Relations of established aging biomarkers (IL-6, D-dimer, s-VCAM) to glomerular filtration rate and mortality in community-dwelling elderly adults

BACKGROUND: Biomarkers improving risk prediction for elderly populations with chronic kidney disease (CKD), an independent predictor of mortality, could be particularly useful. We previously observed that interleukin-6 (IL-6), D-dimer and soluble vascular adhesion molecule (s-VCAM) were independent biomarkers of mortality in elderly individuals. Therefore, we investigated whether these established biomarkers were independently associated with both estimated glomerular filtration rate (eGFR) and mortality. METHODS: The Established Populations for Epidemiologic Studies of the Elderly (EPESE) is a longitudinal cohort of community-dwelling elderly individuals. We investigated the association among eGFR, the biomarkers (IL-6, D-dimer and s-VCAM) and 4-year all-cause mortality using restricted cubic splines within Cox proportional hazards models. RESULTS: Among 1907 participants in EPESE, 1342 had available creatinine and biomarker measures. Incidence of all-cause mortality was 21.6%. eGFR was associated with all-cause mortality (P < 0.01); individuals at the lowest (<30 mL/min/1.73 m(2)) levels had the highest mortality rates. D-dimer and s-VCAM were associated (P < 0.01) with mortality, and after adjustment for IL-6, D-dimer and s-VCAM, the mortality risk varied by eGFR level. CONCLUSIONS: In community-dwelling elderly individuals, we observed an association among eGFR, 4-year mortality and IL-6, D-dimer and s-VCAM. eGFR was independently associated with mortality, and the relation between eGFR and mortality was modified by IL-6, D-dimer and s-VCAM, which was most notable in individuals with severely reduced eGFR. These findings suggest that IL-6, D-dimer and s-VCAM may be useful biomarkers for improving risk prediction, but further studies are needed examining the role of these biomarkers in elderly individuals with CKD.