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Published on: November 8, 2015
Age-Related Differences in Rejection Rates, Infections, and Tacrolimus Exposure in Pediatric Kidney Transplant
Maral Baghai Arassi1,2, Manuel Feißt3, Kai Krupka1
1Department of Pediatrics I, Medical Faculty, Heidelberg University, University Children's Hospital Heidelberg, Heidelberg, Germany.
Insights
Pediatric kidney transplant recipients show age-related differences in infections and rejection. Younger children experience more infections, while adolescents have higher acute rejection rates, indicating a need for personalized immunosuppression.
Area of Science:
- Pediatric Nephrology
- Transplantation Immunology
- Pharmacokinetics
Background:
- Limited data exists on age-specific outcomes for pediatric kidney transplant recipients (pKTRs) on tacrolimus-based immunosuppression.
- Understanding these differences is crucial for optimizing treatment strategies and improving long-term graft survival.
Purpose of the Study:
- To analyze age-related differences in rejection rates, infectious episodes, and tacrolimus exposure in pKTRs.
- To identify distinct risk profiles across different age groups for tailored immunosuppressive therapy.
Main Methods:
- A large-scale analysis of 802 pKTRs from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry.
- Patients were stratified into three age groups: infants/young children (<6 years), school-aged children (6-12 years), and adolescents (>12 years).
- Outcomes including rejection, infections, and tacrolimus levels were assessed over a minimum 2-year follow-up period.
Main Results:
- Infants and young children (<6 years) had significantly higher infection rates (80.6%) and hospital days compared to adolescents (55.0%).
- Adolescents (>12 years) showed a higher incidence of biopsy-proven acute rejection in the first year (21.7%) versus younger children (12.6%).
- Younger children exhibited lower tacrolimus trough levels, lower concentration-to-dose ratios, and higher interpatient variability, suggesting increased tacrolimus clearance.
Conclusions:
- Significant age-related variations exist in rejection, infection, and tacrolimus pharmacokinetics among European pKTRs.
- Immunosuppressive therapy requires age-specific tailoring to address heterogeneous risk profiles in pKTRs.
- This study provides a benchmark for future research on novel immunosuppressive agents in pediatric transplantation.
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.
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