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

Neil John Glassford, Antoine Schneider, Shengyuan Xu, Glenn M Eastwood, Helen Young, Leah Peck, Per Venge, Rinaldo Bellomo

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46 Citations (Scopus)

Abstract

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 [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 ?mol/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. 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.
Original languageEnglish
Pages (from-to)1714-1724
Number of pages11
JournalIntensive Care Medicine
Volume39
Issue number10
DOIs
Publication statusPublished - 2013

Keywords

  • Apache Acute Kidney Injury/*diagnosis/etiology/urine Acute-Phase Proteins/*urine Aged Area Under Curve Biomarkers/blood/urine Blotting, Western Creatinine/blood *Critical Illness Female Humans Intensive Care Units/statistics & numerical data Lipocalins/blood/*urine Male Middle Aged Oliguria/complications/diagnosis/etiology Predictive Value of Tests Prospective Studies Risk Assessment/methods Systemic Inflammatory Response Syndrome/*complications/diagnosis Victoria

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