Minimizing calcineurin inhibitor drugs in renal transplantation

Calcineurin inhibitor drugs (CNI), primarily cyclosporine then tacrolimus, have been the centerpieces of maintenance immunosuppression for kidney transplantation since their introduction in the 1980s. While these drugs have been responsible for improved short-term outcomes and diminished rates of acute rejection, they are nephrotoxic and can cause permanent renal injury in many patients. Indeed, some have found that at 10 years after transplantation, the benefits of CNI drugs have been lost compared to the previous generation of maintenance immunosuppression. The use of these agents over many years contributes to the antigen-independent decline in renal function referred to as chronic allograft nephropathy. However, it remains unclear to what degree the use of CNI drugs contribute to ultimate graft loss. For these reasons immunosuppressive alternatives to CNI drugs have begun to emerge during the past few years. The recent introduction of the potent immunosuppressive agent sirolimus has afforded an opportunity to develop a regimen designed to maximize prophylaxis of early acute rejection, absent drug-induced nephrotoxicity. It was our feeling that the combination of antibody induction therapy combined with sirolimus substitution in a three-drug maintenance regimen, would provide the best posttransplant renal function and lowest rates of acute rejection. We have developed a CNI-free immunosuppressive regimen consisting of basiliximab induction, followed by sirolimus, MMF and steroids. Using this protocol we demonstrated comparable transplant outcomes with improved renal function in adult recipients of primary renal transplants. Limiting nephrotoxic immunosuppression should be considered an important goal; but requires sufficient long-term follow-up to support the benefits suggested from initial analysis of the data.