No “optimal timing” of renal-replacement therapy in critically ill patients with acute kidney injury

Acute kidney injury (AKI) represents a sudden decrease in renal function from a number of disparate causes (1). Using KDIGO (Kidney disease: Improving Global Outcomes) definition, a meta-analysis indicated that the world incidence rates of AKI were approximately 21% in adults and 33% in children (2). Acute tubular necrosis (ATN) accounts for the majority cases of AKI especially in critical care setting with mortality rate exceeding 50% (3). The current medical management of AKI/ATN, however, is limited to supportive care and renal-replacement therapy (RRT) if indicated, while various therapeutic modalities have been attempted without success. Although there is little controversy for initiation of RRT in critical ill patients with AKI complicated by life-threatening or medically refractory conditions such as severe hyperkalemia, metabolic acidosis or diuretic-resistant fluid overload with pulmonary edema, the appropriate timing of RRT in other situations remains a subject of debate. The theoretical benefits of RRT (Table 1) must be weighed against its potential drawbacks (Table 2) in the absence of life-threatening complications and early sign of kidney recovery since the renal dysfunction in AKI/ ATN could have high likelihood to recover spontaneously. However, evidence-based studies to guide clinical practice are essentially absent in this area, resulting in wide variations in decision-making process and inconsistent and potentially suboptimal quality of care. For the past 20 years, several randomized trials focused on various timings of RRT initiation on clinical outcomes in critical ill patients with AKI were completed, including high-profile ELAIN (The Early Versus Late Initiation of Renal Replacement Therapy in Critically III Patients with Acute Kidney Injury) and AKIKI (The Artificial Kidney Initiation in Kidney Injury) trials (4). The ELAIN trial is a single-center randomized trial conducted in Germany, which evaluates the effects of early (initiating RRT at KDIGO stage 2 AKI) vs. delayed (initiating RRT at KDIGO stage 3 AKI or upon an severe medically refractory complication requiring RRT was present) initiation of RRT in the course of critically ill patients with AKI (5). Among 231 patients enrolled in the study, all patients assigned to early-initiation (n=112) and majority of patients in the delayed-initiation group (n=108/119) received RRT. The primary outcome of 90-day mortality was significantly better in the early-initiation group (39.3% vs. 54.7% in the delayed-initiation group, P=0.03). Secondary outcomes including less dialysis independence and short duration of RRT, and shortening of hospital stay were also in favor of early initiation of RRT. The AKIKI trial is a multicenter randomized trial conducted from 31 intensive care units (ICU) in France, which examines the effect of early (initiating RRT immediately after randomization) vs. delayed (initiating RRT only upon development of severe medically refractory complications requiring RRT) initiation of RRT in