title: Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury.
abstract: OBJECTIVE
  To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury.
  
  
  METHODS
  Secondary data analysis from a multicenter, randomized clinical trial.
  
  
  METHODS
  Intensive care units in ten university medical centers.
  
  
  METHODS
  A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial.
  
  
  METHODS
  Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design.
  
  
  RESULTS
  We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003).
  
  
  CONCLUSIONS
  Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury.
authors: Division of Nephrology, University of California, San Francisco, CA, USA. Kathleen.liu@ucsf.edu
authors: Kathleen D
authors: KD
authors: Liu
authors: David V
authors: DV
authors: Glidden
authors: Mark D
authors: MD
authors: Eisner
authors: Polly E
authors: PE
authors: Parsons
authors: Lorraine B
authors: LB
authors: Ware
authors: Arthur
authors: A
authors: Wheeler
authors: Anna
authors: A
authors: Korpak
authors: B Taylor
authors: BT
authors: Thompson
authors: Glenn M
authors: GM
authors: Chertow
authors: Michael A
authors: MA
authors: Matthay
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007362:Intensive Care Units; D015850:Interleukin-6 / Q000097:blood; D007677:Kidney Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D012372:ROC Curve; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012128:Respiratory Distress Syndrome / Q000150:complications*; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept