Original Investigation
Pathogenesis and Treatment of Kidney Disease
Accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Diagnosis and Prognosis in Acute Kidney Injury: A Systematic Review and Meta-analysis

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Background

Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker for the early diagnosis of acute kidney injury (AKI); however, a wide range in its predictive value has been reported.

Study Design

Meta-analysis of diagnostic test studies using custom-made standardized data sheets sent to each author.

Setting & Population

Different clinical settings of AKI.

Selection Criteria for Studies

MEDLINE, EMBASE, and CENTRAL databases and congress abstracts were searched for studies reporting the value of NGAL to predict AKI.

Index Tests

Plasma/serum and urine NGAL within 6 hours from the time of insult (if known) or 24-48 hours before the diagnosis of AKI if the time of insult was not known.

Reference Tests

The primary outcome was AKI, defined as an increase in serum creatinine level > 50% from baseline within 7 days or contrast-induced nephropathy (creatinine increase > 25% or concentration > 0.5 mg/dL in adults or > 50% increase in children within 48 hours). Other outcomes predicted using NGAL were renal replacement therapy initiation and in-hospital mortality.

Results

Using a hierarchical bivariate generalized linear model to calculate the diagnostic odds ratio (DOR) and sample size–weighted area under the curve for the receiver-operating characteristic (AUC-ROC), we analyzed data from 19 studies and 8 countries involving 2,538 patients, of whom 487 (19.2%) developed AKI. Overall, the DOR/AUC-ROC of NGAL to predict AKI was 18.6 (95% CI, 9.0-38.1)/0.815 (95% CI, 0.732-0.892). The DOR/AUC-ROC when standardized platforms were used was 25.5 (95% CI, 8.9-72.8)/0.830 (95% CI, 0.741-0.918) with a cutoff value > 150 ng/mL for AKI compared with 16.7 (95% CI, 7.1-39.7)/0.732 (95% CI, 0.656-0.830) for “research-based” NGAL assays. In cardiac surgery patients, the DOR/AUC-ROC of NGAL was 13.1 (95% CI, 5.7-34.8)/0.775 (95% CI, 0.669-0.867); in critically ill patients, 10.0 (95% CI, 3.0-33.1)/0.728 (95% CI, 0.615-0.834); and after contrast infusion, 92.0 (95% CI, 10.7-794.1)/0.894 (95% CI, 0.826-0.950). The diagnostic accuracy of plasma/serum NGAL (17.9 [95% CI, 6.0-53.7]/0.775 [95% CI, 0.679-0.869]) was similar to that of urine NGAL (18.6 [95% CI, 7.2-48.4]/0.837 [95% CI, 0.762-0.906]). We identified age to be an effective modifier of NGAL value with better predictive ability in children (25.4 [95% CI, 8.9-72.2]/0.930 [95% CI, 0.883-0.968]) compared with adults (10.6 [95% CI, 4.8-23.4]/0.782 [95% CI, 0.689-0.872]). NGAL level was a useful prognostic tool with regard to the prediction of renal replacement therapy initiation (12.9 [95% CI, 4.9-33.9]/0.782 [95% CI, 0.648-0.917]) and in-hospital mortality (8.8 [95% CI, 1.9-40.8]/0.706 [95% CI, 0.530-0.747]).

Limitations

Serum creatinine level was used for AKI definition.

Conclusions

NGAL level appears to be of diagnostic and prognostic value for AKI.

Section snippets

Data Sources and Search Strategy

The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for the conduct of meta-analyses of observational cohort studies33 were followed. Two investigators (M.H. and P.D.) independently searched MEDLINE (through PubMed interface), EMBASE, CENTRAL, and Congress abstracts (to May 31, 2009) to identify potentially relevant articles or abstracts. Our search included 1 search term: neutrophil gelatinase-associated lipocalin or NGAL. There were no language restrictions. We

Search Results and Study Characteristics

The electronic database searches identified 244 citations of studies and abstracts. After evaluating these citations and the bibliographies of included studies, we included 19 studies with 23 data sets.13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 These comprised data from 4 conference abstracts.27, 29, 30, 32 A flow chart detailing the process of study identification and selection is shown in Fig 1, and characteristics of included studies are listed in Table 1. The

Discussion

The need for a simple, accurate, and minimally invasive marker of AKI has been a limiting factor in clinical nephrology research and practice. Although serum creatinine level is the current standard as such a marker, its limitations are well known and include its dependence on age, sex, and muscle mass.7, 17 More accurate methods, such as radiolabelled tracer clearances, are invasive, may involve radiation, and require several hours to perform. Of several recently characterized novel renal

Acknowledgements

Members of the NGAL Meta-analysis Investigator Group are Sean M. Bagshaw, MD (University of Alberta Hospital, Edmonton, Canada), Rinaldo Bellomo, MD (Department of Intensive Care, Austin Health, Melbourne, Australia), Richard Bogle, PhD, MRCP (Hammersmith Campus, Imperial College London, UK), Cao Changchun, MD (Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China), Jean-M. Constantin, MD, PhD (Hotel-Dieu Hospital, University Hospital of Clermont-Ferrand,

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    Originally published online as doi:10.1053/j.ajkd.2009.07.020 on October 22, 2009.

    Members of the NGAL Meta-analysis Investigator Group are listed at the end of this article.

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