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Received April 2, 2008
Accepted on August 29, 2008

CLINICAL EPIDEMIOLOGY

Association of Serum Phosphate with Vascular and Valvular Calcification in Moderate CKD

Kathryn L. Adeney ^*, David S. Siscovick , Joachim H. Ix , Stephen L. Seliger , Michael G. Shlipak ^||, Nancy S. Jenny ^¶, and Bryan R. Kestenbaum ^**1

*Department of Epidemiology, F-263 Health Sciences, Departments of Medicine and Epidemiology, Cardiovascular Health Research Unit, and **Division of Nephrology, Harborview Medical Center, University of Washington, Seattle, Washington; Division of Nephrology and Hypertension, Veterans Affairs San Diego Healthcare System, University of California San Diego, San Diego, California; Division of Nephrology, School of Medicine, University of Maryland, Baltimore, Maryland; ||University of California San Francisco and Veterans Affairs Medical Center, General Internal Medicine Section, San Francisco, California; and ¶Department of Pathology, College of Medicine, Colchester Research Facility, University of Vermont, Colchester, Vermont

¹ To whom correspondence should be addressed. E-mail: brk{at}u.washington.edu.

	Abstract

Within the normal range, higher serum phosphate concentrations are associated with cardiovascular events and mortality in individuals with chronic kidney disease (CKD) and in those with normal kidney function. Experimental models suggest that phosphate has a direct calcifying effect on vascular smooth muscle. We examined associations of serum phosphate concentrations with vascular and valvular calcification in 439 participants from the Multi-Ethnic Study of Atherosclerosis who had moderate CKD and no clinical cardiovascular disease. Serum phosphate concentrations were within the normal range (2.5 to 4.5 mg/dl) in 95% of study participants. The prevalence of calcification in the coronary arteries, descending thoracic aorta, aortic valve, and mitral valve was 67, 49, 25, and 20%, respectively, measured by electron-beam or multi-detector row computed tomography. After adjustment for demographics and estimated GFR, each 1-mg/dl increment in serum phosphate concentration was associated with a 21% (P = 0.002), 33% (P = 0.001), 25% (P = 0.16), and 62% (P = 0.007) greater prevalence of coronary artery, thoracic, aortic valve, and mitral valve calcification, respectively. Adjustment for traditional risk factors for atherosclerosis, parathyroid hormone, or 1,25-dihydroxyvitamin D levels did not alter these associations. In conclusion, higher serum phosphate concentrations, although still within the normal range, are associated with a greater prevalence of vascular and valvular calcification in people with moderate CKD. It remains to be determined whether lowering phosphate concentrations will impact calcification risk in the setting of kidney disease.

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