Cyclosporine monitoring in peripheral blood mononuclear cells: feasibility and interest. A prospective study on 20 renal transplant recipients

Abstract

Cyclosporine (CsA) has potent immunosuppressive properties, reflecting its ability to block the transcription of cytokine genes (mainly interleukin 2) in CD4+ T lymphocytes, markedly improving transplantation outcomes in the past 20 years. CsA pharmacokinetic variability and renal toxicity require whole blood (WB) monitoring by 4-hour area under the drug concentration curves (AUC0-4) or 2-hour postdose concentration (C2) monitoring. Nevertheless, graft rejection can occur despite target blood levels, suggesting that WB monitoring does not guarantee optimal immunosuppression. For a decade, pharmacologists and clinicians have worked to optimize CsA doses; some authors, inspired by its mechanism of action, have proposed therapeutic drug monitoring using peripheral blood mononuclear cells (PBMC; lymphocytes and monocytes). The aim of this study was to assess the feasibility and interest of CsA monitoring in PBMC ([CsA]PBMC). We also measured in vitro distribution of CsA in CD4+ and CD4- subsets.