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

Abstract

Introduction: CMV viremia and disease is frequent and is associated with inferior long-term patient and graft survival. This single center prospective study compares the effect of 3 immunosuppressive regimens on the incidence of CMV infection in kidney transplant recipients. Methods: Low immunological risk recipients of first kidney transplant were randomized (stratified according to donor source, living or deceased donors) to one of the following groups (G1) single 3 mg/kg dose of antithymocyte globulin, reduced exposure tacrolimus (TAC 4 ng/ml), everolimus (EVR 4-8 ng/mL) and prednisone or (G2) basiliximab, reduced exposure tacrolimus (TAC 6 ng/ml), everolimus (EVR 4-8 ng/mL) and prednisone or (G3) basiliximab, reduced exposure tacrolimus (TAC 8 ng/ml), mycophenolate and prednisone. The primary outcome in this study is the incidence of CMV infection or disease during the first year of transplantation. None of the patients received CMV prophylaxis. CMV infection is monitored weekly using concomitant PCR viral load and antigenemia test during the first 6 months of transplant. Here we show preliminary results of the first 63 out of 300 patients. Results: The mean age of this population was 44.5±12.3 years with 52.3% Caucasian, 62 % male and 76.2% recipients from deceased donor. Mean donor age was 43.6±10.9 years and among deceased donors transplants, the mean cold ischemia time was 22.9 ± 5 hours. This analysis includes 15 patients in G1, 19 in G2 and 29 in G3. Donor positive/recipient negative CMV was observed in 1 patient in G1 and 1 patient in G3, only. Overall, 12 (19%) episodes of acute rejection were diagnosed, 7 were biopsy confirmed (G1=0; G2=4; G3=3), 4 borderline changes (G1=2; G2=1; G3=1) and 1 interstitial nephritis (G3). Two patients in G2 and one patient in G3 required thymoglobulin to treat acute rejection (for 2A; 2B and 2A rejections, respectively). At time of acute rejection diagnosis tacrolimus trough blood concentrations were 3.8 ± 1.3 ng/mL for G1; 5.8 ± 1.2 ng/mL for G2 and 8.0 ± 3.1 ng/mL for G3. Mean serum creatinine at 3 months was 1.5 ± 0.5 mg/dL in G1, 1.5 ± 0.2mg/dL in G2 and 1.2 ± 0.3mg/dL in G3. Eight episodes of CMV infection were diagnosed (7 viremia and 1 disease; 2 recurrences) at mean time of 55.1 ± 32.9 days after transplant, all in G3 patients. Two patients had received previous treatment with thymoglobulin for acute rejection. Conclusions: This preliminary analysis indicates that patients receiving everolimus, with or without thymoglobulin, are at lower risk to develop CMV infection. These regimens also appear to provide comparable efficacy for the prevention of acute rejection and similar renal function.