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This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/F359    most recent 00442.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Krämer, S. Articles by Peters, H. Search for Related Content PubMed PubMed Citation Articles by Krämer, S. Articles by Peters, H.

Mycophenolate mofetil slows progression in anti-thy1-induced chronic renal fibrosis but is not additive to a high dose of enalapril

¹Department of Nephrology and Center of Cardiovascular Research, Charité University Medicine Berlin, Charité Campus Mitte, Humboldt University, Berlin, Germany; and ²Department of Cell Biology and Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Submitted 9 December 2004 ; accepted in final form 6 March 2005

Tubulointerstitial inflammation and fibrosis are hallmarks of chronic progressive renal diseases. To characterize the functional interaction between cell infiltration and matrix expansion, this study compared the immunosuppressant mycophenolate mofetil (MMF), intended as primarily anti-inflammatory intervention, the angiotensin-converting enzyme inhibitor enalapril, intended as primarily an anti-fibrotic drug, and a combination of both as anticipated anti-inflammatory/anti-fibrotic intervention. The model used was anti-thy1-induced chronic-progressive glomerulosclerosis (cGS) in the rat, where a brief anti-thy1-induced glomerular injury progresses spontaneously toward tubulointerstitial fibrosis and renal insufficiency. cGS was induced by injection of anti-thy1 antibody into uninephrectomized Wistar rats. One week after disease induction, animals were randomly assigned to the following groups: cGS, cGS plus MMF (20 mg·kg body wt^–1·day^–1), cGS plus high-dose enalapril (12 mg·kg body wt^–1·day^–1), and cGS plus both. At week 16 after disease induction, MMF or enalapril alone reduced signs of chronic renal disease significantly and similarly compared with the untreated cGS group. Variables measured included proteinuria, blood pressure, tubulointerstitial and glomerular matrix accumulation, expression of transforming growth factor-₁, fibronectin, and plasminogen activator inhibitor-1, infiltration of lymphocytes and macrophages, plasma creatinine and urea levels, and glomerular filtration rate. Combined MMF and enalapril treatment was not superior to single therapy. In conclusion, MMF slows the progression of chronic renal fibrosis and renal insufficiency as effectively as high-dose enalapril in the anti-thy1-induced chronic-progressive glomerulosclerosis model. The dual anti-inflammatory/anti-fibrotic intervention does not yield additive renoprotective effects, indicating that MMF and enalapril interfere with similar or very closely related pathways involved in progression of renal disease.

angiotensin-converting enzyme inhibition; transforming growth factor-₁

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