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Mycophenolate mofetil attenuates renal injury in the rat remnant kidney
C K Fujihara1, D M Malheiros, R Zatz
1Renal Division, Department of Clinical Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
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.
Insights
Mycophenolate mofetil (MMF) reduced kidney injury and cellular infiltration in a rat model of chronic kidney disease. This immunosuppressant shows potential for treating non-immunologic progressive renal diseases.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Mycophenolate mofetil (MMF) is an immunosuppressant used to prevent allograft rejection.
- Its effect on non-immunologic progressive renal injury is not well understood.
Purpose of the Study:
- To investigate the efficacy of MMF in mitigating progressive renal injury in a rat model of 5/6 renal ablation.
Main Methods:
- Eighty-eight rats underwent 5/6 renal ablation and received either MMF (10 mg/kg/day) or vehicle.
- Sham-operated rats served as controls.
- Immunohistochemistry and assessments of renal injury markers were performed.
Main Results:
- MMF treatment attenuated interstitial lymphocyte and macrophage infiltration post-ablation.
- MMF largely attenuated glomerulosclerosis and interstitial expansion at 60 days.
- MMF did not correct glomerular hypertension/hypertrophy or reduce proteinuria.
Conclusions:
- MMF demonstrates a protective effect against progressive renal injury of non-immunologic origin in this rat model.
- This study provides the first evidence of MMF's potential benefit in such conditions.