IntroductionAcute 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.MethodsThis is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED.ResultsBlood NGAL and serum creatinine (sCr) were 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 out of 665 patients (33%), while RIFLE AKI by expert nephrologists was confirmed in 49 out of 665 patients (7%). The ED physician's initial judgement lacked sensitivity and specificity, overpredicting the diagnosis of AKI in 27% of the cohort, while missing 20% of those with AKI as a 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 formula (0.78) (P = 0.022 and P = 0.020 respectively). The model obtained by combining NGAL with the 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 cutoff of 400 ng/ml.ConclusionsOur 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 the ED physician's clinical judgment may prove useful in deciding the appropriate strategies for patients at risk for the development of AKI.See related commentary by Legrand et al., http://ccforum.com/content/17/2/132

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We have recently reported that the insulin receptor (IR), a tetrameric transmembrane protein located on the surface of target cells, is present as a soluble form in human plasma. In the present study we investigated whether human cells in culture release an intact and functional form of the IR. We found that IRs are secreted into the incubation medium by four cell lines (IM-9 human lymphoblasts, MCF-7 human breast cancer cells, HepG2 human hepatoma cells, and 3T3 mouse fibroblasts transfected with human IRs). IR secretion was further characterized in IM-9 cells. IR release was time, temperature, and energy dependent, and enhanced by incubation with insulin. The dilution slope of secreted IRs in a specific IR RIA was parallel to that produced by highly purified human placenta IRs. Ligand binding studies revealed that secreted receptors bound insulin with high affinity, and the Scatchard analysis revealed two orders of binding sites (the high affinity site had a dissociation constant of 0.32 +/- 0.08 nM). Analysis of secreted receptors by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a molecular size of 135 kilodaltons for the alpha-subunit and 95 kilodaltons for the beta-subunit. Other experiments indicated that the beta-subunit tyrosine kinase activity of the secreted receptor was stimulated by insulin. These studies indicate, therefore, that a soluble, intact, and functional IR is secreted by cultured cells, and that this soluble protein could be involved in certain insulin-mediated functions, such as receptor down-regulation.