| Combined therapy with renin-angiotensin system and calcium channel blockers in type 2 diabetic hypertensive patients with proteinuria: effects on soluble TWEAK, PTX3, and flow-mediated dilation. | |
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MedLine Citation:
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PMID: 20430947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND OBJECTIVES: Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7+/-5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. RESULTS: All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (beta=0.25, P=0.006) or PTX3 (beta=-0.24, P=0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. CONCLUSIONS: This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570. |
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Authors:
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Mahmut Ilker Yilmaz; Juan Jesús Carrero; Jose Luis Martín-Ventura; Alper Sonmez; Mutlu Saglam; Turgay Celik; Halil Yaman; Mujdat Yenicesu; Tayfun Eyileten; Juan Antonio Moreno; Jesús Egido; Luis Miguel Blanco-Colio |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-04-29 |
Journal Detail:
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Title: Clinical journal of the American Society of Nephrology : CJASN Volume: 5 ISSN: 1555-905X ISO Abbreviation: Clin J Am Soc Nephrol Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-08 Completed Date: 2010-10-26 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 101271570 Medline TA: Clin J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 1174-81 Citation Subset: IM |
Affiliation:
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Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey. |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00921570 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Amlodipine / therapeutic use Angiotensin II Type 1 Receptor Blockers / therapeutic use* Antihypertensive Agents / therapeutic use* C-Reactive Protein / metabolism* Calcium Channel Blockers / therapeutic use* Chi-Square Distribution Diabetes Mellitus, Type 2 / blood, drug therapy*, physiopathology Diabetic Nephropathies / blood, drug therapy*, physiopathology Drug Therapy, Combination Female Humans Hypertension / blood, drug therapy*, physiopathology Male Middle Aged Prospective Studies Renin-Angiotensin System / drug effects* Serum Amyloid P-Component / metabolism* Tetrazoles / therapeutic use Time Factors Treatment Outcome Tumor Necrosis Factors / blood* Turkey Valine / analogs & derivatives, therapeutic use Vasodilation / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Serum Amyloid P-Component; 0/TNFSF12 protein, human; 0/Tetrazoles; 0/Tumor Necrosis Factors; 137862-53-4/valsartan; 148591-49-5/PTX3 protein; 7004-03-7/Valine; 88150-42-9/Amlodipine; 9007-41-4/C-Reactive Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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