Sirolimus-based immunosuppression after cardiac transplantation: predictors of recovery from calcineurin inhibitor-induced renal dysfunction

BACKGROUND: Proliferation signal inhibitors (PSI) facilitate reduction in calcineurin inhibitor exposure resulting in an improvement in creatinine clearance (CrCl) in cardiac transplant recipients with renal dysfunction. Predictors of improvement in renal function after conversion to PSI-based treatment remain unknown.

METHODS: We studied estimated CrCl (eCrCl) before and after initiating sirolimus and concomitant lowering (n = 20) or discontinuing (n = 18) calcineurin inhibitor in 38 patients with renal dysfunction (eCrCl < 50 ml/min) who had undergone cardiac transplantation a median (25%-75% percentiles) 81.8 months (17.4-129.5 months) earlier. The median sirolimus starting dose was 2.0 mg, and the blood level after 1 month was 8.0 ng/ml (4.5-13.4 ng/ml).

RESULTS: Median eCrCl at conversion was 22.9 ml/min (19.1-30.6 ml/min), which increased after 1, 3, and 6 months to 25.9 (18.6-37.1), 25.6 (17.9-34.5), and 28.8 (18.7-38.7) ml/min, respectively. Age, gender, eCrCl at baseline, CNI reduction vs discontinuation, and presence or absence of diabetes or hypertension did not predict improvement in eCrCl after conversion. Only time from transplantation to conversion and eCrCl 3 months before conversion were correlated to the improvement in renal function after conversion to sirolimus (p < 0.05 and p < 0.01 for correlation after 1 month, respectively). Five patients (13%) experienced a grade 3A rejection episode while being treated with sirolimus.

CONCLUSIONS: Treatment with sirolimus facilitates CNI lowering or discontinuation associated with a significant improvement in renal function after 1 month. Better renal function 3 months before conversion and a shorter time from transplant to conversion were associated with a greater improvement in renal function after conversion to sirolimus.