BACKGROUND: While providing potent immunosuppression for liver transplant recipients, calcineurin inhibitors (CNI) exhibit nephrotoxicity as a major side effect. The purpose of this study was to evaluate the safety and efficacy of conversion from CNI to sirolimus (SRL) among liver transplant recipients with CNI-induced chronic nephrotoxicity. METHODS: Between January 2004 and June 2005, we performed conversion in 16 recipients after a median period of 8.5 months after liver transplantation. The indication for conversion was CNI-related nephrotoxicity with a serum creatinine (sCr) value >132.6 umol/L. Renal function was measured before and after conversion to SRL. Clinical and laboratory data related to the clinical course of the patients were recorded to investigate the safety and efficacy of conversion. RESULTS: Sixteen patients were converted to SRL after developing nephrotoxicity. Their renal function improved gradually after conversion. The levels of sCr decreased significantly within the first 30 days (164.1 +/- 12.48 micromol/L to 130.1 +/- 5.573 micromol/L), and over the next 60 days after conversion (97.86 +/- 11.69 micromol/L to 90.7 +/- 8.95 micromol/L) (P < .01). Similarly, the mean glomerular filtration rate (GFR) increased significantly during the same period. Four recipients experienced hypercholesterolemia, 1 with ankle edema, and 1 with acute rejection. The median follow-up was 2.4 years. No patient discontinued SRL due to side effects. No patient needed dialysis or kidney transplantation during the study period. CONCLUSIONS: SRL is a safe, effective replacement agent as primary immunosuppressive therapy following withdrawal of CNIs in liver transplant recipients with CNI-induced chronic nephrotoxicity.
BACKGROUND: While providing potent immunosuppression for liver transplant recipients, calcineurin inhibitors (CNI) exhibit nephrotoxicity as a major side effect. The purpose of this study was to evaluate the safety and efficacy of conversion from CNI to sirolimus (SRL) among liver transplant recipients with CNI-induced chronic nephrotoxicity. METHODS: Between January 2004 and June 2005, we performed conversion in 16 recipients after a median period of 8.5 months after liver transplantation. The indication for conversion was CNI-related nephrotoxicity with a serum creatinine (sCr) value >132.6 umol/L. Renal function was measured before and after conversion to SRL. Clinical and laboratory data related to the clinical course of the patients were recorded to investigate the safety and efficacy of conversion. RESULTS: Sixteen patients were converted to SRL after developing nephrotoxicity. Their renal function improved gradually after conversion. The levels of sCr decreased significantly within the first 30 days (164.1 +/- 12.48 micromol/L to 130.1 +/- 5.573 micromol/L), and over the next 60 days after conversion (97.86 +/- 11.69 micromol/L to 90.7 +/- 8.95 micromol/L) (P < .01). Similarly, the mean glomerular filtration rate (GFR) increased significantly during the same period. Four recipients experienced hypercholesterolemia, 1 with ankle edema, and 1 with acute rejection. The median follow-up was 2.4 years. No patient discontinued SRL due to side effects. No patient needed dialysis or kidney transplantation during the study period. CONCLUSIONS:SRL is a safe, effective replacement agent as primary immunosuppressive therapy following withdrawal of CNIs in liver transplant recipients with CNI-induced chronic nephrotoxicity.