Improvement of renal function in pediatric heart transplant recipients treated with low-dose calcineurin inhibitor and mycophenolate mofetil

Background. Renal dysfunction is a major complication in heart transplant recipients treated with calcineurin inhibitors. The goal of the study was to investigate the effect of a reduction of calcineurin inhibitor dosage with the concomitant introduction of mycophenolate mofetil on both renal function and cardiac allograft function. Methods. Fourteen of 52 consecutive pediatric cardiac allograft recipients experienced a progressive decrease of renal function. A renal biopsy was performed before the dose of calcineurin inhibitors was reduced by 50% and azathioprine was replaced by mycophenolate mofetil. Renal function was evaluated by inulin clearance and maximal urinary osmo-lality before and yearly after the therapeutic changes. Acute rejection was monitored clinically, by echocardiography and endomyocardial biopsies. Results. Inulin clearance in the fourteen children decreased from 84.2 mL/min/1.73 m 2 at one year posttransplantation to 46.5±9.6 mL/min/1.73 m 2 at the time of the change in immunosuppressive therapy. Significant renal lesions were observed in the renal biopsies performed before the change. At 1 year, inulin clearance had increased by 67%. In six patients who had a second determination 2 years after the switch, inulin clearance was not significantly different from the value at 1 year. There were three reversible acute rejection episodes in three patients. The incidence of rejection episodes was not different from a control group of patients whose treatment was not changed. Conclusion. The reduction of calcineurin inhibitor dosage and replacement of azathioprine by mycophenolate mofetil is a safe way to improve renal function in children with heart transplants and calcineurin inhibitor induced nephrotoxicity.