Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort

Samuel A P Short; Katherine Wilkinson; D Leann Long; Deidra C Crews; Orlando M Gutierrez; Marguerite R Irvin; Marsha Wheeler; Mary Cushman; Katharine L Cheung

doi:10.1016/j.ekir.2024.04.056

Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort

Kidney Int Rep. 2024 May 1;9(7):2016-2027. doi: 10.1016/j.ekir.2024.04.056. eCollection 2024 Jul.

Authors

Affiliations

¹ Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
² Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
³ Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁶ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁷ Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
⁸ Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT.

Abstract

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.

Keywords: albuminuria; biomarkers; chronic kidney disease; endothelial dysfunction; risk factors.