Mycophenolate mofetil attenuates renal injury in the rat remnant kidney

Abstract

Background: Mycophenolate mofetil (MMF), an inhibitor of lymphocyte proliferation, has been used to prevent allograft rejection. We investigated whether MMF also limits progressive renal injury in rats with 5/6 renal ablation, a model not primarily related to immunologic mechanisms.

Methods: Eighty-eight adult male Munich-Wistar rats underwent ablation and received either vehicle (N = 42) or oral MMF (N = 46), 10 mg/kg/day. Forty-seven sham-operated rats were also studied.

Results: Thirty days after surgery, remnant kidneys exhibited glomerular hypertension 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 after ablation, especially in tubules, declining in number along the following weeks. By contrast, the number of macrophages was moderately increased in the first weeks, attaining values eightfold as high as control 60 days after ablation. MMF attenuated these cellular events at all phases of the study. Sixty days after ablation, marked albuminuria, glomerulosclerosis and interstitial expansion were prominent in untreated rats. MMF treatment largely attenuated glomerular and interstitial injury without changing proteinuria.

Conclusion: This is the first evidence that MMF may impact favorably on progressive renal diseases of "nonimmunologic" origin.