Is the failure of recent trials on withdrawal of calcineurin inhibitors due to inadequate mycophenolic acid dosing?

Calcineurin inhibitors (CNIs) are the mainstay immunosuppressive therapy after kidney transplantation, despite their side effects. Recently, several randomized controlled trials attempting CNI withdrawal or minimization in stable, low-risk kidney transplant recipients led to an unacceptable risk of acute rejection and de novo HLA antibody formation. In the opinions of many, these trials definitively demonstrated that CNI-free regimens in the context of mycophenolate mofetil (MMF) maintenance are too risky. It can be argued, however, that the investigators failed to optimize the dose of the remaining immunosuppressive therapy. In particular, the potential benefit of MMF dosing based on the targeted mycophenolic acid (MPA) concentration was not taken into account. In this review, we present an overview of the studies on CNI withdrawal, both recent and older, paying specific attention to the MMF dose and elaborating on the possible benefit of MPA monitoring in this setting.