Experience with the use of sirolimus in liver transplantation - Use in patients for whom calcineurin inhibitors are contraindicated

Sirolimus (SRL) provides effective immunosuppression for kidney transplanta tion and may be useful in patients with delayed allograft function after ki dney transplantation. We review our experience with SRL in liver transplant recipients for whom calcineurin inhibitors are undesirable. Fourteen patie nts with renal insufficiency or acute mental status impairment were adminis tered SRL after liver transplantation (5- to 10-mg load, 1 to 4 mg/d). Immu nosuppression also consisted of mycophenolate mofetil and corticosteroids. On resolution of neurological or renal dysfunction (return to baseline ment al status or serum creatinine level), tacrolimus (TAC) therapy was initiate d. Twelve patients received primary transplants, 1 patient received a combi ned liver-kidney transplant, and I patient received a third transplant. Fol low-up was 2 to 7 months. Calcineurin inhibitors were initially withheld in 9 patients, and therapy was aborted because of toxicity in the remaining 5 patients. Mean times to the initiation of SRL, and TAC therapy were 5.4 +/ - 4.6 and 26.8 +/- 24.4 days, respectively. Serum trough levels of SRL, did not correlate with dose or other patient variables, Two patients died afte r prolonged pretransplantation hospital courses in the intensive care unit. Six patients experienced acute rejection, but only I patient required anti lymphocyte therapy. Serum creatinine levels at the start of SRL therapy wer e 2.2 +/- 1.1 and 1.2 +/- 0.6 mg/dL at 3 months. All 3 patients with neurol ogical indications for SRL had a return to their baseline mental status. Al l patients had improved liver function chemistry test results and prothromb in times. No patients developed leukopenia or thrombocytopenia SRL, is safe after liver transplantation in patients with acute neurological or renal i mpairment. SRL, is an attractive alternative when calcineurin inhibitors ar e undesirable, but serum trough levels of SRL, should be monitored. A prosp ective randomized study of an SRL-based calcineurin inhibitor-avoiding regi men compared with standard therapy in patients with renal insufficiency wil l further evaluate the role for SRL in liver transplantation.