Background. Data on age-related differences in rejection rates, infectious episodes and tacrolimus exposure in pediatric kidney transplant recipients (pKTR) on a uniform tacrolimus-based immunosuppressive regimen are scarce. Methods. We therefore performed a large-scale analysis of 802 pKTR from the CERTAIN registry from 40 centers in 14 countries. Inclusion criteria were a tacrolimus-based immunosuppressive regimen and at least two years of follow-up. The patient population was divided into three age groups (infants <6 years, school-aged children 6-12 years, and adolescents >12 years) to assess age-related differences in outcome. Results. Median follow-up was 48 months (IQR, 36-72). Within the first 2 years post-transplant, infants 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 post-transplant (21.7%) than infants (12.6%, P=0.007). Infants had significantly lower tacrolimus trough levels, lower concentration-to-dose ratios as an approximation for higher tacrolimus clearance, and higher intra-patient variability (all P < 0.01) than adolescents. Conclusions. This largest study to date in European pKTR on a tacrolimus-based immunosuppressive regimen shows important age-related differences in rejection rates, infection episodes, tacrolimus exposure and clearance. These data suggest that immunosuppressive therapy in pKTR should be tailored according to the age-specific risk profiles of this heterogeneous patient population.

Burkhard Tonshoff has received research grants from Novartis, Astellas, and Chiesi, and consulting fees from Bristol-Myers Squibb, CSL Behring Biotherapies for Life, Vifor and Chiesi. The other authors declare no conflicts of interest.

We acknowledge funding from the Medical Faculty of Heidelberg to Maral Baghai Arassi. The authors gratefully acknowledge the funding of the CERTAIN registry by a grant from the Dietmar Hopp Foundation, the European Society for Pediatric Nephrology (ESPN), the German Society for Pediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis.

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