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Cited by 30Cardiovascular Health and Disease PreventionNitric Oxide and Endothelin EffectsChronic Kidney Disease and Diabetes

Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease

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Nowak, Kristen L., Jovanovich, Anna, Farmer-Bailey, Heather, Bispham, Nina, Struemph, Taylor, Malaczewski, Mikaela, Wang, Wei, Chonchol, Michel·2020·Kidney360
DOI 10.34067/kid.0000962019PMC PMC7725223
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Abstract

Background: Increased arterial stiffness and vascular endothelial dysfunction are important nontraditional cardiovascular risk factors evident in patients with CKD. Vascular oxidative stress and inflammation may contribute to vascular dysfunction in CKD, but direct evidence is lacking. Methods: We assessed carotid-femoral pulse-wave velocity (arterial stiffness) and brachial artery flow-mediated dilation (vascular endothelial function) in participants with moderate-to-severe CKD (eGFR 15–59 ml/min per 1.73 m 2 ) and in healthy controls. Change in brachial artery flow-mediated dilation after an acute infusion of ascorbic acid to inhibit vascular oxidative stress (versus saline) was also measured. Protein expression of vascular endothelial cells collected from a peripheral vein and ELISAs to assess circulating markers were also performed. Results: A total of 64 participants with CKD (mean±SD, 65±8 years) and 17 healthy controls (60±5 years) were included. Carotid-femoral pulse-wave velocity was greater in participants with CKD compared with healthy controls (1071±336 versus 732±128 cm/s; P <0.001). Brachial artery flow-mediated dilation was lower in participants with CKD compared with healthy controls (3.5%±2.8% versus 5.5%±3.2%; P =0.02). Circulating inflammation markers (C-reactive protein and IL-6) were elevated in the CKD group ( P ≤0.02). Endothelial cell protein expression of NADPH (intensity versus human umbilical vein endothelial cell control, 1.48±0.28 versus 1.25±0.31; P =0.05) was greater in participants with CKD. However, ascorbic acid significantly improved brachial artery flow-mediated dilation in control participants (saline, 5.5±3.2; ascorbic acid, 6.8±3.6); as compared with participants with CKD (saline, 3.5±2.8; ascorbic acid, 3.6±3.2) (group×condition interaction P =0.04), suggesting vascular oxidative stress could not be overcome with ascorbic acid in participants with CKD. Conclusions: Vascular oxidative stress is present in CKD, which cannot be overcome with acute infusion of ascorbic acid.

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  • In CKD, reduced NO bioavailability and increased oxidative stress contribute to vascular dysfunction and elevated cardiovascular risk.

    “In CKD, reduced NO bioavailability and increased oxidative stress contribute to vascular dysfunction and elevated cardiovascular risk [218].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [218]

    The Discussion says oxidative stress is a likely promoter of reduced NO bioavailability and identifies reduced NO as a mechanism of arterial stiffness and endothelial dysfunction. It describes oxidative stress as a possible contributor to vascular dysfunction in moderate-to-severe CKD and reduced cardiovascular risk from treating it as a possibility, so the claim states these links more definitively than the paper does. (LLM, conf=0.86)

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Authors
Nowak, K. L., Jovanovich, A., Farmer-Bailey, H., Bispham, N., Struemph, T., Malaczewski, M., Wang, W., & Chonchol, M.
Affiliations
  • University of Colorado Anschutz (US)
  • Veterans Health Administration (US)
  • Anschutz Medical Campus, University of Colorado, Aurora, Colorado
Corresponding author
Nowak, Kristen L.
ORCID
Venue
Kidney360
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2020-06
Volume
1
Issue
6
Pages
501-509
ISSN
2641-7650 (ISSN-L)
DOI
10.34067/kid.0000962019
PMC
PMC7725223
OpenAlex
W3022908696
Cited by
30
References
47
Citations by year
2026: 8 · 2025: 10 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2
FWCI
1.24
Type
journal article
Language
en
Open access
Locations
  • Kidney360 (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (K01DK103678)
  • Center for Integrated Healthcare, U.S. Department of Veterans Affairs (5IK2CX001030)
  • American Heart Association (12POST11920023)
  • HHS | NIH | National Center for Advancing Translational Sciences (UL1 TR001082)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
chronic kidney disease, vascular dysfunction, arterial stiffness, endothelial dysfunction, oxidative stress, inflammation, pulse wave velocity, flow-mediated dilation, vitamin C, NADPH oxidase, C-reactive protein, interleukin-6, endothelial cells
MeSH terms
Endothelium, Vascular, Humans, Inflammation, Oxidative Stress, Endothelial Cells, Renal Insufficiency, Chronic

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