A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function.

Renal impairment is common in patients after liver transplantation and is attributable in large part to the use of calcineurin inhibitor (CNI)-based immunosuppression. We sought to determine whether conversion to sirolimus-based immunosuppression was associated with improved renal function. In a single-center, randomized, controlled trial, 30 patients at least 6 months post liver transplantation were randomized to remain on CNI-based immunosuppression or to switch to sirolimus-based immunosuppression. The primary outcome measure was change in measured glomerular filtration rate (GFR) between baseline and 12 months. Of 30 patients randomized, 3 were withdrawn at randomization, leaving 14 patients on CNI and 13 on sirolimus. There was a significant improvement in delta GFR following conversion to sirolimus at 3 months (7.7 mL/minute/1.73 m2; 95% confidence interval, 3.5-11.9) and 1 yr (6.1 mL/minute/1.73 m2; 95% confidence interval, 0.9-11.4). The difference in absolute GFR between the 2 study groups was significant at 3 months (P=0.02), but not at 12 months (P=0.07). The principal adverse events following conversion were the development of skin rash (9 of 13 patients, 69%) and mouth ulcers (5 of 13 patients, 38%). Two patients developed acute rejection at 2 and 3 months following conversion, 1 in association with low sirolimus levels and 1 having stopped the drug inadvertently. In conclusion, overall, this study suggests that conversion to sirolimus immunosuppression is associated with a modest improvement in renal function. Side effects were common, but tolerable in most patients and controlled with dose reduction.