Recent studies have demonstrated that urinary NGAL may be an early marker of AKI. These studies have generally been done in populations where the timing on the renal injury is fairly clear (ie: post-cardiac surgery). These populations have also been fairly homogenous with minimal “background noise” that may impact biomarker performance. Although NGAL is an important regulator of iron balance and renal tubular epithelial health, it is also one of the most highly expressed proteins during ischemic AKI. In this paper by Siew et al, 451 patients whom were enrolled in a study evaluating the use of biomarkers in ALI/ARD, were followed prospectively for the development of AKI by AKIN criteria (minimum 50% or = 0.3 mg/dl increase in Scr within 48hr of enrollment). Almost 20% of the enrolled patients met criteria for AKI. As expected, patients with AKI were more likely to have CKD, DM, sepsis, higher severity of illness and need for vasopressors. Urinary NGAL was independently associated with development of AKI, mortality and need for dialysis. However, there was minimal added benefit beyond known clinical predictors including age, APACHE II score, Scr at enrollment, sepsis and ICU location. Many factors may account for this including systemic release of NGAL resulting in decreased specificity for AKI and limitations imposed by overly-sensitive definitions of AKI in patients with underlying CKD. Indeed, the use of a creatinine based definition of AKI may not be an appropriate “gold standard” for studies of kidney injury biomarkers (Waikar et al Nephrol Dial Transplant 2009). Further studies are necessary to evaluate biomarker panels in critically ill patients, in an attempt to optimize sensitivity and specificity in this heterogeneous patient population. These evaluations must go beyond serum creatinine, and be powered for detection of important endpoints like mortality, progressive/severe AKI and need for dialysis. Benjamin J Freda, DO