Neutrophil gelatinase-associated lipocalin (NGAL) is a poor diagnostic marker for sepsis in the ICU – An observational multicentre study

BACKGROUND: Sepsis is a major public health challenge, and reliable biomarkers are essential for distinguishing sepsis from other conditions. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has shown promise as a diagnostic marker due to its role in the immune response. This study evaluates plasma NGAL as a diagnostic tool at the time of ICU admission. METHODS: We analysed plasma NGAL and C-reactive protein (CRP) levels in 2950 adult patients admitted to four ICUs between 2015 and 2018. All patients were retrospectively screened for Sepsis-3 criteria at ICU admission. The discriminative performance of NGAL and CRP for sepsis was assessed using receiver operating characteristic (ROC) analysis, with NGAL levels adjusted for chronic kidney disease (CKD) and age. Patients were stratified by renal function. FINDINGS: Plasma NGAL levels were significantly higher in septic patients (p < 0.001). For the whole cohort, NGAL alone yielded an area under the curve (AUC) of 0.66 (confidence interval (CI) 0.64-0.68), CRP yielded an AUC of 0.71 (CI 0.69-0.73, p < 0.001), and combining NGAL with CRP nominally improved discriminative performance ([Formula: see text]AUC 0.018, 95% CI 0.011-0.027). Stratified analyses indicated that NGAL, together with CRP, significantly outperformed CRP alone in patients with no kidney injury and those with Acute Kidney Injury (AKI) only. In contrast, differences were not significant in patients with CKD only or CKD and AKI. CONCLUSION: In this large cohort, NGAL showed modest discrimination for sepsis, with a nominal improvement when combined with CRP. These findings do not indicate that NGAL meaningfully improves sepsis diagnosis in the ICU.