De Novo Everolimus (EVR) Versus Mycophenolate (MPA) in Kidney Transplant Recipients Receiving Tacrolimus (TAC).

Abstract

Introduction: Head-to-head comparison of the efficacy of de novo use of EVR or MPA has not been investigated in kidney transplant recipients receiving TAC. Methods:This is a single center prospective randomized study including 288 low immunological risk kidney transplant recipients receiving: (G1, N=85) single 3 mg/kg dose of antithymocyte globulin, reduced exposure TAC (<5 ng/ml), EVR (4-8 ng/mL) and prednisone; (G2, N=102) basiliximab, reduced exposure TAC (6 ng/ml for 3 months then <5 ng/mL thereafter), EVR (4-8 ng/mL) and prednisone; (G3, N=101) basiliximab, TAC (6-8 ng/ml), MPA(1440 mg/day) and prednisone. None of the patients received any CMV prophylaxis. All patients were followed for 6 months after transplant and 28%, 29% and 27% reached one year of follow up, respectively. This report includes detailed analysis of the incidence and characteristics of acute rejection (AR) up to one year after transplantation (mean follow up of 297±98 days). Results: There were no differences in demography including recipient age, gender, race, PRA, CMV recipient status, donor age and donor source. The incidence of delayed graft function was high but comparable among the groups (48 vs. 53 vs. 45%, p=0.391), respectively. The incidence of biopsy proven acute rejection (BPAR) was not different among the groups (8.2 vs. 19.6 vs 13.9%, p=0.085). There was no significant difference in mean time to first treated AR (64±55 vs 34±53 vs 60±113 days, p=0.419) or in the total number of BPAR episodes (10 vs. 24 vs. 17 p=0.112). Vascular involvement (grade IIA or IIB, Banff 97) was less frequent in G1 (0 vs. 29 vs. 52%, p=0.01) while the incidence of AR episodes requiring antithymocyte globulin treatment was not different (10 vs. 29 vs. 47%, p=0.07). There was no difference in the number of patients with recurrent AR episodes (3 vs. 4 vs. 3). Also, there were no differences in the number of graft losses (1 vs. 3 vs. 6) and patient death (3 vs. 3 vs. 4). The incidence of CMV infection was lower in EVR groups (4.7 vs. 7.8 vs. 35.6%, p<0.0001) with no differences in mean estimated GFR (64±24 vs. 58±23 vs. 66±29 ml/min, p=0.08 ml/min). Conclusions: In this cohort of patients receiving TAC, a single dose 3mg/kg antithymocyte globulin induction combined with reduced exposure TAC and EVR is associated with less severe AR and lower incidence of CMV infection compared to MPA.