ABSTRACT: INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients. The aim of this study was to evaluate the utility of blood neutrophil gelatinase-associated lipocalin (NGAL) assessment as an aid in the early risk evaluation for AKI development in admitted patients. METHODS: This is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED. RESULTS: Blood NGAL and serum creatinine (sCr) where determined at ED presentation (T0), and at: 6 (T6), 12 (T12), 24 (T24) and 72 (T72) hours after hospitalization. A preliminary assessment of AKI by the treating ED physician occurred in 218 of 665 patients (33%), while RIFLE AKI by expert nephrologists was confirmed in 49 of 665 patients (7%). ED physician's initial judgement lacked sensitivity and specificity, over predicting the diagnosis of AKI in 27% of the cohort, while missing 20% of those with AKI final diagnosis. The area under the receiver operating characteristic curve (AUC), obtained at T0, for blood NGAL alone in the AKI group was 0.80. When NGAL at T0 was added to the ED physician's initial clinical judgment the AUC was increased to 0.90, significantly greater when compared to the AUC of the T0 estimated glomerular filtration rate (eGFR) obtained either by modification of diet in renal disease (MDRD) equation (0.78) or Cockroft-Gault (0.78) formula (p=0.022 and p=0.020 respectively). The model obtained by combining NGAL with ED physician's initial clinical judgement compared to the model combining sCr with the ED physician's initial clinical judgement, resulted in a net reclassification index of 32.4 percentage points. Serial assessment of T0 and T6 hours NGAL provided a high negative predictive value (NPV) (98%) in ruling out the diagnosis of AKI within 6 hours of patients' ED arrival. NGAL (T0) showed the strongest predictive value for in-hospital patient's mortality at a cut-off of 400 ng/ml. CONCLUSIONS: Our study demonstrated that assessment of a patient's initial blood NGAL when admitted to hospital from the ED improved the initial clinical diagnosis of AKI and predicted in-hospital mortality. Blood NGAL assessment coupled with ED physician's clinical judgment may provide utility in deciding the appropriate strategies for patients at risk for the development of AKI.