Association of graft survival with tacrolimus metabolism in pediatric and young adult kidney transplant recipients: an international Collaborative Transplant Study analysis

Abstract Introduction Evidence on the association between tacrolimus concentration-to-dose ratio (CDR), a surrogate marker of tacrolimus metabolism, and graft outcome in pediatric and young adult kidney transplant recipients is limited. Methods We retrospectively analyzed 3768 pediatric (1–17 years old) and young adult (18–24 years old) kidney transplant recipients from the Collaborative Transplant Study database. CDR was assessed at one year post-transplant and normalized to body weight to account for pediatric heterogeneity and improve comparability with adult values. Pediatric recipients were stratified into children (1–11 years) and adolescents (12–17 years). We examined associations between CDR and death-censored graft loss during post-transplant years 2–5. Results Adolescents and young adults had a significantly higher risk of graft loss than children ( P < 0.001). A one-year CDR below 0.58 was independently associated with an increased risk of graft failure in adolescents (adjusted hazard ratio [aHR] 1.74, P = 0.004) and young adults (aHR 1.98, P < 0.001), but not in children ( P = 0.98). CDR was below 0.58 in 25.2% of adolescents and 13.8% of young adults. Among young adults, its association with graft failure was stronger in patients with higher immune reactivity (positive PRA at baseline, P < 0.001). Conclusions In the largest cohort to date of pediatric and young adult kidney transplant recipients receiving tacrolimus-based immunosuppression, low CDR identified adolescents and young adults as a high-risk subgroup for graft loss, whereas graft survival in children was largely independent of CDR. These findings support age-specific risk stratification and individualized immunosuppression according to developmental stage.