KDIGO Clinical Practice Guideline for Acute Kidney Injury
Staging AKI: Recommendations and Rationale

Table 2 | Staging of AKI

• 2.1.2: AKI is staged for severity according to the following criteria (Table 2). (Not Graded)
• 2.1.3: The cause of AKI should be determined whenever possible. (Not Graded)

Rationale

Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. AKI is one of a number of acute kidney diseases and disorders (AKD), and can occur with or without other acute or chronic kidney diseases and disorders (Figure 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 < 15 ml/min per 1.73 m² body 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).

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.

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, 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 > 4.0 mg/dl ( > 354 µmol/l), rather than require an acute increase of ≥ 0.5 mg/dl ( ≥ 44 µmol/l) over an unspecified time period, we instead require that the patient first achieve the creatininebased change specified in the definition (either ≥ 0.3mg/dl [ ≥ 26.5 µmol/l] within a 48-hour time window or an increase of ≥ 1.5 times baseline). This change brings the definition and staging criteria to greater parity and simplifies the criteria.

Figure 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 http://cjasn.asnjournals.org/content/3/3/864.full

Table 3 | Comparison of RIFLE and AKIN criteria for diagnosis and classification of AKI

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 < 48 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 µmol/l) to > 4 mg/dl ( > 354 µmol/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 Dis 2008; 15: 213–221 with permission from National Kidney Foundation⁴⁶; accessed http://www.ackdjournal.org/article/S1548-5595(08)00049-9/fulltext

Table 4 | Cross-tabulation of patients classified by RIFLE vs. AKIN

*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/

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 > 4.0 mg/dl ( > 354 µmol/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 µmol/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 < 35 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 µmol/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 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).

Table 5 | Causes of AKI and diagnostic tests

AKI, acute kidney injury.