Steroid and Calcineurin Inhibitor—Sparing Protocols in Kidney Transplantation

Abstract

Recent improvements in kidney transplantation have been driven largely by lower acute rejection rates attributed to better immunosuppressive agents. In an effort to reduce the long-term toxicities of immunosuppressant drugs, corticosteroid- and calcineurin inhibitor (CNI)–sparing immunosuppression protocols have become increasingly popular in managing kidney transplant recipients. Nevertheless, these strategies may increase the risk of acute and chronic allograft injury (CAI) that may worsen the fate of transplant recipients. This article focuses on steroid and CNI sparing protocols to elucidate their safety and efficacy in patients receiving a kidney transplant. Steroid avoidance protocols are rapidly and increasingly being used. Studies have shown that corticosteroids are not essential to achieve excellent short- and intermediate-term results. However, the role of steroid withdrawal is only marginally beneficial and very often benefit overstated. CNI-sparing strategies have been used to help maintain the balance between allograft survival and nephrotoxicity. Trials evaluating CNI minimization have shown reduced incidence of CAI and preservation of allograft function. CNI withdrawal within 3 to 12 months after kidney transplantation improved graft function despite increased risk of acute rejection. This approach may be feasible with adequate exposure and proper usage of mammalian target of rapamacin inhibitors. Late withdrawal or conversion did not show a clear benefit. Timing and degree of renal dysfunction are key determining factors. With regards to CNI avoidance, earlier trials, such as the Symphony study, did not support the use of a CNI-free regimen of low-dose sirolimus as initial immunosuppression. However, recent studies using costimulatory blockade-based immusouppression showed that CNI avoidance is possible. The best maintenance immunosuppressive with CNI- or steroid-sparing is a work in progress and awaits longer term follow-up. The availability of newer biologics for costimulatory blockade and new immunosuppressive agents with novel mechanisms of action have the potential of using CNI- and steroid-sparing protocols to minimize the incidence of CAI and improve long-term outcomes in kidney transplant recipients.