Cited by 1,179Dialysis and Renal Disease ManagementAntioxidant Activity and Oxidative StressNitric Oxide and Endothelin Effects

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The elephant in uremia: Oxidant stress as a unifying concept of cardiovascular disease in uremia

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Himmelfarb, Jonathan, Stenvinkel, Peter, Ikizler, T. Alp, Hakim, Raymond M.·2002·Kidney International

DOI 10.1046/j.1523-1755.2002.00600.x

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Abstract

Cardiovascular disease is the leading cause of mortality in uremic patients. In large cross-sectional studies of dialysis patients, traditional cardiovascular risk factors such as hypertension and hypercholesterolemia have been found to have low predictive power, while markers of inflammation and malnutrition are highly correlated with cardiovascular mortality. However, the pathophysiology of the disease process that links uremia, inflammation, and malnutrition with increased cardiovascular complications is not well understood. We hereby propose the hypothesis that increased oxidative stress and its sequalae is a major contributor to increased atherosclerosis and cardiovascular morbidity and mortality found in uremia. This hypothesis is based on studies that conclusively demonstrate an increased oxidative burden in uremic patients, before and particularly after renal replacement therapies, as evidenced by higher concentrations of multiple biomarkers of oxidative stress. This hypothesis also provides a framework to explain the link that activated phagocytes provide between oxidative stress and inflammation (from infectious and non-infections causes) and the synergistic role that malnutrition (as reflected by low concentrations of albumin and/or antioxidants) contributes to the increased burden of cardiovascular disease in uremia. We further propose that retained uremic solutes such as beta-2 microglobulin, advanced glycosylated end products (AGE), cysteine, and homocysteine, which are substrates for oxidative injury, further contribute to the pro-atherogenic milieu of uremia. Dialytic therapy, which acts to reduce the concentration of oxidized substrates, improves the redox balance. However, processes related to dialytic therapy, such as the prolonged use of catheters for vascular access and the use of bioincompatible dialysis membranes, can contribute to a pro-inflammatory and pro-oxidative state and thus to a pro-atherogenic state. Anti-oxidative therapeutic strategies for patients with uremia are in their very early stages; nonetheless, early studies demonstrate the potential for significant efficacy in reducing cardiovascular complications.

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See all 1,179

Authors: Himmelfarb, J., Stenvinkel, P., Ikizler, T. A., & Hakim, R. M.
Affiliations: Maine Medical Center (US)
Corresponding author: Himmelfarb, Jonathan
ORCID: Himmelfarb, Jonathan
Stenvinkel, Peter
Ikizler, T. Alp
Hakim, Raymond M.
Venue: Kidney International
Publisher: Elsevier BV
Published: 2002-11
Volume: 62
Issue: 5
Pages: 1524-1538
ISSN: 0085-2538 (ISSN-L)
DOI: 10.1046/j.1523-1755.2002.00600.x
OpenAlex: W1996978408
Cited by: 1,179
References: 294
Citations by year: 2026: 15 · 2025: 16 · 2024: 29 · 2023: 31 · 2022: 36 · 2021: 51 · 2020: 40 · 2019: 30 · 2018: 43 · 2017: 57 · 2016: 49 · 2015: 57 · 2014: 58 · 2013: 71 · 2012: 68
FWCI: 10.70
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4784 d)
Locations: Kidney International (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: uremia, oxidative stress, cardiovascular disease, atherosclerosis, inflammation, malnutrition, dialysis, uremic solutes, beta2-microglobulin, homocysteine, cysteine, antioxidant therapy, vascular access catheters, cardiovascular mortality
MeSH terms: Cardiovascular Diseases, Humans, Uremia, Oxidative Stress

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The elephant in uremia: Oxidant stress as a unifying concept of cardiovascular disease in uremia

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