Background. There is a lack of robust evidence regarding immunosuppressive therapy in children and adolescents after kidney transplantation (KTx), and as such, international practice is highly variable. Recent clinical practice recommendations advocating individualized immunosuppressive strategies that incorporate newer agents are often not implemented. This can potentially contribute to reduced patient and renal allograft survival. Methods. The guideline was developed between January 1, 2024, and December 12, 2025, according to the Guidance Manual of the German Association of Scientific Medical Societies by the German Societies for Pediatric Nephrology, Nephrology, Transplantation, and Pediatrics, the German Kidney Association, the International Pediatric Transplant Association, the European Society for Pediatric Nephrology and the Members of the Cooperative European Pediatric Renal Transplant Initiative. Results. This evidence- and consensus-based guideline provides up-to-date, state-of-the-art recommendations for immunosuppressive therapy after KTx in pediatric kidney transplant recipients. It is based on the best available evidence and the consensus of the relevant German Medical Societies, Members of the Cooperative European Paediatric Renal Transplant Initiative, and the working group on transplantation of the European Society for Paediatric Nephrology, and the International Pediatric Transplant Association. Conclusions. The formal consensus reached is particularly significant in cases of weak or inconclusive evidence and where recommendations are based solely on expert opinion.

Background Hypertension (HTN) is a well-known complication among patients on pediatric kidney replacement therapy (KRT). We aimed to evaluate demographics, longitudinal changes and outcomes of high blood pressure (BP) among children and adolescents on KRT. Methods Data on BP and antihypertensive (AH) medications reported to the ESPN/ERA Registry on 6071 patients from 28 European countries starting KRT < 20 years of age between 2007 and 2021, were included. Results Hypertension (HTN), AH medication use, and uncontrolled HTN were reported in 60.7%, 45.0%, and 32.0% of patients, respectively. Prevalence of uncontrolled HTN was 49.7% in HD, 42.3% in PD, and 27.3% in transplanted patients. Younger age, dialysis, and shorter KRT vintage were risk factors for uncontrolled HTN. AH medication use was lower among young patients, females and those on dialysis, and higher with a shorter KRT vintage and non-CAKUT kidney disease. Among AH medication users, 27.9% of transplantation, 48.1% of PD and 58.9% of HD patients showed a systolic BP > 95th percentile. Uncontrolled HTN significantly decreased over time in HD patients (52.3% at dialysis start vs. 42.5% after 5 years; annual percentage change [APC] - 3.5%; 95%CI: - 6.2; -0.7), despite similar AH medication use. After 5 years, transplanted patients showed a significant reduction in both prevalence of uncontrolled HTN (APC - 3.6%; 95%CI: - 5.7; - 1.5) and AH medication use (APC - 1.6%; 95%CI: - 2.6; - 0.6%). No trends were found for PD patients. Uncontrolled HTN was not associated with mortality (aHR 1.02; 95%CI: 0.79-1.33). Conclusions HTN is highly prevalent in children and adolescents on KRT. Younger children and HD patients should be carefully evaluated for BP status after entering dialysis or shortly after transplantation

In adults with autosomal dominant polycystic kidney disease (ADPKD), episodes of macroscopic hematuria are relatively common and are predictors of hypertension. We hypothesized that a history of macroscopic hematuria will be associated with hypertension also in children with ADPKD. We retrospectively analyzed 289 children (median age 10.2 years) with ADPKD who were followed in four European tertiary nephrology centers. The presence of ≥ 1 episode of macroscopic hematuria (MaHu) defines a group of MaHu+ patients; the absence defines a group of MaHu− patients. Hypertension was defined as the use of antihypertensive drugs upon the last investigation. Macroscopic hematuria occurred in 7.2

Data on the presentation of Autosomal Dominant Polycystic Kidney Disease (ADPKD) in children have been based on small/regional cohorts and practices regarding both asymptomatic screening in minors and genetic testing differ greatly between countries. To provide a global perspective, we analyzed over 2100 children and adolescents with ADPKD from 32 countries in six World Health Organization regions: 1060 children from the multi-national ADPedKD registry were compared to 269 pediatric patients from the United Kingdom (RaDaR) and 825 from the European Rare Kidney Disease Registry (ERKReg). Asymptomatic family screening was a common mode of presentation (48% in ADPedKD, 62% in ERKReg) with broad international variability (19%-75%), but fairly stable temporal trends in both registries with no correlation to genetic testing. The national rates of genetic testing varied and correlated significantly with healthcare expenditure (odds ratio 1.030 per 100 United States Dollars/capita/year, in the ERKReg cohort), with little variation over time. Diagnosis due to prenatal abnormalities was more common than anticipated at 14% increasing steadily from 2000 onward in both registries. Realistically, a high proportion of children were diagnosed with ADPKD by active screening, underlining that families affected by ADPKD have a high need for counselling on the complex issues around presymptomatic diagnosis. Regional variations in rate of genetic testing appeared to be driven by economic factors. However, large differences in rate of active screening were not correlated to healthcare spending and probably reflect the influence of different of cultural, legal and ethical frameworks on families and clinicians in different healthcare systems.

Proteinuria is a relatively frequent complication in both adults and children after kidney transplantation (40%-80%). It is usually mild and predominantly of tubular origin and is caused mainly by rejection, mTOR inhibitors, or hypertension; however, proteinuria could also be in the nephrotic range and of glomerular origin if caused by the recurrence of idiopathic FSGS or rejection. Proteinuria is a risk factor impacting graft and patient survival in adults and graft survival in children. Proteinuria should be assessed by protein/creatinine ratio regularly in pediatric kidney transplant recipients. In children with idiopathic FSGS, proteinuria should be assessed daily during the first 2-3 weeks post-transplant to enable prompt diagnosis of recurrence. The etiology of proteinuria should be identified (recurrence, rejection, mTOR-inhibitors, hypertension, etc.). If no apparent cause is found, a graft biopsy should be considered. Antiproteinuric therapy is primarily focused on treating the causes of the proteinuria, and this is usually done using Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). The long-term follow-up goal should be normalization of proteinuria with a protein/creatinine ratio < 20 mg/mmol (200 mg/g). Because of the role elevated blood pressure may play in exacerbating proteinuria, antihypertensive medications should be used in those who are resistant to initial antiproteinuric therapy to achieve lower BP.

Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are inherited disorders that share many features such as kidney cysts, hypertension, urinary concentrating defects, and progressive chronic kidney disease. The underlying pathogenic mechanisms for both include cilia dysfunction and dysregulated intracellular signaling. ADPKD has been traditionally regarded as an adult-onset disease whereas ARPKD has been classically described as an infantile or childhood condition. However, clinicians must recognize that both disorders can present across all age groups, ranging from fetal life and infancy to childhood and adolescence as well as adulthood. Here we highlight the points of overlap and distinct features for these disorders with respect to pathogenesis, diagnostic modalities (radiological and genetic), clinical assessment, and early therapeutic management. In particular, we consider key issues at 2 critical points for transition of care: fetal life to infancy and adolescence to adulthood. These time points are poorly covered in the extant literature. Therefore, we recommend guiding principles for transitions of clinical care at these critical junctures in the life span. Although there is no cure for polycystic kidney disease (PKD), recent insights into pathogenic mechanisms have identified promising therapeutic targets that are currently being evaluated in a growing portfolio of clinical trials. We summarize the key findings from these largely adult-based trials and discuss the implications for designing child-focused studies. Finally, we look forward to the next horizon for childhood PKD, highlighting gaps in our current knowledge and discussing future directions and strategies to attenuate the full burden of disease for children affected with PKD.

Hypertension (HTN) is a significant public health concern affecting individuals across all age groups, including those with and without disabilities. Among children and adolescents, particularly those with intellectual disabilities, the risk of HTN is heightened due to factors such as obesity, low physical activity, and comorbid conditions. Regular blood pressure (BP) monitoring is essential, considering the challenges in measurement accuracy among children with intellectual disabilities. Beyond traditional lifestyle modifications, individualized dietary interventions and structured physical activity programs play a fundamental role in HTN prevention and management. Additionally, optimizing sleep quality and addressing comorbidities are essential for improving long-term health outcomes. The updated recommendations emphasize a broader specialist involvement, including endocrinologists, nephrologists, cardiologists, and rehabilitation specialists, to ensure comprehensive care. The integration of these approaches, along with appropriate pharmacological strategies whenever necessary, is crucial for achieving health benefit. This article provides practical guidance for primary care providers, specialists, and caregivers, advocating for a collaborative, patient-centered approach to reducing cardiovascular risks and enhancing the quality of life for children with intellectual disabilities.

Pediatric blood pressure (BP) assessment and management is increasingly important. Uncontrolled systolic and combined hypertension leads to hypertension-mediated organ damage. The impact of isolated diastolic hypertension is less clearly understood. We analyzed the prevalence of ambulatory isolated diastolic hypertension (IDH) in primary (PH) and secondary (SH) hypertension, and associations with BMI Z-score (BMIz) and left ventricular mass index adjusted to the 95th percentile (aLVMI) in a large, multicenter cohort of hypertensive children. Hypertensive children were divided and analyzed in three ambulatory hypertension subgroups: 24-h, daytime, and nighttime. Specifically, we sought to determine the prevalence of ambulatory 24-h, daytime, or nighttime IDH. Prevalence of IDH varied based on ambulatory phenotypes, ranging from 6 to 12

BackgroundThere is a lack of information on the current healthcare systems for children with kidney diseases across Europe. The aim of this study was to explore the different national approaches to the organization and delivery of pediatric nephrology services within Europe.MethodsIn 2020, the European society for Paediatric Nephrology (ESPN) conducted a cross-sectional survey to identify the existing pediatric nephrology healthcare systems in 48 European countries covering a population of more than 200 million children.ResultsThe reported three most important priorities in the care of children with kidney diseases were better training of staff, more incentives for physicians to reduce staff shortages, and more hospital beds. Positive achievements in the field of pediatric nephrology included the establishment of new specialized pediatric nephrology centers, facilities for pediatric dialysis and transplant units in 18, 16, and 12 countries, respectively. The most common problems included no access to any type of dialysis (12), inadequate transplant programs for all ages of children (12), lack of well-trained physicians and dialysis nurses (12), inadequate reimbursement of hospitals for expensive therapies (10), and lack of multidisciplinary care by psychologists, dieticians, physiotherapists, social workers and vocational counsellors (6). Twenty-five of 48 countries (52%) expected to have a shortage of pediatric nephrologists in the year 2025, 63% of clinical nurses and 56% of dialysis nurses. All three groups of health care professionals were expected to be lacking in 38% of countries. Prenatal assessment and postnatal management of renal malformations by a multidisciplinary team including obstetricians, geneticists, pediatricians, and pediatric surgeons was available in one third of countries.ConclusionsOur study shows that there are still very marked differences in pediatric health care systems across the European countries and highlights the need need for appropriate services for children with kidney disease in all European countries.

Objective: The recently published analysis of the 4C-T study demonstrated an association of stricter cumulative office blood pressure (BP) control with lower left ventricular mass (LVM) in children after kidney transplantation. The aim of our study was to investigate whether stricter control of ambulatory BP is also associated with improved LVMI and regression of left ventricular hypertrophy (LVH) in pediatric kidney transplant recipients. Design and method: A post-hoc analysis of nineteen patients (median age at baseline 9.7 years, range 3.3–15.1, median time after transplantation 4.3 years, range 1.0-13.1) from our previous ESCORT trial who had echocardiography performed at baseline (T0), 1 (T1), 2 (T2) and 3 (T3) years was performed. Cumulative 24-hour mean arterial pressure (MAP) Z-scores (CMAPz) were calculated according to 4C-T study (Sugianto et al. 2023). Left ventricular hypertrophy (LVH) was defined as LVMi>40 g/m^2.7 in girls >9 yrs of age and LVMi>45 g/m^2.7 in boys >9 yrs of age; in children <=9 yrs the LVH was defined as LVMi >95th percentile (Khoury et al 2009). Results: The median CMAPz decreased from a median +0.27 (IQR=-0.09 to +0.38) in the 1st year down to -0.06 (IQR=-0.26 to +0.32) in the 2nd year (p=0.02) and to +0.05 (IQR=-0.32 to 0.27) in the 3rd year (p=0.04) of follow-up. The prevalence (number) of children with LVH was 26% (5/19) at T0, 16% (3/19) at T1, 23% (3/13) at T2 and 0% (0/11) at T3 (trend in proportions p=0.06). All 5 children with elevated LVMi>0.9 at T0 decreased / normalized their LVMi at T3 (p=0.07), on contrary children without LVH at baseline did not significantly change their LVMi during follow-up. Conclusions: This first prospective interventional study demonstrated an association between stricter cumulative ambulatory MAP and regression of LVH in patients after kidney transplantation. Our data suggest that aiming stricter ambulatory BP can improve the often unfavourable cardiac phenotype in these patients. However, randomized control trial is required to confirm our findings.

Around 180 genes have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in mice, and represent promising novel candidate genes for human CAKUT. In whole-exome sequencing data of two siblings with genetically unresolved multicystic dysplastic kidneys (MCDK), prioritizing variants in murine CAKUT-associated genes yielded a rare variant in the teashirt zinc finger homeobox 3 (TSHZ3) gene. Therefore, the role of TSHZ3 in human CAKUT was assessed. Twelve CAKUT patients from 9/301 (3

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, which is mainly caused by pathogenic variants in two particular genes: PKD1 and PKD2. ADPKD caused by variants in other genes (GANAB or IFT140) is very rare. Case Report: In a 6-year-old girl examined for abdominal pain, a cystic mass in the upper part of the right kidney was detected during an abdominal ultrasound. She was referred to pediatric oncology and urology for suspicion of a tumorous mass and the condition was assessed as a cystic nephroma. A heminephrectomy was then performed on the upper cystic part of the right kidney. The histological examination was inconclusive; therefore, genetic testing was recommended. Kidney and liver cysts were detected sonographically in the mother, but DNA analysis of the PKD1 and PKD2 genes did not reveal any pathogenic variant; the cause of the pathological formation in the kidneys remained unclear. Nine years later, next-generation sequencing of a panel of genes for kidney disease was performed and a heterozygous deletion was found on chromosome 16; this included exon 13 of the IFT140 gene. The same deletion was found in the patient’s mother. Currently, the patient is 14 years old and has mild sonographic findings, normal glomerular filtration, mild proteinuria, and hypertension. Conclusion: Pathogenic variants of the IFT140 gene very rarely cause ADPKD; however, they should be considered in all children with autosomal dominant forms of PKD and asymmetric/atypical cystic kidney involvement or negative findings of PKD1 and PKD2.

BackgroundPrimary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours.MethodsIn 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology.ResultsThe care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists.ConclusionGaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.