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PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. RESULTS: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. CONCLUSION: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection.

Critical illness is often complicated by acute kidney injury (AKI). In patients with severe AKI, renal replacement therapy (RRT) is deployed to address metabolic dysfunction and volume excess until kidney function recovers. This review is intended to provide a comprehensive update on key aspects of RRT prescription and delivery to critically ill patients. Recently completed trials have enhanced the evidence base regarding several RRT practices, most notably the timing of RRT initiation and anticoagulation for continuous therapies. Better evidence is still needed to clarify several aspects of care including optimal targets for ultrafiltration and effective strategies for RRT weaning and discontinuation., Author(s): Ron Wald [sup.1] [sup.2] , William Beaubien-Souligny [sup.3] , Rahul Chanchlani [sup.4] , Edward G. Clark [sup.5] , Javier A. Neyra [sup.6] , Marlies Ostermann [sup.7] , Samuel A. [...]

Author(s): Matthieu Legrand [sup.1] [sup.2], Alexander Zarbock [sup.3] Author Affiliations: (1) grid.266102.1, 0000 0001 2297 6811, Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine, University of California, [...]

Author(s): Thilo C. von Groote [sup.1] , Marlies Ostermann [sup.2] , Lui G. Forni [sup.3] [sup.4] , Melanie Meersch-Dini [sup.1] , Alexander Zarbock [sup.1] , Christoph Schmidt, Andreas Hoffmeier, Hugo [...]

Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints., Author(s): Peter Pickkers [sup.1], Marlies Ostermann [sup.2], Michael Joannidis [sup.3], Alexander Zarbock [sup.4], Eric Hoste [sup.5] [sup.6], Rinaldo Bellomo [sup.7] [sup.8], John Prowle [sup.9] [sup.10], Michael Darmon [sup.11], Joseph V. [...]

This article discusses the use of balanced solutions (BS) versus saline in critically ill patients. The administration of large volumes of saline as resuscitation or maintenance fluid can lead to adverse effects such as metabolic acidosis and acute kidney injury. Recent trials have evaluated the effect of balanced crystalloids versus saline on patient outcomes, with mixed results. A new post-hoc analysis of a previous study found that septic patients who received more fluid had a better prognosis with BS. However, further randomized studies are needed for confirmation. [Extracted from the article]

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified. [ABSTRACT FROM AUTHOR]