Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.
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Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.
SubjectChronic Renal Insufficiency Cohort Study Investigators
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Fibroblast Growth Factors
Tomography, X-Ray Computed
Severity of Illness Index
Renal Insufficiency, Chronic
Coronary Artery Disease
Published Version (Please cite this version)10.1038/ki.2013.3
Publication InfoScialla, Julia J; Lau, Wei Ling; Reilly, Muredach P; Isakova, Tamara; Yang, Hsueh-Ying; Crouthamel, Matthew H; ... Chronic Renal Insufficiency Cohort Study Investigators (2013). Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney international, 83(6). pp. 1159-1168. 10.1038/ki.2013.3. Retrieved from https://hdl.handle.net/10161/18486.
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Adjunct Associate Professor in the Department of Medicine
Dr. Scialla is an Associate Professor of Medicine in Nephrology at Duke University and a faculty member at the Duke Clinical Research Institute. Dr. Scialla trained in Internal Medicine, Nephrology, and Clinical Epidemiology at the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health. Her research focuses on chronic kidney disease (CKD) epidemiology and prevention, with an emphasis on the role of metabolic complications and nutri
Charles Johnson, M.D. Distinguished Professor of Medicine
The focus of my research is disordered mineral metabolism across the spectrum of chronic kidney disease, including dialysis, kidney transplantation and earlier stages.My research has been published in leading general medicine and subspecialty journals, including the New England Journal of Medicine, JAMA, the Journal of Clinical Investigation, Circulation, Cell Metabolism, Journal of the American Society of Nephrolog
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