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

Abstract

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.