5­year follow-up of a randomized clinical study comparing everolimus plus reduced-dose cyclosporine with mycophenolate mofetil plus standard-dose cyclosporine in de novo kidney transplantation: Retrospective single center assessment

• 5-­year follow­up of randomized clinical study on everolimus­ (EVR)-based regimen in a single center.
• Efficacy and safety were compared between low-­dose CSA plus EVR and standard­-dose CSA plus mycophenolate mofetil.
• Everolimus regimen was effective for preventing CMV infection.
• Graft outcome including rejection, de novo DSA production, eGFR and new­onset diabetes did not differ between two regimens.
• Hyperlipidemia and proteinuria were tolerable adverse effects when EVR trough levels were maintained between 3 and 8 ng/ml.

The aim of this study is to evaluate the efficacy and safety of everolimus plus reduced­dose cyclosporine compared with mycophenolate mofetil plus standard­dose cyclosporine 5 years after living donor kidney transplantation.Between March 2008 and August 2009, 24 living donor kidney transplantations were enrolled in a 2-year, multicenter, randomized phase 3 study (RAD001A1202 study). 24 recipients were randomly classified into two groups and closely observed for 5 years. 13 recipients were administered steroid, reduced­dose cyclosporine, everolimus and basiliximab (EVR group). 11 recipients were administered steroid, standard-dose cyclosporine, mycophenolate mofetil and basiliximab (STD group). Two groups were compared not only in graft function including estimated glomerular filtration rate (eGFR), and proteinuria, but also in adverse events such as de novo donor-specific antibody (DSA) production, rejection, new­onset diabetes, hyperlipidemia, and cytomegalovirus (CMV) infection.No graft loss was identified in 5 years. The incidences of acute T cell rejection, de novo DSA production, hyperlipidemia, and new­onset diabetes were similar. eGFR levels throughout the observation periods were similar. Three cases of proteinuria were identified in STD group. One case of proteinuria observed in EVR group was well controlled with angiotensin receptor blocker. Incidence of CMV infection in CMV antibody­positive recipients was significantly lower in EVR group.The safety and efficacy of reduced­dose cyclosporine and everolimus protocol were similar to those of standard­dose cyclosporine and mycophenolate mofetil other than for superior prevention of CMV infection.