2). Whereas CKD has a well-established conceptual model and definition that has been useful in clinical medicine, research, and public health,42–44 the definition for AKI is evolving, and the concept of AKD is relatively new. An operational definition of AKD for use in the diagnostic approach to alterations in kidney function and structure is included in Chapter 2.5, with further description in Appendix B. The conceptual model of AKI (Figure 3) is analogous to the conceptual model of CKD, and is also applicable to AKD.42,45 Circles on the horizontal axis depict stages in the development (left to right) and recovery (right to left) of AKI. AKI (in red) is defined as reduction in kidney function, including decreased GFR and kidney failure. The criteria for the diagnosis of AKI and the stage of severity of AKI are based on changes in SCr and urine output as depicted in the triangle above the circles. Kidney failure is a stage of AKI highlighted here because of its clinical importance. Kidney failure is defined as a GFR o15 ml/min per 1.73 m2 body http://www.kidney-international.org chapter 2.1 & 2012 KDIGO Table 2 | Staging of AKI Stage Serum creatinine Urine output 1 1.5–1.9 times baseline OR X0.3 mg/dl (X26.5 mmol/l) increase o0.5 ml/kg/h for 6–12 hours 2 2.0–2.9 times baseline o0.5 ml/kg/h for X12 hours 3 3.0 times baseline OR Increase in serum creatinine to X4.0 mg/dl (X353.6 mmol/l) OR Initiation of renal replacement therapy OR, In patients o18 years, decrease in eGFR to o35 ml/min per 1.73 m2 o0.3 ml/kg/h for X24 hours OR Anuria for X12 hours Kidney International Supplements (2012) 2, 19–36 19 surface area, or requirement for RRT, although it is recognized that RRT may be required earlier in the evolution of AKI. Further description is included in Chapter 2.5 and Appendix A. It is widely accepted that GFR is the most useful overall index of kidney function in health and disease, and changes in SCr and urine output are surrogates for changes in GFR. In clinical practice, an abrupt decline in GFR is assessed from an increase in SCr or oliguria. Recognizing the limitations of the use of a decrease in kidney function for the early detection and accurate estimation of renal injury (see below), there is a broad consensus that, while more sensitive and specific biomarkers are needed, changes in SCr and/or urine output form the basis of all diagnostic criteria for AKI. The first international interdisciplinary consensus criteria for diagnosis of AKI were the RIFLE criteria32 proposed by the ADQI. Modifications to these criteria have been proposed in order to better account for pediatric populations (pRIFLE)32 and for small changes in SCr not captured by RIFLE (AKIN criteria).23 Recommendations 2.1.1 and 2.1.2 represent the combination of RIFLE and AKIN criteria (Table 3). Existing evidence supports the validity of both RIFLE and AKIN criteria to identify groups of hospitalized patients with increased risk of death and/or need for RRT.2,5,25,28–30 Epidemiological studies, many multicentered, collectively enrolling more than 500 000 subjects have been used to establish RIFLE and/or AKIN criteria as valid methods to diagnose and stage AKI. Recently, Joannidis et al.29 directly compared RIFLE criteria with and without the AKIN modification. While AKI classified by either criteria were associated with a similarly increased hospital mortality, the two criteria identified somewhat different patients. The original RIFLE criteria failed to detect 9% of cases that were detected by AKIN criteria. However, the AKIN criteria missed 26.9% of cases detected by RIFLE. Examination of the cases missed by either criteria (Table 4) shows that cases identified by AKIN but missed by RIFLE were almost exclusively Stage 1 (90.7%), while cases missed by AKIN but identified by RIFLE included 30% with RIFLE-I and 18% RIFLE-F; furthermore, these cases had hospital mortality similar to cases identified by both criteria (37% for I and 41% for F). However, cases missed by RIFLE but identified as Stage 1 by AKIN also had hospital mortality rates nearly twice that of patients who had no evidence of AKI by either criteria (25% vs. 13%). These data provide strong rationale for use of both RIFLE and AKIN criteria to identify patients with AKI. Staging of AKI (Recommendation 2.1.2) is appropriate because, with increased stage of AKI, the risk for death and need for RRT increases.2,5,25,28–31 Furthermore, there is now accumulating evidence of long-term risk of subsequent development of cardiovascular disease or CKD and mortality, even after apparent resolution of AKI.47–49 For staging purposes, patients should be staged according to the criteria that give them the highest stage. Thus when creatinine and urine output map to different stages, AKD CKD AKI Figure 2 | Overview of AKI, CKD, and AKD. Overlapping ovals show the relationships among AKI, AKD, and CKD. AKI is a subset of AKD. Both AKI and AKD without AKI can be superimposed upon CKD. Individuals without AKI, AKD, or CKD have no known kidney disease (NKD), not shown here. AKD, acute kidney diseases and disorders; AKI, acute kidney injury; CKD, chronic kidney disease. Death Complications Normal Increased risk Antecedents Intermediate Stage AKI Outcomes Damage ↓ Stages defined by creatinine and urine output are surrogates Markers such as NGAL, KIM-1, and IL-18 are surrogates GFR Damage Kidney failure ↓ GFR Figure