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Background: Many centers accept a minimum body weight of 10 kg as threshold for kidney transplantation (Tx) in children. As solid evidence for clinical outcomes in multinational studies is lacking, we evaluated practices and outcomes in European children weighing below 10 kg at Tx., Methods: Data were obtained from the European Society of Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry on all children who started kidney replacement therapy at <2.5 y of age and received a Tx between 2000 and 2016. Weight at Tx was categorized (<10 versus ≥10 kg) and Cox regression analysis was used to evaluate its association with graft survival., Results: One hundred of the 601 children received a Tx below a weight of 10 kg during the study period. Primary renal disease groups were equal, but Tx <10 kg patients had lower pre-Tx weight gain per year (0.2 versus 2.1 kg; P < 0.001) and had a higher preemptive Tx rate (23% versus 7%; P < 0.001). No differences were found for posttransplant estimated glomerular filtration rates trajectories (P = 0.23). The graft failure risk was higher in Tx <10 kg patients at 1 y (graft survival: 90% versus 95%; hazard ratio, 3.84; 95% confidence interval, 1.24-11.84), but not at 5 y (hazard ratio, 1.71; 95% confidence interval, 0.68-4.30)., Conclusions: Despite a lower 1-y graft survival rate, graft function, and survival at 5 y were identical in Tx <10 kg patients when compared with Tx ≥10 kg patients. Our results suggest that early transplantation should be offered to a carefully selected group of patients weighing <10 kg., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Kidney transplantation (KT) is the optimal treatment for children with end-stage kidney disease. The aim of this study was to evaluate the impact of preemptive kidney transplantation (PKT) and of pretransplant dialysis duration on graft survival among French pediatric kidney transplant recipients., Methods: We analyzed all first pediatric kidney-only transplantations performed in France between 1993 and 2012. A Cox multivariable model was used to investigate the association of PKT and pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis, or retransplant, whichever occurred first., Results: Patients (n = 1911) were included, of which 380 (19.8%) received a PKT. Median time of follow-up was 7.0 y. PKT was associated with a 55% reduction of the hazard of graft failure at any time after KT compared with patients transplanted after dialysis (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62), after adjustment for recipient sex and age, primary kidney disease, donor age and type (living or deceased donor), number of HLA mismatches, cold ischemia time, and year of transplantation. A reduction of the hazard of graft failure was found in PKT whatever the compared duration of dialysis, even when <6 mo and whatever the dialysis modality. Results were similar in multiple sensitivity analyses., Conclusions: In France, PKT among pediatric patients is associated with a better graft survival when compared with KT after dialysis, even when <6 mo. Based on these findings, we suggest that PKT should be considered as the treatment of choice for children with end-stage kidney disease., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The renal transplantation is the best treatment for end-stage renal disease in children. We present the findings of an analysis of our institution's paediatric transplant outcomes comparing recipients under 15 kg, who represent this potentially higher risk group, to those above 15 kg., Methods: We retrospectively identified consecutive paediatric kidney transplants from a prospectively collected database for analysis. We included all recipients under the age of 18 years at the time of transplant between 2006 and 2018 without any exclusion criteria. The primary outcome was death-censored graft survival at 1 year, 5 years and 10 years., Results: 109 paediatric kidney transplants were performed in 100 children. Graft survival in the all population was 98%, 96% and 76% at 1 year, 5 years and 10 years, respectively. Recipient weight below 15 kg was not found to be a risk factor of graft loss. Overall, we found no individual factor to be statistically significantly associated with renal graft lost. The overall complication rate was 16% (18/109) with 12 early complications (11%) and 6 late ones (5%)., Conclusion: Kidney transplantation in children weighing < 15 kg seems safe and offers the same patient and graft survival outcomes as in other (> 15 kg) pediatric recipients with equally low complication rates., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Socioeconomic status is an important determinant of health. Its impact on kidney transplantation outcome has been studied among adults but data in children are scarce, especially in Europe. Here, we investigate the association between the level of social deprivation (determined by the continuous score European Deprivation Index) and graft failure risk in pediatric kidney transplant recipients. All patients listed under 18 years of age who received a first kidney transplant between 2002 and 2014 in France were included. Of 1050 kidney transplant recipients (males 59%, median age at transplantation 13.2 years, preemptive transplantation 23%), 211 graft failures occurred within a median followup of 5.9 years. Thirty-seven percent of these patients belong to the most deprived quintile, suggesting that deprivation is more frequent in pediatric patients with end-stage kidney disease (ESKD) than in the general population. Five- and ten-year graft survival were 85% and 69%, respectively, in the most deprived quintile vs. 90% and 83%, respectively, in the least deprived quintile. At any time after transplantation, patients in the most deprived quintile had almost a two-fold higher hazard of graft failure compared with the least deprived quintile, after adjustment for age at renal replacement therapy, duration of dialysis, primary kidney disease, and rural/urban living environment (hazard ratio 1.99; 95% confidence interval 1.20-3.28). The hazard of graft failure did not differ significantly between girls and boys. Thus, our findings suggest a lower socioeconomic status is independently associated with poor graft outcome in pediatric kidney transplantation., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Despite major technical improvements in the care of children requiring renal replacement therapy (RRT) before 2 years of age, the management of those patients remains challenging and transplantation is generally delayed until the child weighs 10 kg or is 2 years old. In this national cohort study, we studied patient and graft survival in children starting RRT before 2 years of age to help clinicians and parents when deciding on RRT initiation and transplantation management., Methods: All children starting RRT before 24 months of age between 1992 and 2012 in France were included through the national Renal Epidemiology and Information Network (REIN) registry. The primary endpoints were patient survival on dialysis and 10-year graft survival., Results: A total of 224 patients were included {62% boys, median age 10.5 months [interquartile range (IQR) 5.8-15.6]}. The 10-year survival rate was 84% (IQR 77-89). Suffering from extrarenal comorbidities was the only factor significantly associated with both an increased risk of death on dialysis [hazard ratio 5.9 (95% confidence interval 1.8-19.3)] and a decreased probability of being transplanted. During follow-up, 174 renal transplantations were performed in 171 patients [median age at first transplantation 30.2 (IQR 21.8-40.7) months]. The 10-year graft survival was 74% (IQR 67-81). Factors associated with graft loss in multivariate analysis were the time spent on dialysis before transplantation, donor/recipient height ratio with an increased risk for both small and tall donors and presenting two human leucocyte antigen-antigen D-related mismatches., Conclusions: This study confirms the good outcome of children starting RRT before 2 years of age. The main question remains when and how to transplant those children. Our study provides data on the optimal morphological and immunological matching in order to help clinicians in their decisions.

Treatment of SRNS is a challenge. Antiproliferative agents and depleting antibodies have been reported to be effective. However, these agents are not always successful, and use of ofatumumab could provide a different treatment option. Our patient was diagnosed with a SRNS at 5 years of age. She developed ESRD, with FSGS. This was cause for a first renal transplantation. The NS relapsed, leading to loss of the graft, and a second renal transplantation was performed. Due to the recurrence of the NS, IAds were initiated and led to a complete remission. Our patient remained dependent on IAds, however, despite treatments with calcineurin inhibitors, corticosteroids, rituximab, and abatacept. Ofatumumab was introduced and led to a remission, thus allowing cessation of the IAd treatment. Another infusion of ofatumumab was administered 8 months after the last one, due to the recurrence of the NS and a renewed increase in B cells. Although it did not result in a complete remission, the proteinuria was stabilized in the absence of IAds. Ofatumumab may be an alternative treatment for post-transplantation rituximab-resistant SRNS, although this needs to be confirmed by further studies., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The risk of graft failure in young kidney transplant recipients has been found to increase during adolescence and early adulthood. However, this question has not been addressed outside the United States so far. Our objective was to investigate whether the hazard of graft failure also increases during this age period in France irrespective of age at transplantation., Methods: Data of all first kidney transplantation performed before 30 years of age between 1993 and 2012 were extracted from the French kidney transplant database. The hazard of graft failure was estimated at each current age using a 2-stage modelling approach that accounted for both age at transplantation and time since transplantation. Hazard ratios comparing the risk of graft failure during adolescence or early adulthood to other periods were estimated from time-dependent Cox models., Results: A total of 5983 renal transplant recipients were included. The risk of graft failure was found to increase around the age of 13 years until the age of 21 years, and decrease thereafter. Results from the Cox model indicated that the hazard of graft failure during the age period 13 to 23 years was almost twice as high as than during the age period 0 to 12 years, and 25% higher than after 23 years., Conclusions: Among first kidney transplant recipients younger than 30 years in France, those currently in adolescence or early adulthood have the highest risk of graft failure.

Background: Patients with HNF1B mutations develop progressive chronic renal failure, diabetes mellitus (40-50%), and liver tests abnormalities (40-70%). In HNF1B patients who reach end-stage renal disease, single kidney transplantation (SKT) or combined kidney-pancreas transplantation can be considered., Methods: A retrospective multicenter study including 18 HNF1B patients receiving SKT or kidney-pancreas transplantation, and in vitro experiments including the characterization of the HNF1B expression after calcineurin inhibitor (CNI) exposure., Results: After SKT, 50% of the HNF1B patients develop early posttransplantation diabetes mellitus, whereas 40% experience new-onset or severe worsening of preexisting abnormalities of liver tests, including severe cholestasis. In liver biopsies, disorders of the cholangiocytes primary cilium and various degrees of bile duct paucity and dysplasia were identified. In vitro studies combining CNI exposure and siRNA-mediated inhibition of NFATc revealed that calcineurin inhibition decreases HNF1B expression in epithelial cells but independent of NFATc., Conclusions: Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1β transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach.

Background: Identification of patient groups by risk of renal graft loss might be helpful for accurate patient counselling and clinical decision-making. Survival tree models are an alternative statistical approach to identify subgroups, offering cut-off points for covariates and an easy-to-interpret representation., Methods: Within the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data we identified paediatric patient groups with specific profiles for 5-year renal graft survival. Two analyses were performed, including (i) parameters known at time of transplantation and (ii) additional clinical measurements obtained early after transplantation. The identified subgroups were added as covariates in two survival models. The prognostic performance of the models was tested and compared with conventional Cox regression analyses., Results: The first analysis included 5275 paediatric renal transplants. The best 5-year graft survival (90.4%) was found among patients who received a renal graft as a pre-emptive transplantation or after short-term dialysis (<45 days), whereas graft survival was poorest (51.7%) in adolescents transplanted after long-term dialysis (>2.2 years). The Cox model including both pre-transplant factors and tree subgroups had a significantly better predictive performance than conventional Cox regression (P < 0.001). In the analysis including clinical factors, graft survival ranged from 97.3% [younger patients with estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2) and dialysis <20 months] to 34.7% (adolescents with eGFR <60 mL/min/1.73 m(2) and dialysis >20 months). Also in this case combining tree findings and clinical factors improved the predictive performance as compared with conventional Cox model models (P < 0.0001)., Conclusions: In conclusion, we demonstrated the tree model to be an accurate and attractive tool to predict graft failure for patients with specific characteristics. This may aid the evaluation of individual graft prognosis and thereby the design of measures to improve graft survival in the poor prognosis groups., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Chronic kidney insufficiency (CKI) in children: Failure to thrive, feeding disorders and/or excessive thirst must evoke CKI in children. More than 50% of renal diseases in children with CKI are congenital or inherited. Major issues are growth, nutrition and renal osteodystrophy. Psychological and social management are crucial aspects of the therapeutic project. Peritoneal dialysis is the renal replacement therapy of choice, especially in children under 2 years, with an important risk of peritonitis. Kidney transplant, which can be performed in children more than 10 kg, is the best treatment of end-stage renal failure in children. Pediatric transplant specificities are increased risks of thrombosis, post-transplant lymphoproliferative disorders in EBV-negative recipients, and poor compliance to medication during adolescence., (Copyright © 2011. Published by Elsevier Masson SAS.)