Indications:Graft rejection prophylaxis in 41 patients who underwent renal transplantation.Patients:41 patients were studied but only 20 (10 males and 10 females, 16 adults and 4 children) were included in the final analysis.TypeofStudy:A prospective observational study evaluating the effectiveness of sirolimus in a Sandimmun elimination regimen in combination with mycophenolate mofetil (MMF) and steroids in high-risk renal transplant recipients (RTR) and recipients with calcineurin inhibitor (CNI) nephrotoxicity.DosageDuration:Initial dose of 7 mg/kg daily from day of transplant tapered to 1-2 mg/kg daily in 6 months. Duration: more than 6 months.Results:Among the 20 subjects who completed more than 6 months follow up were 6 RTR who experienced AR on therapeutic doses of Sandimmun during the first 3 months posttransplant; 10 with CNI toxicity on therapeutic doses of Sandimmun; and 4 de novo high-risk second transplants. All patients were converted from Sandimmun to sirolimus. Treatment with sirolimus showed significant improvement in creatinine clearance posttreatment (82 ± 24.9 mL/min) compared to pretreatment (54.7 ± 23) and best pretreatment (75.1 ± 27) (P<0.01) levels.AdverseEffects:17 patients experienced nephrotoxicity (hemolytic uremic syndrome).AuthorsConclusions:Low-dose sirolimus in combination with MMF was effective and safe as a CNI elimination alternative for high-risk RTR in this short-term study.FreeText:The study included RTR who experienced biopsy-proven acute rejection (AR) despite therapeutic doses of Sandimmun during the first 3 months posttransplant (n = 20), CNI toxicity with therapeutic doses of Sandimmun (hemolytic uremic syndrome, nephrotoxicity; n = 17), and de novo second or third transplantation (n = 4). Basic immunosuppression in addition to Sandimmun consisted of prednisolone tapered from 1 mg/kg from the day of transplant to 10 mg/kg daily by 6 months; mycophenolate mofetil 1 g twice daily from the day of transplant. In addition all subjects received prophylaxis for the first 6 months with acyclovir, cotrimoxazole, and mycostatin daily. Other concomitant medications included antithymocyte globulin or interleukin-2 receptor antibodies. Both for CNI elimination and de novo immunosuppression, sirolimus was used at a loading dose of 6 mg and maintenance dose of 2 mg daily in adults and 3 mg loading with 1 mg daily maintenance in children. Tests: serum creatinine level and creatinine clearance.
