title: High Uric Acid Ameliorates Indoxyl Sulfate-Induced Endothelial Dysfunction and Is Associated with Lower Mortality among Hemodialysis Patients.
abstract: High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatable with regard to the association between high UA and poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of <6.1 mg/dL was associated with a higher risk of all-cause mortality compared with a UA level of >8.1 mg/dL [HR, 1.20, 95% CI (1.10-1.31)] adjusting for baseline demographic and biochemical parameters. Moreover, a UA level of <6.1 mg/dL was associated with greater risks of cardiovascular mortality [HR, 1.26, 95% CI (1.13-1.41)] and stroke-related mortality [HR, 1.59, 95% CI (1.12-2.25)], respectively. In vitro experiments further showed an increase in oxidative stress and an inhibition nitric oxide synthesis by indoxyl sulfate (IS) in human aortic endothelial cells, which were significantly attenuated by UA in a dose-dependent manner. We concluded that higher UA in serum was associated with lower risk of all-cause and cardiovascular mortality among HD patients probably through its antioxidant property in ameliorating the IS-related vascular toxicity.
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. lasote521@gmail.com.|Faculty of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. lasote521@gmail.com.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. syli@vghtpe.gov.tw.|Faculty of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. syli@vghtpe.gov.tw.
authors.forename: Szu-Yuan
authors.initials: SY
authors.lastname: Li
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan. sgazn.tw@gmail.com.
authors.forename: Jia-Sin
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Faculty of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. huangbs@vghtpe.gov.tw.|Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. huangbs@vghtpe.gov.tw.|Cardiovascular Research Center, National Yang-Ming University, Taipei 11217, Taiwan. huangbs@vghtpe.gov.tw.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. sjlin@vghtpe.gov.tw.|Cardiovascular Research Center, National Yang-Ming University, Taipei 11217, Taiwan. sjlin@vghtpe.gov.tw.|Department of Medical Research, Taipei Veterans General Hospital, Taipe 11217, Taiwan. sjlin@vghtpe.gov.tw.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Institute of Population Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan. cch@nhri.org.tw.|Department of Health Services Administration, China Medical University, Taichung 40402, Taiwan. cch@nhri.org.tw.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. linyp@vghtpe.gov.tw.|Faculty of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. linyp@vghtpe.gov.tw.
authors.forename: Yao-Ping
authors.initials: YP
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. dctarng@vghtpe.gov.tw.|Faculty of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. dctarng@vghtpe.gov.tw.|Department and Institute of Physiology, National Yang-Ming University, Taipei 11217, Taiwan. dctarng@vghtpe.gov.tw.
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000097:blood* / Q000401:mortality; D007200:Indican / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D014527:Uric Acid; D009569:Nitric Oxide; D007200:Indican
keywords: cardiovascular mortality; hemodialysis; indoxyl sulfate; uric acid; vascular toxicity