3 | Conceptual model for AKI. Red circles represent stages of AKI. Yellow circles represent potential antecedents of AKI, and the pink circle represents an intermediate stage (not yet defined). Thick arrows between circles represent risk factors associated with the initiation and progression of disease that can be affected or detected by interventions. Purple circles represent outcomes of AKI. ‘‘Complications’’ refers to all complications of AKI, including efforts at prevention and treatment, and complications in other organ systems. AKI, acute kidney injury; GFR, glomerular filtration rate. Adapted from Murray PT, Devarajan P, Levey AS, et al. A framework and key research questions in AKI diagnosis and staging in different environments. Clin J Am Soc Nephrol 2008; 3: 864–868 with permission from American Society of Nephrology45 conveyed through Copyright Clearance Center, Inc.; accessed International Supplements (2012) 2, 19–36 chapter 2.1 the patient is staged according to the highest (worst) stage. The changes in GFR that were published with the original RIFLE criteria do not correspond precisely to changes in SCr. As SCr is measured and GFR can only be estimated, creatinine criteria should be used along with urine output for the diagnosis (and staging) of AKI. One additional change in the criteria was made for the sake of clarity and simplicity. For patients reaching Stage 3 by SCr 44.0 mg/dl (4354 mmol/l), rather than require an acute increase of X0.5 mg/dl (X44 mmol/l) over an unspecified time period, we instead require that the patient first achieve the creatininebased change specified in the definition (either X0.3 mg/dl [X26.5 mmol/l] within a 48-hour time window or an increase of X1.5 times baseline). This change brings the definition and staging criteria to greater parity and simplifies the criteria. Recommendation 2.1.2 is based on the RIFLE and AKIN criteria that were developed for average-sized adults. The creatinine change–based definitions include an automatic Stage 3 classification for patients who develop SCr 44.0 mg/dl (4354 mmol/l) (provided that they first satisfy the definition of AKI in Recommendation 2.1.1). This is problematic for smaller pediatric patients, including infants and children with low muscle mass who may not be able to achieve a SCr of 4.0 mg/dl (354 mmol/l). Thus, the pediatricmodified RIFLE AKI criteria32 were developed using a change in estimated creatinine clearance (eCrCl) based on the Schwartz formula. In pRIFLE, patients automatically reach Stage 3 if they develop an eCrCl o35 ml/min per 1.73 m2 . However, with this automatic pRIFLE threshold, the SCr change based AKI definition (recommendation 2.1.1) is applicable to pediatric patients, including an increase of 0.3 mg/dl (26.5 mmol/l) SCr.32 There are important limitations to these recommendations, including imprecise determination of risk (see Chapter 2.2) and incomplete epidemiology of AKI, especially outside the ICU. Clinical judgment is required in order to determine if patients seeming to meet criteria do, in fact, have disease, as well as to determine if patients are likely to have AKI even if incomplete clinical data are available to apply the diagnostic criteria. The application of the diagnostic and staging criteria Table 3 | Comparison of RIFLE and AKIN criteria for diagnosis and classification of AKI AKI staging Urine output RIFLE Serum creatinine (common to both) Class Serum creatinine or GFR Stage 1 Increase of more than or equal to 0.3 mg/dl (X26.5 mmol/l) or increase to more than or equal to 150% to 200% (1.5- to 2-fold) from baseline Less than 0.5 ml/kg/h for more than 6 hours Risk Increase in serum creatinine 1.5 or GFR decrease 425% Stage 2 Increased to more than 200% to 300% (42- to 3-fold) from baseline Less than 0.5 ml/kg per hour for more than 12 hours Injury Serum creatinine 2 or GFR decreased 450% Stage 3 Increased to more than 300% (43-fold) from baseline, or more than or equal to 4.0 mg/dl (X354 mmol/l) with an acute increase of at least 0.5 mg/dl (44 mmol/l) or on RRT Less than 0.3 ml/kg/h for 24 hours or anuria for 12 hours Failure Serum creatinine 3, or serum creatinine 44 mg/dl (4354 mmol/l) with an acute rise 40.5 mg/dl (444 mmol/l) or GFR decreased 475% Loss Persistent acute renal failure=complete loss of kidney function 44 weeks End-stage kidney disease ESRD 43 months Note: For conversion of creatinine expressed in SI units to mg/dl, divide by 88.4. For both AKIN stage and RIFLE criteria, only one criterion (creatinine rise or urine output decline) needs to be fulfilled. Class is based on the worst of either GFR or urine output criteria. GFR decrease is calculated from the increase in serum creatinine above baseline. For AKIN, the increase in creatinine must occur in o48 hours. For RIFLE, AKI should be both abrupt (within 1–7 days) and sustained (more than 24 hours). When baseline creatinine is elevated, an abrupt rise of at least 0.5 mg/dl (44 mmol/l) to 44 mg/dl (4354 mmol/l) is sufficient for RIFLE class Failure (modified from Mehta et al. 23 and the report of the Acute Dialysis Quality Initiative consortium22). AKI, acute kidney injury; AKIN, Acute Kidney Injury Network; ESRD, end-stage renal disease; GFR, glomerular filtration rate; RIFLE, risk, injury, failure, loss, and end stage; RRT, renal replacement therapy. Reprinted from Endre ZH. Acute kidney injury: definitions and new paradigms. Adv Chronic Kidney