title: Combined use of vitamin D status and FGF23 for risk stratification of renal outcome.
abstract: OBJECTIVE
  Hyperphosphatemia, vitamin D deficiency, hyperparathyroidism, and high serum fibroblast growth factor 23 (FGF23) levels, when studied separately, were found to predict the progression of CKD. However, studies with simultaneous measurement of mineral bone disorder (MBD)-related factors were scarce. This study aimed to identify factors predicting renal outcome independent of other factors.
  
  
  METHODS
  This was a prospective cohort study of 738 Japanese predialysis outpatients in the nephrology departments of two hospitals. The outcome was defined as a doubling of serum creatinine or initiation of dialysis.
  
  
  RESULTS
  Mean estimated GFR (eGFR) was 35 ml/min per 1.73 m(2). At enrollment, the increase in intact FGF23 with decreasing eGFR was the earliest among changes in MBD-related factors, followed by 1,25-dihydroxyvitamin D decrease, parathyroid hormone increase, and phosphate increase. During a median duration of 4.4 years, 213 patients reached the endpoint. In a multivariable Cox model, high FGF23 and low 25-hydroxyvitamin D (25D) levels were the only MBD-related factors associated with a higher risk of renal endpoint (adjusted hazard ratio [95% confidence interval] per unit change of log FGF23 and 10 ng/ml of 25D: 1.83 [1.28-2.61] and 0.61 [0.41-0.90], respectively). There was no significant interaction between 25D and FGF23 (P=0.11). Active vitamin D therapy, serum phosphate, 1,25-dihydroxyvitamin D, and parathyroid hormone levels were not related to the renal endpoint. Treating death as a competing risk or multiple imputation for missing values yielded similar results.
  
  
  CONCLUSIONS
  Combined use of two markers is useful for the risk stratification of renal outcome.
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: 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: Yoshitsugu
authors.initials: Y
authors.lastname: Obi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okada
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001847:Bone Diseases / Q000097:blood* / Q000150:complications; D016001:Confidence Intervals; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D018570:Risk Assessment; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D003404:Creatinine