Everolimus-Based Immunosuppression Improves Renal Function in Long-Term Heart Transplanted Patients: Five Years Results of a Prospective Randomized Trial

Abstract

Purpose Renal insufficiency is a leading cause of morbidity and mortality after heart transplantation (Htx). CyA-based immunosuppression may contribute to kidney disease and a reduction of CyA seems reasonable. We aimed to assess whether changing from a CyA- to an Everolimus-based (EVL) immunosuppression can reduce the incidence of renal insufficiency in long-term Htx pts. We compared, in a prospective randomized trial, a reduction of >75% of CyA dose and EVL administration with conventional treatment. Methods and Materials Randomization was stratified by age, creatinine, gender and f-up in 213 pts >18 yrs (1-20 yrs of f-up, median 9). They were assigned to CyA reduction + EVL (n=108) or conventional treatment (n=105). At enrollment, 6 months, 1, 2, 3, 4 and 5 yrs f-up we estimated MDRD, creatinine, albuminuria, dialysis, and clinical outcome. An improvement in renal function was defined as an increase of > than 5 ml/min in MDRD. Results At entry, the two groups were similar. Eleven deaths were observed in each group. Renal function worsened in the conventional treatment pts. Mean creatinine (1,6±0,6) increased to 1,7±0,8 after 5 yrs in the control group and decreased to 1,5±0,86 in the EVL group (p = 0,01). MDRD improved from 55±24 to 64±34 ml/min (p Conclusions Conversion of a CyA- to EVL-based immunosuppression improves 5 yrs renal function in patients without proteinuria. Survival is not affected. This practice may be harmful for kidney function in the presence of heavy proteinuria.