Tacrolimus Trough Intravariability in Patients Treated With the Prolonged-Release Formulation Is a Risk Factor for Acute Graft Rejection.

Abstract

OBJECTIVES\nTacrolimus has a narrow therapeutic window, and lack of adherence to the therapeutic regimen is a main risk factor for acute graft rejection; hence, the prolonged-release formulation was created. A high intrapatient variability for tacrolimus trough levels has been associated with worse graft outcomes; therefore, we investigated the correlation between the tacrolimus variation coefficient and the development of biopsy-proven acute graft rejection in kidney transplant patients with typical maintenance immunosuppression versus the prolonged-release formulation.\n\n\nMATERIALS AND METHODS\nThis was a single-center observational retrospective study that included all adult kidney transplants from deceased donors between January 2011 and December 2014 for which the transplant recipients were given maintenance therapy with tacrolimus prolonged-release formulation (Advagraf). The overall tacrolimus variation coefficient was calculated for the follow-up period from transplant until December 2019. Biopsy-proven acute graft rejection results were collected throughout follow-up. Statistical analysis was performed with SPSS software.\n\n\nRESULTS\nThe study was composed of 147 patients with a mean follow-up time of 60.4 ± 15 months. The mean age of the patients was 47.5 ± 11.9 years and 67.3% were men. Of these 147 patients, 29 had at least 1 episode of acute graft rejection during follow-up. There was a significant correlation between patients with a higher tacrolimus variation coefficient and the presence of biopsy-proven acute graft rejection. Receiver operating characteristic curves were used to determine an intrapatient variability cutoff point of 28.3% for tacrolimus. Younger patients were also more likely than older patients to develop acute graft rejection in our sample.\n\n\nCONCLUSIONS\nHigh intrapatient variability of tacrolimus trough levels is a risk factor for acute graft rejection in kidney transplant patients.