Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease

Nat Rev Nephrol. 2014 May;10(5):268-78. doi: 10.1038/nrneph.2014.49. Epub 2014 Apr 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Aged
  • Animals
  • Atherosclerosis / chemically induced
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / prevention & control
  • Dietary Proteins / administration & dosage
  • Endothelial Cells / drug effects
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / physiology*
  • Glucuronidase / metabolism
  • Humans
  • Phosphates / metabolism*
  • Vascular Calcification / chemically induced

Substances

  • Dietary Proteins
  • Phosphates
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Glucuronidase
  • klotho protein