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

Julia J. Scialla; Wei Ling Lau; Muredach P. Reilly; Tamara Isakova; Hsueh Ying Yang; Matthew H. Crouthamel; Nicholas W. Chavkin; Mahboob Rahman; Patricia Wahl; Ansel P. Amaral; Takayuki Hamano; Stephen R. Master; Lisa Nessel; Boyang Chai; Dawei Xie; Radhakrishna R. Kallem; Jing Chen; James P. Lash; John W. Kusek; Matthew J. Budoff; Cecilia M. Giachelli; Myles Wolf

doi:10.1038/ki.2013.3

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

Julia J. Scialla, Wei Ling Lau, Muredach P. Reilly, Tamara Isakova, Hsueh Ying Yang, Matthew H. Crouthamel, Nicholas W. Chavkin, Mahboob Rahman, Patricia Wahl, Ansel P. Amaral, Takayuki Hamano, Stephen R. Master, Lisa Nessel, Boyang Chai, Dawei Xie, Radhakrishna R. Kallem, Jing Chen, James P. Lash, John W. Kusek, Matthew J. BudoffCecilia M. Giachelli, Myles Wolf^*

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Article › peer-review

277 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1159-1168
Number of pages	10
Journal	Kidney international
Volume	83
Issue number	6
DOIs	https://doi.org/10.1038/ki.2013.3
State	Published - Jun 2013

Funding

Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the University of Pennsylvania CTRC CTSA UL1 RR-024134, Johns Hopkins University UL1 RR-025005, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1RR024986, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, and Kaiser NIH/NCRR UCSF-CTSI UL1 RR-024131. Computed tomography scans were supported in part by R01DK071224 to MPR, measurement of FGF23 by R01DK081374 to MW, and the experimental studies by R01HL62329 and R01HL081785 to CMG. WLL was supported by T32HL007828 and T32DK007467, and MHC by T32HL007828.

Keywords

Chronic kidney disease
Fibroblast growth factor 23
Phosphate
Vascular calcification
Vascular smooth muscle

ASJC Scopus subject areas

Nephrology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ki.2013.3

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Scialla, J. J., Lau, W. L., Reilly, M. P., Isakova, T., Yang, H. Y., Crouthamel, M. H., Chavkin, N. W., Rahman, M., Wahl, P., Amaral, A. P., Hamano, T., Master, S. R., Nessel, L., Chai, B., Xie, D., Kallem, R. R., Chen, J., Lash, J. P., Kusek, J. W., ... Wolf, M. (2013). Fibroblast growth factor 23 is not associated with and does not induce arterial calcification. Kidney international, 83(6), 1159-1168. https://doi.org/10.1038/ki.2013.3

@article{3d6f94f18b3f4faab30ea6e5dd517d99,

title = "Fibroblast growth factor 23 is not associated with and does not induce arterial calcification",

abstract = "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.",

keywords = "Chronic kidney disease, Fibroblast growth factor 23, Phosphate, Vascular calcification, Vascular smooth muscle",

author = "Scialla, {Julia J.} and Lau, {Wei Ling} and Reilly, {Muredach P.} and Tamara Isakova and Yang, {Hsueh Ying} and Crouthamel, {Matthew H.} and Chavkin, {Nicholas W.} and Mahboob Rahman and Patricia Wahl and Amaral, {Ansel P.} and Takayuki Hamano and Master, {Stephen R.} and Lisa Nessel and Boyang Chai and Dawei Xie and Kallem, {Radhakrishna R.} and Jing Chen and Lash, {James P.} and Kusek, {John W.} and Budoff, {Matthew J.} and Giachelli, {Cecilia M.} and Myles Wolf",

note = "Funding Information: Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the University of Pennsylvania CTRC CTSA UL1 RR-024134, Johns Hopkins University UL1 RR-025005, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1RR024986, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, and Kaiser NIH/NCRR UCSF-CTSI UL1 RR-024131. Computed tomography scans were supported in part by R01DK071224 to MPR, measurement of FGF23 by R01DK081374 to MW, and the experimental studies by R01HL62329 and R01HL081785 to CMG. WLL was supported by T32HL007828 and T32DK007467, and MHC by T32HL007828. ",

year = "2013",

month = jun,

doi = "10.1038/ki.2013.3",

language = "English (US)",

volume = "83",

pages = "1159--1168",

journal = "Kidney international",

issn = "0085-2538",

publisher = "Nature Publishing Group",

number = "6",

}

Scialla, JJ, Lau, WL, Reilly, MP, Isakova, T, Yang, HY, Crouthamel, MH, Chavkin, NW, Rahman, M, Wahl, P, Amaral, AP, Hamano, T, Master, SR, Nessel, L, Chai, B, Xie, D, Kallem, RR, Chen, J, Lash, JP, Kusek, JW, Budoff, MJ, Giachelli, CM & Wolf, M 2013, 'Fibroblast growth factor 23 is not associated with and does not induce arterial calcification', Kidney international, vol. 83, no. 6, pp. 1159-1168. https://doi.org/10.1038/ki.2013.3

TY - JOUR

T1 - Fibroblast growth factor 23 is not associated with and does not induce arterial calcification

AU - Scialla, Julia J.

AU - Lau, Wei Ling

AU - Reilly, Muredach P.

AU - Isakova, Tamara

AU - Yang, Hsueh Ying

AU - Crouthamel, Matthew H.

AU - Chavkin, Nicholas W.

AU - Rahman, Mahboob

AU - Wahl, Patricia

AU - Amaral, Ansel P.

AU - Hamano, Takayuki

AU - Master, Stephen R.

AU - Nessel, Lisa

AU - Chai, Boyang

AU - Xie, Dawei

AU - Kallem, Radhakrishna R.

AU - Chen, Jing

AU - Lash, James P.

AU - Kusek, John W.

AU - Budoff, Matthew J.

AU - Giachelli, Cecilia M.

AU - Wolf, Myles

N1 - Funding Information: Funding for the CRIC Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the University of Pennsylvania CTRC CTSA UL1 RR-024134, Johns Hopkins University UL1 RR-025005, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1RR024986, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, and Kaiser NIH/NCRR UCSF-CTSI UL1 RR-024131. Computed tomography scans were supported in part by R01DK071224 to MPR, measurement of FGF23 by R01DK081374 to MW, and the experimental studies by R01HL62329 and R01HL081785 to CMG. WLL was supported by T32HL007828 and T32DK007467, and MHC by T32HL007828.

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - Chronic kidney disease

KW - Fibroblast growth factor 23

KW - Phosphate

KW - Vascular calcification

KW - Vascular smooth muscle

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UR - http://www.scopus.com/inward/citedby.url?scp=84882238083&partnerID=8YFLogxK

U2 - 10.1038/ki.2013.3

DO - 10.1038/ki.2013.3

M3 - Article

C2 - 23389416

AN - SCOPUS:84882238083

SN - 0085-2538

VL - 83

SP - 1159

EP - 1168

JO - Kidney international

JF - Kidney international

IS - 6

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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