Intensive Care Medicine

, Volume 39, Issue 10, pp 1714–1724 | Cite as

The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury

  • Neil J. Glassford
  • Antoine G. Schneider
  • Shengyuan Xu
  • Glenn M. Eastwood
  • Helen Young
  • Leah Peck
  • Per Venge
  • Rinaldo Bellomo
Seven-Day Profile Publication



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.


We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGALE1 and uNGALE2] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L.

Measurements and main results

Bland–Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGALE1 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.


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.


Acute kidney injury Oliguria Critical illness Intensive care Biomarker Systemic inflammatory response syndrome 



This study was supported by the Austin Hospital Intensive Care Trust Fund. The ELISA testing was funded by a grant from the Swedish Medical Research Council to Uppsala University.

Conflicts of interest

Shengyuan Xu holds patents with, and receives royalties from, Diagnostics Development. Per Venge holds patents with, and stock in, P&M Venge AB. He has received royalties from Phadia. The remaining authors declare that they have no conflicts of interest.

Supplementary material

134_2013_3040_MOESM1_ESM.docx (91 kb)
Supplementary material 1 (DOCX 90 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • Neil J. Glassford
    • 1
  • Antoine G. Schneider
    • 1
  • Shengyuan Xu
    • 2
  • Glenn M. Eastwood
    • 1
  • Helen Young
    • 1
  • Leah Peck
    • 1
  • Per Venge
    • 2
  • Rinaldo Bellomo
    • 1
    • 3
  1. 1.Department of Intensive CareAustin HospitalMelbourneAustralia
  2. 2.Department of Medical Sciences, Clinical ChemistryUppsala UniversityUppsalaSweden
  3. 3.Australian and New Zealand Intensive Care Research Centre and Department of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia

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