Diagnostic Accuracy of Serum and Urinary Neutrophil Gelatinase-associated Lipocalin for Predicting Sepsis-associated Acute Kidney Injury: A Systematic Review and Meta-Analysis

Abstract

Introduction. Sepsis‑associated acute kidney injury (SA‑AKI) is a 
frequent and serious complication among critically ill patients and 
is associated with substantial morbidity and mortality. Conventional 
diagnostic markers such as serum creatinine and urine output 
often detect kidney injury only after functional decline and may 
be confounded in septic states. Neutrophil gelatinase‑associated 
lipocalin (NGAL) has emerged as a potential early biomarker of 
tubular injury; however, its diagnostic performance in sepsis remains 
uncertain. This systematic review and meta‑analysis evaluated the 
diagnostic accuracy of serum and urinary NGAL for predicting 
SA‑AKI in adults with sepsis.
Methods. A systematic search of the PubMed database was conducted 
from inception to 2025 to identify studies evaluating serum, plasma, or 
urinary NGAL in adult patients with sepsis. Eligible studies reported 
diagnostic accuracy for AKI defined according to KDIGO, AKIN, 
or RIFLE criteria. Data extraction was performed independently by 
two reviewers. Pooled sensitivity, specificity, diagnostic odds ratios 
(DORs), and summary receiver operating characteristic (SROC) curves 
were estimated using a bivariate random‑effects model. Subgroup 
analyses explored differences according to clinical setting and timing 
of biomarker measurement.
Results. Seventeen studies met the inclusion criteria. For serum NGAL, 
the pooled sensitivity was 0.77 (95% CI: 0.63 to 0.86) and pooled 
specificity was 0.68 (95% CI: 0.52 to 0.80), with an AUC of 0.773 and 
a diagnostic odds ratio of 6.15 (95% CI: 4.38 to 8.64). Urinary NGAL 
demonstrated comparable but slightly higher diagnostic performance, 
with pooled sensitivity of 0.75 (95% CI: 0.66 to 0.82), specificity of 
0.71 (95% CI: 0.64 to 0.78), an AUC of 0.782, and a diagnostic odds 
ratio of 7.12 (95% CI: 4.17 to 12.16). Subgroup analyses suggested 
modestly improved diagnostic performance in ICU populations.
Conclusions. Both serum and urinary NGAL demonstrate moderate 
diagnostic accuracy for predicting SA‑AKI in adult patients with 
sepsis. Urinary NGAL showed slightly better discriminatory 
performance in several clinical contexts. Rather than replacing 
established KDIGO‑based diagnostic criteria, NGAL may serve as a 
complementary biomarker to support early risk stratification. Larger 
prospective studies with standardized assay methods and diagnostic 
thresholds are needed before routine clinical implementation.