Plasma FGF23 levels increase rapidly after acute kidney injury

Kidney Int. 2013 Oct;84(4):776-85. doi: 10.1038/ki.2013.150. Epub 2013 May 8.

Abstract

Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs, we used a murine folic acid-induced nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 h of AKI, with an 18-fold increase at 24 h. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or the vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 h following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice, this increase is independent of established modulators of FGF23 secretion.

Publication types

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

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / physiopathology*
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers / blood
  • Case-Control Studies
  • Cohort Studies
  • Disease Models, Animal
  • Female
  • Fibroblast Growth Factors / blood*
  • Folic Acid / adverse effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Prospective Studies
  • Signal Transduction / physiology*
  • Time Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • 1,25-dihydroxyvitamin D
  • fibroblast growth factor 23
  • Folic Acid