title: The urine protein NGAL predicts renal replacement therapy, but not acute kidney injury or 90-day mortality in critically ill adult patients.
abstract: BACKGROUND
  Urine neutrophil gelatinase-associated lipocalin (uNGAL) is increasingly used as a biomarker for acute kidney injury (AKI). However, the clinical value of uNGAL with respect to AKI, renal replacement therapy (RRT), or 90-day mortality in critically ill patients is unclear. Accordingly, we tested the hypothesis that uNGAL is a clinically relevant biomarker for these end points in a large, nonselected cohort of critically ill adult patients.
  
  
  METHODS
  We prospectively obtained urine samples from 1042 adult patients admitted to 15 Finnish intensive care units. We analyzed 3 samples (on admission, at 12 hours, and at 24 hours) with NGAL ELISA Rapid Kits (BioPorto® Diagnostics, Gentofte, Denmark). We chose the highest uNGAL (uNGAL24) for statistical analyses. We calculated the areas under receiver operating characteristics curves (AUC) with 95% confidence intervals (95% CIs), the best cutoff points with the Youden index, positive likelihood ratios (LR+), continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). We performed sensitivity analyses excluding patients with AKI or RRT on day 1, sepsis, or with missing baseline serum creatinine concentration.
  
  
  RESULTS
  In this study population, the AUC of uNGAL24 (95% CI) for development of AKI (defined by the Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was 0.733 (0.701-0.765), and the continuous NRI for AKI was 56.9%. For RRT, the AUC of uNGAL24 (95% CI) was 0.839 (0.797-0.880), and NRI 56.3%. For 90-day mortality, the AUC of uNGAL24 (95% CI) was 0.634 (0.593 to 0.675), and NRI 15.3%. The LR+ (95% CI) for RRT was 3.81 (3.26-4.47).
  
  
  CONCLUSIONS
  In this study, we found that uNGAL associated well with the initiation of RRT but did not provide additional predictive value regarding AKI or 90-day mortality in critically ill patients.
authors.affiliation: From the Department of Surgery, Division of Anesthesia and Intensive Care Medicine, Intensive Care Units, Helsinki University Central Hospital, Helsinki; Department of Intensive Care Medicine, Critical Care Medicine Research Group, Tampere University Hospital, Tampere, Finland; Department of Epidemiology and Preventive Medicine, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia; Department of Surgical Sciences/Anesthesiology and Intensive Care, University of Uppsala, Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Nisula
authors.forename: Runkuan
authors.initials: R
authors.lastname: Yang
authors.forename: Kirsi-Maija
authors.initials: KM
authors.lastname: Kaukonen
authors.forename: Suvi T
authors.initials: ST
authors.lastname: Vaara
authors.forename: Anne
authors.initials: A
authors.lastname: Kuitunen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
authors.forename: Ville
authors.initials: V
authors.lastname: Pettilä
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Korhonen
mesh_terms: D058186:Acute Kidney Injury / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000368:Aged; D019540:Area Under Curve; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D017582:Renal Replacement Therapy
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins