A Prospective Randomized Trial Aimed to Reduce the Incidence of Cytomegalovirus (CMV) Infection in Kidney Transplant Recipients.

Abstract

Introduction: CMV infection is associated with inferior long-term patient and graft survival. This single center prospective randomized study compares the influence of 3 immunosuppressive regimens on the incidence of CMV infection in kidney transplant recipients. Methods: This is a single center prospective randomized study included 288 low immunological risk kidney transplant recipients to receive: (G1, N=85) single 3 mg/kg dose of antithymocyte globulin, reduced exposure tacrolimus (TAC<5 ng/ml), everolimus (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), mycophenolate (MPA) and prednisone. None of the patients received any CMV prophylaxis. CMV viral replication was monitored weekly using pp65 antigenemia and PCR. The primary outcome is the incidence of CMV infection (viremia or disease) during the first year of transplantation. This report includes data of all patients up to 6 month after transplantation. Results: There were no differences in demographic characteristics including pre-transplant CMV donor/recipient serostatus. The incidence of first CMV infection episode was lower in EVR groups (4.7 vs. 7.8 vs. 35.6%, p<0.0001). There was no difference comparing mean time to first CMV infection episode or mean time of ganciclovir treatment. The total number of CMV infection episodes was also lower in EVR groups (4 vs. 14 vs. 55) because there were no recurrent episodes in G1 but 6 in G2 and 19 in G3. Twelve patients were converted from MPA to EVR due to CMV infection. There were no differences in incidence of biopsy proven acute rejection (8 vs. 20 vs. 14%, p=0.085), wound-healing adverse events (28 vs. 35 vs. 25%, p=0.2), delayed graft function (48 vs. 53 vs. 45%, p=0.4), mean estimated GFR (64±24 vs. 58±23 vs. 66±29 ml/min, p=0.06) and mean protein/creatinine ratio (0.5±1.0 vs. 0.4±0.7 vs. 0.3±0.9, p=0.5). There were 8 deaths (G1=2; G2=3; G3=3) and 6 graft losses (G1=0; G2=3; G3=3). Conclusions: This 6 month analysis indicates that patients receiving EVR are at lower risk of developing CMV infection compared to patients receiving MPA. Patients receiving EVR showed efficacy and safety profiles comparable to those receiving MPA. DISCLOSURES:Tedesco, H.: Grant/Research Support, Novartis.