Novel Risk Factors for Chronic Kidney Disease

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DESCRIPTION (provided by applicant): This application is written in response to Program Announcement PA-03-091, "Ancillary Studies of Kidney Disease Accessing Information from Clinical Trials, Epidemiological Studies, and Databases". Its aims are to determine the relation of: (1) biomarkers of inflammation (high sensitivity C-reactive protein, interleukin 6, tumor necrosis factor-alpha Receptor 2); (2) biomarkers of oxidative stress (plasma free F2-isoprostanes, plasma protein carbonyl content); (3) biomarkers of endothelial dysfunction (E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1); and (4) retinal microvascular diameters to estimated glomerular filtration rate (GFR), 15-year change in estimated GFR, and the development of incident chronic kidney disease (CKD) over a 15-year interval. This project is designed as an ancillary study to the Beaver Dam Studies. The information necessary to test the specific aims of the project will be obtained by combining new data from stored laboratory measures and data already collected in the Beaver Dam Studies, ongoing population-based studies of persons 43-86 years who were examined at 5-year intervals beginning in 1988- 1990.. The design will be a nested case-cohort study within the Beaver Dam Studies. We anticipate 269 cases of incident CKD and will select 1150 persons for the random sample. Incident CKD will be defined as an estimated GFR<60 mL/min per 1.73 meter[2]. The estimated GFR will be calculated using the Modification of Diet in Renal Disease equation. Baseline frozen plasma samples will be batch-analyzed for biomarkers of inflammation, endothelial dysfunction, and oxidative stress. Retinal vessel diameters have been measured using a computer-assisted program. Data from this study will provide a unique opportunity to evaluate the relationship of inflammation,, oxidative stress, endothelial dysfunction, microvascular characteristics and CKD. The new data may provide insights into the relative protective value of low levels of these markers on the incidence CKD in an aging population.