Serum FGF23 levels in normal and disordered phosphorus homeostasis.
We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia.


BACKGROUND
Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin.


METHODS
Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis.


CONCLUSIONS
FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p < 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = -0.60) and calcium and phosphorus (Ca x P) product (r = -0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca x P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.
Weber
Thomas J
TJ
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Liu
Shiguang
S
Indridason
Olafur S
OS
Quarles
L Darryl
LD
D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006706:Homeostasis; D006801:Humans; D017674:Hypophosphatemia / Q000097:blood*; D007015:Hypophosphatemia, Familial / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood / Q000378:metabolism*
C000717427:FGF23 protein, human; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23