When should renal replacement therapy for acute kidney injury be initiated and discontinued?

BACKGROUND Critically ill patients with acute kidney injury (AKI) are at high risk for death and frequently require initiation of renal replacement therapy (RRT). There is wide variation in clinical practice on the indications for and timing of initiation and discontinuation of RRT. Numerous clinical and biochemical factors (i.e. uremic, metabolic, fluid balance) have been used; however, at present there is no consensus to guide clinicians on the most favorable time to initiate and/or discontinue RRT to optimize patient outcomes. METHODS In this review, we appraise the available clinical studies that have assessed timing of initiation and/or discontinuation of RRT for critically ill patients with AKI. 'Timing' of initiation has been variably defined including use of conventional biomarkers (i.e. serum urea and creatinine), urine output, fluid balance, and time relative to intensive care unit admission. CONCLUSIONS Numerous studies consistently point toward a survival benefit to early initiation of RRT; however, there is a paucity of high-quality randomized trials. If early RRT is associated with clinical benefit, it remains uncertain whether this is attributable to more rapid metabolic/uremic control, management of fluid balance or a combination of clinical factors. In addition, timing of RRT initiation is likely context-specific and varies by clinical factors and/or etiology of AKI. There is also little data to accurately distinguish in advance between the injured kidney that will need extracorporeal renal support and one that retains capacity for early recovery. Fewer studies have evaluated the process of weaning of RRT or ideal methods to predict sufficient recovery to avoid re-initiation. Longer duration of RRT support, higher illness severity and lower urine output (independent of diuretic therapy) have all predicted need for re-initiation. Additional investigations on these issues are clearly warranted and urgently needed.