Does a sirolimus - based immunosuppression in calcineurin inhibitor-free regime improve chronic renal failure in cardiac transplant recipients independent from blood pressure?

Abstract

The standard immunosuppression in cardiac transplantation (CTX) includes calcineurin inhibitors (CNI) to prevent allograft vasculopathy as limiting factor of graft survival. The most important side effect of CNI is the multifactorial pathogenesis of chronic renal failure after HTX. Progression to end-stage renal failure is worsening the cardiac transplant outcome. To prevent of futher nephrotoxicity, immunosuppression in cardiac transplant recipients has been changed to a CNI-free immunosuppressive regime with sirolimus. Sirolimus (SIR) is one of the new powerful immunosuppressants with antiproliverative and antimigratory properties on cells by binding to FK 506-binding protein. In our prospective observational study 26 patients (1 female, 25 male) with chronic renal failure, grade II-III, 2 to 13 years after cardiac transplantation have been included and switched overlapping from a former triple drug CNI-containing regime containing mycophenolate mofetil or azathioprine and prednisolone to a drug regime with sirolimus instead of CNI. The blood pressure, s-creatinine and creatinine clearance was measured regularly before and after CNI withdrawal and switch to SIR. During the 17- to 27-month follow-up cardiac transplant status including blood pressure and renal function was examined every 1–3 months. No acute CTX-rejection occured during follow-up. Prior to conversion the serum-creatinine ranged from 1.9 – 3.9 mg/dl. Without significant changing of the blood pressure after withdrawal of CNI to SIR, CTX patients with CNI-induced renal failure showed a recovery of the renal function within the first months. The decrease of s-creatinine was up to 1.1 mg/dl. Nevertheless, in the following month, an increase in s-creatinine was observed again. In CTX-recipients with CNI-induced chronic renal failure, conversion from CNI to SIR is safe, shows no significant effect to the blood pressure and anticipates cardiac graft rejection. CNI withdrawal and SIR introduction can slow progression of renal failure. To prevent CNI nephrotoxicity after CTX, SIR-based immunosuppression should be considered in earlier stages of renal failure.