Interleukin-2 receptor antagonist therapy leads to increased tacrolimus levels after kidney transplantation.

Publication Type
Journal Article
Year of Publication
Lin, Sonia; Henning, Alice K; Akhlaghi, Fatemeh; Reisfield, Robin; Vergara-Silva, Andrea; First, M Roy
Ther Drug Monit
Date Published
2015 Apr
Adult; Animals; Antilymphocyte Serum; Dose-Response Relationship, Drug; Drug interactions; Female; Glucocorticoids; Graft Survival; Humans; Immunosuppressive Agents; kidney transplantation; Male; Middle Aged; Rabbits; Randomized Controlled Trials as Topic; Receptors, Interleukin-2; Retrospective Studies; Survival Rate; Tacrolimus; Time Factors

BACKGROUND: Tacrolimus (TAC) is a known substrate for cytochrome P450 (CYP) enzyme. CYP enzyme activity can be modulated by activation of IL-2 receptors (IL-2R) expressed on hepatocytes and intestinal cells. IL-2R antagonists (IL-2RA) may promote preferential binding of circulating IL-2 to IL-2Rs on these cells by blocking IL-2Rs on activated T cells. This downregulates CYP enzymes, leading to increased calcineurin inhibitor levels. This analysis evaluates the significance of this drug-drug interaction in kidney transplant recipients.

METHODS: Data were used from a previous 5-year randomized, controlled study comparing outcomes associated with maintenance immunosuppression using 2 corticosteroid regimens: long-term therapy versus early withdrawal. Patients received either IL-2RAs or rabbit anti-thymocyte globulin (rATG) for induction. Serial TAC trough levels and doses were compared between induction agents within each corticosteroid arm. Rejection rates, patient/graft survival, and TAC adverse effects were also evaluated.

RESULTS: In the first week, IL-2RA-treated patients achieved significantly higher trough levels and required lower doses (in milligram per kilogram) to achieve target levels than rATG-treated patients. No significant differences in rejection rates, patient/graft survival, or rate of adverse effects were observed through 1 year.