title: SuPAR and PAI-1 in critically ill, mechanically ventilated patients.
abstract: OBJECTIVE
  SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients.
  
  
  METHODS
  We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan-Meier analysis were performed.
  
  
  RESULTS
  Baseline suPAR was 11.6 ng/ml (quartiles Q1-Q3, 9.6-14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5-11.0). PAI-1 concentrations were 2.67 ng/ml (1.53-4.69) and 0.3 ng/ml (0.3-0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55-0.67), sepsis 0.68 (0.61-0.76), ALI/ARDS 0.64 (0.56-0.73) and RRT 0.65 (0.56-0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37-4.64, p = 0.003) for 90-day mortality and 3.16 (1.19-8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC's for suPAR were 90-day mortality 0.61 (0.54-0.68), RRT 0.73 (0.64-0.83), sepsis 0.70 (0.60-0.80), ALI/ARDS 0.61 (0.51-0.71). Predictive value of PAI-1 was negligible.
  
  
  CONCLUSIONS
  In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.
authors.affiliation: Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, PO BOX 2000, 33521 Tampere, Finland. ville.jalkanen@pshp.fi
authors.forename: Ville
authors.initials: V
authors.lastname: Jalkanen
authors.forename: Runkuan
authors.initials: R
authors.lastname: Yang
authors.forename: Rita
authors.initials: R
authors.lastname: Linko
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Marjatta
authors.initials: M
authors.lastname: Okkonen
authors.forename: Tero
authors.initials: T
authors.lastname: Varpula
authors.forename: Ville
authors.initials: V
authors.lastname: Pettilä
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000209:etiology; D012131:Respiratory Insufficiency / Q000097:blood* / Q000150:complications* / Q000401:mortality / Q000628:therapy; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D055293:Receptors, Urokinase Plasminogen Activator