Serum Calcification Activity in Patients with Chronic Kidney Disease

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DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) affects 11% of American adults and substantially increases the risks of cardiovascular disease and premature death. Novel tools are urgently needed to accurately measure the adverse metabolic milieu of kidney failure to catalyze discovery of kidney-specific cardiovascular disease mechanisms. Dystrophic calcification of the vasculature and soft tissues is highly prevalent among CKD patients and may represent one key mechanism linking kidney and cardiovascular diseases. No individual biomarker, or group of markers, is able to quantify the overall serum vascular calcification activity in individual CKD patients. Radiographic measurements of calcification change too slowly to indicate response to treatment and cannot distinguish intimal from medial vascular calcification. In this grant, we propose to develop a novel assay that will measure the total calcification activity of CKD patient serum. We will utilize stored samples from a prospective coronary artery calcification study, incubate patient serum in an established human aortic smooth muscle culture system, and determine the serum calcification activity relative to control material. We will evaluate whether in-vitro calcification activity can predict the prevalence and progression of clinically obtained coronary calcification scores, and will investigate candidate calcification mechanisms using individual CKD patient serum. We envision the proposed calcification assay will serve as a novel translational research tool with application that include (1) use as a biomarker in epidemiologic studies of clinical calcification outcomes, (2) use as a surrogate marker of treatment response in clinical trials of calcification inhibitors, and (3) use as a selection tool to identify individuals who may be at greatest risk of calcification progression and may benefit most from novel therapies. Interdisciplinary collaboration in Nephrology, Bioengineering, and Epidemiology will be used to achieve the study objectives.