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

Michael Haase*, Rinaldo Bellomo, Prasad Devarajan, Peter Schlattmann, Anja Haase-Fielitz, Sean M. Bagshaw, Richard Bogle, Cao Changchun, Jean M. Constantin, Dinna Cruz, Duska Dragun, Ulrich Frei, Stuart L. Goldstein, Jay Koyner, Catherine D. Krawczeski, Emerson Q. Lima, Wang Ling, Konstantinos Makris, Jolanta Malyszko, Patrick MurrayThomas L. Nickolas, Valentina Puntmann, Claudio Ronco, Gebhard Wagener, Derek S. Wheeler, Chen Xin, Michael Zappitelli, Ni Zhaohui

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

889 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1012-1024
Number of pages13
JournalAmerican Journal of Kidney Diseases
Volume54
Issue number6
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Keywords

  • acute kidney injury (AKI)
  • meta-analysis
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • plasma NGAL
  • urine NGAL

ASJC Scopus subject areas

  • Nephrology

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