Mycophenolate mofetil and sirolimus as calcineurin inhibitor-free immunosuppression for late cardiac-transplant recipients with chronic renal failure

Background. Calcineurin-inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this study was to introduce a CNI-free immunosuppressive regimen to HTx recipients with late posttransplant renal impairment and to evaluate the impact of conversion to this new immunosuppression. (mycophenolate mofetil [MMF] and sirolimus [Sir]) treatment on renal function. Methods and Results. Thirty-one HTx patients (25 men, 6 women; 0.2 - 14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine greater than 1.9 mg/dL were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Mean patient age was 50 +/- 14 (range 19 - 74) years. Conversion was started with 6 mg Sir, continued with 2 mg, and the dose was adjusted to achieve target trough levels between 8 and 14 ng/mL. MMF was continued with trough level adjusted (1.5 - 4 mug/mL). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up (first and every 3 months after conversion) included endomyocardial biopsies, echocardiography, and laboratory studies. Survival was 90% after a mean follow-up of 13 +/- 5 months. No acute rejection episode was detected during the study period. Renal function improved significantly after conversion: creatinine preconversion vs. postconversion: 3.14 +/- 0.76 mg/dL vs. 2.14 +/- 0.83 mg/dL, P = 0.001. Cystatin preconversion vs. postconversion: 2.95 +/- 1.06 mg/L vs. 2.02 +/- 1.1 mg/L, P = 0.01. In three patients, hemodialysis therapy was stopped completely after conversion. Graft function remained stable. Fractional shortening preconversion vs. postconversion: 36.9 +/- 6% vs. 36.4 +/- 6%. There were no serious adverse events. One patient had to be excluded because of noncompliance. Conclusions. Conversion from CNI-based immunosuppression to MMF and Sir in HTx patients with chronic renal failure was safe, preserved graft function, and improved renal function.