title: Fibroblast growth factor 23 correlates with volume status in haemodialysis patients and is not reduced by haemodialysis.
abstract: Recent data suggest a role for fibroblast growth factor 23 (FGF-23) in volume regulation. In haemodialysis patients, a large ultrafiltration volume (UFV) reflects poor volume control, and both FGF-23 and a large UFV are risk factors for mortality in this population. We studied the association between FGF-23 and markers of volume status including UFV, as well as the intradialytic course of FGF-23, in a cohort of haemodialysis patients.
  
  
  
  We carried out observational, post hoc analysis of 109 prevalent haemodialysis patients who underwent a standardized, low-flux, haemodialysis session with constant ultrafiltration rate. We measured UFV, plasma copeptin and echocardiographic parameters including cardiac output, end-diastolic volume and left ventricular mass index at the onset of the haemodialysis session. We measured the intradialytic course of plasma C-terminal FGF-23 (corrected for haemoconcentration) and serum phosphate levels at 0, 1, 3 and 4 h after onset of haemodialysis and analysed changes with linear mixed effect model.
  
  
  
  Median age was 66 (interquartile range: 51-75) years, 65% were male with a weekly Kt/V 4.3 ± 0.7 and dialysis vintage of 25.4 (8.5-52.5) months. In univariable analysis, pre-dialysis plasma FGF-23 was associated with UFV, end-diastolic volume, cardiac output, early diastolic velocity e' and plasma copeptin. In multivariable regression analysis, UFV correlated with FGF-23 (standardized β: 0.373, P < 0.001, model R(2): 57%), independent of serum calcium and phosphate. The association between FGF-23 and echocardiographic volume markers was lost for all but cardiac output upon adjustment for UFV. Overall, FGF-23 levels did not change during dialysis [7627 (3300-13 514) to 7503 (3109-14 433) RU/mL; P = 0.98], whereas phosphate decreased (1.71 ± 0.50 to 0.88 ± 0.26 mmol/L; P < 0.001).
  
  
  
  FGF-23 was associated with volume status in haemodialysis patients. The strong association with UFV suggests that optimization of volume status, for example by more intensive haemodialysis regimens, may also benefit mineral homeostasis. A single dialysis session did not lower FGF-23 levels.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jelmer K
authors.initials: JK
authors.lastname: Humalda
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ineke J
authors.initials: IJ
authors.lastname: Riphagen
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Solmaz
authors.initials: S
authors.lastname: Assa
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Yoran M
authors.initials: YM
authors.lastname: Hummel
authors.affiliation: Dialysis Center Groningen, Groningen, The Netherlands.
authors.forename: Ralf
authors.initials: R
authors.lastname: Westerhuis
authors.affiliation: Department of Nephrology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Casper F M
authors.initials: CF
authors.lastname: Franssen
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002306:Cardiac Volume / Q000502:physiology*; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000378:metabolism; D006435:Renal Dialysis; D014462:Ultrafiltration
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: fibroblast growth factor 23; haemodialysis; phosphate; ultrafiltration; volume status