Alpha Omega Alpha Honor Medical Society

2013 Research Abstract

Impact of Chronic Kidney Disease on Circulating Myeloid Calcifying Cells

Investigator: Ryan M. Gillihan, MSII, University of Kansas School of Medicine

Mentor: Jason R. Stubbs, M.D., Associate Professor of Medicine, Division of Nephrology and Hypertension, University of Kansas School of Medicine

Support: This work was supported by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship and an ASN Foundation for Kidney Research Student Scholar Grant.

Abstract: Patients with chronic kidney disease exhibit numerous bone and mineral metabolism defects that contribute to the excess vascular calcification observed in this population. Despite evidence that vascular calcification reduces vascular compliance and promotes cardiac hypertrophy, the pathophysiology responsible for vascular calcification remains unclear. Recent evidence suggests that several populations of osteocalcin-positive (OCN+) cells circulate in blood that exhibit calcifying abilities in vitro, raising the possibility that circulating cells may play a role in the pathogenesis of vascular calcification. The purpose of this pilot study was to quantify levels of circulating OCN+ cells in healthy volunteers and an end-stage renal disease (ESRD) population that is at high risk for vascular calcification. Thus, we isolated peripheral blood mononuclear cells (PBMCs) from sixteen patients (eight patients with ESRD and eight healthy controls) and evaluated OCN expression in these cells by flow cytometry. We found that ESRD patients exhibited a higher percentage of OCN+ cells from the total PBMC population (6.8 ± 1.7% vs. 2.7 ± 0.7% in controls; P<0.05). Furthermore, in a sub-analysis of myeloid-derived (CD14+) PBMCs, ESRD patients exhibited a higher percentage of CD14+OCN+ cells compared to controls with normal kidney function (77.1 ± 10.9% vs. 61.7 ± 13.3% in controls; P=NS). Further stratification of the CD14+ cells into CD16+ and CD16- sub-fractions, revealed ESRD patients to exhibit a higher percentage of OCN+ cells in the CD14+CD16+ subset (or “inflammatory” monocytes) (44.1 ± 6.8 % vs. 24.4 ± 6.7% in controls, P=0.06). Thus, patients with ESRD demonstrate higher levels of myeloid-derived, OCN+ cells in peripheral blood, which we hypothesize may contribute to the higher propensity of this population to form vascular calcification. Future studies will focus on functional assays to identify differences in the calcifying capacity of myeloid-derived, OCN+ cells from patients with ESRD versus controls with normal kidney function.

Last Updated: 1/28/14

Updated on January 28, 2014.

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