Conversion from calcineurin inhibitors to mTOR inhibitors

Purpose of review The nephrotoxicity of the calcineurin inhibitors and the availability of newer nonnephrotoxic immunosuppressive agents have stimulated interest in calcineurin inhibitor-sparing protocols. This article focuses on studies in which the mTOR inhibitor, sirolimus, has been used to replace calcineurin inhibitors in kidney transplant recipients with chronic allograft nephropathy or chronic calcineurin inhibitor nephrotoxicity. Recent findings Collective experience with over 2000 patients, reported in randomized or nonrandomized clinical trials, suggests that conversion from calcineurin inhibitors to sirolimus generally is accompanied by short-term improvements in renal function. Sirolimus exhibits multiple side effects, and discontinuation rates in the reviewed conversion trials are consistently high. The most concerning and recently recognized side effect of sirolimus is proteinuria. The largest randomized trial to date indicates that outcomes of patients converted from calcineurin inhibitors to sirolimus are optimal when glomerular filtration is well preserved, and when histologic hallmarks of chronic allograft nephropathy and urine protein excretion are minimal. Summary Conversion from calcineurin inhibitors to sirolimus is increasingly accepted as a strategy for managing patients with chronic allograft nephropathy, despite the well known side effects of sirolimus. Short-term improvements in renal function are most dramatic when conversion is performed in patients with minimal renal dysfunction, The mechanisms and consequences of sirolimus-induced proteinuria warrant further study.