New strategies to reduce nephrotoxicity.

Since the introduction of cyclosporine, CNIs have formed the basis of immunosuppressive therapy in renal transplantation. The propensity of these agents to ultimately damage the very organs they were intended to protect was always recognized, but largely ignored due to their impressive ability to improve short-term outcomes. With the availability of equally powerful new immunosuppressive agents devoid of major nephrotoxicity, the irony of this situation has become all too apparent, and investigators are beginning to reevaluate the role of CNIs in renal transplantation. In this paper, we looked at strategies using MMF or sirolimus to reduce, withdraw, or replace CNIs in renal transplantation. Although MMF has proved effective in combination with CNIs, particularly in reducing acute rejection rates, its use as base therapy to allow CNI therapy to be withdrawn or eliminated is questionable. On the basis of initial trials, sirolimus holds promise for use as base therapy. To date, it is probably the only agent used in renal transplantation that provides immunosuppression comparable to cyclosporine or tacrolimus, which may someday allow sirolimus to replace. CNIs or allow early withdrawal of CNI therapy. Further study is needed to better clarify the role of sirolimus in improving long-term renal transplantation outcomes.