Drug Level Changes Predict Renal Transplant Success in Kids
In paediatric kidney transplant recipients, high variability in tacrolimus trough blood levels was significantly associated with allograft rejection occurring beyond 12 months post-transplant; however, rapid tacrolimus metabolism was significantly associated with rejection episodes occurring between 6 and 12 months.
METHODOLOGY:
Tacrolimus remains essential in contemporary immunosuppressive regimens, yet its narrow therapeutic window and wide interpatient and intrapatient variability complicate dosing. Although high variability in tacrolimus blood levels and a low concentration-to-dose (C/D) ratio — an approximation of tacrolimus metabolism — predict kidney transplant rejection in adults, comparable paediatric data are scarce.
Researchers in Germany conducted a retrospective study to assess the predictive value of tacrolimus intrapatient variability (TacIPV) and C/D ratio for transplant outcomes in children receiving kidney transplantation.
They analysed 13,159 tacrolimus trough blood levels in 255 paediatric kidney transplant recipients (median age at transplantation, 11 years; 59% boys) who received a tacrolimus-based immunosuppressive regimen; the median follow-up duration was 60 months.
TacIPV was quantified during months 6-12 post-transplant, and the C/D ratio was evaluated during both early (first 6 months) and late (6-12 months) periods.
Measured outcomes encompassed the incidence of allograft rejection, the occurrence of opportunistic infections, and the degree of graft dysfunction.
TAKEAWAY:
Overall, allograft rejection occurred in 45% of patients — 9% within the first 6 months post-transplant, 6% between 6 and 12 months, and 30% after 12 months.
High TacIPV during months 6-12 post-transplant was associated with an increased risk for allograft rejection beyond 12 months post-transplant (hazard ratio [HR], 1.04; P = .002); a TacIPV threshold of more than 23% could distinguish patients who did vs did not experience allograft rejection.
A low C/D ratio during the first 6 months post-transplant was correlated with a higher risk for allograft rejection between months 6 and 12 (inverse HR, 3.13; 95% CI, 1.05-9.09; P = .04); a C/D ratio cutoff of less than 1.0 could distinguish patients who did vs did not experience allograft rejection.
Opportunistic infections and graft dysfunction occurred in 42% and 10% of patients, respectively.
IN PRACTICE:
"TacIPV and C/D ratio may serve as cost-effective, non-invasive predictive markers for early identification of patients at risk for rejection," the authors wrote.
SOURCE:
This study was led by Maral Baghai Arassi, Department of Pediatrics I, Medical Faculty, University Children's Hospital, Heidelberg, Germany. It was published online on July 21, 2025, in Pediatric Nephrology.
LIMITATIONS:
This study could not establish direct causal relationships between tacrolimus exposure, the factors influencing it, and transplant outcomes. The cohort may not fully represent the broader population of kidney transplant recipients as patients with incomplete tacrolimus monitoring data were excluded. Additionally, as most patients were of Caucasian descent, the findings may not fully generalise to more diverse populations.
DISCLOSURES:
This study was supported by a Young Investigator Award from the European Society for Paediatric Nephrology; a grant from Chiesi, Germany; and other sources. One author reported receiving research grants and consulting fees from various pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
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