Diagnosis and prognosis of neutrophil gelatinase-associated lipocalin for acute kidney injury with sepsis: a systematic review and meta-analysis

BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for prediction of acute kidney injury (AKI). However, the utility of NGAL to predict the occurrence of AKI in septic patients remains controversial. We performed a systematic review and meta-analysis to evaluate the evidence on diagnosis of sepsis AKI and the prediction of other clinical outcomes. METHOD The MEDLINE, EMBASE, Cochrane Library, Wanfang, and CNKI databases were systematically searched up to August 19, 2015. Quality assessment was applied by using the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool. The diagnostic performance of NGAL for the prediction of AKI in sepsis was evaluated using pooled estimates of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio (DOR), as well as summary receiver operating characteristic curves (SROC). RESULTS Fifteen studies with a total of 1,478 patients were included in the meta-analysis. For plasma NGAL, the pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.83 (95% CI: 0.77 - 0.88) and 0.57 (95% CI: 0.54 - 0.61), respectively. The pooled positive likelihood ratio (PLR) was 3.10 (95% CI: 1.57 - 6.11) and the pooled negative likelihood ratio (NLR) was 0.24 (95% CI: 0.13 - 0.43). The pooled DOR was 14.72 (95% CI: 6.55 - 33.10) using a random effects model. The area under the curve (AUC) for SROC to summarize diagnostic accuracy was 0.86. For urine NGAL, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC values were 0.80 (95% CI: 0.77 - 0.83), 0.80 (95% CI: 0.77 - 0.83), 4.42 (95% CI: 2.84 - 6.89), 0.21 (95% CI: 0.13 - 0.35), 24.20 (95% CI: 9.92 - 59.05) and 0.90, respectively. Significant heterogeneity was explored as a potential source. There was no notable publication bias observed across the eligible studies. NGAL for prediction of renal replacement therapy (RRT) and mortality associated with AKI in septic patients were also evaluated. CONCLUSION To a certain extent, NGAL is not only an effective predictive factor for AKI in the process of sepsis, but also shows potential predictive value for RRT and mortality. However, future trials are needed to clarify this controversial issue.