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Replacement of Calcineurin-Inhibitors With Sirolimus as Primary Immunosuppression in Stable Cardiac Transplant Recipients

Background. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. Methods. CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR ≤50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. Results. In the SRL group, GFR increased from 47.0±18.0 to 61.2±22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5±12.7 to 53.9±19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2±15.8 to 83.5±27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5±14.0 mL/min to 36.4±12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299±622 mg/day to 517±795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637±806 vs. 514±744 mg/day, P=0.39). Uric acid decreased from 7.6±2.4 to 6.2±1.9 mg/dL (P=0.0007) in the SRL group. Conclusions. Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.