title: Disordered FGF23 and mineral metabolism in children with CKD.
abstract: OBJECTIVE
  In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study.
  
  
  METHODS
  Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR.
  
  
  RESULTS
  Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2).
  
  
  CONCLUSIONS
  In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.
authors: Department of Pediatrics, University of California, San Francisco, California;, †Department of Medicine and, §Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida;, ‡Department of Pediatrics, Harvard Medical School, Boston, Massachusetts;, ‖Department of Pediatrics, Weill Cornell Medical College, New York, New York;, ¶Department of Pediatrics, University of California, Los Angeles, California;, *Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York;, ††Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, ‡‡Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
authors: Anthony A
authors: AA
authors: Portale
authors: Myles
authors: M
authors: Wolf
authors: Harald
authors: H
authors: Jüppner
authors: Shari
authors: S
authors: Messinger
authors: Juhi
authors: J
authors: Kumar
authors: Katherine
authors: K
authors: Wesseling-Perry
authors: George J
authors: GJ
authors: Schwartz
authors: Susan L
authors: SL
authors: Furth
authors: Bradley A
authors: BA
authors: Warady
authors: Isidro B
authors: IB
authors: Salusky
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000378:metabolism; D002170:Canada; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood; D042241:Early Diagnosis; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology; D007223:Infant; D007668:Kidney / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D012720:Severity of Illness Index; D014481:United States; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000209:etiology
chemical_list: D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C000717427:FGF23 protein, human; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D005346:Fibroblast Growth Factors; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine; D002118:Calcium