title: Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease.
abstract: BACKGROUND
  Fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, is elevated in chronic kidney disease (CKD). There are scarce data on the levels of its essential co-receptor klotho, and longitudinal changes in FGF23 levels are also unknown.
  
  
  METHODS
  We examined FGF23 and soluble klotho (s-klotho) levels over 1 year in 154 children with CKD Stages 1-5 (CKD1-5), were on dialysis or who have received a transplantation.
  
  
  RESULTS
  In children with CKD1-5 and who were receiving dialysis, FGF23 correlated inversely with the estimated glomerular filtration rate (eGFR) (P < 0.001), whereas a decrease in s-klotho was observed with a lower eGFR (P = 0.01). There was no correlation between FGF23 and serum phosphate (P) or parathyroid hormone (PTH) in our cohort wherein 89 and 66%, respectively, had normal levels. FGF23 increased by 6-fold over a 12-month period in children with eGFR of 15-29 mL/min/1.73 m(2), with an overall 5% annual increase in the CKD1-5 and dialysis cohort. High FGF23 levels were seen with high calcium (Ca) levels (P < 0.001). FGF23 levels were high when 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were deficient (P = 0.05 and P < 0.001, respectively). s-klotho levels correlated positively with 25(OH)D (P < 0.001) and negatively with PTH (P = 0.04) and age (P = 0.03). Multivariate regression analysis demonstrated a strong relationship between FGF23 and eGFR, whereas the association between s-klotho and eGFR as observed in univariate analysis was lost following the adjustment of confounders. In transplanted patients, FGF23 correlated with eGFR (P = 0.02) and 25(OH)D (P = 0.05).
  
  
  CONCLUSIONS
  This study shows increasing FGF23 and reduced s-klotho levels with progressive renal failure even in a population of children with well-controlled P levels. Novel associations between FGF23 and serum Ca as well as 25(OH)D warrant further investigation.
authors.affiliation: Renal Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Mandy
authors.initials: M
authors.lastname: Wan
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.forename: Vanita
authors.initials: V
authors.lastname: Shah
authors.forename: Ambrose
authors.initials: A
authors.lastname: Gullet
authors.forename: David
authors.initials: D
authors.lastname: Wells
authors.forename: Lesley
authors.initials: L
authors.lastname: Rees
authors.forename: Rukshana
authors.initials: R
authors.lastname: Shroff
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D008137:Longitudinal Studies; D008297:Male; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins