Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

Abstract

RATIONALE & OBJECTIVE:

The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

STUDY DESIGN:

Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

SETTING & STUDY POPULATIONS:

Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

SELECTION CRITERIA FOR STUDIES:

PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

DATA EXTRACTION:

Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

ANALYTICAL APPROACH:

Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

RESULTS:

We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.

LIMITATIONS:

Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.

CONCLUSIONS:

Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.

• Authors: Christian Albert, Antonia Zapf, Michael Haase, Christian Röver, John W Pickering, Annemarie Albert, Rinaldo Bellomo, Tobias Breidthardt, Fabrice Camou, Zhongquing Chen, Sidney Chocron, Dinna Cruz, Hilde R H de Geus, Prasad Devarajan, Salvatore Di Somma, Kent Doi, Zoltan H Endre, Mercedes Garcia-Alvarez, Peter B Hjortrup, Mina Hur, Georgios Karaolanis, Cemil Kavalci, Hanah Kim, Paolo Lentini, Christoph Liebetrau, Miklós Lipcsey, Johan Mårtensson, Christian Müller, Serafim Nanas, Thomas L Nickolas, Chrysoula Pipili, Claudio Ronco, Guillermo J Rosa-Diez, Azrina Ralib, Karina Soto, Rüdiger C Braun-Dullaeus, Judith Heinz, Anja Haase-Fielitz
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 76 Issue 6 Pg. 826-841.e1 (12 2020) ISSN: 1523-6838 [Electronic] United States
• PMID: 32679151 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Systematic Review)
• Copyright: Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Lipocalin-2

Topics

• Acute Kidney Injury (diagnosis, metabolism, therapy)
• Biomarkers (blood, urine)
• Humans
• Lipocalin-2 (blood)
• Predictive Value of Tests
• Renal Dialysis