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Background: The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed "standard") with another in which RRT is further delayed for a longer period (termed "delayed strategy").Methods/design: This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects.Discussion: The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019.Trial Registration: ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018. [ABSTRACT FROM AUTHOR]

Rationale: Post-cardiac surgery shock is associated with high morbidity and mortality. By removing toxins and proinflammatory mediators and correcting metabolic acidosis, high-volume hemofiltration (HVHF) might halt the vicious circle leading to death by improving myocardial performance and reducing vasopressor dependence.Objectives: To determine whether early HVHF decreases all-cause mortality 30 days after randomization.Methods: This prospective, multicenter randomized controlled trial included patients with severe shock requiring high-dose catecholamines 3-24 hours post-cardiac surgery who were randomized to early HVHF (80 ml/kg/h for 48 h), followed by standard-volume continuous venovenous hemodiafiltration (CVVHDF) until resolution of shock and recovery of renal function, or conservative standard care, with delayed CVVHDF only for persistent, severe acute kidney injury.Measurements and Main Results: On Day 30, 40 of 112 (36%) HVHF and 40 of 112 (36%) control subjects (odds ratio, 1.00; 95% confidence interval, 0.64-1.56; P = 1.00) had died; only 57% of the control subjects had received renal-replacement therapy. Between-group survivors' Day-60, Day-90, intensive care unit, and in-hospital mortality rates, Day-30 ventilator-free days, and renal function recovery were comparable. HVHF patients experienced faster correction of metabolic acidosis and tended to be more rapidly weaned off catecholamines but had more frequent hypophosphatemia, metabolic alkalosis, and thrombocytopenia.Conclusions: For patients with post-cardiac surgery shock requiring high-dose catecholamines, the early HVHF onset for 48 hours, followed by standard volume until resolution of shock and recovery of renal function, did not lower Day-30 mortality and did not impact other important patient-centered outcomes compared with a conservative strategy with delayed CVVHDF initiation only for patients with persistent, severe acute kidney injury. Clinical trial registered with www.clinicaltrials.gov (NCT 01077349). [ABSTRACT FROM AUTHOR]