Delivery of Renal Replacement Therapy in Acute Kidney Injury: What Are the Key Issues? Andrew Davenport,* Catherine Bouman, † Ashok Kirpalani, ‡ Peter Skippen, § Ashita Tolwani,  Ravindra L. Mehta, ¶ and Paul M. Palevsky** *University College London Center for Nephrology, Royal Free and University College Medical School, London, United Kingdom; † Department of Intensive Care, Amsterdam Medical Center, University of Amsterdam, Amsterdam, Netherlands; ‡ Department of Nephrology, Bombay Hospital Institute of Medical Sciences, Mumbai, India; § Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada;  Department of Medicine, University of Alabama, Birmingham, Alabama; ¶ Department of Medicine, University of California, San Diego, San Diego, California; and **Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Background and objectives: The prescription and delivery of renal replacement therapy for acute kidney injury is subject to a wide variation and is conditioned by a multiplicity of factors. A variety of renal replacement therapy modalities are now available to treat acute kidney injury; however, there are no standards for the dosage, choice of modality, and intensity and duration of these therapies. Although several observational and interventional studies have addressed these topics, there are no consensus recommendations in this field. Design, setting, participants, & measurements: The available literature on this topic and draft consensus recommendations for research studies in this area were developed using a modified Delphi approach and an international multidisciplinary network. Results: The following questions were most important: What is the “dosage” of renal replacement therapy delivered to patients with stage 3 acute kidney injury? What is the optimal “dosage” of renal replacement therapy to maximize patient and renal survival? Is there a minimal “dosage” of renal replacement therapy required in patients with single-organ failure? Does modality of renal replacement therapy selected have an effect on patient and/or renal survival? In cases of continuous renal replacement therapy, does citrate anticoagulation confer a benefit? Conclusions: This report summarizes the available evidence and elaborates on the key questions and the methods that should be used so that the goal of standardizing the care of patients with acute kidney injury and improving outcomes can be achieved. Clin J Am Soc Nephrol 3: 869-875, 2008. doi: 10.2215/CJN.04821107 G iven the wide variation in clinical practice relating to the indications for and timing of renal replacement therapy (RRT), patients who receive RRT are consid- ered to have reached stage 3 acute kidney injury (AKI; or stage F of the RIFLE criteria [risk, injury, failure, loss, ESRD]), irre- spective of the stage that they are in at the time of RRT initiation (1,2). In the early 1980s, the options for RRT were limited to intermittent hemodialysis (IHD) and acute peritoneal dialysis (PD). At that time, IHD was routinely performed thrice weekly, typically using acetate-based dialysate, warmed to body tem- perature, with low-flux cellulosic membrane dialyzers and di- alysis machines that lacked accurate volumetric control. IHD treatments in the intensive care setting were frequently com- plicated by hypotension, as a result of the amount of ultrafil- tration required, often exacerbated by the use of parenteral nutrition. In an attempt to overcome these problems, continu- ous forms of RRT (CRRT) were developed, based on the orig- inal description by Kramer et al. (3) of a simple ultrafiltration device. Initially, these devices were spontaneous, using in- dwelling arterial catheters; however, the clearances derived from such continuous arteriovenous hemofiltration (CAVH) circuits were often insufficient, with additional IHD treatments required (4). For increasing the efficiency, dialysate was added (CAVHD), and then pumped venovenous circuits developed (continuous venovenous hemofiltration [CVVH] and continu- ous venovenous hemodiafiltration [CVVHDF]), initially by en- thusiasts and finally by industry with purpose-designed CRRT Published online ahead of print. Publication date available at www.cjasn.org. Correspondence: Dr. Andrew Davenport, UCL Center for Nephrology, Royal Free & University College Medical School, Hampstead Campus, Rowland Hill Street, London NW3 2PF, UK. Phone: 44-2078302930; Fax: 44-2073178591; E-mail: andrew.davenport@royalfree.nhs.uk Copyright © 2008 by the American Society of Nephrology ISSN: 1555-9041/303–0869