title: Plasma fibroblast growth factor 23 concentration is increased and predicts mortality in patients on the liver-transplant waiting list.
abstract: High plasma fibroblast growth factor-23 (FGF23) concentration predicts the risk of death and poor outcomes in patients with chronic kidney disease or chronic heart failure. We checked if FGF23 concentration could be modified in patients with end stage liver disease (ESLD) and predict mortality. We measured plasma FGF23 in 200 patients with ESLD registered on a liver transplant waiting list between January 2005 and October 2008. We found that median plasma FGF23 concentration was above normal values in 63% of the patients. Increased FGF23 concentration was not explained by its classical determinants: hyperphosphataemia, increased calcitriol concentration or decreased renal function. FGF23 concentration correlated with the MELD score, serum sodium concentration, and GFR. Forty-six patients died before being transplanted and 135 underwent liver transplantation. We analyzed the prognostic value of FGF23 levels. Mortality was significantly associated with FGF23 levels, the MELD score, serum sodium concentration and glomerular filtration rate. On multivariate analyses only FGF23 concentration was associated with mortality. FGF23 levels were independent of the cause of the liver disease. To determine if the damaged liver can produce FGF23 we measured plasma FGF23 concentration and liver FGF23 mRNA expression in control and diethyl-nitrosamine (DEN)-treated mice. FGF23 plasma levels increased with the apparition of liver lesions in DEN-treated mice and that FGF23 mRNA expression, which was undetectable in the liver of control mice, markedly increased with the development of liver lesions. The correlation between FGF23 plasma concentration and FGF23 mRNA expression in DEN-treated mice suggests that FGF23 production by the liver accounts for the increased plasma FGF23 concentration. In conclusion chronic liver lesions can induce expression of FGF23 mRNA leading to increased FGF23 concentration, which is associated with a higher mortality in patients on a liver-transplant waiting list. In these patients FGF23 concentration was the best predictor of mortality.
authors.affiliation: Université Paris Descartes, Faculté de Médecine, INSERM U845, Hôpital Necker-Enfants Malades, AP-HP, Paris, France. dominique.prie@inserm.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Prié
authors.forename: Anne
authors.initials: A
authors.lastname: Forand
authors.forename: Claire
authors.initials: C
authors.lastname: Francoz
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cohen
authors.forename: Marie
authors.initials: M
authors.lastname: Courbebaisse
authors.forename: Dominique
authors.initials: D
authors.lastname: Eladari
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.forename: Gerard
authors.initials: G
authors.lastname: Friedlander
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000401:mortality; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D014850:Waiting Lists; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23