Low-dose Cyclosporine with Mycophenolate Mofetil Induces Similar Calcineurin Activity and Cytokine Inhibition As Does Standard-dose Cyclosporine in Stable Renal Allografts

One strategy to minimize nephrotoxicity in maintenance immunosuppression in renal transplantation is reduction of cyclosporine (CsA) with addition of mycophenolate mofetil (MMF). This approach seems safe, but concern exists about whether it yields adequate immunosuppression in the long term. Thus, we investigated the pharmacodynamic response to CsA in stable renal allografts treated with standard CsA (n = 17, CsA-C0h > or = 125 ng/mL) and low CsA plus MMF (n = 18 CsA-C0h <100 ng/mL). Patients treated with MMF without CsA (n = 13) and healthy subjects (n = 7) were used as controls. We observed that inhibition of calcineurin (CN) activity in peripheral blood mononuclear cells (PBMC), as well as interleukin (IL)-2 and interferon (IFN)-gamma production were similar in Standard-CsA and Low-CsA+MMF groups. Moreover, addition of MMF to a low CsA dose regime improved the correlation between CsA-C2h and both CN activity and IL-2 production. Thus, our results suggest that MMF could be synergistic with the pharmacodynamic effect of low CsA in maintenance immunosuppression.