title: 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 When target trough levels were achieved, CNI was withdrawn.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.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. bernayelken@yahoo.com.tr
authors.forename: Berna
authors.initials: B
authors.lastname: Yelken
authors.forename: Yasar
authors.initials: Y
authors.lastname: Caliskan
authors.forename: Oktay
authors.initials: O
authors.lastname: Ozkan
authors.forename: Numan
authors.initials: N
authors.lastname: Gorgulu
authors.forename: Halil
authors.initials: H
authors.lastname: Yazici
authors.forename: Aydin
authors.initials: A
authors.lastname: Turkmen
authors.forename: Mehmet S
authors.initials: MS
authors.lastname: Sever
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus