title: Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship?
abstract: BACKGROUND
  Circulating fibroblast growth factor-23 (FGF23) promotes renal phosphate excretion and is markedly increased in patients with chronic kidney disease. High serum FGF23 is associated with cardiovascular risk factors and was recently identified as a predictor of total mortality in haemodialysis patients. Herein, our aim was to evaluate the relation between FGF23 and mortality, including the impact of gender and cardiovascular disease (CVD), in a Swedish cohort of 'incident' dialysis patients.
  
  
  METHODS
  Two hundred and twenty-nine incident dialysis patients (149 males; mean age 55 years) were included. Serum intact FGF23, calcium, phosphate, S-albumin, parathyroid hormone, high-sensitivity C-reactive protein and interleukin-6 were measured at baseline. Cardiovascular disease was defined as clinical symptoms and/or a history of CVD.
  
  
  RESULTS
  During a median follow-up time of 23 months, 66 patients (29%) died. FGF23 levels positively correlated to calcium (r = 0.27, P < 0.0001), phosphate (r = 0.40, P < 0.0001), calcium x phosphate product (r = 0.52, P < 0.0001) and creatinine (r = 0.18, P = 0.007). In Cox proportional hazard models, FGF23 was not associated with increased mortality risk, neither in crude nor in multivariate adjusted models. However, in a subgroup analysis of men with prevalent CVD, FGF23 level above median was associated with higher mortality risk in crude models [hazard ratio 2.19, 95% confidence interval 1.04-4.60, P = 0.04].
  
  
  CONCLUSIONS
  In primary analysis, serum FGF23 was not associated with increased mortality risk in this cohort of 'incident' dialysis patients. Our data support that the impact of FGF23 on mortality may be modified by gender and CVD and, as previously shown, is blunted in the setting of pronounced hyperphosphatemia.
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hannes
authors.initials: H
authors.lastname: Olauson
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Tetsu
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Peter
authors.initials: P
authors.lastname: Barany
authors.forename: Olof
authors.initials: O
authors.lastname: Heimburger
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011379:Prognosis; D006435:Renal Dialysis / Q000401:mortality*; D012307:Risk Factors; D012737:Sex Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; D015850:Interleukin-6; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium