BACKGROUND:Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis, growth failure nephrocalcinosis, nephrolithiasis and chronic kidney disease (CKD). Previous retrospective data suggested improved outcome with adequate metabolic control, but confirmation from prospective data is lacking. Since 2019, the European dRTA registry has collected prospective data on patients with dRTA. Herein we present results of the first data analysis. METHODS:The registry is hosted as a subregistry of the European Rare Kidney Disease Network (www.ERKnet.org). In addition to the standard items of growth and plasma creatinine, additional data on plasma and urine biochemistries, genetics, treatment and clinical manifestations were collected from February 2019 through May 2024. Logistic regression analysis was used to identify predictors of CKD and impairedgrowth. RESULTS:Of the 214 patients enrolled in the registry, only 22% were >18 years at the last visit. A genetic cause was documented in 69% of patients.On average, low blood bicarbonate levels (<22 mmol/L) and hypercalciuria were observed in 42% and 25% of patients, respectively, independently from age. Multivariable analysis showed that height standard deviation score (SDS) was positively associated with serum bicarbonate levels (p=0.008) and with early diagnosis (p=0.005). Further modelling based on odds ratios indicated that height SDS increased progressively with serum bicarbonate levels until they reached 22-24 mmol/L. Patients aged >30 years had significantly lower eGFR (p<0.001) and the overall prevalence of CKD ≥stage 2 was 36%. Patients with SLC4A1 variants were at higher risk of CKD>1 (p=0.013). CONCLUSION:Our results in this primarily paediatric cohort highlight the importance of metabolic control and support increasing the blood bicarbonate level for therapy to 24 mmol/L to improve growth. Compared to the overall population, patients with dRTA are at higher risk of CKD from childhood, particularly if they have underlying SLC4A1 variants.

Subspecialty recognition and certification in Pediatric Nephrology remain heterogeneous across Europe and globally, resulting in variations in training standards and professional mobility. To address this gap, the European Society for Paediatric Nephrology (ESPN) launched the European Board Certification in 2020 as a pan-European and curriculum-based assessment of knowledge and clinical reasoning in Pediatric Nephrology. We performed a descriptive and analytical evaluation of candidates who applied for the ESPN Board Certification in Pediatric Nephrology between 2020 and 2025. Candidate characteristics, examination performance, and factors associated with success were analyzed. The exam consisted of 100 case-based multiple-choice questions developed according to a predefined blueprint. Multivariable logistic regression was used to identify factors independently associated with passing. Additionally, a cross-sectional survey assessed candidates’ perceptions of the examination and its professional impact. A total of 349 pediatric nephrologists from 52 countries and four continents completed the examination. Median age was 38.2 years (IQR 34.7–43.5), and 59.9

Non-communicable diseases, such as chronic kidney disease (CKD), are becoming increasingly prevalent worldwide. Genetic factors, including apolipoprotein L1 (APOL1) risk variants (G1 and G2), have been identified as modifiers for the development and progression of CKD, particularly predisposing individuals of African descent to kidney disease. Identifying these risk variants is therefore crucial for enabling early preventative measures and effective disease monitoring. However, current clinical methods for APOL1 genotyping are costly and require advanced technical expertise and equipment, which are often unavailable in low-income countries. To address this gap, this study developed and validated a simple, cost-effective multiplex allele-specific polymerase chain reaction assay for detecting APOL1 risk variants. The assay demonstrated a 96% concordance with Sanger sequencing, confirming its reliability and diagnostic potential as a practical alternative for APOL1 genotyping in low-resource settings.

Early diagnosis of cystinosis is critical to limit disease progression. YKL-40, a protein in the chitinase family, released by inflammatory cells, may be a useful biomarker for cystinosis. In a case-control study of 10 children with cystinosis and 20 without cystinosis, matched by age and baseline eGFR, we measured urine YKL-40, NGAL, and EGF. A lateral flow device (LFD) for YKL-40 was also developed and tested. Urine YKL-40 was over 200-fold higher in children with cystinosis (64.6 ng/mL [IQR: 23.4, 83.8]) compared with controls (0.3 [IQR: 0.3, 0.79]; P = 0.0001) with excellent diagnostic discrimination (AUC = 0.99) that was superior to other biomarkers. LFD measurements for YKL-40 showed similar results (AUC = 0.93). YKL-40 results were verified in 5 cystinosis patients, and YKL-40 staining was markedly higher in kidney biopsies from cystinosis patients than in healthy controls. Urine YKL-40 has excellent diagnostic potential for cystinosis, and point-of-care technologies may facilitate early screening and management of this disease.

Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in CTNS, which encodes cystinosin, a H+/cystine symporter that mediates cystine efflux from lysosomes. Defective cystinosin leads to accumulation of cystine in lysosomes and the formation of cystine crystals in most tissues. In its more severe and frequent form, infantile nephropathic cystinosis, patients present with renal Fanconi syndrome in the first 2 years of life, which progresses to chronic kidney disease. Since the 1970s, cysteamine therapy and improvements in dialysis and transplantation have substantially improved patient outcomes, and currently most patients survive into adulthood. Consequently, the diagnosis and management of extra-renal complications that develop later in life have become increasingly important. In addition to the kidneys, commonly affected organs include the eyes, the musculoskeletal system, the central nervous system, exocrine glands and endocrine organs. Cystinosis therefore requires integrated care that involves multiple medical specialties and a structured transition plan from paediatric to adult care. Herein, we present evidence-based and expert opinion-based clinical practice recommendations, developed by a team of international specialists and patient representatives following the GRADE methodology, to improve the diagnosis and management of cystinosis in children and adults.

Urinary screening is a useful and non-invasive tool for identifying occult kidney disease in asymptomatic children and may be an important initial step in preventing progressive kidney disease. However, this screening is not commonly performed in children living in low-resource countries, including the Democratic Republic of the Congo (DRC). This study aimed to determine the prevalence of albuminuria and its associated factors among healthy school children living in DRC. In addition, the study examined the prevalence of urinary abnormalities detected by dipstick in this population. This cross-sectional study was conducted in 17 schools in Kinshasa. A multistage sampling procedure was applied, and 497 healthy school children aged 6 to 16 were randomly recruited. Anthropometric and clinical data were collected. Using a single-sample measurement, urinary albumin-to-creatinine ratio (ACR) was determined by an immunoturbidimetric method, and dipstick tests were performed to detect other urinary abnormalities (leukocyturia, nitrituria, proteinuria, hematuria). Albuminuria was defined as ACR ≥ 30 mg/g. Logistic regression was used to identify clinical factors associated with albuminuria. Among the 497 school children (208 boys and 289 girls), 58 had single-sample albuminuria, corresponding to a prevalence of 11.7

OBJECTIVE:X-linked hypophosphataemia (XLH) is a rare genetic disorder characterised by defective bone and tooth mineralisation. Burosumab is a recombinant, human, anti-fibroblast growth factor 23 monoclonal antibody approved for treating XLH. Due to the rarity of the disease, additional safety data for the treatment of XLH with burosumab are required. DESIGN:A post-authorisation safety study analysis of data for paediatric participants from the International X-linked Hypophosphataemia Registry. This study included standard diagnostic and monitoring clinical data at participating centres, regardless of treatment. METHODS:This was a second interim analysis performed 5 years after study initiation in the paediatric population. Primary objectives assessed safety outcomes in children and adolescents with XLH. The secondary objective compared safety outcomes with burosumab vs phosphate and/or active vitamin D. RESULTS:In total, 340 participants were treated with ≥1 dose of burosumab, and 91 were treated with phosphate and/or active vitamin D. Overall, 37.4% and 22.0% of participants in the burosumab or phosphate and/or active vitamin D cohorts, respectively, experienced ≥1 adverse event. The proportions of participants with events were similar among children and adolescents. Forty-nine (14.4%) participants reported events possibly/probably related to burosumab. No events led to the withdrawal of burosumab. In both cohorts, no serious adverse events were considered related to treatment, and there were no deaths. Hospitalisations occurred in ∼71% of participants. Hyperphosphataemia, elevated parathyroid hormone, and ectopic mineralisation events were rare. CONCLUSIONS:The safety profile of burosumab was consistent with previous studies, and no new safety concerns were reported for children or adolescents.

INTRODUCTION:Ischemia-reperfusion injury remains a critical determinant of graft outcomes in kidney transplantation, contributing to delayed graft function and reduced long-term survival. Machine perfusion has emerged as a dynamic preservation strategy offering a therapeutic window to condition organs prior to implantation. The integration of stem cells and extracellular vesicles (EVs), known for their immunomodulatory and cytoprotective properties, into perfusion protocols represents a novel and potentially synergistic approach. However, the evidence base remains limited and heterogeneous. METHODS:This systematic review and meta-analysis evaluated the therapeutic potential of stem cell-based interventions during machine perfusion, following PRISMA guidelines. PubMed, Embase, and Scopus were searched for experimental studies using stem cells or EVs during hypothermic or normothermic machine perfusion in animal or discarded human kidneys. Outcomes included renal function, injury biomarkers, inflammation, and histology. RESULTS:Nine studies were included, seven in meta-analysis. Several reported reductions in inflammatory cytokines (IL-6, IL-1β) and biomarkers (NGAL) following stem cell or EV administration. However, meta-analysis showed no significant effects on creatinine clearance (SMD: 0.00; 95% CI: -0.54 to 0.55), urine output (SMD: 0.54; 95% CI: -0.46 to 1.55), or NGAL (SMD: -1.68; 95% CI: -5.60 to 2.25). Stem cell retention was limited, mechanisms of action remain incompletely understood, and only one study assessed post-transplant function. CONCLUSION:Despite potential immunomodulatory and cytoprotective effects, consistent functional benefits were not demonstrated. Standardized studies incorporating transplant models and long-term outcomes are needed to clarify therapeutic potential and optimize delivery strategies.

Adolescents and young adults with chronic kidney disease (CKD), particularly those with genetic kidney diseases, face unique challenges as they transition from paediatric to adult nephrology care. This period is marked not only by changes in healthcare providers but also by significant developmental, psychosocial and medical complexities. In response, the European Renal Association Working Group on Genes and Kidney and the European Society for Paediatric Nephrology Working Group on Inherited Kidney Diseases have collaborated to develop practical advice for healthcare professionals involved in transition care across Europe and beyond. This document outlines key principles and offers practical recommendations to support a successful transition, emphasizing the need for early planning, patient education, individualized approaches and multidisciplinary coordination. Special considerations are highlighted for patients with genetic kidney diseases, including those with syndromic manifestations, reproductive implications and the need for continuity of care across specialties. The document also identifies knowledge gaps, proposes directions for future research and collaboration and encourages the implementation of transition protocols adapted to national and local healthcare systems. By harmonizing practices and fostering shared responsibility between paediatric and adult nephrology teams, this joint initiative aims to improve health outcomes, patient empowerment and long-term engagement in care for young people with CKD.

Cystinosis is a rare systemic disease characterized by the accumulation of cystine in tissues, leading to multi-organ damage. Infantile nephropathic cystinosis is the dominant and severe form of cystinosis with critical renal manifestations that require kidney transplantation at an early age if left untreated. Cysteamine, the lifelong cystine-depleting therapy, is the mainstay treatment of nephropathic cystinosis. Cysteamine prevents cystine crystal formation and delays disease progression. While the initially introduced cysteamine consists of an immediate-release (IR) formulation, a delayed-release (DR) formulation has been developed with a simplified dosing regimen (Q12H instead of Q6H) and an improved quality of life while maintaining comparable efficacy. Due to the rare incidence of the disease and lack of international guidelines, diagnosis and treatment initiation are oftentimes delayed, leading to a poor prognosis. Pediatric and adult nephrologists from Kuwait, Saudi Arabia, the United Arab Emirates (UAE), and Qatar, in addition to one international expert from Amsterdam, convened to share their clinical experience, reflecting on the challenges encountered and therapeutic approaches followed in the management of nephropathic cystinosis in the Gulf Cooperation Council (GCC) region. Experts completed a multiple-choice questionnaire and engaged in structured discussions, where they shed light on gaps and limitations with regard to diagnostic tests and criteria to ensure early diagnosis and timely treatment initiation. Based on available literature, experts suggested an algorithm to help guide nephropathic cystinosis management in the GCC. It is highly recommended for patients who do not tolerate IR-cysteamine and do not adhere to IR-cysteamine treatment to switch to DR-cysteamine. Given the systemic nature of the disease, a multi-disciplinary approach is required for optimal disease management.

Disclosure: G. Ariceta: Advicenne, Alexion, Alnylam, Chiesi, Kyowa Kirin, Recordati Rare Diseases. S. Beck-Nielsen: Inozyme, Kyowa Kirin. A. Boot: Kyowa Kirin, Ultragenyx. M. Brandi: Amgen, Ascendis, Bruno Farmaceutici, Calcilytix, Kyowa Kirin, Alexion, Amgen, Amolyt, CoGeDi, Echolight, Gedeon Richter, Monte Rosa Therapeutics, UCB, Aboca, Enterabio, Personal Genomics, Septerna. K. Briot: Amgen, Kyowa Kirin, Theramex,, UCB. C. Collantes: Alexion, Chiesi, Kyowa Kirin. F. Emma: Avrobio, Chiesi, Kyowa Kirin, Otsuka, Recordati Rare Diseases.. S. Giannini: None. D. Haffner: Biologix, Chiesi, Kyowa Kirin, Ultragenyx. R. Keen: Kyowa Kirin. E. Levtchenko: Advicenne, Chiesi, Kyowa Kirin, Novartis, Recordati. O. Nilsson: BioMarin, Kyowa Kirin. O. Mäkitie: BridgeBio, Kyowa Kirin, Ultragenyx. M. Mughal: Inozyme Pharma, Ipsen, Kyowa Kirin. D. Schnabel: BioMarin, Kyowa Kirin, Novo Nordisk, Sandoz. L. Tripto-Shkolnik: Amgen, Kyowa Kirin. M.C. Zillikens: Amgen, Kyowa Kirin. E. Benchekroun: Kyowa Kirin. E. Eltahan: Kyowa Kirin. M. Melogno-Klinkas: Kyowa Kirin. P. Joos-Vandewalle: Kyowa Kirin. Aims/Purpose Burosumab, a fully human anti-FGF23 antibody, is approved for treating X-linked hypophosphataemia (XLH), a rare, genetic, progressive disease. As part of the burosumab risk management plan, a post-authorisation safety study (PASS) was initiated, utilizing International XLH Registry (NCT03193476) data. Methods The PASS is a 10-year multi-centre, non-interventional, observational study. Primary objectives assessed burosumab safety outcomes in adults with XLH, including long term safety, outcomes in pregnancy and participants with mild to moderate chronic kidney disease (CKD) at baseline. Secondary objective compared burosumab and oral phosphate and/or active vitamin D (Pi/VitD) safety. Results By 18 June 2024, 67 enrolees received burosumab (BUR+) and 255 received Pi/VitD (Pi/VitD+) only. Adverse event (AE) reporting was solicited in BUR+ and unsolicited in Pi/VitD+. Of BUR+ participants, 44 (65.7%) had any AE; 8 (11.9%) had AEs considered related to burosumab. No AEs led to death or treatment withdrawal. A serious adverse event (SAE), cholecystitis, occurred in 1 (1.5%) participant; no SAEs were related to burosumab. Of Pi/VitD+ participants, 52 (20.4%) had an AE; 8 (3.1%) had AEs considered related to Pi/VitD. AEs led to 1 (0.4%) death, related to cancer, and 2 (0.8%) treatment withdrawals. SAEs occurred in 14 (5.5%) participants; 1 (0.4%) had SAEs related to Pi/VitD. Common AEs in BUR+ were asthenia, pain and arthralgia and in Pi/Vit+ were urinary tract infections, arthralgia and back pain. Pregnancy occurred in 0 BUR+ and 5 (2.0%) Pi/VitD+ participants. Hospitalisation for any reason occurred in 59 (88.1%) BUR+ and 166 (65.1%) Pi/VitD+ participants; 1 (1.5%) BUR+ participant was hospitalised for cholecystitis (unlikely related to burosumab). Increased parathyroid hormone occurred in 3 (4.5%) BUR+, without hypercalcemia, and 2 (0.8%) Pi/VitD+ participants, 1 with hypercalcemia. Ectopic mineralisation occurred in 2 (3.0%) participants in BUR+ (1 unrelated chondrocalcinosis; 1 related nephrolithiasis) and 3 (1.2%) in PiVitD+. No hyperphosphataemia was reported and cardiovascular disease and cancer were rare and not treatment related. For this analysis, CKD outcomes were too limited to interpret. Conclusion The safety profile of burosumab was consistent with previous reports, with no new safety concerns. No deaths, events of hyperphosphataemia or SAE considered related to burosumab were reported. The higher AE rate in BUR+ vs Pi/VitD+ is likely attributed to differences in reporting. Presentation: Sunday, July 13, 2025

BACKGROUND:Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have become an essential part of therapy, but their use is associated with immune-related adverse events (irAE). Specifically, nephrotoxicity is well documented in adult populations but data regarding irAEs are limited in pediatric populations. This review examines the renal manifestations of ICIs and relevant clinical measures and treatments. MATERIALS AND METHODS:A comprehensive review of existing literature was conducted to assess the incidence, pathophysiology, and management of ICI-associated renal injuries in pediatric and adult populations. RESULTS:The most common renal irAE associated with ICIs is acute kidney injury; however, ICIs have been implicated in transplant rejection and electrolyte disturbances including hyponatremia, hyperkalemia, hypophosphatemia, and metabolic acidosis. Pediatric ICI manifestation patterns are similar to those in adults, but research suggests earlier onset compared to adults. Though corticosteroids are the primary treatment for irAEs, standardized pediatric management guidelines require further improvement. CONCLUSION:ICIs carry concerning risks in pediatric populations, yet research in this area is lacking. This warrants further research into the recognition, treatment, and prevention of renal irAEs, particularly for the improvement of long-term outcomes.

Cystinuria is an autosomal recessive disease characterized by defective transepithelial transport of cystine, lysine, arginine, and ornithine in the renal proximal tubule. The high urine cystine concentrations put cystinuria patients at great risk for the development of cystine stones. The treatment consists of lifestyle advices, hyperhydration and alkalizing supplements, whereas in refractory cases cystine-binding drugs, such as tiopronin or D-penicillamine, are used to lower the risk for renal stone disease and subsequent chronic kidney disease. Because of limited number of manufacturers and high costs, the availability of cystine-binding drugs is highly variable. An online questionnaire was distributed to members of the European Reference Network for Rare Kidney Diseases (ERKNet) on behalf of the Metabolic Nephropathy Workgroup to assess the availability of cystine-binding drugs for patients with cystinuria. Additional questions about the local availability of tiopronin and/or D-penicillamine were asked when physicians prescribed these drugs in the last two years. We excluded participants who completed less than 95% of the questionnaire. The collected data were analyzed using descriptive statistics. We included 40 physicians from 15 countries (Fig. 1A), including pediatric nephrologists (55%), adult nephrologists (40%) and adult urologists (5%). The majority had 5–10 (28%) or 10–20 (35%) years of clinical experience with treating cystinuria patients and had treated a median of 15 [IQR 8–38] patients. The use of cystine-binding drugs in clinical practice varied substantially among physicians (Fig. 1B; median 35% [IQR 20–68]). Tiopronin was the drug of preference for 53% of the physicians, whereas 25% preferred D-penicillamine. Tiopronin was recently prescribed by 57%, but 83% of the prescribing physicians (19/23) experienced problems with access of tiopronin. Sixteen (70%) physicians experienced problems with the availability, in 20% [IQR, 5%–35%] of the prescriptions (Fig. 1C). Restricted access to tiopronin due to policies of insurance companies was reported by 22% of the prescribing physicians. Thirty percent of the physicians had no access to tiopronin at all. D-penicillamine was recently prescribed by 45% of the physicians and 61% of the prescribing physicians experienced problems with the availability of D-penicillamine (Fig. 1C). Cystine-binding drugs are currently poorly available for the treatment of cystinuria in Europe. Considering the added value of these drugs for the treatment of cystinuria, the availability should be improved.