Cyclosporine and Mycophenolate Mofetil 48 Hours Before Renal Transplantation Enables the Use of Low Cyclosporine Doses and Achieves Better Graft Function H. Maamoun, A. Soliman, and B. Zayed ABSTRACT Reducing calcineurin-inhibitor induced nephrotoxicity and simultaneously avoiding long- term side effects are desirable goals in renal transplantation. We examined the hypothesis that administration of cyclosporine and mycophenolate mofetil (MMF) 48 hours before renal transplantation allows reduction in the target cyclosporine C2 concentration, thus decreasing toxicity and improving graft function. We enrolled 80 kidney recipients in a single-center study comparing 2 cyclosporine-based protocols. Group I patients (n  40) received a standard dose of cyclosporine (blood cyclosporine C2, 800 –1500 ng/mL) with MMF and standard doses of corticosteroids. Group II patients (n  40) were treated with a low dose of cyclosporine (blood cyclosporine C2, 450 – 800 ng/mL) and MMF plus low doses of corticosteroids after induction 48 hours before surgery with cyclosporine and MMF. Patient (97.5% vs 100%) and graft survivals (92.5% vs 95%) at 1 year were not different between the groups, although patients in group II experienced significantly fewer acute rejection episodes (10% vs 30%; P  .01). Delayed graft function occurred less often among group I than group II (17.5 vs 20%), but the difference was not significant. Graft function at 1 year was significantly better among group II (serum creatinine 1.31 vs 1.64 mg/dL and creatinine clearance 63 mL/min versus 47 mL/min; P  .05). We concluded that administration of cyclosporine and MMF 48 hours before renal transplantation allowed the safe effective use of low target C2 cyclosporine concentrations, enabling an early decrease in cyclosporine dose. These preliminary results indicated better 1-year graft function compared with the normal cyclosporine dose regimen. C alcineurin inhibitor (CNI)–mediated nephrotoxicity is not only limited to renal transplantation but also well documented in heart, 1,2 liver, 3 and bone marrow 4 trans- plantation. Reducing CNI-mediated nephrotoxicity has been the focus of many trials in renal transplantation. Studies examining CNI-free immunosuppressive drug pro- tocols were successful to obtain better graft function, they have been hampered by a high frequency of acute rejection episodes or treatment failure. 5,6 Trials have unsuccessfully sought to lower CNI blood concentrations to reduce renal toxicity. 7 In the present work, we examined the hypothesis that achieving lower cyclosporine target blood concentrations at 2 hours after the dose (C2) from the first day after transplantation resulted in more favorable renal graft func- tion and a reduced incidence of delayed graft function (DGF). To maintain at least a similar incidence of acute rejection episodes and using information from earlier CNI- free and reduced dose trials, we extended induction therapy to 48 hours before transplantation surgery by administiring cyclosporine plus full doses of mycophenolate mofetil (MMF). METHODS Study Population We enrolled 80 patients between January 2006 and June 2007. They were randomized into either a standard-dose cyclosporine From the Department of Internal Medicine, Cairo University, Cairo, Egypt. Address reprint requests to Hoda Maamoun, MD, Cairo Uni- versity, 7 School St, Omrania, Sharquia, Cairo, Giza, Egypt. E-mail: hodamamoun@yahoo.com © 2010 by Elsevier Inc. All rights reserved. 0041-1345/–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2010.09.065 Transplantation Proceedings, 42, 4033– 4036 (2010) 4033