title: The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury.
abstract: BACKGROUND
  Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients.
  
  
  METHODS
  We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL(E1) and uNGAL(E2)] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L.
  
  
  RESULTS
  Bland-Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGAL(E1) were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95% CI 82.03-450.44 ng/mg creatinine; limits of agreement: -1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction.
  
  
  CONCLUSIONS
  uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker.
authors.affiliation: Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, Melbourne, VIC, 3084, Australia.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Glassford
authors.forename: Antoine G
authors.initials: AG
authors.lastname: Schneider
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Xu
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Eastwood
authors.forename: Helen
authors.initials: H
authors.lastname: Young
authors.forename: Leah
authors.initials: L
authors.lastname: Peck
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D018806:APACHE; D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine*; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D054834:Lipocalins / Q000097:blood / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009846:Oliguria / Q000150:complications / Q000175:diagnosis / Q000209:etiology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications* / Q000175:diagnosis; D014739:Victoria
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D054834:Lipocalins; D003404:Creatinine
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