title: Investigating FGF-23 concentrations and its relationship with declining renal function in paediatric patients with pre-dialysis CKD Stages 3-5.
abstract: BACKGROUND
  The aims of our study were to investigate (i) the prevalence of elevated fibroblast growth factor-23 (FGF-23), (ii) the relationship between FGF-23 concentrations and level of renal dysfunction and (iii) the main determinants of elevation of FGF-23 concentration in children with pre-dialysis chronic kidney disease (CKD) Stages 3-5.
  
  
  METHODS
  In this single-centre prospective observational study, 71 children with pre-dialysis CKD Stages 3-5, aged 11.9 ± 3.1 years, had FGF-23 levels measured. Anthropometry and routine laboratory investigations were measured.
  
  
  RESULTS
  Fourteen (19.7%) patients had normal FGF-23 concentrations defined as < 50 ng/L. FGF-23 [median (interquartile range)] concentrations were 78.7 (55.6-137.6) ng/L and following log transformation normalized data with log FGF-23 [mean (SD)] values of 1.96 ± 0.4 ng/L. Log FGF-23 concentrations had a negative reciprocal relationship with estimated glomerular filtration rate (eGFR) (P < 0.0001) and 1,25 vitamin D3 levels (P = 0.01) and a positive relationship with phosphate (P = 0.03) and percent fractional excretion of phosphate (P = 0.01) but not with log-intact parathyroid hormone (PTH) (P = 0.22). Multiple linear regression demonstrated a strong relationship between log FGF-23 and eGFR only.
  
  
  CONCLUSIONS
  Elevated FGF-23 concentrations were observed in the majority of a carefully managed cohort of children with non-dialysis CKD with a dominant effect on FGF-23 concentrations with glomerular filtration rate (GFR). These data allow the potential confounding effects of PTH and phosphate elevation with declining GFR to be removed, leaving a clearer picture of the FGF-23-GFR relationship.
authors.affiliation: Department of Paediatric Nephrology, Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK. manish.sinha@gstt.nhs.uk
authors.forename: Manish D
authors.initials: MD
authors.lastname: Sinha
authors.forename: Charles
authors.initials: C
authors.lastname: Turner
authors.forename: R N
authors.initials: RN
authors.lastname: Dalton
authors.forename: Pernille
authors.initials: P
authors.lastname: Rasmussen
authors.forename: Simon
authors.initials: S
authors.lastname: Waller
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Booth
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldsmith
mesh_terms: D002648:Child; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D011446:Prospective Studies; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23