TWO-DOSE DACLIZUMAB IN CONJUNCTION WITH TACROLIMUS-BASED PROTOCOL IN KIDNEY TRANSPLANTATION - PROSPECTIVE, RANDOMIZED STUDY

Abstract

P757 Aims: Five doses of daclizumab given initially after kidney transplantation have been shown to reduce acute rejection (AR). Most previous studies with daclizumab were performed mainly in cyclosporine treated recipients and only few were done in patients on tacrolimus-based protocol. The aim of this study was to determine the safety and efficacy of two doses of daclizumab combined with tacrolimus (Tac), mycophenolate mofetil (MMF) and corticosteroids (CS) in prevention of acute rejection in primary kidney allograft. Methods: 25 patients were recruited and randomized into induction (n=11) and control (n=14) groups. All patients received initially 0.15mg/kg of Tac tapered to 0.1mg/kg (mean blood levels 10.9 +/− 2.5 ng/dL at first 3 months, 9.5 +/− 2,9 ng/dL at 6 months and 7.9+/− 2.0 ng/dL at one year), MMF at 2gr/bw/day and CS tapered from 100 to 10 mg/bw/day at 6 month. The induction group received two doses of 1mg/kg daclizumab: before engraftment and on postoperative day 14. All patients received CMV prophylaxis with oral gancyclovir. Patient demographics, PRA status and donor organ characteristics were not significantly different between induction and study group. The mean follow up was 16.8 +/− 4,3 months. Fisher Exact and Student T tests were used as appropriate to compare groups. Results: At one year, biopsy proven AR was diagnosed in 5/14 (35%) of control patients not receiving daclizumab and in none of patients with induction (0/11, 0%) (p 0.05). One patient from control group died from cardiac infarction with functioning renal graft. Delayed graft function, defined as absence of spontaneous reduction of creatinine requiring dialysis support, occurred in 6 out of 14 patients (42.8%) from the control group and in 3/11 (27%) patients treated with daclizumab, p NS. Mean creatinine at one year was 1.47+/−0.8 mg/dL in induction and 1.55+/−0.9 mg/dL in control group (NS), the non censored one year patient and graft survival was 100%/100% and 92.8%/ 85.7% (NS) in daclizumab and control group respectively. There were no adverse effects related to daclizumab administration. The infectious complications (UTI and wound infections) occurred in 5/11 and 9/14 (NS) patients from induction and control groups respectively. Conclusions: Our data suggest that the two doses of daclizumab combined with tacrolimus-MMF-CS protocol is effective in preventing acute rejection, reducing incidence of delayed graft function rate and in maintaining satisfactory graft function. The additional advantages of limited dose daclizumab-tacrolimus combination protocol, could be it’s cost effectiveness as well as lesser likelihood of development of neutralizing anti-daclizumab antibodies.