Monitoring of blood immunosuppressant concentrations and lymphocyte activation for predicting viral infections following kidney transplantation: A pilot study

The current standard pharmacokinetic monitoring of immunosuppressive therapy does not consider inter- and intra-individual differences in the biological response to multidrug immunosuppressive therapy. The authors evaluated the blood levels of the immunosuppressive drugs IL-2 and IFN-γ in circulating lymphocytes as surrogate indicators of the development of viral infections after living kidney transplantation. This single-center prospective study included 20 kidney transplant recipients who underwent living-donor transplantation at the Mie University Hospital. All the study participants received tacrolimus, mycophenolic acid, methylprednisolone, and basiliximab. The area under the concentration curves (AUCs) of blood tacrolimus and serum mycophenolic acid were measured 1 day prior to transplantation and on post-transplantation days (PTD) for up to 5 months. IL-2 and IFN-γ levels in circulating lymphocytes were measured simultaneously. One recipient experienced an acute graft rejection. Although the AUC of tacrolimus at PTD 7 was significantly higher in the virus-infected group than that in the non-infected group, the AUC of mycophenolic acid did not differ significantly between the 2 groups. The expression levels of IFN-γ(+) NK, IFN-γ(+) CD4(+) T, and CD8(+) T cells in the infected group also tended to be higher than those in the noninfected group. During the study period, there was a clear difference in the expression of IFN-γ(+) CD8(+) T cells, which increased significantly during or after infection. Circulating IFN-γ(+) CD8(+) T cell counts may serve as promising biomarkers for predicting opportunistic viral infections early after kidney transplantation.