Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.

Scialla, Julia J

Lau, Wei Ling

Reilly, Muredach P

Isakova, Tamara

Yang, Hsueh-Ying

Crouthamel, Matthew H

Chavkin, Nicholas W

Rahman, Mahboob

Wahl, Patricia

Amaral, Ansel P

Hamano, Takayuki

Master, Stephen R

Nessel, Lisa

Chai, Boyang

Xie, Dawei

Kallem, Radhakrishna R

Chen, Jing

Lash, James P

Kusek, John W

Budoff, Matthew J

Giachelli, Cecilia M

Wolf, Myles

Chronic Renal Insufficiency Cohort Study Investigators

2019-05-01T15:50:30Z

2019-05-01T15:50:30Z

2013-06

2019-05-01T15:50:28Z

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.

S0085-2538(15)55875-4

0085-2538

1523-1755

https://hdl.handle.net/10161/18486

eng

Elsevier BV

Kidney international

10.1038/ki.2013.3

Chronic Renal Insufficiency Cohort Study Investigators

Muscle, Smooth, Vascular

Aorta, Thoracic

Coronary Vessels

Cells, Cultured

Myocytes, Smooth Muscle

Animals

Humans

Mice

Aortic Diseases

Phosphates

Calcium

Glucuronidase

Fibroblast Growth Factors

RNA, Messenger

Tomography, X-Ray Computed

Aortography

Coronary Angiography

Severity of Illness Index

Prevalence

Multivariate Analysis

Logistic Models

Risk Factors

Chi-Square Distribution

Prospective Studies

Up-Regulation

Time Factors

Adult

Aged

Middle Aged

United States

Female

Male

Renal Insufficiency, Chronic

Coronary Artery Disease

Young Adult

Vascular Calcification

Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.

Journal article

Wolf, Myles|0000-0002-1127-1442

1159

1168

6

School of Medicine

Duke

Duke Clinical Research Institute

Institutes and Centers

Medicine, Nephrology

Medicine

Clinical Science Departments

Population Health Sciences

Basic Science Departments

Published

83