Importantly, by defining the syndrome of acute changes in renal function more broadly, RIFLE criteria move beyond ARF. The term ‘‘acute kidney injury/impairment’’ has been proposed to encompass the entire spectrum of the syndrome from minor changes in markers of renal function to requirement for renal replacement therapy (RRT).23 Thus, the concept of AKI, as defined by RIFLE creates a new paradigm. AKI is not ATN, nor is it renal failure. Instead, it encompasses both and also includes other, less severe conditions. Indeed, as a syndrome, it includes patients without actual damage to the kidney but with functional impairment relative to physiologic demand. Including such patients in the classification of AKI is conceptually attractive because these are precisely the patients that may benefit from early intervention. However, it means that AKI includes both injury and/or impairment. Rather than focusing exclusively on patients with renal failure or on those who receive dialysis or on those that have a clinical syndrome defined by pathology, which is usually absent (ATN), the strong association of AKI with hospital mortality demands that we change the way we think about this disorder. In a study by Hoste et al.,2only 14% of patients reaching RIFLE ‘‘F’’ received RRT, yet these patients experienced a hospital mortality rate more than five times that of the same ICU population without AKI. Is renal support underutilized or delayed? Are there other supportive measures that should be employed for these patients? Sustained AKI leads to profound alterations in fluid, electrolyte, acid-base and hormonal regulation. AKI results in abnormalities in the central nervous, immune, and coagulation systems. Many patients with AKI already have multisystem organ failure. What is the incremental influence of AKI on remote organ function and how does it affect outcome? A recent study by Levy et al. examined outcomes for over 1000 patients enrolled in the control arms of two large sepsis trials.24 Early improvement (within 24 hours) in cardiovascular (P = 0.0010), renal (P < 0.0001), or respiratory (P = 0.0469) function was significantly related to survival. This study suggests that outcomes for patients with severe sepsis in the ICU are closely related to early resolution of AKI. While rapid resolution of AKI may simply be a marker of a good prognosis, it may also indicate a window of therapeutic opportunity to improve outcome in such patients.