title: Vitamin D bioavailability and catabolism in pediatric chronic kidney disease.
abstract: BACKGROUND
  Vitamin D-binding protein (DBP) and catabolism have not been examined in the clinical setting of childhood chronic kidney disease (CKD).
  
  
  METHODS
  The concentrations of serum vitamin D {25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], 24,25-dihydroxyvitamin D [24,25(OH)(2)D]}, DBP, intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF23) were measured in 148 participants with CKD stages 2-5D secondary to congenital anomalies of the kidney/urinary tract (CAKUT), glomerulonephritis (GN), or focal segmental glomerulosclerosis (FSGS). Free and bioavailable 25(OH)D concentrations were calculated using total 25(OH)D, albumin, and DBP concentrations.
  
  
  RESULTS
  The concentrations of all vitamin D metabolites were lower with more advanced CKD (p < 0.001) and glomerular diagnoses (p ≤ 0.002). Among non-dialysis participants, DBP was lower in FSGS versus other diagnoses (FSGS-dialysis interaction p = 0.02). Winter season, older age, FSGS and GN, and higher FGF23 concentrations were independently associated with lower concentrations of free and bioavailable 25(OH)D. Black race was associated with lower total 25(OH)D and DBP, but not free or bioavailable 25(OH)D. 24,25(OH)(2)D was the vitamin D metabolite most strongly associated with iPTH. Lower 25(OH)D and higher iPTH concentrations, black race, and greater CKD severity were independently associated with lower levels of 24,25(OH)(2)D, while higher FGF23 concentrations and GN were associated with higher levels of 24,25(OH)(2)D.
  
  
  CONCLUSIONS
  Children with CKD exhibit altered catabolism and concentrations of DBP and free and bioavailable 25(OH)D, and there is an important impact of their underlying disease.
authors.affiliation: The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. denburgm@email.chop.edu
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Denburg
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Kalkwarf
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
authors.forename: Justine
authors.initials: J
authors.lastname: Shults
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.forename: David
authors.initials: D
authors.lastname: Stokes
authors.forename: Debbie
authors.initials: D
authors.lastname: Foerster
authors.forename: Benjamin
authors.initials: B
authors.lastname: Laskin
authors.forename: Anthony
authors.initials: A
authors.lastname: Ramirez
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
mesh_terms: D000293:Adolescent; D001682:Biological Availability; D002117:Calcitriol / Q000378:metabolism / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008297:Male; D010530:Peritoneal Dialysis; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000378:metabolism; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol