Mycophenolate mofetil in pediatric renal transplantation

Since mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), has been approved for maintenance immunosuppressive therapy also in children after renal transplantation it has become an important part of immunosuppressive protocols. By inhibiting inosine monophosphate dehydrogenase, the key enzyme in the de novo purine biosynthesis of proliferating T and B lymphocytes, MMF acts as a relatively specific inhibitor of human lymphocyte proliferation. MMF is more effective than azathioprine in combination with cyclosporin A (CsA) and corticosteroids and distinctly reduces the incidence of acute rejection episodes in the 1st year post-transplant in adults as well as in children. Beneficial effects on steroid-resistant rejection and chronic allograft dysfunction have been shown. In general, MMF is well tolerated. Major adverse events in pediatric renal transplant recipients include leukopenia, infections and gastrointestinal problems. Pharmacokinetic monitoring of MPA can help to optimise MMF therapy after renal transplantation, as associations between the risk of acute rejection episodes and MPA-AUC values and MPA predose levels have been demonstrated. The incidence of MMF-related side effects such as leukopenia and/or infections, however, is associated with pharmacokinetic parameters of free MPA. Reference data of relevant pharmacokinetic parameters are available. The possible steroid-sparing potential of MMF is an important issue in pediatric renal transplantation. Preliminary data demonstrate improved longitudinal growth, less cushingoid habitus and lower blood pressure after steroid-withdrawal in pediatric renal transplant recipients under MMF and CsA therapy.