title: Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis.
abstract: OBJECTIVE
  Low 25-hydroxyvitamin D (25D), increased levels of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were reported to be risk factors for mortality in chronic kidney disease (CKD). However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD.
  
  
  METHODS
  In this prospective cohort study, we enrolled 738 predialysis outpatients in the two nephrology departments. We employed Cox proportional hazards analyses to elucidate predictors of the endpoint, defined as fatal or non-fatal cardiovascular event requiring hospitalization. Multiple imputation was performed for missing values.
  
  
  RESULTS
  Mean estimated glomerular filtration rate (eGFR) was 35 mL/min/1.73 m(2). During a median duration of 4.4 years, 86 patients developed the endpoint, of whom 62 patients achieved it before the initiation of dialysis. Multivariable analyses revealed that high serum intact FGF23 levels predicted the outcome preceding dialysis initiation (hazard ratio (HR) per lnFGF23 (SD), 1.64 (1.27-2.30)), while 25D, PTH, and bone-specific ALP did not. Adding FGF23 to the conventional model of age, sex, diabetes, prior CVD, pulse pressure, and eGFR, led to a net reclassification improvement of 6.87% (P=0.04). Not censoring the patients at the start of dialysis and continuing follow-up even after dialysis, FGF23 levels did not predict the outcome (HR, 1.16 (0.91-1.48)). Complete case analyses yielded similar results.
  
  
  CONCLUSIONS
  Intact FGF23 levels in predialysis CKD predicted incident cardiovascular events requiring hospitalization before starting dialysis, but did not predict events during the entire follow-up period, including post dialysis initiation.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamano
authors.forename: Naohiko
authors.initials: N
authors.lastname: Fujii
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Obi
authors.forename: Isao
authors.initials: I
authors.lastname: Matsui
authors.forename: Kodo
authors.initials: K
authors.lastname: Tomida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mikami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Inoue
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shimomura
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okada
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000150:complications; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase