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.

RATIONALE & OBJECTIVE The usefulness of measures of neutrophil gelatinase-associated lipocalin in urine or plasma (u/pNGAL) obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and severe AKI requiring kidney 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 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 urine 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 providing authors data specifications tailored to their studies and requesting standardized patient-level data analysis. ANALYTICAL APPROACH Individual-study-data meta-analysis utilized a bivariate time-to-event model for interval-censored data from which discriminative ability (area under the receiver operating characteristic curve (AUC)) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, as well as optimal sensitivity and specificity were also estimated. Models incorporated as confounders clinical setting and use versus non-use of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those studies 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 datasets for the individual-study-data meta-analysis with 837 AKI events, 304 severe AKI events, and 103 severe AKI-D events for analyses of urine NGAL and 705 AKI events, 271 severe AKI events, and 178 AKI-D events for analyses of plasma NGAL. Discriminative performance was similar in individual-study-data meta-analysis and literature-based meta-analysis. Individual-study-data meta-analysis AUCs for uNGAL were 0.75 (95% CI 0.73-0.76) and 0.80 (0.79-0.81) for severe AKI and AKI-D, respectively; for pNGAL, the corresponding values were 0.80 (0.79-0.81) and 0.86 (0.84-0.86). Cut-off-concentrations at 95% specificity for uNGAL were >580 ng/mL with 27% sensitivity for severe AKI and >589 ng/mL with 24% sensitivity for AKI-D. Corresponding cut-offs for pNGAL were >364 ng/mL with 44% sensitivity and >546 ng/mL with 26% sensitivity, respectively. LIMITATIONS Practice variability on initiation of acute 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 reported cut-off concentrations in this study require prospective evaluation.