Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort

Abstract

IntroductionChronic 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. MethodsREGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 years. Baseline levels of ICAM-1, VCAM-1, factor VIII, and E-selectin were measured in 3,300 participants without baseline CKD or albuminuria who attended a second visit 9.4 years later. Kidney outcomes were incident CKD (eGFR <60 mL/min/1.73m2 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. ResultsMedian age of participants was 62, 49% were women, and 46% identified as Black. 228 (6.9%) developed CKD, 613 (18.9%) experienced ≥30% decline in eGFR, and 356 (11.4%) developed albuminuria. The adjusted odds ratios for incident CKD per 1 standard deviation increment biomarker was 1.12 for ICAM-1 (95% CI 1.02-1.22), 1.10 for VCAM-1 (95% CI 1.01-1.20), 1.15 for factor VIII (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 factor VIII was positively associated. ConclusionsHigher concentration of ICAM-1, VCAM-1, factor VIII, and E-selectin were associated with incident CKD and ≥30% eGFR decline in a large cohort study. Higher factor VIII was also associated with incident albuminuria.