71 54 In studies of adult intensive care patients, plasma NGAL co

71.54 In studies of adult intensive care patients, plasma NGAL concentrations on admission constituted a very good to outstanding biomarker for development of AKI within the next 2 days, with AUC-ROC ranges of 0.78–0.92.55,57 In subjects undergoing liver transplantation, a single plasma NGAL level obtained within 2 h of reperfusion was highly predictive of subsequent AKI, with an AUC-ROC of 0.79.58 Finally, in a study of adults in the emergency department setting, a single measurement of urine NGAL at the time of initial presentation predicted AKI with an outstanding AUC-ROC of 0.95, and reliably distinguished pre-renal azotemia from intrinsic AKI and

from CKD.59 Thus, NGAL Erlotinib is a useful early AKI marker that predicts development of AKI even in heterogeneous groups of patients with multiple comorbidities and with unknown timing of kidney injury. However, it should be noted that patients with septic AKI display the highest concentrations of both plasma and urine NGAL when compared with those with non-septic AKI,56 a confounding factor that may add to the heterogeneity of the results in the critical care setting. The variable performance of biomarkers such as NGAL in the critical care setting may also be attributable to the fact that this patient population is extremely heterogeneous,

and the aetiology and timing of AKI is often unclear. A high proportion of patients may have already sustained AKI on admission to the ICU. Although sepsis accounts for 30–50% of all AKI encountered in critically ill patients, other aetiologies include exposure to nephrotoxins, selleck kinase inhibitor hypotension, kidney ischaemia,

mechanical ventilation and multi-organ disease. Each of these aetiologies is associated with distinct mechanisms of injury that are likely to be active at different times with different intensities and may act synergistically. Despite the myriad confounding variables, a recent meta-analysis revealed an overall for AUC-ROC of 0.73 for prediction of AKI, when NGAL was measured within 6 h of clinical contact with critically ill subjects and AKI was defined as a >50% increase in serum creatinine.41 Because of its high predictive properties for AKI, NGAL is also emerging as an early biomarker in interventional trials. For example, a reduction in urine NGAL has been employed as an outcome variable in clinical trials demonstrating the improved efficacy of a modern hydroxyethylstarch preparation over albumin or gelatin in maintaining renal function in cardiac surgery patients.60–62 Similarly, the response of urine NGAL was attenuated in adult cardiac surgery patients who experienced a lower incidence of AKI after sodium bicarbonate therapy when compared with sodium chloride.63 In addition, urinary NGAL levels have been used to document the efficacy of a miniaturized cardiopulmonary bypass system in the preservation of kidney function when compared with standard cardiopulmonary bypass.

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