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The Urine Protein NGAL Predicts Renal Replacement Therapy, but Not Acute Kidney Injury or 90-Day Mortality in Critically Ill Adult Patients

Nisula, Sara MD*; Yang, Runkuan MD; Kaukonen, Kirsi-Maija PhD; Vaara, Suvi T. PhD*; Kuitunen, Anne PhD; Tenhunen, Jyrki PhD†§; Pettilä, Ville PhD*; Korhonen, Anna-Maija PhD*

doi: 10.1213/ANE.0000000000000243
Critical Care, Trauma, and Resuscitation: Research Report

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).

CONCLUSION: 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.

Supplemental Digital Content is available in the text.Published ahead of print May 7, 2014

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.

Accepted for publication January 16, 2014.

Published ahead of print May 7, 2014

Funding: Clinical Research funding (EVO) TYH 2010109/2011210 and T102010070 from Helsinki University Hospital (VP), and grants from the Finnish Society of Intensive Care, the Academy of Finland (MK), the Juselius Foundation (VP) and the Päivikki and Sakari Sohlberg Foundation (VP), and the Finnish Society of Anesthesiologists (SN). Laboratory analyses were funded by a grant from the Academy of Finland (MK) and external funding for Critical Care Medicine Research Group (JT).

The authors declare no conflicts of interest.

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Address correspondence to Sara Nisula, MD, Department of surgery, Intensive Care Units, Division of Anaesthesia and Intensive Care Medicine, Institution: Helsinki University Central Hospital, Box 340, 00029 HUS, Finland. Address e-mail to

© 2014 International Anesthesia Research Society