A Framework and Key Research Questions in AKI Diagnosis and Staging in Different Environments Patrick T. Murray,* Prasad Devarajan, † Andrew S. Levey, ‡ Kai U. Eckardt,* § Joseph V. Bonventre,  Raul Lombardi, ¶ Stefan Herget-Rosenthal,** and Adeera Levin †† *Section of Nephrology, University of Chicago, Chicago, Illinois; † Division of Nephrology and Hypertension, University of Cincinnati, Cincinnati, Ohio; ‡ Division of Nephrology, Tufts University-New England Medical Center, Boston, Massachusetts; § Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany;  Renal Division, Brigham and Women’s Hospital, Harvard University, Boston, Massachusetts; ¶ Department of Critical Care Medicine, Instituto Me ´dico de Previsio ´n y Asistencia IMPASA, Montevideo, Uruguay; **Division of Nephrology, University of Duisburg-Essen, Essen, Germany; and †† Division of Nephrology, University of British Columbia, Vancouver, Canada Background and objectives: Acute Kidney Injury (AKI) is common worldwide, and associated with significant morbidity, mortality, and resource utilization. The RIFLE system of staging AKI correlates with survival in AKI in several settings. A similar AKI definition and staging system that also incorporates lesser degrees of serum creatinine elevation was proposed at the inaugural Acute Kidney Injury Network (AKIN) meeting in 2005. At the Second AKIN meeting in Vancouver, Canada in September 2006, our group developed a research agenda that would test the utility of these diagnostic and staging criteria to predict patient outcomes in a variety of clinical settings and patient groups. Design, setting, participants & measurements: Three-day, international, consensus conference. A multidisciplinary stake- holder committee was divided into work groups. Recommendations for clinical practice and for future research were developed by the committee as an iterative process. This procedure consisted of a literature review phase and focus group interactions with presentations to the entire committee. Results: We first proposed a conceptual framework of disease that describes a series of AKI stages, antecedents and outcomes, and allows a description of research recommendations based on transition between AKI stages. We further proposed methods for testing of the definition and development of research questions to establish the utility of new biomarkers for the diagnosis and staging of AKI and associated illnesses. Conclusions: Retrospective studies should be conducted to initiate the process of validating the AKIN definition of AKI, followed by comprehensive prospective studies that incorporate sampling for emerging AKI biomarkers. Clin J Am Soc Nephrol 3: 864-868, 2008. doi: 10.2215/CJN.04851107 A cute kidney injury (AKI) is common worldwide and is associated with significant morbidity, mortality, and resource use (1,2). Efforts to provide effective prophylaxis or therapy for AKI have been hampered by the lack of a standard definition of this syndrome. In 2002, the Acute Dialysis Quality Initiative (ADQI) consensus group pro- posed a graded classification system (the “RIFLE” criteria [risk, injury, failure, loss, ESRD]) to “stage” the severity of acute kidney dysfunction incorporating levels of oliguria in addition to fractional serum creatinine elevation (1). Emerging evidence suggests that severity of acute renal dysfunction measured by this system correlates with survival in general populations of hospitalized or critically ill patients (3,4) and other settings; however, this system does not include lesser elevations of serum creatinine (50% above baseline), and there is emerging evidence that lesser changes in serum creatinine are common and have important prognostic value in many of the same settings (5,6). Specifically, for example, in cardiac surgery pa- tients, postoperative serum creatinine increments of 20 –25% are associated with mortality increases from 0 –1% to 12–14%, and even increments of 0.1– 0.3 mg/dl are associated with significant increased mortality (5). The Acute Kidney Injury Network (AKIN) was formed in 2004 with the overall objective of optimizing outcomes in AKI by leveraging the resources and perspectives of organizations that are interested in AKI around the globe. The AKIN defini- tion of AKI was proposed after the group’s inaugural consen- sus meeting in Amsterdam in 2005 (2). Compared with the Published online ahead of print. Publication date available at www.cjasn.org. Correspondence: Dr. Patrick T. Murray, Department of Medicine, Section of Nephrology, MC 5100, Room S-511, University of Chicago Hospitals, 5841 South Maryland Avenue, Chicago, IL 60637. Phone: 773-834-0374; Fax: 773-702-5818; E-mail: pmurray@medicine.bsd.uchicago.edu Copyright © 2008 by the American Society of Nephrology ISSN: 1555-9041/303–0864