MYCOPHENOLATE-MOFETIL ATTENUATES RENAL INJURY IN THE RAT REMNANT KIDNEY

Background. Mycophenolate mofetil (MMF), an inhibitor of lymphocyte pr oliferation, has been used to prevent allograft rejection. We investig ated whether MMF also limits progressive renal injury in rats with 5/6 renal ablation, a model not primarily related to immunologic mechanis ms. Methods. Eighty-eight adult male Munich-Wistar rats underwent abla tion and received either vehicle (N = 42) or oral MMF (N = 46), 10 mg/ kg/day. Forty-seven sham-operated rats were also studied. Results. Thi rty days after surgery, remnant kidneys exhibited glomerular hypertens ion and hypertrophy. MMF treatment did not correct these abnormalities . Immunohistochemistry revealed interstitial lymphocyte infiltration 7 and 30 days after ablation. Proliferating cells abounded seven days a fter ablation, especially in tubules, declining in number along the fo llowing weeks. By contrast, the number of macrophages was moderately i ncreased in the first weeks, attaining values eightfold as high as con trol 60 days after ablation. MMF attenuated these cellular events at a ll phases of the study. Sir;ty days after ablation, marked albuminuria , glomerulosclerosis and interstitial expansion were prominent in untr eated rats. MMF treatment largely attenuated glomerular and interstiti al injury without changing proteinuria. Conclusion. This is the first evidence that MMF may impact favorably on progressive renal diseases o f ''nonimmunologic'' origin.