Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant Recipients in the CERTAIN Registry

Overview

Journal Kidney Int Rep

Publisher Elsevier

Specialty Nephrology

Date 2024 Nov 13

PMID 39534206

Authors

Maral Baghai Arassi

Manuel Feisst

Kai Krupka

Atif Awan

Elisa Benetti

Ali Duzova

Isabella Guzzo

Jon Jin Kim

Birgitta Kranz

Mieczyslaw Litwin

Jun Oh

Anja Buscher

Lars Pape

Licia Peruzzi

Mohan Shenoy

Sara Testa

Lutz T Weber

Jakub Zieg

Britta Hocker

Alexander Fichtner

Burkhard Tonshoff

Affiliations

Soon will be listed here.

Abstract

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, < 0.001) and a significantly higher number of cumulative hospital days (median 13 days vs. 7 days in adolescents, < 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%, = 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 < 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.

Citing Articles

Second kidney transplant during childhood: clinical aspects, outcomes, and risk factors for graft survival.

de Santis Feltran L, Hamamoto F, Genzani C, Fonseca M, de Carvalho M, Koch-Nogueira P Pediatr Nephrol. 2025; .

PMID: 39954072 DOI: 10.1007/s00467-025-06685-6.

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