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- Title
Enhanced Effect of Combined Treatment with SMP-534 (Antifibrotic Agent) and Losartan in Diabetic Nephropathy.
- Authors
Sugaru, Eiji; Nakagawa, Tsutomu; Ono-Kishino, Michiko; Nagamine, Jun; Tokunaga, Teruhisa; Kitoh, Makoto; Hume, W. Ewan; Nagata, Ryu; Taiji, Mutsuo
- Abstract
Background/Aims: Diabetic nephropathy is now the most common cause of end-stage renal disease. It is also clear that the current therapy, angiotensin II blockage, cannot prevent the progression of diabetic nephropathy. We had previously demonstrated that an antifibrotic agent, SMP-534, reduced extracellular matrix production induced by transforming growth factor-β in vitro, and that SMP-534 prevented renal fibrosis and urinary albumin in diabetic db/db mice via a nonantihypertensive mechanism. We expected that combined use of SMP-534 and losartan would produce a more highly renoprotective action. Methods: We examined the effects of combined treatment with SMP-534 and losartan on urinary albumin and glomerular fibrosis in db/db mice. Diet containing these agents was provided from age 9 to 25 weeks. Blood and urine analyses were performed at 8, 17, and 25 weeks. At the end of the study, kidney tissues were histologically analyzed. Results: SMP-534 significantly suppressed an increase in urinary albumin excretion and ameliorated the progression of glomerular fibrosis in db/db mice, whereas losartan did not. Combined treatment with SMP-534 and losartan markedly prevented the increase of urinary albumin excretion compared with treatment with either SMP-534 or losartan alone. In contrast, renal histological analysis revealed that combined treatment did not significantly prevent an increase of mesangial expansion in the kidney compared with treatment with SMP-534 alone. Conclusion: A combination of the two agents, SMP-534 and losartan, might be a valuable therapeutic approach for the treatment of diabetic nephropathy. Copyright © 2006 S. Karger AG, Basel
- Subjects
DIABETIC nephropathies; CHRONIC kidney failure; DIABETES complications; ANGIOTENSINS; ALBUMINS; FIBROSIS
- Publication
American Journal of Nephrology, 2006, Vol 26, Issue 1, p50
- ISSN
0250-8095
- Publication type
Article
- DOI
10.1159/000091786