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Uninephrectomized rats made diabetic by streptozotocin were orally treated from 4 (when proteinuria and renal lesions had developed) to 8 mo with vehicle, lisinopril plus candesartan, lisinopril plus candesartan plus rosuvastatin, or rosuvastatin alone. Systolic blood pressure increased in diabetic rats and was significantly lowered by combined therapies. Dual RAS blockade significantly reduced proteinuria compared with vehicle. Addition of statin further lowered proteinuria to control levels. Glomerulosclerosis was ameliorated by RAS inhibitors or statin, and regression was achieved by the addition of statin. Loss of podocytes of diabetic rats was limited by ACE inhibitor plus ARB while normalized by the three drugs. Defective nephrin expression of diabetes was increased by dual RAS blockade or statin and restored by the triple therapy. Tubular damage, interstitial inflammation, and expression of the fibrotic markers transforming growth factor (TGF)-\u03b21 and phosphorylated Smad 2\/3 in tubuli were significantly reduced by the triple regimen. These data suggest a strategy to target proteinuria to try to achieve regression of renal disease in diabetic patients who do not fully benefit from RAS inhibition alone.<\/jats:p>","DOI":"10.1152\/ajprenal.00045.2010","type":"journal-article","created":{"date-parts":[[2010,8,19]],"date-time":"2010-08-19T02:00:12Z","timestamp":1282183212000},"page":"F1203-F1211","source":"Crossref","is-referenced-by-count":42,"title":["Adding a statin to a combination of ACE inhibitor and ARB normalizes proteinuria in experimental diabetes, which translates into full renoprotection"],"prefix":"10.1152","volume":"299","author":[{"given":"Carla","family":"Zoja","sequence":"first","affiliation":[{"name":"Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Corna","sequence":"additional","affiliation":[{"name":"Mario Negri Institute for 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