title: High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients.
abstract: BACKGROUND
  Fibroblast growth factor (FGF)-23, a novel bone-derived phosphaturic factor involved in mineral metabolism, is increased in chronic kidney disease (CKD); in dialysis patients, it has been linked to increased mortality rates and vascular calcification (VC). The present investigation aimed to study the factors associated with elevated serum FGF-23 levels in patients treated with long haemodialysis (LHD) sessions and to determine whether a relationship exists between serum FGF-23 levels and patient survival.
  
  
  METHODS
  All patients treated in one haemodialysis centre from September 2006 were included in the study. Standard laboratory values, medical history, cardiovascular events and risk factors, medication and FGF-23 levels [ELISA (C-Term) Immutopics] were recorded. Patients received haemodialysis three times a week, on a 5- to 8-h schedule. Patient data were analysed according to FGF-23 quartiles. The effect of FGF-23 on the 2-year survival rate was assessed using the Cox proportional hazard model, adjusted for confounding variables and according to the serum phosphate tertiles.
  
  
  RESULTS
  The study included 219 patients. Serum FGF-23 levels were high: 7060 +/- 13 500 RU/mL (median, 2740 RU/mL). In logistical regressions, only calcaemia (P = 0.002), phosphataemia (P = 0.008) and warfarin use (P = 0.04) were associated with the highest FGF-23 quartile. In the subgroup of patients with an estimated VC score, the third and fourth quartiles of the FGF-23 levels were associated with more severe VC. In multivariate linear regressions, only phosphataemia remained significantly correlated with FGF-23 (P = 0.04). The 2-year mortality rate was significantly higher for haemodialysis patients with serum FGF-23 levels in the higher quartile [P = 0.007; hazard ratio, 2.5 (1.3-5)] than in the first quartile, whereas within the phosphataemia tertiles, the lowest serum FGF-23 quartile was associated with lowered mortality.
  
  
  CONCLUSIONS
  This study demonstrated a high level of circulating FGF-23 in LHD patients, despite infrequent hyperphosphataemia. However, phosphataemia is still the main factor correlating with serum FGF-23. The association of higher serum FGF-23 levels with mortality and VC, regardless of the serum phosphate levels, has thus been confirmed.
authors.affiliation: Centre de Rein Artificiel, Tassin la Demi-lune, France. guillaume-jean-crat@wanadoo.fr
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jean
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Terrat
authors.forename: Thierry
authors.initials: T
authors.lastname: Vanel
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Hurot
authors.forename: Christie
authors.initials: C
authors.lastname: Lorriaux
authors.forename: Brice
authors.initials: B
authors.lastname: Mayor
authors.forename: Charles
authors.initials: C
authors.lastname: Chazot
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005602:France / Q000453:epidemiology; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods / Q000401:mortality*; D012307:Risk Factors; D013997:Time Factors
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23