title: Biomarkers of inflammation, fibrosis, cardiac stretch and injury predict death but not renal replacement therapy at 1 year in a Canadian chronic kidney disease cohort.
abstract: BACKGROUND
  Newer biomarkers, reflective of biological processes, such as inflammation and fibrosis, cardiac stretch or damage and vascular health may be useful in understanding clinical events in chronic kidney disease (CKD). We assessed whether these newer biomarkers, alone or as a panel, improve risk prediction for renal replacement therapy or death, over and above conventional clinical, demographic and laboratory variables.
  
  
  METHODS
  We conducted a prospective observational Canadian cohort study in 2544 CKD patients with estimated glomerular filtration rate (eGFR) of 15-45 mL/min/1.73 m(2), under nephrology care, in urban and rural centers. We measured traditional clinical and laboratory risk factors, as well as newer biomarkers: cystatin C, high sensitivity c-reactive protein (hsCRP), interleukin 6 (IL6), transforming growth factor β1 (TGFβ1), fibroblast growth factor 23 (FGF23), N-terminal probrain natriuretic peptide (NT-proBNP), troponin I and asymmetric dimethylarginine (ADMA). Key outcomes were renal replacement therapy (RRT, dialysis or transplantation) and death, during the first year follow-up after enrollment: a time point important for clinical decision-making for patients and providers.
  
  
  RESULTS
  Newer biomarkers do not improve the prediction of RRT, when added to conventional risk factors such as eGFR, urine albumin to creatinine ratio, hemoglobin, phosphate and albumin. However, in predicting death within 1 year, cystatin C, NT-proBNP, hsCRP and FGF23 values significantly improved model discrimination and reclassification: c statistic increased by absolute 4.3% and Net Reclassification Improvement for categories of low, intermediate and high risk at 11.2%.
  
  
  CONCLUSIONS
  Our findings suggest that the addition of newer biomarkers may be useful in predicting death in patients with established CKD within a 1-year timeframe. This information may be useful in informing prognosis and redirect resources to serve patients at higher risk to improve outcomes and sustainability of the nephrology care system.
authors.affiliation: University of British Columbia, Vancouver, Canada.
authors.forename: Adeera
authors.initials: A
authors.lastname: Levin
authors.forename: Claudio
authors.initials: C
authors.lastname: Rigatto
authors.forename: Brendan
authors.initials: B
authors.lastname: Barrett
authors.forename: François
authors.initials: F
authors.lastname: Madore
authors.forename: Norman
authors.initials: N
authors.lastname: Muirhead
authors.forename: Daniel
authors.initials: D
authors.lastname: Holmes
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clase
authors.forename: Mila
authors.initials: M
authors.lastname: Tang
authors.forename: Ognjenka
authors.initials: O
authors.lastname: Djurdjev
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002170:Canada; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005355:Fibrosis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006331:Heart Diseases / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy; D017582:Renal Replacement Therapy; D015996:Survival Rate
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23
keywords: CKD; biomarkers; cohort study; outcomes; prediction