Conversion to sirolimus in solid organ transplantation: A single-center experience

Background. Calcineurin inhibitors are associated with adverse events, including nephrotoxicity and diabetes that might reduce the benefits of long-term graft survival. We report our experience in converting kidney (K), kidney-pancreas (KP), pancreas (P), and (L) recipients from a calcineurin inhibitor/mycophenolate mofetil (MMF)/prednisone dose-induced nephrotoxicity (K = 9, KP = 5, P = 1, L = 5), hemolytic uremic syndrome (HUS) (K = 7, KP = 5), chronic allograft nephropathy (K = 12, L = 1), and glucose intolerance (K = 9, KP = 6, P = 2, L = 2). Methods. The conversion protocol consisted of an abrupt discontinuation of the calcineurin inhibitor with sirolimus (8-12 mg, PO loading dose) initiated 24-72 hours after stopping the calcineurin inhibitor. Sirolimus was titrated to target trough levels of 12-16 ng/mL. Daclizumab 2 mg/kg IV was given to all KP and P recipients on days 0 and 14 postconversion. Results. Resolution of HUS occurred in 12 of 12 patients (100%) with a drop in serum creatinine from 3.3 ± 1.5 to 1.8 ± 0.9 mg/dL (P = .04). Sirolimus conversion due to nephrotoxicity, HUS, and chronic allograft nephropathy improved serum creatinine from 2.9 ± 1.4 to 2.2 ± 0.9 mg/dL (P = .01). Eleven of 19 patients (58%) resolved glucose intolerance. Two patients suffered rejection due to noncompliance. Increases in cholesterol (208 ± 70 to 243 ± 77 mg/dL, P < .05) and triglycerides (232 ± 145 to 265 ± 148 mg/dL, P = NS), and minimal reduction in platelet values (243 ± 85 to 237 ± 85, P = NS) occurred. Conclusions. These data suggest that a calcineurin inhibitor-free immunosuppressive regimen with sirolimus, mycophenolate mofetil, and steroids preserves graft function in patients with clinical indications warranting calcineurin inhibitor discontinuation.