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

The DOI matches its Crossref record; 294 of the 294 references it cites were found in a registry or an index.

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

Open access
Himmelfarb, Jonathan, Stenvinkel, Peter, Ikizler, T. Alp, Hakim, Raymond M.·2002·Kidney International
DOI 10.1046/j.1523-1755.2002.00600.x
Open this paper in CoChat — free account

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.

Overview

Integrity signals

Registry

Crossref · 10.1046/j.1523-1755.2002.00600.x

Cites

294 of 294 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 294 references

Research works printed but not linked: 1

  1. Bloembergen, 1995, The relationship of dialysis membrane and cause-specific mortality in chronic hemodialysis patients, J Am Soc Nephrol, 6, 521

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Himmelfarb, J., Stenvinkel, P., Ikizler, T. A., & Hakim, R. M.
Affiliations
Maine Medical Center (US)
Corresponding author
Himmelfarb, Jonathan
ORCID
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
Licence
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review