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The role of fibroblast growth factor-23 in cardiorenal syndrome.
Nephron Clin Pract. 2013; 123(3-4):194-201.NC

Abstract

Abnormalities in chronic kidney disease-related bone and mineral metabolism (CKD-MBD) have emerged as novel risk factors in excess cardiovascular mortality in patients with CKD and end-stage renal disease (ESRD). The pathophysiological links between CKD-MBD and adverse cardiovascular events in this patient population are unclear. Hyperphosphatemia through induction of vascular calcifications and decreased active vitamin D production leading to activation of the renin angiotensin system (RAS) along with defects in innate immunity are purported to be the proximate cause of CKD-MBD-associated mortality in CKD. Recently, this view has been challenged by the observation that fibroblast growth factor-23 (FGF23), a newly discovered hormone produced in the bone that regulates phosphate and vitamin D metabolism by the kidney, is a strong predictor of adverse cardiovascular outcomes in patients with CKD and ESRD. Whether these associations between elevated circulating FGF23 levels and cardiovascular outcomes are causative, and if so, the mechanisms mediating the effects of FGF23 on the cardiovascular system are not clear. The principal physiological functions of FGF23 are mediated by activation of FGF receptor/α-klotho coreceptor complexes in target tissues. Elevated FGF23 has been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF23 may induce myocardial hypertrophy through a direct effect on cardiac myocytes. A direct 'off target' effect of FGF23 on LVH is controversial, however, since α-klotho (which is believed to be indispensable for the physiologic actions of FGF23) is not expressed in the myocardium. Another possibility is that FGF23's effect on the heart is mediated indirectly, via 'on target' regulation of hormonal pathways in the kidney, which include suppression of angiotensin-converting enzyme 2, Cyp27b1and α-klotho, which would be predicted to act on circulating factors known to regulate RAS, 1,25(OH)2D production and ion transport in the myocardium. Understanding of FGF23's pathophysiology and mechanisms of action responsible for its negative effects will be necessary to develop therapeutic strategies to treat CKD-MBD.

Authors+Show Affiliations

University of Tennessee Health Science Center, Memphis, Tenn., USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23942553

Citation

Kovesdy, Csaba P., and L Darryl Quarles. "The Role of Fibroblast Growth Factor-23 in Cardiorenal Syndrome." Nephron. Clinical Practice, vol. 123, no. 3-4, 2013, pp. 194-201.
Kovesdy CP, Quarles LD. The role of fibroblast growth factor-23 in cardiorenal syndrome. Nephron Clin Pract. 2013;123(3-4):194-201.
Kovesdy, C. P., & Quarles, L. D. (2013). The role of fibroblast growth factor-23 in cardiorenal syndrome. Nephron. Clinical Practice, 123(3-4), 194-201. https://doi.org/10.1159/000353593
Kovesdy CP, Quarles LD. The Role of Fibroblast Growth Factor-23 in Cardiorenal Syndrome. Nephron Clin Pract. 2013;123(3-4):194-201. PubMed PMID: 23942553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of fibroblast growth factor-23 in cardiorenal syndrome. AU - Kovesdy,Csaba P, AU - Quarles,L Darryl, Y1 - 2013/08/06/ PY - 2013/8/15/entrez PY - 2013/8/15/pubmed PY - 2014/9/23/medline SP - 194 EP - 201 JF - Nephron. Clinical practice JO - Nephron Clin Pract VL - 123 IS - 3-4 N2 - Abnormalities in chronic kidney disease-related bone and mineral metabolism (CKD-MBD) have emerged as novel risk factors in excess cardiovascular mortality in patients with CKD and end-stage renal disease (ESRD). The pathophysiological links between CKD-MBD and adverse cardiovascular events in this patient population are unclear. Hyperphosphatemia through induction of vascular calcifications and decreased active vitamin D production leading to activation of the renin angiotensin system (RAS) along with defects in innate immunity are purported to be the proximate cause of CKD-MBD-associated mortality in CKD. Recently, this view has been challenged by the observation that fibroblast growth factor-23 (FGF23), a newly discovered hormone produced in the bone that regulates phosphate and vitamin D metabolism by the kidney, is a strong predictor of adverse cardiovascular outcomes in patients with CKD and ESRD. Whether these associations between elevated circulating FGF23 levels and cardiovascular outcomes are causative, and if so, the mechanisms mediating the effects of FGF23 on the cardiovascular system are not clear. The principal physiological functions of FGF23 are mediated by activation of FGF receptor/α-klotho coreceptor complexes in target tissues. Elevated FGF23 has been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF23 may induce myocardial hypertrophy through a direct effect on cardiac myocytes. A direct 'off target' effect of FGF23 on LVH is controversial, however, since α-klotho (which is believed to be indispensable for the physiologic actions of FGF23) is not expressed in the myocardium. Another possibility is that FGF23's effect on the heart is mediated indirectly, via 'on target' regulation of hormonal pathways in the kidney, which include suppression of angiotensin-converting enzyme 2, Cyp27b1and α-klotho, which would be predicted to act on circulating factors known to regulate RAS, 1,25(OH)2D production and ion transport in the myocardium. Understanding of FGF23's pathophysiology and mechanisms of action responsible for its negative effects will be necessary to develop therapeutic strategies to treat CKD-MBD. SN - 1660-2110 UR - https://www.unboundmedicine.com/medline/citation/23942553/The_role_of_fibroblast_growth_factor_23_in_cardiorenal_syndrome_ L2 - https://www.karger.com?DOI=10.1159/000353593 DB - PRIME DP - Unbound Medicine ER -