Validation of a dynamic prediction model of kidney allograft survival in pediatric kidney transplant recipients

Introduction: Accurate prediction models of kidney allograft loss are lacking in children. Dynamic models allow the integration of new data throughout a patient’s follow-up making them better fitted from clinical use than traditional predictive models. In this study, we aim at externally validating a dynamic score of kidney allograft loss, developed in a derivation cohort of 793 French pediatric kidney transplant recipients, in a large cohort from the United States. Methods: All patients aged < 21 years old, transplanted in the US between January 1st 2002 and December 31st 2015 recorded in the SRTR registry were included in the validation cohort. Two predictive models were previously developed using joint models on the French National Registry data (REIN) and included recipient, donor and transplant characteristics and follow-up data (eGFR, eGFR slope). Individual predictions of allograft loss at 3 and 5 years were made by applying these two models on the validation cohort. Model accuracy was evaluated based on its discrimination (AUC) and calibration (R2). Results: 10,613 patients were included. Among them, 94% were younger than 18 years old at the time of transplantation, 59% were male, 28% received a preemptive transplant and 43% a living donor transplant. Over a median follow-up time of 6.6 [4.0;9.7] years, 2420 patients (23%) lost their graft and 316 (6%) died. The performances of the models were good with excellent discrimination (AUCs between 0.8 and 0.9) and good calibration (Figure 1). The performance of the reduced model were similar to those of the full model. Conclusion: This predictive model demonstrated high accuracy in predicting kidney allograft loss in children and support the benefit of incorporating longitudinal information to improve prediction performance. This model can be used prospectively to assess patients’ risk of graft loss and further study evaluating the impact of using this model in clinical practice are needed

Datasheet1_Post-transplant lymphoproliferative disorder risk and outcomes in renal transplant patients treated with belatacept immunosuppression.docx

IntroductionPost-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening malignancy that arises in the setting of immunosuppression (IS) after solid organ transplant. IS regimens containing belatacept have been associated with an increased risk of PTLD in Epstein–Barr virus (EBV)-seronegative renal transplant recipients, and the use of belatacept is contraindicated in this population. However, the impact of belatacept-based regimens on PTLD risk and outcomes in EBV-seropositive renal transplant recipients is less well characterized.MethodsA case-control study was conducted to investigate how combinatorial IS regimens impact the risk of PTLD and survival outcomes in renal transplant recipients at a large transplant center between 2010 and 2019. In total, 17 cases of PTLD were identified and matched 1:2 to controls without PTLD by age, sex, and transplanted organ(s). We compared baseline clinical characteristics, examined changes in IS regimen, viral loads, and renal function over time, and evaluated time-to-event analyses, including graft rejection and survival.ResultsCases of PTLD largely resembled matched controls in terms of baseline characteristics, although expected differences in EBV serostatus trended toward significance (42.9% of PTLD cases were donor-positive/recipient-negative vs. 8.3% controls, p = 0.063). PTLD cases were not more likely to have received belatacept than controls. Belatacept was not associated with graft rejection or failure, re-transplant, hospitalization, or decreased survival.ConclusionsBelatacept was not associated with an increased risk of PTLD, and was not associated with decreased survival in either PTLD cases or in the entire cohort. Our case-control study supports the concept that belatacept remains a safe and effective option for IS in EBV-seropositive renal transplant patients.</p