Induction therapy and mTOR inhibition: minimizing calcineurin inhibitor exposure in de novo renal transplant patients

Abstract

Use of induction therapy with mTOR inhibitor maintenance immunosuppression to facilitate reduced calcineurin inhibitor (CNI) exposure in de novo kidney transplant patients has been explored in a series of randomized trials. These studies have typically employed interleukin-2 receptor antagonist (IL-2RA) induction, in low or standard immunological risk recipients. Although no study has directly compared mTOR inhibition plus reduced CNI exposure with or without induction, inclusion of IL-2RA induction appears to permit a substantial reduction in CNI exposure without the need for high mTOR inhibitor dosing. IL-2RA induction with an mTOR inhibitor and steroids has consistently shown similar efficacy to standard-exposure CNI with mycophenolic acid and steroids and may improve renal function among patients who remain on the mTOR inhibitor-based regimen. With modern mTOR inhibitor dosing, wound healing complications are of less concern and may be no more frequent than in mycophenolic acid-based regimens. The incidence of cytomegalovirus infection appears lower in patients receiving de novo mTOR inhibition. The available evidence demonstrates that IL-2RA induction with an mTOR inhibitor can successfully reduce CNI exposure by at least half without a penalty in terms of rejection in low- or moderate-risk de novo transplant recipients and may offer renal and antiviral benefits.

Keywords: antithymocyte globulin; basiliximab; calcineurin inhibitors; daclizumab; everolimus; induction; kidney transplantation; mTOR inhibitors; minimization; sirolimus.