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Although overt fluid overload is often seen in AKI and may prompt attention for the use of diuretics, often these agents are used in the absence of fluid retention. Over the last decade several new agents have become available for volume removal. We reviewed the literature on this topic and addressed four key questions for the appropriate utilization of these agents. These include the drug targets and mechanism of action of available agents; clinical goals and criteria for timing of intervention; adaptation of therapy for specific clinical settings and measures required for monitoring effectiveness and patient safety. This report details our current knowledge in this area, provides evidence-based clinical practice recommendations where appropriate, and formulates a research agenda to address unanswered questions. 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