therapy is an important part of the diagnostic approach. There are few specific tests to establish the etiology of AKI. However, a patient’s response to treatment (e.g., discontinuation of a possible nephrotoxic agent) provides important information as to the diagnosis. Nephrotoxic drugs account for some part of AKI in 20–30% of patients. Often, agents like antimicrobials (e.g., aminoglycosides, amphotericin) and radiocontrast are used in patients that are already at high risk for AKI (e.g., critically ill patients with sepsis). Thus, it is often difficult to discern exactly what contribution these agents have on the overall course of AKI. Nevertheless, it seems prudent to limit exposure to these agents whenever possible and to weigh the risk of developing or worsening AKI against the risk associated with not using the agent. For example, when alternative therapies or diagnostic approaches are available they should be considered. In order to ensure adequate circulating blood volume, it is sometimes necessary to obtain hemodynamic variables. Static variables like central venous pressure are not nearly as useful as dynamic variables, such as pulse-pressure variation, inferior vena cava filling by ultrasound and echocardiographic appearance of the heart (see also Appendix D). Note that while the actions listed in Figure 4 provide an overall starting point for stage-based evaluation and management, they are neither complete not mandatory for an individual patient. For example, the measurement of urine output does not imply that the urinary bladder catheterization is mandatory for all patients, and clinicians should balance the risks of any procedures with the benefits. Furthermore, clinicians must individualize care decisions based on the totality of the clinical situation. However, it is advisable to include AKI stage in these decisions. The evaluation and management of patients with AKI requires attention to cause and stage of AKI, as well as factors that relate to further injury to the kidney, or complications from decreased kidney function. Since AKI is a risk factor for CKD, it is important to evaluate patients with AKI for new onset or worsening of pre-existing CKD. If patients have CKD, manage patients as detailed in the KDOQI CKD Guideline (Guidelines 7–15). If patients do not have CKD, consider them to be at increased risk for CKD and care for them as detailed in the KDOQI CKD Guideline 3 for patients at increased risk for CKD. RESEARCH RECOMMENDATIONS K Clinical research aimed at testing early management strategies is urgently needed. Such trials should also address the risks and benefits of commonly used fluidmanagement strategies, including intravenous (i.v.) fluids and diuretics. K Methods to better assess fluid status in critically ill and other hospitalized patients at risk for AKI are needed. K Research is needed, with follow-up beyond hospital stay, to better understand the clinical consequences of AKI in patients with and without underlying CKD. SUPPLEMENTARY MATERIAL Appendix C: Risk Determination. Appendix D: Evaluation and General Management Guidelines for Patients with AKI. Supplementary material is linked to the online version of the paper at ternational Supplements (2012) 2, 19–36 27 chapter 2.3 Chapter 2.4: Clinical applications This chapter provides a detailed application of the AKI definition and staging for clinical diagnosis and management. The definitions and classification system discussed in Chapter 2.1 can be used easily in many patients and requires little clinical interpretation. However, in real time, clinicians do not always have a complete dataset to work with and individual patients present with unique histories. As discussed in the previous chapter, it is difficult to distinguish AKI from CKD in many cases. In addition, as many as two-thirds of all cases of AKI begin prior to hospitalization (community-acquired AKI). Therefore, clinicians may be faced with patients in whom kidney function is already decreased and, during the hospitalization, improves rather than worsens. Finally, many patients do not have a prior measurement of kidney function available for comparison. This chapter provides detailed examples of the application of these definitions to the clinical setting. Examples of application of AKI definitions Table 7 illustrates a number of examples whereby patients presenting with possible AKI can be diagnosed. Cases A-F have a measurement of baseline SCr. To simplify decisionmaking, baseline estimated glomerular filtration rate (eGFR) exceeds 60 ml/min per 1.73 m2 in these patients, so none has pre-existing CKD. Cases A-F can all be diagnosed with AKI by applying the first two criteria in Recommendation 2.1.1. (a documented increase of at least 0.3 mg/dl (426.5 mmol/l) [within 48 hours or a 50% increase from presumed baseline). Note that a patient can be diagnosed with AKI by fulfilling either criterion 1 or 2 (or 3, urine output) and thus cases B,C,D, and F all fulfill the definition of AKI. Note also that patients may be diagnosed earlier using criterion 1 or 2. Early diagnosis may improve outcome so it is advantageous to diagnose patients as rapidly as possible. For example, case A can be diagnosed with AKI on day 2 by the first criterion, whereas the second criterion is not satisfied until day 3 (increase from 1.3 to 1.9). However, this is only