| Modulation of advanced glycation end products by candesartan in patients with diabetic kidney disease--a dose-response relationship study. | |
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MedLine Citation:
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PMID: 19829095 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria ≥500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure. At baseline and after each dosing period, blood pressure measurements and 24-hour urine collections were obtained. Urinary carboxymethyl lysine, an AGE biomarker, was reduced over the 12-week dose escalation protocol (r = 0.38, P = 0.01) in DKD participants. Creatinine clearance increased slightly, but albuminuria was unaffected by candesartan administration. Baseline urinary transforming growth factor-β₁ excretion was lower in DKD participants than in controls and did not change during the study period. Reducing kidney exposure to AGEs may be a mechanism of protection by angiotensin receptor blockade in DKD. AGEs may also impact the diabetic kidney through mechanisms independent of transforming growth factor-β₁. |
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Authors:
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Sandeep A Saha; Brian K LaSalle; G Dennis Clifton; Robert A Short; Katherine R Tuttle |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of therapeutics Volume: 17 ISSN: 1536-3686 ISO Abbreviation: Am J Ther Publication Date: 2010 Nov-Dec |
Date Detail:
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Created Date: 2010-11-09 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9441347 Medline TA: Am J Ther Country: United States |
Other Details:
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Languages: eng Pagination: 553-8 Citation Subset: IM |
Affiliation:
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Providence Medical Research Center, Sacred Heart Medical Center, Spokane, WA 99204, USA. sahas@u.washington.edu |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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