There is no consensus as to the optimal immunosuppressive regimen for preventing rejection and promoting graft survival after orthotopic liver transplant. Primary immunosuppression based on cyclosporine (CyA) contributes to progressive deterioration in renal function in some patients. Mycophenolate mofetil (MMF, Cellcept.) has been approved in the United States, Canada, and the European Union for the prophylaxis of organ rejection in renal allograft recipients. The major side effects of MMF are dose related gastritis, leukopenia, and anemia. Potential complications of treatment with MMF include opportunistic infections and rarely lymphoproliferative disorders. There is no nephrotoxicity related to MMF. Nephrotoxicity of oral CyA is generally dose related. Reducing the dose of CyA is the first stop in decreasing the nephrotoxicity and thus helping to improve renal function. It is likely that MMF, a potent immunosuppresive agent with no known nephrotoxicity, may provide adequate immunosuppression upon withdrawal of CyA and thus improve renal function or prevent further damage. However, the risk of allograft rejection may increase with the withdrawal or reduction of CyA. Purpose: The objective is the evaluate whether MMF can be used as a mainstay immunosuppressive therapy in post liver transplant patients with impaired renal function, thereby decreasing the exposure to other immunosuppressive agents which are potentially nephrotoxic. Safety and efficacy of each treatment regimen will be evaluated, including graft/patient survival, biopsy-confirmed or presumptive acute cellular rejection, and the incidence of adverse events, opportunistic infections and abnormal laboratory evaluations. Methods: This is a phase IIIB, open-label active controlled study to evaluate the use of Cellcept. (mycophenolate mofetil, MMF) in post-liver transplant patients with renal impairment who are currently on Neoral. (cyclosporine A). A study is currently underway to evaluate the use of MMF in combination with cyclosporine and corticosteroids compared to standard treatment with azathioprine, cyclosporine and corticosteroids in liver allograft recipients. Post-liver transplant recipients > 18 years of age who meet all study entry requirements will be randomized (computer generated) with equal allocation to two groups. Both groups will have Imuran discontinued. Group A will be maintained on MMF 1.5 gm bid, prednisone, and CyA will be tapered to 50% at week 2 and discontinued at week 4. Group B will be maintained on MMF 1.5 gm bid, prednisone, and CyA will be tapered to 50% at week 2 and maintained throughout the study. Patients will be followed for 1 year post- enrollment. Glomerular filtration rate (GFR) using iohexol clearance will be measured on both groups of patients at enrollment, and at 1, 2, 4, 7, and 1 months following enrollment. In addition, routine labwork will be followed at months 3, 5, 6, 8, 9, and 10. A total of 35 ml of blood will be drawn for research purposes. A total of 30 patients will be enrolled at 3 centers. It is expected that 10 patients will be enrolled at Duke, 3 patients have been enrolled. The primary efficacy parameter will be measured by the change in GFR from baseline to week 28 post-randomization. Results: No results are available at this time.
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