Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after kidney transplantation (Tx). The randomized controlled IVIST trial demonstrated that additional steering of immunosuppressive therapy by virus-specific CD4+ T cells (Tvis) is safe and reduces exposure to immunosuppressants. The adenovirus-specific CD4+ T cells (ADV-Tvis) proved to be particularly suitable due to their stability and high prevalence. Another promising biomarker for post-Tx immunomonitoring is the Torque Teno virus (TTV) but pediatric data are very limited. This descriptive longitudinal analysis aimed to evaluate the post-Tx course of TTV load compared to Tvis levels after pediatric Tx. In the IVIST trial, 31 pediatric kidney recipients were randomized to the intervention group with Tvis-guided immunosuppression. The immunosuppressive therapy consisted of basiliximab, cyclosporine A (CsA), everolimus (Eve), and prednisolone. In 27 out of 31 intervention group patients, TTV-DNA was analysed retrospectively in frozen plasma samples from 20 visits [1-24 months (mo) after Tx]. Associations of TTV-DNA with ADV-Tvis and with immunosuppressants over the post-Tx period were evaluated using linear mixed models, adjusted for time since Tx and accounting for repeated measurements within patients. Mean TTV-DNA (n = 474) ± standard deviation was 4.4 ± 1.3 log10 copies/ml (1.4 to 9.4 log10). TTV-DNA was associated with post-Tx follow-up time. Under intensive immunosuppression immediately after Tx, TTV-DNA increased, peaking at 3 mo post-Tx (5.5 ± 1.4 log10); after reduction of immunosuppression, TTV load decreased (6 mo: 4.3 ± 1.1 log10; 16 mo: 3.9 ± 0.9 log10). Mean ADV-Tvis levels showed a minimum at 2 mo post-Tx and increased over time: from 1.5 ± 1.1 cells/µl (2 mo) to 2.0 ± 1.8 cells/µl (6 mo) and 2.4 ± 1.7 cells/µl (22 mo). TTV-DNA showed overall positive correlations with mean daily doses and trough levels of CsA and Eve. The longitudinal analysis of TTV load presented an opposite post-Tx course compared to ADV-Tvis. TTV-DNA was associated with post-Tx follow-up time and with immunosuppressants after pediatric Tx. In comparison to ADV-Tvis minimum, the mean TTV-DNA showed a late peak at 3 mo post-Tx suggesting delayed response to drug dose changes.

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.

Background:Shiga toxin-producing Escherichia coli (STEC)-associated hemolytic uremic syndrome (HUS) is a leading cause of pediatric acute kidney injury. Between August and October 2025, Germany experienced an outbreak of the rare STEC serotype O45:H2, comprising 53 laboratory-confirmed pediatric HUS cases. Because O45:H2-associated HUS had previously been reported only sporadically, this study characterized its clinical course and compared it with HUS caused by non-O45:H2 STEC serotypes. Methods:We retrospectively included all pediatric STEC-HUS cases treated in Northeastern Germany during the outbreak period. Microbiological confirmation was performed through cultivation and molecular typing at the National Reference and Consulting Laboratories. Patients were classified as O45:H2 or non-O45:H2 based on serotyping and the Robert Koch Institute (RKI) O45:H2 outbreak case definition. Clinical and laboratory parameters, dialysis requirements, transfusion needs, and short-term outcomes were compared. Results:Thirty-seven children with STEC-associated HUS were included: 18 with O45:H2 and 19 with other serotypes. Patients with O45:H2 were significantly younger (median 2.0 vs 4.0 years, P = .01), while renal impairment at onset was comparable (minimal estimated glomerular filtration rate 8.0 vs 12 mL/min/1.73 m2). Dialysis was required in 65% of patients in both groups, with a trend toward longer duration in O45:H2 cases (median 10 vs 6 days). Hematologic parameters, markers of hemolysis, transfusion needs, neurological symptoms, and intensive care treatment were similar. One child died from myocardial failure. At 3-month follow-up, kidney function had recovered well in both groups. Conclusions:O45:H2-associated HUS was comparable in severity to non-O45:H2 STEC-HUS, while the younger age of affected children may indicate distinct host susceptibility or exposure patterns.

We report a rare case of centrally caused hypertension in a 17-year-old adolescent due to neurovascular compression of the root entry/exit zone of the ninth/tenth cranial nerves of the rostral ventrolateral medulla oblongata on the left side. The patient underwent a comprehensive diagnostic workup to exclude other causes of secondary hypertension. A cranial magnetic resonance imaging (cMRI) indicated a neurovascular compression. The patient underwent microvascular decompression (MVD) twice. After the first MVD, blood pressure values significantly decreased to normotensive levels without any antihypertensive medication. After one year without clinical symptoms, the patient experienced recurrent hypertension and underwent a second MVD. Again, the blood pressure normalized without any medication or clinical symptoms within six-month follow-up. This case report highlights neurovascular compression at brainstem level as an important differential diagnosis of centrally caused hypertension, even in the absence of specific cranial nerve deficits. MVD is an effective treatment option.

Background. Kidney transplantation (KTx) from small donors is associated with inferior graft survival in registry studies, whereas single-center studies show favorable results. Methods. We compared 175 pediatric KTx from small donors <= 20 kg (SDKTx) with 170 age-matched recipients from adult donors (ADKTx) from 20 centers within the Cooperative European Paediatric Renal Transplant Initiative registry. Graft survival and estimated glomerular filtration rate (eGFR) were analyzed by Cox regression and mixed models. Detailed data on surgical and medical management were tested for association with graft survival. Results. One-year graft survival was lower after SDKTx compared with ADKTx (90.9% versus 96.5%; odds ratio of graft loss, 2.92; 95% confidence interval [CI], 1.10-7.80; P = 0.032), but 5-y graft survival was comparable (90.9% versus 92.7%; adjusted hazard ratio of graft loss 1.9; 95% CI, 0.85-4.25; P = 0.119). SDKTx recipients had an annual eGFR increase of 8.7 +/- 6.2 mL/min/1.73 m2 compared with a decrease of 6.9 +/- 5.7 mL/min/1.73 m2 in ADKTx recipients resulting in a superior 5-y eGFR (80.5 +/- 25.5 in SDKTx versus 65.7 +/- 23.1 mL/min/1.73 m2 in ADKTx; P = 0.008). At 3 y posttransplant, eGFR after single SDKTx was lower than after en bloc SDKTx (86.6 +/- 20.4 versus 104.6 +/- 35.9; P = 0.043) but superior to ADKTx (68.1 +/- 23.9 mL/min/1.73 m2). Single-kidney SDKTx recipients had a lower rate of hypertension at 3 y than ADKTx recipients (40.0% versus 64.7%; P = 0.008). Conclusions. Compared with ADKTx, 5-y graft function is superior in SDKTx and graft survival is similar, even when performed as single KTx. Utilizing small donor organs, preferably as single kidneys in experienced centers, is a viable option to increase the donor pool for pediatric recipients.

Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS) is associated with high morbidity and relevant mortality. Previous small studies showed that volume expansion could improve the course and outcome of STEC-HUS. The aim of this single-center study was to evaluate the effect of volume expansion on the clinical course and outcome in STEC-HUS. Data of pediatric patients with STEC-HUS were analyzed retrospectively. Course and outcome of patients treated with volume expansion (VE) from 2019 to 2022 (n = 38) were compared to historical controls (HC) from 2009 to 2018 (n = 111). Patients in the VE group had a significant relative median weight gain compared to HC (7.8

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare disorders in childhood with a variable clinical presentation. Given ANCA vasculitides' rarity, data informing clinical practice and treatment are mainly based on adult data. The purpose of this study was to characterize clinical characteristics of ANCA-associated glomerulonephritis (AAGN) in childhood to determine factors associated with adverse renal outcome and the requirement for kidney replacement therapy (KRT) across a global study population. This was a retrospective cross-sectional international survey distributed through professional pediatric nephrology organizations from December 2019 to March 2020 intended to create a registry of children with AAGN to understand clinical practices. Through an online form, pediatric nephrologists entered demographic and clinical information on all children with AAGN in their center in de-identified fashion. All centers were required to obtain their own institutional ethics or governance approval. Inclusion criteria were patients under 20 years at presentation who were diagnosed with AAGN in 2000-2019 and had kidney involvement. Data elements that were collected included baseline demographic data, clinical features at presentation, treatment received (maintenance and induction), and data on 3 clinical outcomes: requirement for KRT, serum creatinine concentration (Scr), and death. Specifically, nephrologists were asked to report the peak Scr and any requirement for KRT in the first 3 months after presentation during the induction treatment period. Nephrologists were also asked to report on the need for KRT and vital status at last known follow-up. Further methodological details are in Item S1. Based on responses received from 114 different clinicians, 337 children from 41 different countries were included in the final analysis. Median duration between initial presentation and last known follow-up was 26 (IQR, 11-57) months. Table S1 details baseline characteristics of included children. Table S2 shows the organ involvement at presentation across different clinical phenotypes. Table 1 shows the most frequent induction and maintenance treatments used in the entire cohort. A total of 113 children (34%) received plasma exchange at induction. Sixteen deaths were reported in this cohort (5% mortality), with a mean age at death of 13.7 ±5.7 years.Table 1Main Combinations of Induction and Maintenance Treatment in Entire AAGN CohortMain Treatment CombinationsValueInductionSteroids,aIntravenous or oral. cyclophosphamide100 (30%)Steroids,aIntravenous or oral. cyclophosphamide, PE (± IVIG)56 (17%)Steroids,aIntravenous or oral. rituximab25 (7%)SteroidsaIntravenous or oral.22 (7%)Steroids,aIntravenous or oral. cyclophosphamide, rituximab, PE (± IVIG)21 (6%)Steroids,aIntravenous or oral. mycophenolate mofetil13 (4%)Other combinations96 (28%)None4 (1%)MaintenanceMycophenolate mofetil and steroids100 (31%)Azathioprine and steroids49 (15%)Cyclophosphamide and steroids25 (8%)Steroids20 (6%)Steroids and rituximab19 (6%)Azathioprine17 (5%)Mycophenolate mofetil8 (2%)Rituximab8 (2%)Other combinations62 (19%)None15 (5%)Induction therapy information was available from all 337 patients, maintenance treatment data from 327 patients. "Other combinations" refers to multiple different combinations used less commonly. Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange.a Intravenous or oral. Open table in a new tab Induction therapy information was available from all 337 patients, maintenance treatment data from 327 patients. "Other combinations" refers to multiple different combinations used less commonly. Abbreviations: IVIG, intravenous immunoglobulin; PE, plasma exchange. Table 2 characterizes the clinical factors and treatment according to KRT requirements at initial presentation and at last known follow-up. We found a high prevalence of adverse renal outcomes, with 40% of children requiring KRT at last known follow-up, slightly higher than previously published data.1Calatroni M. Consonni F. Allinovi M. et al.Prognostic factors and long-term outcome with ANCA-associated kidney vasculitis in childhood.Clin J Am Soc Nephrol. 2021; 16: 1043-1051https://doi.org/10.2215/CJN.19181220Crossref PubMed Scopus (8) Google Scholar, 2Özçelik G. Sönmez H.E. Şahin S. et al.Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis.Pediatr Nephrol. 2019; 34: 847-854https://doi.org/10.1007/s00467-018-4162-5Crossref PubMed Scopus (8) Google Scholar, 3Morishita K.A. Moorthy L.N. Lubieniecka J.M. et al.Early outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis.Arthritis Rheumatol. 2017; 69: 1470-1479https://doi.org/10.1002/art.40112Crossref PubMed Scopus (39) Google Scholar, 4Sacri A.-S. Chambaraud T. Ranchin B. et al.Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study.Nephrol Dial Transplant. 2015; 30: i104-i112https://doi.org/10.1093/ndt/gfv011Crossref PubMed Scopus (70) Google Scholar Children who did (vs did not) require KRT at last known follow-up had a higher peak Scr during the first 3 months after their initial presentation. There was a higher proportion of girls and a higher proportion of myeloperoxidase-ANCA positivity in children who required KRT at last known follow-up, compared to those who did not require KRT. We note that children who required KRT at last known follow-up were more likely to have received plasma exchange as induction treatment, but this may simply be because children with more severe kidney involvement at presentation were more likely to be treated with plasma exchange. We note that mycophenolate mofetil was used more commonly as maintenance treatment for children compared to azathioprine, which differs from suggestions in the adult literature.5Hiemstra T.F. Walsh M. Mahr A. et al.Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial.JAMA. 2010; 304: 2381-2388https://doi.org/10.1001/jama.2010.1658Crossref PubMed Scopus (468) Google ScholarTable 2Clinical Variables and the Requirement for KRT During the First 3 Months After Initial Presentation and Last Known Follow-up in 326 Children With AAGNRequired KRT at Initial PresentationRequired KRT at Last Known Follow-upYesNoYesNoNo. of patients119207132194Female sex75%69%78%68%Age at presentation, y12.1 ± 4.412.5 ± 5.411.9 ± 4.612.7 ± 5.3MPO-ANCA71%64%77%60%High-income GDP61%66%58%68%Peak Scr during initial presentation, μmol/L736 ± 345173 ± 121616 ± 333218 ± 115Organ involvement at presentation Respiratory tract50%42%50%41% Ear, nose, and throat12%17%10%19% Skin13%32%17%30% Musculoskeletal9%24%18%19% Neurological16%8%18%6% Eye5%10%7%9%Induction treatment IV steroids95%80%92%81% Rituximab29%27%25%29% IV cyclophosphamide55%57%64%56% Plasma exchange57%19%44%26%Maintenance treatment Azathioprine22%27%24%27% Mycophenolate mofetil46%45%43%47% Rituximab17%17%14%19%Continuous variables given as mean ± SD. Follow-up on the need for KRT was not available on 11 children; therefore data on 326 children are presented in this table. Conversion factor for Scr μmol/L to mg/dL, ×0.0113. Abbreviations: GDP, gross domestic product; IV, intravenous; MPO, myeloperoxidase. Open table in a new tab Continuous variables given as mean ± SD. Follow-up on the need for KRT was not available on 11 children; therefore data on 326 children are presented in this table. Conversion factor for Scr μmol/L to mg/dL, ×0.0113. Abbreviations: GDP, gross domestic product; IV, intravenous; MPO, myeloperoxidase. This study is unique, as it was conducted across 41 countries, giving a broad cross-sectional assessment of demographics and baseline characteristics of children affected by AAGN. Potential limitations of this study include an over-representation of children with severe renal outcomes, given the collection of data through a survey of pediatric nephrologists; but this is also a strength, as this study focuses on the subgroup of children with ANCA vasculitis who have kidney involvement. Data were only available at disease presentation and latest follow-up, which limits our ability to comment on kidney function over time. In addition, we did not collect data on histology, meaning that the diagnosis of AAGN was clinical rather than histological and we had limited ability to relate histology to clinical outcomes. We also do not have data on proteinuria at presentation, which is a further limitation. In conclusion, this large international cohort of children with AAGN demonstrates the high risk of chronic kidney disease and requirement for KRT in this population. Designed the study, collected and collated data, conducted and reviewed analyses: MM, TW, NP, FS, MV, KT; devised the statistical analysis plan, conducted statistical analyses: DK, RK, LS; reviewed patients for inclusion, collected data: MA, IA, AA, JB, RB, BB, ZB, OB, EY-hC, DC, SD, ED, MD-D, LAE, LE, VF, HF, JF-D, AG, VG, MLG, MHansen, MHattori, XH, NH, DI, HGK, VK, IK, AL, SM, AMaxted, AMoczulska, RM, TN, MP, CP, IP, CS-K, SS, RSchild, MS, RSinha, APS, MStack, MSzczepanska, AT, JT, VU, CZ, JZ. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. This study has been supported by the European Rare Kidney Disease Network (ERKNet). ERKNet is co-funded by the European Union within the framework of the Third Health Programme "ERN-2016 - Framework Partnership Agreement 2017-2021." The funders had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. The authors declare that they have no relevant financial interests. We are grateful to the European Society of Paediatric Nephrology (ESPN) and the International Paediatric Nephrology Association (IPNA) for their support in administering this study. We are grateful to all colleagues and pediatric nephrology centers contributing cases to this study. Aspects of this work were presented in abstract form at the 53rd ESPN Annual Meeting held in Amsterdam, The Netherlands, in September 2021. Received February 11, 2022. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form May 18, 2022. Download .pdf (.29 MB) Help with pdf files Supplementary File (PDF)Item S1; Tables S1, S2.

The coronavirus SARS-CoV-2 disease (COVID-19) pandemic affected lifestyles and resulted in significant weight gain in the general population. Its impact on children after kidney transplantation (KTx) is unknown. We retrospectively evaluated body mass index (BMI) z-scores during the COVID-19 pandemic in 132 pediatric KTx patients, followed-up at three German hospitals. Among those, serial blood pressure measurements were available for 104 patients. Lipid measurements were available from 74 patients. Patients were categorized according to gender and age group, i.e., children versus adolescents. Data were analyzed by a linear mixed model approach. Before the COVID-19 pandemic, female adolescents presented with higher mean BMI z-scores compared to male adolescents (difference: − 1.05, 95

ABSTRACTBackgroundData on comorbidities in children on kidney replacement therapy (KRT) are scarce. Considering their high relevance for prognosis and treatment, this study aims to analyse the prevalence and implications of comorbidities in European children on KRT.MethodsWe included data from patients <20 years of age when commencing KRT from 2007 to 2017 from 22 European countries within the European Society of Paediatric Nephrology/European Renal Association Registry. Differences between patients with and without comorbidities in access to kidney transplantation (KT) and patient and graft survival were estimated using Cox regression.ResultsComorbidities were present in 33% of the 4127 children commencing KRT and the prevalence has steadily increased by 5% annually since 2007. Comorbidities were most frequent in high-income countries (43% versus 24% in low-income countries and 33% in middle-income countries). Patients with comorbidities had a lower access to transplantation {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61–0.74]} and a higher risk of death [aHR 1.79 (95% CI 1.38–2.32)]. The increased mortality was only seen in dialysis patients [aHR 1.60 (95% CI 1.21–2.13)], and not after KT. For both outcomes, the impact of comorbidities was stronger in low-income countries. Graft survival was not affected by the presence of comorbidities [aHR for 5-year graft failure 1.18 (95% CI 0.84–1.65)].ConclusionsComorbidities have become more frequent in children on KRT and reduce their access to transplantation and survival, especially when remaining on dialysis. KT should be considered as an option in all paediatric KRT patients and efforts should be made to identify modifiable barriers to KT for children with comorbidities.

The situation of limited data concerning the response to COVID-19 mRNA vaccinations in immunocom-promised children hinders evidence-based recommendations. This prospective observational study investigated humoral and T cell responses after primary BNT162b2 vaccination in secondary immunocompromised and healthy children aged 5–11 years. Participants were categorized as: children after kidney transplantation (KTx, n = 9), proteinuric glomerulonephritis (GN, n = 4) and healthy children (controls, n = 8). Expression of activation-induced markers and cytokine secretion were determined to quantify the T cell response from PBMCs stimulated with peptide pools covering the spike glycoprotein of SARS-CoV-2 Wuhan Hu-1 and Omicron BA.5. Antibodies against SARS-CoV-2 spike receptor-binding domain were quantified in serum. Seroconversion was detected in 56% of KTx patients and in 100% of the GN patients and controls. Titer levels were significantly higher in GN patients and controls than in KTx patients. In Ktx patients, the humoral response increased after a third immunization. No differences in the frequency of antigen-specific CD4+ and CD8+ T cells between all groups were observed. T cells showed a predominant anti-viral capacity in their secreted cytokines; however, this capacity was reduced in KTx patients. This study provides missing evidence concerning the humoral and T cell response in immunocompromised children after COVID-19 vaccination.

IntroductionCombined or sequential liver and kidney transplantation (CLKT/SLKT) restores kidney function and corrects the underlying metabolic defect in children with end-stage kidney disease in primary hyperoxaluria type 1 (PH1). However, data on long-term outcome, especially in children with infantile PH1, are rare.MethodsAll pediatric PH1-patients who underwent CLKT/SLKT at our center were analyzed retrospectively.ResultsEighteen patients (infantile PH1 n = 10, juvenile PH1 n = 8) underwent transplantation (CLKT n = 17, SLKT n = 1) at a median age of 5.4 years (1.5–11.8). Patient survival was 94% after a median follow-up of 9.2 years (6.4–11.0). Liver and kidney survival-rates after 1, 10, and 15 years were 90%, 85%, 85%, and 90%, 75%, 75%, respectively. Age at transplantation was significantly lower in infantile than juvenile PH1 (1.6 years (1.4–2.4) vs. 12.8 years (8.4–14.1), P = 0.003). Median follow-up was 11.0 years (6.8–11.6) in patients with infantile PH1 vs. 6.9 years (5.7–9.9) in juvenile PH1 (P = 0.15). At latest follow-up kidney and/or liver graft loss and/or death showed a tendency to a higher rate in patients with infantile vs. juvenile PH1 (3/10 vs. 1/8, P = 0.59).DiscussionIn conclusion, the overall patient survival and long-term transplant outcome of patients after CLKT/SLKT for PH1 is encouraging. However, results in infantile PH1 tended to be less optimal than in patients with juvenile PH1.

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome.Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form.Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (+/- 1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage >= 2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients >= 25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients.Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.

Background:Early onset de novo focal segmental glomerular sclerosis (FSGS) in the kidney allograft in patients without FSGS in the native kidney is a rare disorder in children. It usually occurs mostly beyond the first year after kidney transplantation and often leads to graft loss. Standardized treatment protocols have not yet been established.Case description:We describe a boy with early onset de novo FSGS in the transplanted kidney and non-selective glomerular proteinuria (maximum albumin-to-creatinine ratio of 3.8 g/g; normal range, ≤0.03 g/g creatinine). Manifestation occurred at 30 days posttransplant and was accompanied by a significant graft dysfunction (eGFR 61 ml/min per 1.73 m2). Treatment with 25 sessions of plasmapheresis over 14 weeks and three consecutive days of methylprednisolone pulse therapy (10 mg/kg per day) followed by oral prednisolone as rejection prophylaxis (3.73 mg/m2 per day) led to sustained remission of proteinuria (albumin-to-creatinine ratio of 0.028 g/g) and normalization of graft function (eGFR 92 ml/min per 1.73 m2) after 14 weeks. The follow-up period was 36 months.Conclusions:This case underlines the efficacy of immunosuppressive and antibody eliminating therapy in early onset de novo FSGS after kidney transplantation.

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical character-istics with declining kidney function.Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218).Results: A total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3-12.0); NPHP1, 13.5 years (interquartile range 10.5-16.5); NPHP4, 16.0 years (interquartile range 11.0-25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7-28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline.Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct pa-tients with NPH and thereby allow personalized counseling.