Association Between Immunosuppressive Drug Concentration and the Incidence of CMV Infection or Biopsy Proven Acute Rejection (BPAR) in Kidney Transplant Recipients.

Abstract

Introduction: The purpose of this analysis was to evaluate the effects of 3 immunosuppressive regimens on the incidence of CMV infection and BPAR in kidney transplant recipients. Methods: This is a single center prospective randomized study including 288 low immunological risk kidney transplant recipients randomized to: (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. All patients were followed for 6 months after transplant. Time-average drug concentrations from day 7 to day 180 were use for this analysis. Results: There were no differences in main demographic characteristics between groups. The mean age was 45 years, 66% male, 52% caucasian and 69% recipients of grafts from deceased donors. In G1 the incidence of CMV infection was 5%. Patients with CMV infection showed higher TAC concentrations compared to those without CMV infection (6.2±0.6 vs. 5.1±1.0 ng/ml, p=0.026) with no differences in EVR concentrations (5.3±1.6 vs. 5.6±1.2 ng/ml, p=ns), respectively. In G2 the incidence of CMV infection was 8%. Patients with CMV infection showed similar TAC concentrations compared to those without CMV infection (7.7 ± 1.7 vs. 6.6 ± 1.8 ng/ml, ns) but lower EVR concentrations (4.3±1.0 vs. 5.4±1.2 ng/ml, p=0.009), respectively. In G3 the incidence of CMV infection was 36%. Patients with CMV infection showed similar TAC concentrations compared to those without CMV infection (7.7±1.6 vs. 7.5±1.1 ng/ml, ns) but higher MPA concentrations (7.2±7.7 vs. 2.3±1.6 ng/ml, p=0.037), respectively. The incidence of BPAR was 8%, 20% and 14% in G1, G2 and G3, respectively (p=0.085). There were no significant differences in TAC, EVR or MPA concentrations comparing patients with or without BPAR in each group. Conclusion: In this population receiving no CMV prophylaxis, lower incidence of CMV infection was observed among patients receiving EVR containing regimens. Higher TAC or MPA and lower EVR concentrations were associated with higher incidence of CMV infection.