Peripheral Lymphocyte Response to Mycophenolic Acid In Vitro and Incidence of Cytomegalovirus Infection in Renal Transplantation

The lymphocyte immunosuppressant sensitivity test (LIST) with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay procedure has been used to predict the pharmacological efficacy of immunosuppressive agents to prevent acute rejection episodes for renal transplant recipients. In this study, mycophenolic acid (MPA) pharmacological efficacies were evaluated by LIST at both prior to and just after renal transplantation. We compared the efficacies to the clinical outcome of these recipients. MPA's pharmacological efficacy was evaluated by LIST not only before the operation but also at 2, 4, and 6 weeks after transplantation in 16 renal transplant recipients. These recipients were divided into high- and low-sensitivity groups according to peripheral blood mononuclear cell (PBMC) sensitivity to MPA in vitro. The MPA sensitivities were compared to cytomegalovirus (CMV) infection and acute rejection episodes in these recipients under MPA immunosuppressive therapy. The rate of CMV infection episodes in the low-MPA pharmacological efficacy group categorized at 2 weeks after renal transplantation was 5/6 (83.3%), which was significantly higher than the rate of 1/10 (10.0%) (p < 0.01) in the high-MPA sensitivity group. However, the MPA pharmacological efficacy evaluated both before and after transplantation had no relationship with the incidence of rejection episodes. These findings suggest that the MPA pharmacological efficacy evaluated by LIST at 2 weeks after operation is a useful biomarker for predicting the following occurrence of CMV infection episodes in renal transplant recipients.