Use of sirolimus to facilitate cyclosporine avoidance or steroid withdrawal in kidney transplant recipients

Abstract

Sirolimus is a non-nephrotoxic cell-cycle progression antagonist that has proven to be highly effective in preventing renal allograft rejection when used in combination with cyclosporine and corticosteroids. On the basis of its immunosuppressive potency alone, sirolimus has emerged as an agent with the potential for facilitating the elimination of calcineurin inhibitors or corticosteroids from the maintenance regimens administered to kidney transplant recipients. The results of three randomized trials suggest that use of sirolimus as a substitute for cyclosporine in patients receiving steroids and either azathioprine or mycophenolate mofetil results in comparable rates of acute rejection and better renal function than in patients maintained on cyclosporine. Preliminary results from uncontrolled trials indicate that use of sirolimus in combination with either cyclosporine or tacrolimus allows withdrawal of steroid therapy with low rates of subsequent acute rejection compared to historical controls. Larger, controlled studies with longer durations of follow-up are warranted to verify the favorable results of these early experiences with the use of sirolimus as a calcineurin inhibitor or steroid-sparing agent.