Proteinuria and Histopathological Change of Everolimus Based Immunosuppression On De Novo Kidney Transplantation With 5 Years Follow-Up in Protocol Biopsies.

Abstract

Purpose: The impact of everolimus (EVR) based immunosuppression in De Novo Kidney Transplantation was evaluated in safety profile, focusing proteinuria and histopathological change through the protocol biopsy findings compared with mycophenolate mofetile (MMF) based immunosuppression. Method: During March 2008 and August 2009, we enrolled 24 living donor kidney transplant patients in a 2-year, multicenter, randomized phase 3 study (RAD001A1202 study) to compare the safety and efficacy with protocol biopsy data between EVR based and MMF based immunosuppression. We extended further 3 years and evaluated clinical outcome in a single center. EVR group received reduced-exposure cyclosporine (target C0 25-50ng/ml after 6 months), and EVR-C0 were adjusted 3-8ng/ml. MMF group received standard-exposure cyclosporine (target C0 100-250ng/ml). Both group received basiliximab induction. We evaluated in safety profile, focusing proteinuria and histopathological change through the protocol biopsy findings. Protocol biopsies were performed at 1hour, 3 weeks, 6 months and 12 months after transplantation. Result: All patients continued in each regimen. With a mean observation period of 60.1 months, current patient and graft survival is 100% in both groups (EVR; n=13, MMF; n=11). eGFR (ml/min/1.73m2) was similar 40.7 in EVR group and 37.4 in MMF group. None of both groups was treated for clinical acute rejection, similar incidence of Banff borderline change on protocol biopsies were observed in 7.7% of EVR group and 18.2% of MMF group. Calcineurin inhibitor nephrotoxicity was observed less in EVR group (7.7%) than in MMF group (27.3%) in biopsies over 12 months. Proteinuria were observed more in EVR group (76.9%) than in MMF group (54.5%) respectively. There were two patients whose proteinuria developed over 2g/day at 12 months or later in EVR group. We could not find any particular glomerular lesion in the biopsies, however neovascular hyalinosis at glomerular vascular pole was noticeable. The proteinuria in EVR group was successfully treated with angiotensin-II receptor blockade. Conclusion: EVR based immunosuppression does not provide particular histological change at the glomerular level even though proteinuria was observed.