Efficacy and Safety of Everolimus Based Immunosuppression On De Novo Kidney Transplantation With 5 Years Follow-Up Especially in Protocol Biopsy Findings and Donor Specific Antibody Production.

Abstract

Purpose: The impact of everolimus (EVR) based immunosuppression in De Novo Kidney Transplantation was evaluated in clinical outcomes, protocol biopsies findings and donor specific antibody (DSA) production.Methods: During 2008 and August 2009, we enrolled twenty-four living donor kidney transplant patients in a 2-year, multicenter, randomized phase 3 study (RAD001A1202 study) to compare the safety and efficacy between EVR based and mycophenolate mofetile (MMF) based immunosuppression. We extended further three years and evaluated clinical outcome in a single center.EVR group received reduced-exposure cyclosporine (target C0 25-50ng/ml after 6 months) + steroid, and EVR-C0 were adjusted 3-8ng/ml. MMF group received standard-exposure cyclosporine (target C0 100-250ng/ml after 6 months) + steroid. Both group received basiliximab induction.Results: All patients continued in each regimen. With a mean observation period of 60.1 (43.8-69.4) months, current patient and graft survival is 100% in both groups (EVR; n=13, MMF; n=11). Renal function expressed as eGFR (ml/min/1.73m2) was similar 40.7±14.6 in EVR group and 37.4±8.6 in MMF group. Significant proteinuria, more than 300mg/day, were observed more in EVR group (76.9%) than in MMF group (54.5%), however the proteinuria in EVR group was successfully treated with angiotensin-II receptor blockade. None of EVR and MMF group was treated for clinical T cell mediated rejection, similar incidence of Banff borderline change on 6 or 12 months protocol biopsies were observed in 7.7% of EVR group and 18.2% of MMF group, but none of both groups revealed peritubular capillaritis. Luminex solid phase assay revealed the similar incidence of class II DSA production in both groups, 7.7% of EVR group at 2 years after transplant and 15.4% of MMF group at 3 years. Protocol oral glucose tolerance test at 6 and 12 months revealed more, but no significantly, worsen profile in 46.1% of EVR group to 18.2% in MMF group.Conclusions: EVR based immunosuppression provides equivalent clinical outcomes as well as the incidence of De Novo DSA production with MMF based immunosuppression with 5 years follow-up.