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Updated: Jun 18, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort
Samuel A P Short1, Katherine Wilkinson2, D Leann Long3
1Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
Insights
Endothelial dysfunction biomarkers, including intercellular cellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), factor VIII (FVIII), and E-selectin, are linked to increased risk of chronic kidney disease (CKD) and kidney function decline.
Area of Science:
- Nephrology
- Cardiovascular Science
- Biomarker Research
Background:
- Chronic kidney disease (CKD) has multifactorial causes beyond traditional risk factors.
- Endothelial dysfunction is a recognized complication in CKD and a potential contributor to its development.
Purpose of the Study:
- To investigate the association between circulating biomarkers of endothelial dysfunction and the incidence of CKD.
- To explore the relationship between these biomarkers and kidney function decline and albuminuria.
Main Methods:
- Utilized data from the Reasons for Geographical and Racial Differences in Stroke (REGARDS) study, a prospective cohort of 30,239 adults.
- Measured baseline levels of ICAM-1, VCAM-1, FVIII, and E-selectin in 3300 participants without prevalent CKD or albuminuria.
- Assessed incident CKD, eGFR decline, and incident albuminuria over a 9.4-year follow-up period using logistic regression models.
Main Results:
- Higher concentrations of ICAM-1, VCAM-1, FVIII, and E-selectin were significantly associated with incident CKD (ORs ranging from 1.10 to 1.15 per SD increment).
- These biomarkers were also associated with a ≥30% decline in estimated glomerular filtration rate (eGFR).
- Elevated FVIII levels were specifically linked to incident albuminuria, while other biomarkers were not.
Conclusions:
- Circulating biomarkers of endothelial dysfunction (ICAM-1, VCAM-1, FVIII, E-selectin) are associated with an increased risk of developing CKD and experiencing significant kidney function decline.
- Factor VIII may play a specific role in the development of albuminuria in addition to its association with overall CKD incidence.
Introduction:
Chronic kidney disease (CKD) is only partly caused by traditional risk factors. Endothelial dysfunction is common in CKD and may contribute to CKD incidence. We studied the association of circulating biomarkers reflecting endothelial dysfunction with incident CKD.
Methods:
The Reasons for Geographical and Racial Differences in Stroke (REGARDS) study is a prospective cohort of 30,239 Black or White adults aged ≥45 years. Baseline levels of intercellular cellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), factor VIII (FVIII), and E-selectin were measured in 3300 participants without baseline CKD or albuminuria who attended a second visit 9.4 years later. Kidney outcomes were incident CKD (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m2 and ≥40% decline or onset of new end-stage kidney disease), incident ≥30% eGFR decline, and incident albuminuria (albumin-to-creatinine ratio [ACR] ≥30 mg/g). Sequentially adjusted logistic regression models assessed the association of biomarkers with kidney outcomes.
Results:
Median age of participants was 62 years, 49% were women, and 46% identified as Black. Of the participants, 228 (6.9%) developed CKD, 613 (18.9%) experienced ≥30% decline in eGFR, and 356 (11.4%) developed albuminuria. The adjusted odds ratios (ORs) for incident CKD per 1 SD increment biomarker was 1.12 for ICAM-1 (95% confidence interval [CI]: 1.02-1.22), 1.10 for VCAM-1 (95% CI: 1.01-1.20), 1.15 for FVIII (95% CI: 1.06-1.24), and 1.10 for E-selectin (95% CI: 1.01-1.20). Results were similar for incident ≥30% eGFR decline but not albuminuria, where only higher FVIII was positively associated.
Conclusion:
Higher concentration of ICAM-1, VCAM-1, FVIII, and E-selectin were associated with incident CKD and ≥30% eGFR decline in a large cohort study. Higher FVIII was also associated with incident albuminuria.
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