The clinical utility window for acute kidney injury biomarkers in the critically ill

Crit Care. 2014 Nov 4;18(6):601. doi: 10.1186/s13054-014-0601-2.


Introduction: 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)).

Conclusion: 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.

Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12610001012066. Registered 12 February 2010.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / urine*
  • Acute-Phase Proteins / urine*
  • Aged
  • Biomarkers / blood
  • Biomarkers / urine
  • Critical Illness*
  • Cystatin C / urine*
  • Female
  • Humans
  • Intensive Care Units / standards
  • Lipocalin-2
  • Lipocalins / blood*
  • Lipocalins / urine*
  • Male
  • Middle Aged
  • Prospective Studies
  • Proto-Oncogene Proteins / blood*
  • Proto-Oncogene Proteins / urine*
  • Time Factors


  • Acute-Phase Proteins
  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins

Associated data

  • ANZCTR/ACTRN12610001012066