Plasma FGF23 levels increase rapidly after acute kidney injury

Marta Christov, Sushrut S. Waikar, Renata C. Pereira, Andrea Havasi, David E. Leaf, David Goltzman, Paola D. Pajevic, Myles Wolf, Harald Jüppner*

*Corresponding author for this work

Research output: Contribution to journalArticle

95 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalKidney international
Volume84
Issue number4
DOIs
StatePublished - Oct 2013

Keywords

  • AKI
  • PTH
  • fibroblast growth factor 23
  • phosphate
  • vitamin D

ASJC Scopus subject areas

  • Nephrology

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    Christov, M., Waikar, S. S., Pereira, R. C., Havasi, A., Leaf, D. E., Goltzman, D., Pajevic, P. D., Wolf, M., & Jüppner, H. (2013). Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney international, 84(4), 776-785. https://doi.org/10.1038/ki.2013.150