reusz, O Horváth, Cs Berecki, A Szabó, T Szabó, O Lakatos, B Gianoglio, I Guzzo, E la Porta, F Paglialonga, C Corrado, E Vidal, E Verrina, A Popova, S Derkevica, V Kuzema, A Jankauskiene, S Rudaitis, V Said-Conti, N Abazi, A Åsberg, AV Reisæter, A Bjerre, A Zurowska, I Zagozdzon, C Mota, JE Esteves, M Abranches, C Gomes, G Mircescu, L Garneata, E Podgoreanu, EA Molchanova, EV Zakharova, AM Andrusev, M Kostić, B Spasojević, M Cvetković, I Gojković, D Paripović, G Miloševski-Lomić, L Podracka, G Kolvek, N Battelino, G Novljan, J Buturovic-Ponikvar, A Alonso Melgar and the Spanish Paediatric Registry, E Maurer, GF Laube, CE Kuehni, P Parvex, S Tschumi, L Mader, S Bakkaloglu, SP Fomina, All the staff of the UK Renal Registry and of the renal units submitting data, and All of the Scottish Renal Registry team.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIPDN Registry Participants:\u003c/em\u003e Laura Alconcher, Patricia G Vallés , Monica Grossman, Paula Alejandra Coccia, Rosana Salim, Sara Testa, Enrico Verrina, Karel Vondrack, Lorena Sànchez Barbosa, Nikoleta Printza, Constantinos J. Stefanidis, Attila Szabo, Rukshana Shroff, Amrit Kaur, Judith Hayes, Chris Reid, Claus Peter Schmitt, Susanne Schaefer, Julia Thumfart, Lars Pape, Marcus Kemper, Günter Klaus, Rainer Buescher, Sandra Habbig.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was made possible by a grant provided by IPNA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe ESPN/ERA Registry, providing data from European countries to the IPNA KRT registry, is funded by the European Society of Pediatric Nephrology (ESPN) and the European Renal Association (ERA).\u003c/p\u003e\n\u003cp\u003eSupport was also received from ERKNet, the European Reference Network for Rare Kidney Diseases. ERKNet is funded by the European Union within the framework of the EU4Health program (101085068).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHarambat J, van Stralen KJ, Kim JJ, Tizard EJ (2012) Epidemiology of chronic kidney disease in children. Pediatr Nephrol 27(3):363\u0026ndash;373\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBecherucci F, Roperto RM, Materassi M, Romagnani P (2016) Chronic kidney disease in children. Clin Kidney J 9(4):583\u0026ndash;591\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSacca E, Hazza I (2006) Pediatric end-stage renal disease: Single center analysis. Saudi J Kidney Dis Transpl 17(4):581\u0026ndash;585\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMong Hiep TT, Janssen F, Ismaili K, Khai Minh D, Vuong Kiet D, Robert A (2008) Etiology and outcome of chronic renal failure in hospitalized children in Ho Chi Minh City, Vietnam. Pediatr Nephrol 23(6):965\u0026ndash;970\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAsinobi AO, Ademola AD, Ogunkunle OO, Mott SA (2014) Paediatric end-stage renal disease in a tertiary hospital in South West Nigeria. BMC Nephrol 15:25\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWarady BA, Chadha V (2007) Chronic kidney disease in children: The global perspective. Pediatr Nephrol 22(12):1999\u0026ndash;2009\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIngelfinger JR, Kalantar-Zadeh K, Schaefer F, World Kidney Day Steering Committee (2016) Averting the legacy of kidney disease: Focus on childhood. Indian J Nephrol 26(2):71\u0026ndash;76\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Ploos S, Noordzij M, Warady BA, Cano F, Craig JC, Groothoff JW et al (2018) Renal replacement therapy for children throughout the world: The need for a global registry. Pediatr Nephrol 33(5):863\u0026ndash;871\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInternational Pediatric Nephrology Association Registry. www.ipna-registry.org [Accessed July 2025]\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eERA Registry PRD codes. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.era-edta-reg.org/en/registry/\u003c/span\u003e\u003cspan address=\"https://www.era-edta-reg.org/en/registry/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed July 2025]\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInternational Pediatric Dialysis Network Registry www.pedpd.org [Accessed July 2025]\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUnited States Renal Data System (USRDS) (2018) USRDS annual data report: Volume 2: End-stage renal disease, Chap. 7\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAustralia and New Zealand Dialysis and Transplant Registry \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.anzdata.org.au/anzdata\u003c/span\u003e\u003cspan address=\"https://www.anzdata.org.au/anzdata\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e/ [Accessed July 2025]\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization Indicator Metadata Registry List \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/data/metadata\u003c/span\u003e\u003cspan address=\"https://www.who.int/data/metadata\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e [Accessed July 2025]\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClimate (2024) Change Knowledge Portal. climateknowledgeportal.worldbank.org. World Bank Group. Retrieved 7 May\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHaas M, Meehan SM, Kagen R, Chang A (2018) Changing etiologies of glomerular disease in the United States: A 10-year review of native kidney biopsies. Nephrol Dial Transpl 33(1):55\u0026ndash;63\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLarsen CP, Butnor KJ, Ylaya K, Racusen LC (2013) The role of HLA and autoantibodies in the pathogenesis of glomerulonephritis. Nat Rev Nephrol 9(7):395\u0026ndash;405\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDavidson A, Diamond B (2001) Autoimmune diseases. N Engl J Med 345(5):340\u0026ndash;350\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl Sabban E (1997) Spectrum of glomerular disease among children in Saudi Arabia. Saudi J Kidney Dis Transpl 8(3):285\u0026ndash;288\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGenovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI et al (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329(5993):841\u0026ndash;845\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhai YH, Xu H, Zhu GH, Wei MJ, Hua BC, Shen Q et al (2007) Efficacy of urine screening at school: Experience in Shanghai, China. Pediatr Nephrol 22(12):2073\u0026ndash;2079\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHonda K, Akune Y, Goto R (2024) Cost-effectiveness of school urinary screening for early detection of IgA nephropathy in Japan. JAMA Netw Open 7(2):e2356412\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eW\u0026uuml;hl E, van Stralen KJ, Verrina E, Bjerre A, Wanner C, Heaf JG et al (2013) Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract. Clin J Am Soc Nephrol 8(1):67\u0026ndash;74\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eErickson RL, Kamath N, Iyengar A, Ademola A, Esezobor C, Lalji R et al (2024) Disparities in kidney care in vulnerable populations: A multinational study from the ISN-GKHA. PLOS Glob Public Health 4(12):e0002885\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKamath N, Erickson RL, Hingorani S, Bresolin N, Duzova A, Lungu A et al (2024) Structures, organization, and delivery of kidney care to children living in low-resource settings. Kidney Int Rep 9(7):2084\u0026ndash;2095\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCer\u0026oacute;n A, Fort MP, Morine CM, Lou-Meda R (2014) Chronic kidney disease among children in Guatemala. Rev Panam Salud Publica Dec. 36(6):376\u0026ndash;382\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRichter-Rodier M, Lange AE, Hinken B, Hofmann M, Stenger RD, Hoffmann W et al (2012) Ultrasound screening strategies for the diagnosis of congenital anomalies of the kidney and urinary tract. Ultraschall Med 33(7):617\u0026ndash;623\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchaefer F, Schramm T, Amann K (2018) Genetic testing in pediatric nephrology: When, how, and why? Pediatr Nephrol 33(3):403\u0026ndash;412\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKrogsb\u0026oslash;ll LT, J\u0026oslash;rgensen KJ, G\u0026oslash;tzsche PC (2015) Screening with urinary dipsticks for reducing morbidity and mortality. Cochrane Database Syst Rev. ;(1):CD010321\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLou-Meda R, Alvarez-El\u0026iacute;as AC, Bonilla-F\u0026eacute;lix M (2022) Mesoamerican Endemic Nephropathy (MeN): A Disease Reported in Adults That May Start Since Childhood? Semin Nephrol 42(5):151337\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Primary Kidney Disease, Kidney Failure, children, regional variation","lastPublishedDoi":"10.21203/rs.3.rs-7393084/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7393084/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThere is a scarcity of demographic information regarding the distribution of the diseases leading to kidney failure (KF) in children living in the emerging world. We used data from international, regional and national registries to provide a global overview of the underlying disease spectrum in children commencing kidney replacement therapy (KRT).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe analyzed KF causes among 23,620 children and adolescents commencing maintenance KRT in 80 countries, using data from the IPNA Global KRT Registry (including ESPN/ERA Registry), the International Pediatric Dialysis Network (IPDN), the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The analysis considered geographic region, country-level gross national income (GNI), average annual temperature, and patient age.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMarked regional differences were observed in the distribution of KF causes. Immune-mediated glomerulopathies (GP) were most common in Southeast Asia, hereditary nephropathies in the Middle East, Africa, and Europe, and systemic GP in Northeast Asia and Latin America. In 14% of cases the cause of KF was unknown, with the highest proportion in Northeast Asia. Disease patterns were also influenced by the countries\u0026rsquo; GNI and average yearly temperature; immune-mediated GP accounted for 43% of diagnoses in low-income countries and were more frequent in warmer climates. Among younger children, congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies were the predominant cause of KF, whereas adolescents more commonly presented with immune-mediated GP.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThere is significant global variability in the spectrum of diseases leading to pediatric KF, which is partially attributable to genetic, environmental, and macroeconomic factors.\u003c/p\u003e","manuscriptTitle":"Regional variation of underlying kidney diseases in children undergoing chronic kidney replacement therapy around the globe","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-03 23:51:39","doi":"10.21203/rs.3.rs-7393084/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor Revisions Needed","date":"2025-10-24T12:36:20+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-08-25T06:03:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-20T13:33:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-20T08:12:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-08-17T10:53:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f5e81fd0-9408-4483-95bb-e3a8ef3375af","owner":[],"postedDate":"September 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:03:18+00:00","versionOfRecord":{"articleIdentity":"rs-7393084","link":"https://doi.org/10.1007/s00467-025-07096-3","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-12-08 15:58:23","publishedOnDateReadable":"December 8th, 2025"},"versionCreatedAt":"2025-09-03 23:51:39","video":"","vorDoi":"10.1007/s00467-025-07096-3","vorDoiUrl":"https://doi.org/10.1007/s00467-025-07096-3","workflowStages":[]},"version":"v1","identity":"rs-7393084","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7393084","identity":"rs-7393084","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}