Mycophenolate mofetil monotherapy in stable liver transplant recipients with progressive renal failure

Abstract

CURRENTLY, STANDARD immunosuppressive protocols for solid organ transplantation include a calcineurin inhibitor (CNI), either cyclosporine or tacrolimus. These drugs are powerful immunosuppressors but present significant immunological side effects. Among them, chronic nephrotoxicity represents a serious clinical challenge even years after transplantation. In particular, many liver transplant recipients who enjoy long-term survival develop progressive end-stage renal disease requiring dialysis and/or renal transplantation. With experience, transplant physicians have learned to use much lower doses of immunosuppressive drugs, thereby reducing the rate and severity of their side effects, but in the long run, low-dose CNI may still induce progressive impairment of renal function. Mycophenolate mofetil (MMF) is a potent inhibitor of inosine monophosphate dehydrogenase with a relatively selective effect on Tand B-lymphocyte activation and proliferation. MMF has no nephrotoxic side effect and seems to have superior immunosuppressive potency compared with azathioprine. In this nonrandomized, consecutive, prospective, pilot study, the authors offered CNI withdrawal to stable liver recipients who experienced progressive chronic renal failure years after successful liver transplantation. CNI was successfully replaced by MMF monotherapy, without signs of chronic graft rejection at follow-up, and with significant improvement of serum creatinine levels.