title: Associations of plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations with death and progression to maintenance dialysis in patients with advanced kidney disease.
abstract: BACKGROUND
  Low vitamin D concentrations are prevalent in patients with chronic kidney disease (CKD). We investigated the relationship between plasma 25-hydroxyvitamin D (25[OH]D) or 1,25-dihydroxyvitamin D (1,25[OH](2)D) concentrations with death, cardiovascular events, and dialysis therapy initiation in patients with advanced CKD.
  
  
  METHODS
  The HOST (Homocysteinemia in Kidney and End Stage Renal Disease) Study was a randomized double-blind trial evaluating the effects of high doses of folic acid on death and long-term dialysis therapy initiation in patients with advanced CKD (stages 4 and 5 not yet on dialysis therapy). 25(OH)D and 1,25(OH)(2)D were measured in stored plasma samples obtained 3 months after trial initiation and evaluated at clinically defined cutoffs (<10, 10-30, and >30 ng/mL) and tertiles (<15, 15-22, and >22 pg/mL), respectively. Cox proportional hazard models were used to examine the association between vitamin D concentrations and clinical outcomes.
  
  
  METHODS
  1,099 patients with advanced CKD from 36 Veteran Affairs Medical Centers.
  
  
  METHODS
  25(OH)D and 1,25(OH)(2)D concentrations.
  
  
  RESULTS
  Death, cardiovascular events, and time to initiation of long-term dialysis therapy.
  
  
  RESULTS
  After a median follow-up of 2.9 years, 41% (n = 453) died, whereas 56% (n = 615) initiated dialysis therapy. Mean 25(OH)D and 1,25(OH)(2)D concentrations were 21 ± 10 ng/mL and 20 ± 11 pg/mL, respectively. After adjustment for potential confounders, the lowest tertile of 1,25(OH)(2)D was associated with death (HR, 1.33; 95% CI, 1.01-1.74) and initiation of long-term dialysis therapy (HR, 1.78; 95% CI, 1.40-2.26) compared with the highest tertile. The association with death and initiation of dialysis therapy was moderately attenuated after adjustment for plasma fibroblast growth factor 23 (FGF-23) concentrations (HRs of lower tertiles of 1.20 [95% CI, 0.91-1.58] and 1.56 [95% CI, 1.23-1.99], respectively, compared with highest tertile). There was no association between 25(OH)D concentrations and outcomes.
  
  
  CONCLUSIONS
  Participants were mostly men.
  
  
  CONCLUSIONS
  Low plasma 1,25(OH)(2)D concentrations are associated with death and initiation of long-term dialysis therapy in patients with advanced CKD. FGF-23 level may attentuate this relationship.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kendrick
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Cheung
authors.forename: James S
authors.initials: JS
authors.lastname: Kaufman
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.forename: William L
authors.initials: WL
authors.lastname: Roberts
authors.forename: Gerard
authors.initials: G
authors.lastname: Smits
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
mesh_terms: D000368:Aged; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D