Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease

Julia J. Scialla, Myles Wolf

Research output: Contribution to journalArticle

Abstract

Disturbances in phosphate homeostasis are common in patients with chronic kidney disease. As kidney function declines, circulating concentrations of phosphate and the phosphate-regulatory hormone, fibroblast growth factor (FGF)-23, rise progressively. Higher serum levels of phosphate and FGF-23 are associated with an increased risk of adverse outcomes, including all-cause mortality and cardiovascular events. The associations between higher FGF-23 levels and adverse cardiovascular outcomes are generally independent of serum phosphate levels, and might be strongest for congestive heart failure. Higher serum phosphate levels are also modestly associated with an increased risk of cardiovascular events even after accounting for FGF-23 levels. This observation suggests that FGF-23 and phosphate might promote distinct mechanisms of cardiovascular toxicity. Indeed, animal models implicate high serum phosphate as a mechanism of vascular calcification and endothelial dysfunction, whereas high levels of FGF-23 are implicated in left ventricular hypertrophy. These seemingly distinct, but perhaps additive, adverse effects of phosphate on the vasculature and FGF-23 on the heart suggest that future population-level and individual-level interventions will need to simultaneously target these molecules to reduce the risk of associated cardiovascular events.

Original languageEnglish (US)
JournalNature Reviews Nephrology
DOIs
StateAccepted/In press - Apr 1 2014
Externally publishedYes

Fingerprint

Cardiovascular Diseases
Phosphates
Serum
Vascular Calcification
fibroblast growth factor 23
Left Ventricular Hypertrophy
Chronic Renal Insufficiency
Homeostasis
Animal Models
Heart Failure
Hormones
Kidney
Mortality
Population

ASJC Scopus subject areas

  • Nephrology

Cite this

Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease. / Scialla, Julia J.; Wolf, Myles.

In: Nature Reviews Nephrology, 01.04.2014.

Research output: Contribution to journalArticle

@article{eeafd25729814a3ba6d7e7c962a1eff0,
title = "Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease",
abstract = "Disturbances in phosphate homeostasis are common in patients with chronic kidney disease. As kidney function declines, circulating concentrations of phosphate and the phosphate-regulatory hormone, fibroblast growth factor (FGF)-23, rise progressively. Higher serum levels of phosphate and FGF-23 are associated with an increased risk of adverse outcomes, including all-cause mortality and cardiovascular events. The associations between higher FGF-23 levels and adverse cardiovascular outcomes are generally independent of serum phosphate levels, and might be strongest for congestive heart failure. Higher serum phosphate levels are also modestly associated with an increased risk of cardiovascular events even after accounting for FGF-23 levels. This observation suggests that FGF-23 and phosphate might promote distinct mechanisms of cardiovascular toxicity. Indeed, animal models implicate high serum phosphate as a mechanism of vascular calcification and endothelial dysfunction, whereas high levels of FGF-23 are implicated in left ventricular hypertrophy. These seemingly distinct, but perhaps additive, adverse effects of phosphate on the vasculature and FGF-23 on the heart suggest that future population-level and individual-level interventions will need to simultaneously target these molecules to reduce the risk of associated cardiovascular events.",
author = "Scialla, {Julia J.} and Myles Wolf",
year = "2014",
month = "4",
day = "1",
doi = "10.1038/nrneph.2014.49",
language = "English (US)",
journal = "Nature Reviews Nephrology",
issn = "1759-507X",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease

AU - Scialla, Julia J.

AU - Wolf, Myles

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Disturbances in phosphate homeostasis are common in patients with chronic kidney disease. As kidney function declines, circulating concentrations of phosphate and the phosphate-regulatory hormone, fibroblast growth factor (FGF)-23, rise progressively. Higher serum levels of phosphate and FGF-23 are associated with an increased risk of adverse outcomes, including all-cause mortality and cardiovascular events. The associations between higher FGF-23 levels and adverse cardiovascular outcomes are generally independent of serum phosphate levels, and might be strongest for congestive heart failure. Higher serum phosphate levels are also modestly associated with an increased risk of cardiovascular events even after accounting for FGF-23 levels. This observation suggests that FGF-23 and phosphate might promote distinct mechanisms of cardiovascular toxicity. Indeed, animal models implicate high serum phosphate as a mechanism of vascular calcification and endothelial dysfunction, whereas high levels of FGF-23 are implicated in left ventricular hypertrophy. These seemingly distinct, but perhaps additive, adverse effects of phosphate on the vasculature and FGF-23 on the heart suggest that future population-level and individual-level interventions will need to simultaneously target these molecules to reduce the risk of associated cardiovascular events.

AB - Disturbances in phosphate homeostasis are common in patients with chronic kidney disease. As kidney function declines, circulating concentrations of phosphate and the phosphate-regulatory hormone, fibroblast growth factor (FGF)-23, rise progressively. Higher serum levels of phosphate and FGF-23 are associated with an increased risk of adverse outcomes, including all-cause mortality and cardiovascular events. The associations between higher FGF-23 levels and adverse cardiovascular outcomes are generally independent of serum phosphate levels, and might be strongest for congestive heart failure. Higher serum phosphate levels are also modestly associated with an increased risk of cardiovascular events even after accounting for FGF-23 levels. This observation suggests that FGF-23 and phosphate might promote distinct mechanisms of cardiovascular toxicity. Indeed, animal models implicate high serum phosphate as a mechanism of vascular calcification and endothelial dysfunction, whereas high levels of FGF-23 are implicated in left ventricular hypertrophy. These seemingly distinct, but perhaps additive, adverse effects of phosphate on the vasculature and FGF-23 on the heart suggest that future population-level and individual-level interventions will need to simultaneously target these molecules to reduce the risk of associated cardiovascular events.

UR - http://www.scopus.com/inward/record.url?scp=84896689858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896689858&partnerID=8YFLogxK

U2 - 10.1038/nrneph.2014.49

DO - 10.1038/nrneph.2014.49

M3 - Article

C2 - 24686452

JO - Nature Reviews Nephrology

JF - Nature Reviews Nephrology

SN - 1759-507X

ER -