INTRODUCTION: Data on age-related differences in rejection rates, infectious episodes, and tacrolimus exposure in pediatric kidney transplant recipients (pKTRs) on a tacrolimus-based immunosuppressive regimen are scarce. METHODS: We performed a large-scale analysis of 802 pKTRs from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry from 40 centers in 14 countries. The inclusion criteria were a tacrolimus-based immunosuppressive regimen and at least 2 years of follow-up. The patient population was divided into 3 age groups (infants and young children aged <6 years, school-aged children 6-12 years, and adolescents aged >12 years) to assess age-related differences in outcome. RESULTS: Median follow-up was 48 months (interquartile range [IQR], 36-72). Within the first 2 years posttransplant, infants, and young children had a significantly higher incidence of infections (80.6% vs. 55.0% in adolescents, P < 0.001) and a significantly higher number of cumulative hospital days (median 13 days vs. 7 days in adolescents, P < 0.001). Adolescents had a significantly higher rate of biopsy-proven acute rejection episodes in the first-year posttransplant (21.7%) than infants and young children (12.6%, P = 0.007). Infants and young children had significantly lower tacrolimus trough levels, lower tacrolimus concentration-to-dose (C/D) ratios as an approximation for higher tacrolimus clearance, and higher tacrolimus interpatient variability (TacIPV) (all P < 0.01) than adolescents. CONCLUSION: This is the largest study to date in European pKTRs on a tacrolimus-based immunosuppressive regimen, and it shows important age-related differences in rejection rates, infection episodes, as well as tacrolimus exposure and clearance. This data suggests that immunosuppressive therapy in pKTRs should be tailored and personalized according to the age-specific risk profiles of this heterogeneous patient population. The data may serve as a benchmark for future studies with novel immunosuppressive drugs.

Department of General Pediatrics University Children's Hospital Münster Münster Germany

Department of Nephrology Kidney Transplantation and Hypertension The Children's Memorial Health Institute Warsaw Poland

Department of Pediatric Nephrology Nottingham University Hospitals Nottingham UK

Department of Pediatric Nephrology Royal Manchester Children's Hospital Manchester UK

Department of Pediatrics 1 Medical Faculty Heidelberg University University Children's Hospital Heidelberg Heidelberg Germany

Department of Pediatrics 2 University Hospital of Essen Essen Germany

Department of Pediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Division of Nephrology Dialysis and Transplant Unit Bambino Gesù Children's Hospital IRCCS Rome Italy

Division of Pediatric Nephrology Hacettepe University Faculty of Medicine Ankara Türkiye

Division of Pediatric Nephrology University Hamburg Eppendorf Hamburg Germany

Institute of Medical Biometry Heidelberg University Heidelberg Germany

National Pediatric Haemodialysis Centre and Renal Transplant Unit Temple Street Children's University Hospital Dublin Ireland

Pediatric Nephrology Children's and Adolescents' Hospital University Hospital of Cologne Faculty of Medicine University of Cologne Köln Germany

Pediatric Nephrology Unit Department of Women's and Children's Health Padua University Hospital Italy

Pediatric Nephrology Unit Dialysis and Transplantation Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Pediatric Nephrology Unit Regina Margherita Department Azienda Ospedaliero Universitaria Città Della Salute e della Scienza Torino Italy

Structural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg Heidelberg Germany

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