Instability of fibroblast growth factor-23 (FGF-23): implications for clinical studies

Clin Chim Acta. 2011 May 12;412(11-12):1008-11. doi: 10.1016/j.cca.2011.02.009. Epub 2011 Feb 12.


Background: Fibroblast growth factor-23 (FGF-23) is a bone secreted hormone that regulates phosphate homeostasis and calcitriol levels. FGF-23 concentrations are elevated in chronic kidney disease (CKD), oncogenic osteomalcia and a number of rare hereditary disorders. Studies systematically evaluating the pre-analytical stability of intact FGF-23 are lacking.

Methods: The stability of FGF-23 was assessed in timed experiments using blood taken into K2-EDTA plasma specimen tubes from a group of healthy participants and from a group with mild-to-moderate CKD. We evaluated the use of aprotinin, a serine protease inhibitor, and a commercially available protease inhibitor cocktail to preserve intact FGF-23 after blood collection. FGF-23 measurements were made using both intact and C-terminal assays.

Results: Both whole blood and separated sample studies demonstrated a rapid loss of intact FGF-23 within 2 h, while concentrations increased using the C-terminal assay. The addition of protease inhibitor cocktail stabilised FGF-23 concentrations for 4 h after blood collection. Intact and C-terminal assay FGF-23 measurements showed poor correlation in both healthy and CKD cohorts.

Conclusion: K2-EDTA plasma samples, even when promptly separated, are unsuitable for measurement of FGF-23 unless stabilised with a protease inhibitor cocktail.

MeSH terms

  • Artifacts
  • Blood Chemical Analysis / methods*
  • Chronic Disease
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Fibroblast Growth Factors / chemistry
  • Humans
  • Kidney Diseases / blood
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Plasma / drug effects
  • Plasma / metabolism
  • Protease Inhibitors / pharmacology
  • Protein Stability / drug effects
  • Time Factors


  • FGF23 protein, human
  • Peptide Fragments
  • Protease Inhibitors
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23