Number of patients classified into the respective stages of AKI by AKIN or RIFLE are cross-tabulated against each other. Hospital mortality of each group is given in parentheses. Shaded fields denote patients assigned to the same degree of AKI by both classification systems. AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; RIFLE, risk, injury, failure, loss, and end stage. With kind permission from Springer Science+Business Media: Intensive Care Med. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. 35 (2009): 1692–1702. Joannidis M, Metnitz B, Bauer P et al. 29; accessed http://www.springerlink.com/content/r177337030550120/ Kidney International Supplements (2012) 2, 19–36 21 chapter 2.1 is discussed in greater detail, along with specific examples in Chapter 2.4. The use of urine output criteria for diagnosis and staging has been less well validated and in individual patients the need for clinical judgment regarding the effects of drugs (e.g., angiotensin-converting enzyme inhibitors [ACE-I]), fluid balance, and other factors must be included. For very obese patients, urine output criteria for AKI may include some patients with normal urine output. However, these recommendations serve as the starting point for further evaluation, possibly involving subspecialists, for a group of patients recognized to be at increased risk. Finally, it is axiomatic that patients always be managed according to the cause of their disease, and thus it is important to determine the cause of AKI whenever possible. In particular, patients with decreased kidney perfusion, acute glomerulonephritis, vasculitis, interstitial nephritis, thrombotic microangiopathy, and urinary tract obstruction require immediate diagnosis and specific therapeutic intervention, in addition to the general recommendations for AKI in the remainder of this guideline (Table 5). It is recognized that it is frequently not possible to determine the cause, and often the exact cause does not dictate a specific therapy. However, the syndrome of AKI includes some patients with specific kidney diseases (e.g., glomerulonephritis) for which a specific treatment is available. As such, it is always necessary to search for the underlying cause of AKI (see Chapter 2.3). Research Recommendations K The role of biomarkers other than SCr in the early diagnosis, differential diagnosis, and prognosis of AKI patients should be explored. Some important areas in which to focus include: J Early detection where the gold standard is AKI by clinical diagnosis after the fact and the biomarker is compared to existing markers (SCr and urine output) at the time of presentation. J Prognosis where a biomarker is used to predict risk for AKI or risk for progression of AKI. J Prognosis where a biomarker is used to predict recovery after AKI vs. death or need for long-term RRT. K The influence of urinary output criteria on AKI staging needs to be further investigated. Influence of fluid balance, percent volume overload, diuretic use, and differing weights (actual, ideal body weight, lean body mass) should be considered. Also, it is currently not known how urine volume criteria should be applied (e.g., average vs. persistent reduction for the period specified). K The influence of SCr or eGFR criteria on AKI staging needs to be further investigated. The use of different relative and absolute SCr increments or eGFR decrements at different time points and with differently ascertained baseline values requires further exploration and validation in various populations. SUPPLEMENTARY MATERIAL Appendix A: Background. Appendix B: Diagnostic Approach to Alterations in Kidney Function and Structure. Supplementary material is linked to the online version of the paper at http://www.kdigo.org/clinical_practice_guidelines/AKI.php Table 5 | Causes of AKI and diagnostic tests Selected causes of AKI requiring immediate diagnosis and specific therapies Recommended diagnostic tests Decreased kidney perfusion Volume status and urinary diagnostic indices Acute glomerulonephritis, vasculitis, interstitial nephritis, thrombotic microangiopathy Urine sediment examination, serologic testing and hematologic testing Urinary tract obstruction Kidney ultrasound AKI, acute kidney injury. 22 Kidney International Supplements (2012) 2, 19–36 chapter 2.1 Chapter 2.2: Risk assessment The kidney is a fairly robust organ that can tolerate exposure to several insults without suffering significant structural or functional change. For this reason, any acute change in kidney function often indicates severe systemic derangement and predicts a poor prognosis. Risk for AKI is increased by exposure to factors that cause AKI or the presence of factors that increase susceptibility to AKI. Factors that determine susceptibility of the kidneys to injury include dehydration, certain demographic characteristics and genetic predispositions, acute and chronic comorbidities, and treatments. It is the interaction between susceptibility and the type and extent of exposure to insults that determines the risk of occurrence of AKI. Understanding individual ‘‘risk factors’’ may help in preventing AKI. This is particularly gratifying in the hospital setting, where the patient’s susceptibility can be assessed before certain exposures as surgery or administration of potentially nephrotoxic agents. Accordingly, some susceptibility factors may be modified,