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Toxins 2017, 9(1), 20; doi:10.3390/toxins9010020

High Uric Acid Ameliorates Indoxyl Sulfate-Induced Endothelial Dysfunction and Is Associated with Lower Mortality among Hemodialysis Patients

1
Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
2
Faculty of Medicine, National Yang-Ming University, Taipei 11217, Taiwan
3
Institute of Population Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan
4
Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
5
Cardiovascular Research Center, National Yang-Ming University, Taipei 11217, Taiwan
6
Department of Medical Research, Taipei Veterans General Hospital, Taipe 11217, Taiwan
7
Department of Health Services Administration, China Medical University, Taichung 40402, Taiwan
8
Department and Institute of Physiology, National Yang-Ming University, Taipei 11217, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: R. Vanholder
Received: 9 November 2016 / Revised: 22 December 2016 / Accepted: 2 January 2017 / Published: 6 January 2017
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
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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. View Full-Text
Keywords: cardiovascular mortality; hemodialysis; indoxyl sulfate; uric acid; vascular toxicity cardiovascular mortality; hemodialysis; indoxyl sulfate; uric acid; vascular toxicity
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MDPI and ACS Style

Hsu, W.-L.; Li, S.-Y.; Liu, J.-S.; Huang, P.-H.; Lin, S.-J.; Hsu, C.-C.; Lin, Y.-P.; Tarng, D.-C. High Uric Acid Ameliorates Indoxyl Sulfate-Induced Endothelial Dysfunction and Is Associated with Lower Mortality among Hemodialysis Patients. Toxins 2017, 9, 20.

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