Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients

Abstract

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 < or =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.