title: FGF-23 and Osteoprotegerin but not Fetuin-A are associated with death and enhance risk prediction in non-dialysis chronic kidney disease stages 3-5.
abstract: OBJECTIVE
  Numerous biomarkers have been shown to associate with clinical endpoints in chronic kidney disease (CKD). There is limited evidence whether biomarkers improve risk prediction in relation to clinical outcomes. Our study investigates whether a small suite of key chronic kidney disease-mineral and bone disorder biomarkers could be used to enhance risk assessment in CKD.
  
  
  METHODS
  Fetuin-A, fibroblast growth factor-23 and osteoprotegerin were measured on baseline plasma samples from 463 patients recruited to the Chronic Renal Insufficiency Standards Implementation Study. The biomarkers were analysed in relation to progression to end stage kidney disease, death and major cardiovascular events.
  
  
  RESULTS
  Over a median follow up of 46 months (interquartile range 21-69), fibroblast growth factor-23 was associated with risk for renal replacement therapy (hazard ratio (HR) 1.35, P = 0.05, 95% confidence interval (CI) 1.001-1.820), cardiovascular events (HR 1.74 P < 0.001, 95% CI 1.303-1.305) and death (HR 1.4 P = 0.005, 95% CI 1.109-1.767). Osteoprotegerin was associated with risk for death (HR 1.06, P = 0.03, 95% CI 1.006-1.117). There was no clear association between Fetuin-A and any of the clinical endpoints. The addition of biomarkers to risk models led to marginal improvement in model discrimination and reclassification.
  
  
  CONCLUSIONS
  Biomarkers are often associated with clinical endpoints, and we observed such associations in our study of patients with advanced CKD. However, the markers analysed in our study were of limited benefit in improving the prediction of these outcomes. Any extra information biomarkers may provide to improve risk prediction in clinical practice needs to be carefully balanced against the potential cost of these tools.
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Helen V
authors.initials: HV
authors.lastname: Alderson
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Ritchie
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Middleton
authors.affiliation: Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institute, Stockholm, Sweden.
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.|Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D053244:Osteoprotegerin / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000628:therapy; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis*
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; C000717427:FGF23 protein, human; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D060749:alpha-2-HS-Glycoprotein; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: CKD-MBD; biomarkers; outcomes; prediction; risk