Children after kidney transplantation (KTx) are prone to mineral and bone disease (MBD) including growth restriction, bone pain, skeletal deformities, fractures, and vascular calcifications. We present a position paper on the diagnosis and management of post-transplant MBD in this population based on the available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD, Dialysis and Transplantation Working Groups. PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and structured literature searches were conducted for a population of children under 18 years of age who were kidney transplant recipients with a functioning allograft. Patients with a failing allograft (i.e., with an eGFR less than 30 mL/min per 1.73 m2) are not discussed here. Clinical practice points (CPPs) were developed and graded using the American Academy of Pediatrics grading matrix. A Delphi consensus method was followed. We present 46 CPPs for the diagnosis and management of MBD in paediatric KTx, including assessment and management before and after KTx, highlighting the specifics of monitoring post-transplant MBD between 0 and 3 months after KTx, and including the impact of steroid minimization and withdrawal. As there are few high-quality studies in this field, the strength of most statements is weak to moderate and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Abstract Background Kidney transplantation in older adults is expanding, but detailed data on infection burden, antibiotic resistance, and sex-specific outcomes remain limited. The aim of the present study was to characterize infection dynamics and determinants of adverse events in recipients aged ≥ 65 years. Methods In this multicenter cohort study, 355 kidney transplant recipients aged 65–80 years (67.6% male) were followed for a median of 3.8 years. Cumulative incidences of infection, graft loss, and death were determined. Independent risk factors were identified using Cox regression analyses. Results Delayed graft function occurred in 23.9%, S-creatinine was 1.72 IQR (1.40–2.45) and eGFR 38.7 (26.2–51.3) one year after transplantation. All-cause mortality was 3.2% at year 1 and 11.8% at year 5 after transplantation. Infectious complications were frequent, with a cumulative incidence of first infection reaching 67.6% at 1 year and 81.9% at 5 years. Bacterial infections predominated, whereas viral infections persisted throughout follow-up and fungal infections occurred mainly in the early post-transplant period. During follow-up, death with a functioning graft (DWFG) was the predominant graft-related endpoint, accounting for 35 of 48 all-cause graft loss events, with infections representing the leading attributed cause (51.4%). In multivariable analyses, prolonged initial hospital stay was consistently associated with infectious outcomes and subsequent DWFG, while delayed graft function was independently associated with increased hazard of DWFG (HR 2.54, 95% CI 1.29–5.00). In time-dependent analyses, fungal infections were independently associated with a higher subsequent hazard of DWFG (HR 2.67, 95% CI 1.23–5.77). Mortality, graft-related outcomes, and infection rates were broadly similar by sex and between recipients aged 65–69 and ≥ 70 years. Conclusions Kidney transplantation in carefully selected older recipients, including those aged ≥ 70 years, was associated with sustained patient and graft survival. Infectious complications occurred frequently and constituted the leading attributed cause of DWFG; this underscores the importance of understanding why some recipients recover from infectious stress, while others experience subsequent clinical deterioration.

Delayed graft function (DGF) in pediatric kidney transplantation is a serious complication with negative impact on graft survival. Currently, there are no reliable methods available to assess the risk of DGF in children. We performed a retrospective analysis of data from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry to develop a DGF risk assessment model for pediatric kidney transplantation, based on parameters available within the first 24 h post-transplant. The model was developed by forward selection and logistic regression. This study included n = 694 patients. The overall rate of DGF was 8.5%. The following key parameters were selected for the DGF risk assessment model: (i) occurrence of post-transplant surgical complications, (ii) immediate graft urine production, (iii) rate of change in recipient’s serum creatinine, (iv) initial calcineurin inhibitor therapy. The significance of these parameters was confirmed by calculating adjusted odds ratios. In the training cohort and the internal validation cohort the ROC-AUCs were 0.9043 and 0.878. This multivariable model based on early post-transplant parameters can predict the occurrence of DGF in pediatric kidney transplant recipients with high accuracy and may facilitate future interventional trials of targeted pharmacological strategies against ischemia-reperfusion injury in this population.

Background:Kidney transplantation (KT) is the preferred treatment for paediatric patients with kidney failure, but information on trends in paediatric KT in Europe is lacking. We aimed to report on time trends in paediatric (0-17 years) KT rates and recipient characteristics in Europe between 2010 and 2021. Methods:Thirty-one countries contributing data from 2010 to 2021 on paediatric KT to the European Society for Paediatric Nephrology/European Renal Association Registry were included. We reported trends in KT rates [per million age-related population (pmarp)], overall and by patient subgroup for Europe, and at macro-economic and country-specific levels. We also reported clinical variables in the first year post-KT. The 2020-21 period was analysed separately to account for the COVID-19 pandemic. Results:The paediatric KT rate was stable at ≈5 pmarp between 2010 and 2019, and about one-fourth were pre-emptive KTs. In 2020-21 the KT rate was 5.6 pmarp. In low-, middle- and high-gross domestic product (GDP) countries, KT rates (pmarp) were 2.1, 6.1 and 7.6, respectively, and increased in low-GDP countries by 4.1% per year from 2010 to 2019, mainly in the youngest recipients. The proportion of pre-emptive KT increased only in middle-GDP countries. Low-GDP countries showed a higher prevalence of short stature while high-GDP countries showed more overweight/obese, hypertensive and anaemic patients. Conclusions:The rate of paediatric KT in Europe has remained stable, with differences between GDP groups. Low-GDP countries had the lowest KT rates, but with an increasing trend over time. Opportunities to further increase access to paediatric KT should be explored.

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.

Infantile nephropathic cystinosis (INC) is characterized by progressive short stature and low body fat. Although birth size is typically normal, early growth data are limited. In this prospective multicenter observational study, 77 conservatively treated children with INC and 527 congenital and hereditary CKD controls, stages 1–5, were analyzed. We investigated birth characteristics and linear body growth (length/stature), weight, and head circumference from birth up to 18 years. Linear mixed-effects models were applied to identify pre- and postnatal predictors of statural growth. Newborns with INC exhibited normal birth morphology, whereas CKD controls showed significantly reduced, disproportionate characteristics (each p < 0.01). Despite preserved birth morphology, born small for gestational age prevalence in INC was nearly twofold higher than in the general population, and CKD peers had an approximately 1.7 times higher prevalence than INC (p < 0.05). In INC, a weight–length dissociation emerged at approximately 6 months of age, followed by marked impairments in both characteristics within the first 2 years, persisting into adulthood. CKD peers showed only mild further decline and more favorable long-term growth. Statural growth in INC was associated with biochemical features of Fanconi syndrome and with birth weight in adolescence, whereas in CKD, birth weight remained the only consistent predictor. In INC, growth deterioration begins around 6 months with weight–length dissociation and progresses to sustained deficits in stature and weight. This pattern resembles early postnatal disturbances that durably constrain somatic development and are driven more by disease-specific disturbances than by reduced glomerular filtration.

BACKGROUND:Prolonged glucocorticoid therapy is the standard initial treatment for idiopathic nephrotic syndrome in children, but is associated with marked toxic effects. We aimed to assess whether a novel treatment protocol with mycophenolate mofetil is as effective as standard therapy with prednisone, while reducing the burden of glucocorticoid-related side-effects. METHODS:INTENT was a multicentre, open-label, randomised, controlled, parallel-group, non-inferiority, phase 3 trial done in 37 community, municipal, and university hospitals in Germany. Patients aged 1-10 years with a first episode of steroid-sensitive nephrotic syndrome were randomly assigned (1:1) by a centralised web-based tool to receive either mycophenolate mofetil or prednisone (standard treatment), after remission induced by prednisone or prednisolone at a dose of 60 mg/m2 body surface area (maximum 80 mg/day) within 28 days. Block randomisation (block size of eight) was stratified by age (<7 years or ≥7 years). Mycophenolate mofetil was given at 1200 mg/m2 body surface area per day, twice daily, as a suspension (200 mg/mL) for a total treatment duration of 12 weeks. Prednisone was administered once, twice, or three times daily for 6 weeks at 60 mg/m2 body surface area per day (maximum 80 mg). Thereafter, prednisone was given for a further 6 weeks at 40 mg/m2 body surface area (maximum 60 mg) once daily in the morning on alternate days. The primary endpoint was the occurrence of a treated relapse during the 24-months of follow-up in the modified intention-to-treat population. The non-inferiority margin was 15%. This trial is registered with the European Union Drug Regulating Authorities Clinical Trials database (EudraCT 2014-001991-76) and has been completed. FINDINGS:Between Oct 12, 2015, and April 23, 2021, 497 patients were screened for eligibility, 272 of whom were randomly assigned (136 to each group). The modified intention-to-treat population comprised 269 patients, of whom 173 (64%) were boys and 96 (36%) were girls (median age 4·0 years [IQR 2·0-5·0]). Mycophenolate mofetil was non-inferior to prednisone for the primary endpoint of treated relapse (106 [79·1%] of 134 vs 101 [74·8%] of 135; difference 4·3% [90% CIs -4·2 to 12·7]; p=0·019). At the end of the first 12 weeks of treatment, fewer glucocorticoid-related side-effects were observed in the mycophenolate mofetil group than the prednisone group, including arterial hypertension (78 [59·1%] of 132 vs 115 [87·1%] of 132; difference -28·0% [95% CI -37·7 to -17·5]), lower BMI (BMI Z score 0·16 [SD 0·85] vs 1·41 [1·02]; difference -1·24 [-1·47 to -1·02]), and fewer psychological abnormalities (37 [27·8%] of 133 vs 77 [57·9%] of 133; difference -30·1% [-40·9 to -18·4]). More patients in the mycophenolate mofetil group than in the prednisone group developed infections (93 [69·9%] of 133 vs 74 [55·6%] of 133; difference 14·3% [2·7 to 25·5]) and there was no statistically significant difference in the number of patients who developed at least one gastrointestinal disorder (22 [16·5%] of 133 vs 13 [9·8%] of 133; difference 6·8% [-1·5 to 14·8]). INTERPRETATION:Our findings suggest that mycophenolate mofetil is non-inferior to standard prednisone treatment, with reduced glucocorticoid-related toxic effects. These findings could modify the initial standard of care for patients with steroid-sensitive nephrotic syndrome. FUNDING:German Federal Ministry of Education and Research.

The medical management of failing kidney allografts is poorly understood even in adult patients with wide variations in practice. We studied failing kidney allografts in European children and provided insights into their management, including cardiovascular, CKD management, and changes to immunosuppression. A 3-year (2020–2023) retrospective study of current practices in the management of children with failing kidney allografts (with at least 1 year of follow-up) was conducted. A failing kidney allograft was defined as an eGFR < 30 mL/min/1.73 m2 for 3 consecutive months, as agreed through an iterative Delphi process. All children who had a kidney transplant performed at < 18 years of age with a failing kidney allograft were included. Data were collected through the CERTAIN (Cooperative European Pediatric Renal Transplant Initiative) registry. Pearson correlation and Spearman’s rank were used for continuous variables. Multivariate Cox proportional hazards models estimated associations of exposure with outcome. All statistical analyses were performed using Stata Version 16.0. A total of 119 patients from 27 European centres were included. At the time of allograft failure, 76

BackgroundShort-term mycophenolic acid (MPA) withdrawal is common in kidney transplant recipients with severe infections and was extended during the COVID-19 pandemic to improve vaccine immunogenicity, yet its effects on immune cell dynamics remain mechanistically understudied.MethodsWe performed high-dimensional flow cytometry combined with unsupervised computational clustering to analyze longitudinal peripheral blood mononuclear cell samples from kidney transplant recipients who received mRNA-1273 vaccination. Samples were collected before and after a 5-week temporary MPA discontinuation, and the results were compared with those of vaccinated patients maintained on standard triple immunosuppression.ResultsCompared with continued triple immunosuppression (N = 13), MPA withdrawal (N = 11) was associated with temporal shifts in major immune compartments, including increases in the frequencies of CD4+ and CD8+ T cells (P = 0.039 and P = 0.001, respectively), as well as decreases in the frequencies of monocytes (P = 0.014) and B cells (P = 0.023). These changes were accompanied by increased relative frequencies of specific T-cell subsets, including CD8+ TEMRA CD38+ cells (P = 0.011) and early activated memory CD4+ T cells (P = 0.023). With increasing time since transplantation, these longitudinal patterns attenuated. Older patient age was associated with lower overall monocyte frequencies, though it did not influence their temporal trajectories. Although exploratory analyses showed subset differences between seroconverters and non-seroconverters after vaccination, no major compartment or individual subset was predictive in regression models.ConclusionsShort-term MPA withdrawal was associated with selective temporal immune shifts, including increased relative frequencies of CD4+/CD8+ T-cell subsets and decreased relative frequencies of monocyte and B-cell subsets. Effects varied by time since transplantation and age, reflecting heterogeneous immune reconstitution. High-dimensional profiling enabled detailed analysis of major and rare immune populations, highlighting its value in mechanistic transplantation studies.

Background:Donor kidneys are allocated to potential pediatric kidney transplant recipients based on criteria such as human leukocyte antigen (HLA) immunology, but explicit guidance for accepting deceased-donor kidney offers is lacking. Methods:A vignette survey was designed with a matrix of 128 fictitious kidney offers consisting of seven dimensions with two levels each: mismatches on HLA A, B, C (≤3/≥4); mismatches on HLA DR, DQ (≤2/≥3); donor estimated glomerular filtration rate (eGFR) (≥50/≤49 ml/min/1.73 m2); donor age (≤1/2-50 years); recipient age (≤1/≥2 years); recipient status (preemptive/on dialysis); donor history of sepsis or bacterial infection (yes/no). Between December 2024 and February 2025, clinicians involved in pediatric kidney transplantation evaluated a randomly assigned set of 16 vignettes. Mixed-effects logistic regression assessed factors associated with acceptance. Results:Forty participants from eleven allocation organizations in Europe, Iran, and Canada, most commonly Eurotransplant (58%), including eight European countries, provided 533 evaluations (3-6 per vignette). In the multivariate analysis, four of the seven vignette dimensions decreased acceptance: ≥4 HLA A, B, C mismatches (P = .011), ≥3 HLA DR, DQ mismatches (P < .001), donor eGFR ≤49 ml/min/1.73 m2 (P < .001), or donor age ≤1 year (P = .003). Recipient age, dialysis status, and donor sepsis/bacterial infection were not significant. Allocation organization and respondent characteristics (gender and experience) did not materially influence decisions. Conclusions:This pilot study suggests that factors such as HLA mismatches, donor eGFR, and donor age, consistently guided decisions, independently of participant's allocation organization. This underscores the potential value of developing evidence-informed donor-offer acceptance guidelines and investigating the impact of these factors on kidney transplantation outcome.

Human leukocyte antigen (HLA) donor-specific antibodies (DSA) are among the most important determinants of late allograft loss after kidney transplantation. However, no uniform monitoring strategy has been validated in pediatric recipients. This educational review recommends that post-transplant HLA antibody monitoring in children should be tailored to the individual patient's immunological risk profile rather than applied as a fixed schedule. Pediatric recipients face a heterogeneous risk landscape due to prolonged allograft exposure, high age-specific risk of nonadherence during adolescence, and the influence of the chosen immunosuppressive regimen, which demands a differentiated approach. Drawing on current international consensus documents, multicenter registry data, and emerging pediatric cohort studies, this review examines the scientific basis of HLA antibody-mediated injury, the available diagnostic tools, and the supporting evidence for risk-adapted monitoring intervals, individualized trigger-based testing, and interpretation of test results as mean fluorescence intensity (MFI) in a clinical context. We give special attention to adolescence and nonadherence as high-risk categories warranting intensified surveillance. We aim to provide a practical framework for tailored personalized HLA antibody monitoring that is applicable in the daily care of pediatric kidney transplant recipients.

BACKGROUND:Clinical practice variation in the management of recurrent idiopathic focal segmental glomerulosclerosis (rFSGS) is poorly defined and likely hinders successful clinical trial design. METHODS:We conducted an online survey between June 2024 and September 2024 of Pediatric Nephrology Research Consortium (PNRC) and European Society for Pediatric Nephrology (ESPN) members to evaluate global clinical practice patterns in the management of pediatric rFSGS and physician perceptions of barriers to rFSGS clinical trial participation. RESULTS:Of 120 responses (50 PNRC members from the US and Canada and 70 ESPN members from Europe, Asia, and South America), all respondents were physicians and 50% were transplant program medical directors. Pretransplant mutation analysis was routine in 104 (87%) centers, and native nephrectomy was routine for patients with and without hypoalbuminemia in 77 (66%) and 23 (19%) centers, respectively. Forty-two (35%) centers reported routine therapeutic interventions to prevent rFSGS prior to kidney transplantation; this increased to 79 centers (66%) in patients with previous recurrence. Plasmapheresis was the first therapeutic intervention in most centers, although it was used significantly more often in North America (96%) than Europe (77%; p = 0.005). Rituximab was administered in 102 (85%) centers as treatment for rFSGS. Common barriers to recruitment and inclusion of patients in clinical trials of rFSGS were limited site resources (36%), recipient/family reluctance (10%), and operational and logistical issues (26%). CONCLUSIONS:Heterogeneity of practice patterns in the management of pediatric rFSGS and barriers to clinical trials requires collaborative efforts to study and reach consensus on prevention and management of rFSGS.

Background A pre-transplant prediction model using commonly available factors is valuable for optimizing donor selection, communication, and counseling for pediatric kidney transplant (PKT) recipients. This study aims to externally validate a Dutch PKT prediction model and assess its international applicability.Materials and methods Data from the Dutch-, CERTAIN-, and CRISTAL registries, covering PKT from 2005 to 2021, were used. The Dutch prediction model was externally validated in a German and French cohort and then adapted to these specific countries. An international prediction model was also developed using all available data. Models were based on 80% derivation cohorts and internally validated using areas under the receiver operating characteristic curve (ROC-AUC) and calibration plots.Results Of 3266 transplantations, 2475 (273 Dutch, 356 German, 1622 French, and 224 other) were used for analysis. Cohorts differed significantly in baseline characteristics and outcomes. Internal validation of the Dutch model showed ROC-AUC of 0.77 and 0.75 at 10 and 15 years. External validation in German and French cohorts yielded 10-year ROC-AUC of 0.63 and 0.60, respectively. Internal validation of the international prediction model showed AUC of 0.61 and 0.60 at 10 and 15 years with poor calibration, indicating inferior performance. The adapted national models showed better internal validation performance, with 10-year ROC-AUC of 0.77, 0.76, and 0.73 in Dutch, French, and German cohorts, respectively.Results Of 3266 transplantations, 2475 (273 Dutch, 356 German, 1622 French, and 224 other) were used for analysis. Cohorts differed significantly in baseline characteristics and outcomes. Internal validation of the Dutch model showed ROC-AUC of 0.77 and 0.75 at 10 and 15 years. External validation in German and French cohorts yielded 10-year ROC-AUC of 0.63 and 0.60, respectively. Internal validation of the international prediction model showed AUC of 0.61 and 0.60 at 10 and 15 years with poor calibration, indicating inferior performance. The adapted national models showed better internal validation performance, with 10-year ROC-AUC of 0.77, 0.76, and 0.73 in Dutch, French, and German cohorts, respectively.Conclusions The Dutch PKT prediction tool requires country-specific adaptations for use in other countries, given the diversity of clinical practice across Europe. A country-specific model is preferable to an international model in the current landscape.

BACKGROUND:Approximately 50% of patients with chronic kidney disease due to C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) will require dialysis and/or kidney transplantation (KTx) within the first 10 years of disease onset. Currently, there are no guidelines regarding the indications for KTx or post-transplant management. METHODS:We therefore initiated an international online survey via Survey Monkey on C3G and IC-MPGN in children with CKD stage 5. All KTx centers of the European Society for Paediatric Nephrology (ESPN) were invited to participate in the survey, which was conducted from August 23 to November 25, 2023. RESULTS:Sixty-five (63%) of the centers (n = 103) participated. Twenty-six percent had made at least one decision against living donation for a child with C3G or IC-MPGN. The main reason for 88.2% of these decisions was concern about the recurrence of the underlying disease in any potential transplant. Eighty-eight percent indicated deceased donation as an option; 12% decided not to proceed with transplantation at all. Regarding KTx decision-making or management, none of them referred to an existing recommendation by any national or regional guideline. For the recurrence of C3G or IC-MPGN post-transplant, eculizumab treatment was suggested by 60% of respondents. CONCLUSION:This survey shows a considerable reluctance of pediatric nephrologists to list patients with CKD stage 5 due to C3G or IC-MPGN for living donor kidney transplantation. This decision is mainly based on the fear of recurrence of the underlying disease combined with the lack of reliable treatment options. This limited access of affected patients to the best treatment option for kidney failure requires further action.

Data on the relevance of tacrolimus intrapatient variability (TacIPV) and concentration-to-dose ratio (C/D ratio) as an approximation of tacrolimus metabolism for predicting outcomes in pediatric kidney transplant (pKTx) recipients are scarce. We conducted a multicenter retrospective study of 255 pKTx recipients from the CERTAIN registry. TacIPV was quantified as the coefficient of variation (CV

Recent reports on allograft survival after repeat kidney transplantation (KTx) and the incidence and determinants of graft failure (GF) are lacking. We analyzed the probability of graft failure (GF) and death with functioning graft following a primary pediatric and sequential kidney transplantation (KTx) in 4528 primary, 1155 second, 259 third, and 41 fourth KTx. We calculated the impact of relevant peri-transplant characteristics on the probability of GF and death with functioning graft (as a composite endpoint due to statistical reasons) for specific recipient profiles. The respective unadjusted 5-year GF probabilities after first, second, third, and fourth KTx were 15