Early Renal Benefit of Rapamycin Combined With Reduced Calcineurin Inhibitor Dose in Pediatric Heart Transplantation Patients

Background

Calcineurin inhibitors such as cyclosporine are effective in preventing rejection in recipients of solid organ transplants. Unfortunately, the prolonged use of calcineurin inhibitors may result in progressive renal injury.

Methods

We studied the renal function of 15 pediatric heart transplant recipients who were taking calcineurin inhibitors. Their renal function was studied before and after rapamycin was introduced to their immunosuppression regimen. With the introduction of rapamycin, the patients were given a lower dose of calcineurin inhibitors, and the calcineurin inhibitor was discontinued in 5 patients.

Results

Renal function improved significantly in the patients by 30 days after these changes in the calcineurin inhibitor dose were instituted. Mean levels of blood urea nitrogen and mean serum creatinine decreased, and mean creatinine clearance increased. Pre-rapamycin, the patients’ mean level of blood urea nitrogen was 27.1 ± 12.4 mg/dl and post-rapamycin they decreased to 18.6 ± 11.1 mg/dl (p = 0.014). Similarly, creatinine decreased from 1.0 ± 0.5 mg/dl to 0.8 ± 0.3 mg/dl (p = 0.019). Their creatinine clearance increased from 88 ± 28 ml/min/1.73 mol/liter² to 105 ± 27 ml/min/1.73 mol/liter² (p = 0.008). The patients’ lipid levels did not change after they were prescribed rapamycin. Biopsy-negative rejection developed in 2 patients.

Conclusions

The introduction of rapamycin to the immunosuppressive regimen of patients taking calcineurin inhibitors, with a concomitant reduction of the calcineurin inhibitor dose, may improve renal function within 30 days, without a significant increase in rejection.