Conversion to Sirolimus in Renal Transplant Recipients: A Single-Center Experience

Abstract

Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 +/- 71 months. Mean serum creatinine level was 1.63 +/- 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 +/- 0.58 mg/dL (P = 0.67), 1.52 +/- 0.53 mg/dL (P = 0.414), 1.62 +/- 0.62 mg/dL (P = 0.734), and 1.48 +/- 0.58 mg/dL (P = 0.065), 1.58 +/- 0.53 mg/dL (P = 0.854), 1.88 +/- 0.77 mg/dL (P = 0.083), respectively. Daily proteinuria levels increased from 0.04 +/- 0.11 g/day at baseline to 0.55 +/- 1.33 g/day (P = 0.037) after conversion, in the responders group. In the nonresponders group, baseline proteinuria was 0.13 +/- 0.25 g/day, and increased to 1.44 +/- 2.44 g/day after conversion (P = 0.008). SRL was discontinued in 16 patients (31%) because of the occurrence of severe side effects. The proportion of patients remaining on SRL therapy over time was 43.1% at 1 year, 15.5% at 2 years after conversion, and 10.3% at 3 years after conversion. SRL conversion may be very useful in patients suffering from neoplasia; however, frequent side effects related with this intervention should be considered, and routine conversion from CNI to SRL to reduce nephrotoxicity should be discouraged.