Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study
Abstract
Background The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric-oxide synthase, which has been linked to endothelial dysfunction and atherosclerosis in the general population, is raised in patients with end-stage renal disease and could contribute to the high cardiovascular risk in patients with chronic renal failure. We investigated the relation between cardiovascular risk factors and plasma ADMA concentration in a cohort of haemodialysis patients (n=225), and tested the predictive power of ADMA for mortality and cardiovascular outcomes.Methods Patients had standard dialysis three times a week. We accurately recorded cardiovascular events over a mean follow-up of 33.4 months (SD 14.6); these events were reviewed by a panel of physicians. We identified correlates of plasma ADMA by univariate and multivariate analyses.Findings On univariate analysis, ADMA concentration in plasma was directly related to concentrations of fibrinogen and L-arginine in plasma, duration of dialysis treatment, and serum cholesterol concentration, and was inversely related to serum albumin concentration. On multivariate analysis, only plasma fibrinogen (p=0.0001) and serum albumin (p=0.04) concentrations were independently related to plasma ADMA concentration (multiple r=0.44, p=0.0001). 83 patients died, 53 (64%) by cardiovascular causes. In a Cox's proportional-hazards model, plasma ADMA ranked as the second factor predicting overall mortality (hazard ratio 1.26, 95% Cl 1.11-1.41, p=0.0001) and cardiovascular events (1.17, 1.04-1.33, p=0.008).Interpretation In haemodialysis patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. These findings lend support to the hypothesis that accumulation of ADMA is an important risk factor for cardiovascular disease in chronic renal failure.
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NOX4 can modulate the role of VEGF-induced dimerization of CD146 necessary for cell adhesion.
“Consistent with this role of NOX4-derived ROS in angiogenesis (642, 989), it has been shown that NOX4 can modulate the role of VEGF-induced dimerization of CD146 necessary for cell adhesion (1065), and NOX4-derived ROS can induce the reversible glutathionylation of SERCA and increase Ca2+ levels, thus regulating VEGF-signaling cell migration (273).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1065]
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- Authors
- Zoccali, C., Bode-Böger, S. M., Mallamaci, F., Benedetto, F. A., Tripepi, G., Malatino, L. S., Cataliotti, A., Bellanuova, I., Fermo, I., Frölich, J. C., & Böger, R. H.
- Affiliations
- University of Catania (IT)
- IRCCS Ospedale San Raffaele (IT)
- Medizinische Hochschule Hannover (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Böger, Rainer H
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 358
- Issue
- 9299
- Pages
- 2113-2117
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2148531805
- Cited by
- 1,087
- References
- 28
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 12 · 2023: 20 · 2022: 27 · 2021: 29 · 2020: 32 · 2019: 27 · 2018: 33 · 2017: 33 · 2016: 24 · 2015: 35 · 2014: 50 · 2013: 52 · 2012: 68
- FWCI
- 25.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medizinischen Hochschule Hannover
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- asymmetric dimethylarginine, end-stage renal disease, hemodialysis, cardiovascular mortality, cardiovascular events, nitric oxide synthase inhibition, endothelial dysfunction, fibrinogen, serum albumin, chronic kidney disease, cardiovascular risk factors, biomarker prediction
- MeSH terms
- Arginine, Cardiovascular Diseases, Cause of Death, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Prospective Studies, Risk Factors, Biomarkers, Causality, Multivariate Analysis, Proportional Hazards Models
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