5‐Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients

Abstract

Background Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment‐related side effects and improve long‐term outcomes of kidney transplantation. The Cistcert study compared the efficacy and safety of these two strategies. Methods In this multi‐center, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA) and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). Results Five‐year patient (89% vs 86%; p=NS) and death‐censored graft survival (95% vs 96%; p=NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm respectively. ⁵¹CrEDTA clearance was comparable in the intention‐to‐treat analysis, but in the on‐treatment population, the EVL/MPA/steroids arm exhibited a superior ⁵¹CrEDTA clearance at 1 and 5 years after transplantation (61.6 vs 52.4, p=0.05 and 59.1 vs 46.2mL/min/1.73 m², p=0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of post‐transplant diabetes (26% versus 6%, p=0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. Conclusions Both regimens provide an excellent long‐term patient and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection.