title: Persistently elevated osteopontin serum levels predict mortality in critically ill patients.
abstract: BACKGROUND
  Inflammatory, autoimmune and metabolic disorders have been associated with alterations in osteopontin (OPN) serum levels. Furthermore, elevated serum levels of OPN were reported from a small cohort of patients with sepsis. We therefore analyzed OPN serum concentrations in a large cohort of critically ill medical patients.
  
  
  METHODS
  A total of 159 patients (114 with sepsis, 45 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) as well as after 3 days of ICU treatment and compared to 50 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately 1 year.
  
  
  RESULTS
  We found significantly elevated serum levels of OPN at admission to the ICU and after 3 days of treatment in critically ill patients compared to healthy controls. OPN concentrations were related to disease severity and significantly correlated with established prognosis scores and classical as well as experimental markers of inflammation and multi-organ failure. In the total cohort, OPN levels decreased from admission to day 3 of ICU treatment. However, persistently elevated OPN levels at day 3 of ICU treatment were a strong independent predictor for an unfavorable prognosis, with similar or better diagnostic accuracy than routinely used markers of organ failure or prognostic scoring systems such as SAPS2 or APACHE II score.
  
  
  CONCLUSIONS
  Persistently elevated OPN serum concentrations are associated with an unfavourable outcome in patients with critical illness, independent of the presence of sepsis. Besides a possible pathogenic role of OPN in critical illness, our study indicates a potential value for OPN as a prognostic biomarker in critically ill patients during the early course of ICU treatment.
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. croderburg@ukaachen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Roderburg
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. fabian.benz@rwth-aachen.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Benz
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. david.vargas@rwth-aachen.de.
authors.forename: David Vargas
authors.initials: DV
authors.lastname: Cardenas
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany. matthias.lutz@uk-sh.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lutz
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany. hans-joerg.hippe@uksh.de.
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Hippe
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. tluedde@ukaachen.de.
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. ctrautwein@ukaachen.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany. norbert.frey@uksh.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. akoch@ukaachen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. frank.tacke@gmx.net.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany. mark.luedde@uksh.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Luedde
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016638:Critical Illness / Q000401:mortality* / Q000628:therapy; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000639:trends*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D053495:Osteopontin / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053495:Osteopontin