title: The clinical utility window for acute kidney injury biomarkers in the critically ill.
abstract: BACKGROUND
  Acute Kidney Injury (AKI) biomarker utility depends on sample timing after the onset of renal injury. We compared biomarker performance on arrival in the emergency department (ED) with subsequent performance in the intensive care unit (ICU).
  
  
  METHODS
  Urinary and plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), and urinary Cystatin C (CysC), alkaline phosphatase, γ-Glutamyl Transpeptidase (GGT), α- and π-Glutathione S-Transferase (GST), and albumin were measured on ED presentation, and at 0, 4, 8, and 16 hours, and days 2, 4 and 7 in the ICU in patients after cardiac arrest, sustained or profound hypotension or ruptured abdominal aortic aneurysm. AKI was defined as plasma creatinine increase ≥ 26.5 μmol/l within 48 hours or ≥ 50% within 7 days.
  
  
  RESULTS
  In total, 45 of 77 patients developed AKI. Most AKI patients had elevated urinary NGAL, and plasma NGAL and CysC in the period 6 to 24 hours post presentation. Biomarker performance in the ICU was similar or better than when measured earlier in the ED. Plasma NGAL diagnosed AKI at all sampling times, urinary NGAL, plasma and urinary CysC up to 48 hours, GGT 4 to 12 hours, and π-GST 8 to 12 hours post insult. Thirty-one patients died or required dialysis. Peak 24-hour urinary NGAL and albumin independently predicted 30-day mortality and dialysis; odds ratios 2.87 (1.32 to 6.26), and 2.72 (1.14 to 6.48), respectively. Urinary NGAL improved risk prediction by 11% (IDI event of 0.06 (0.002 to 0.19) and IDI non-event of 0.04 (0.002 to 0.12)).
  
  
  CONCLUSIONS
  Early measurement in the ED has utility, but not better AKI diagnostic performance than later ICU measurement. Plasma NGAL diagnosed AKI at all time points. Urinary NGAL best predicted mortality or dialysis compared to other biomarkers.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Registry ACTRN12610001012066. Registered 12 February 2010.
authors.affiliation: Department of Anaesthesiology and Intensive Care, International Islamic University Malaysia, Kuantan, Pahang, Malaysia. azrinar@iium.edu.my.|Department of Medicine, University of Otago, Christchurch, New Zealand. azrinar@iium.edu.my.
authors.forename: Azrina Md
authors.initials: AM
authors.lastname: Ralib
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand. john.pickering@otago.ac.nz.
authors.forename: John W
authors.initials: JW
authors.lastname: Pickering
authors.affiliation: Intensive Care Unit, Christchurch Hospital, Christchurch, New Zealand. Geoff.shaw@cdhb.health.nz.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Emergency Department, Christchurch Hospital, Christchurch, New Zealand. martin.than@cdhb.health.nz.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Than
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand. peter.george@cdhb.health.nz.
authors.forename: Peter M
authors.initials: PM
authors.lastname: George
authors.affiliation: Department of Nephrology, Prince of Wales and Clinical School, University of New South Wales, High Street, Randwick, Sydney, NSW, 2031, Australia. zoltan.endre@unsw.edu.au.
authors.forename: Zoltán H
authors.initials: ZH
authors.lastname: Endre
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016638:Critical Illness; D055316:Cystatin C / Q000652:urine*; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000592:standards; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000652:urine*; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins