title: Instability of fibroblast growth factor-23 (FGF-23): implications for clinical studies.
abstract: 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.
  
  
  CONCLUSIONS
  K2-EDTA plasma samples, even when promptly separated, are unsuitable for measurement of FGF-23 unless stabilised with a protease inhibitor cocktail.
authors.affiliation: Department of Clinical Biochemistry & Immunology, Brighton & Sussex University Hospitals NHS Trust, Brighton, BN2 5BE, UK. edward.smith@bsuh.nhs.uk
authors.forename: Edward R
authors.initials: ER
authors.lastname: Smith
authors.forename: Martin L
authors.initials: ML
authors.lastname: Ford
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Tomlinson
authors.forename: Gary
authors.initials: G
authors.lastname: Weaving
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Rocks
authors.forename: Chakravarthi
authors.initials: C
authors.lastname: Rajkumar
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Holt
mesh_terms: D016477:Artifacts; D001774:Blood Chemical Analysis / Q000379:methods*; D002908:Chronic Disease; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007674:Kidney Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D055550:Protein Stability / Q000187:drug effects; D013997:Time Factors
chemical_list: C000717427:FGF23 protein, human; D010446:Peptide Fragments; D011480:Protease Inhibitors; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23