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Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients

Peripheral artery disease (PAD) is highly prevalent among patients with chronic kidney disease (CKD) and portends a very poor prognosis. Indoxyl sulfate has been shown to induce atherothrombosis and impaired neovascularization in uremic mice. However, there is no clinical evidence regarding the role...

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Autores principales: Lin, Ting-Yun, Chou, Hsin-Hua, Huang, Hsuan-Li, Hung, Szu-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693838/
https://www.ncbi.nlm.nih.gov/pubmed/33147880
http://dx.doi.org/10.3390/toxins12110696
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author Lin, Ting-Yun
Chou, Hsin-Hua
Huang, Hsuan-Li
Hung, Szu-Chun
author_facet Lin, Ting-Yun
Chou, Hsin-Hua
Huang, Hsuan-Li
Hung, Szu-Chun
author_sort Lin, Ting-Yun
collection PubMed
description Peripheral artery disease (PAD) is highly prevalent among patients with chronic kidney disease (CKD) and portends a very poor prognosis. Indoxyl sulfate has been shown to induce atherothrombosis and impaired neovascularization in uremic mice. However, there is no clinical evidence regarding the role of indoxyl sulfate in PAD associated with CKD. We examined associations between indoxyl sulfate and incident symptomatic lower extremity PAD events as well as major adverse cardiovascular events (MACE) and all-cause mortality using Cox proportional hazards models in a prospective cohort of 200 hemodialysis patients free of PAD at baseline. Patients were considered as having PAD if they developed PAD symptoms confirmed by an ankle-brachial index with waveforms, duplex ultrasound or angiography, and/or major adverse limb events including revascularization and amputation. During a median follow-up of 6.5 years, 37 patients (18.5%) experienced incident symptomatic PAD. MACE occurred in 52 patients, and a total of 85 patients died. After adjusting for traditional risk factors for PAD, including age, current smoking, diabetes, and cardiovascular disease, indoxyl sulfate was significantly associated with the risk of PAD (hazard ratio (HR), 1.19 for every 10-μg/mL increase in indoxyl sulfate; 95% confidence interval (CI), 1.05–1.35). However, indoxyl sulfate was not associated with risk of MACE (HR, 1.00; 95% CI, 0.90–1.12) or death from any cause (HR, 0.98; 95% CI, 0.90–1.07). Indoxyl sulfate was associated with incident symptomatic PAD but not with MACE or all-cause mortality, suggesting that indoxyl sulfate toxicity may be unique to PAD among hemodialysis patients.
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spelling pubmed-76938382020-11-28 Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients Lin, Ting-Yun Chou, Hsin-Hua Huang, Hsuan-Li Hung, Szu-Chun Toxins (Basel) Article Peripheral artery disease (PAD) is highly prevalent among patients with chronic kidney disease (CKD) and portends a very poor prognosis. Indoxyl sulfate has been shown to induce atherothrombosis and impaired neovascularization in uremic mice. However, there is no clinical evidence regarding the role of indoxyl sulfate in PAD associated with CKD. We examined associations between indoxyl sulfate and incident symptomatic lower extremity PAD events as well as major adverse cardiovascular events (MACE) and all-cause mortality using Cox proportional hazards models in a prospective cohort of 200 hemodialysis patients free of PAD at baseline. Patients were considered as having PAD if they developed PAD symptoms confirmed by an ankle-brachial index with waveforms, duplex ultrasound or angiography, and/or major adverse limb events including revascularization and amputation. During a median follow-up of 6.5 years, 37 patients (18.5%) experienced incident symptomatic PAD. MACE occurred in 52 patients, and a total of 85 patients died. After adjusting for traditional risk factors for PAD, including age, current smoking, diabetes, and cardiovascular disease, indoxyl sulfate was significantly associated with the risk of PAD (hazard ratio (HR), 1.19 for every 10-μg/mL increase in indoxyl sulfate; 95% confidence interval (CI), 1.05–1.35). However, indoxyl sulfate was not associated with risk of MACE (HR, 1.00; 95% CI, 0.90–1.12) or death from any cause (HR, 0.98; 95% CI, 0.90–1.07). Indoxyl sulfate was associated with incident symptomatic PAD but not with MACE or all-cause mortality, suggesting that indoxyl sulfate toxicity may be unique to PAD among hemodialysis patients. MDPI 2020-11-02 /pmc/articles/PMC7693838/ /pubmed/33147880 http://dx.doi.org/10.3390/toxins12110696 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Ting-Yun
Chou, Hsin-Hua
Huang, Hsuan-Li
Hung, Szu-Chun
Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients
title Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients
title_full Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients
title_fullStr Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients
title_full_unstemmed Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients
title_short Indoxyl Sulfate and Incident Peripheral Artery Disease in Hemodialysis Patients
title_sort indoxyl sulfate and incident peripheral artery disease in hemodialysis patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693838/
https://www.ncbi.nlm.nih.gov/pubmed/33147880
http://dx.doi.org/10.3390/toxins12110696
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