Definition and staging criteria of acute kidney injury in adults

INTRODUCTION — Acute kidney injury (AKI) refers to an abrupt decrease in kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. The term AKI has largely replaced acute renal failure (ARF), reflecting the recognition that smaller decrements in kidney function that do not result in overt organ failure are of substantial clinical relevance and are associated with increased morbidity and mortality.

Several consensus definitions of AKI have been developed in order to provide a uniform definition of AKI. These definitions are based exclusively upon the serum creatinine and urine output and are used primarily to identify patients with AKI in epidemiologic and outcome studies. The overall utility of these definitions and staging systems in the clinical assessment and management of patients with AKI remains to be validated.

The potential etiologies, diagnosis, and management of AKI are discussed elsewhere:

●(See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults".)

●(See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting".)

●(See "Overview of the management of acute kidney injury (AKI) in adults".)

DIAGNOSTIC CRITERIA — The definition for AKI used in clinical and epidemiologic studies is based on specific criteria that have been sequentially developed. The Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging system is the most recent and preferred definition [1]. Other criteria include the RIFLE criteria (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) [2] and a subsequent modification proposed by the Acute Kidney Injury Network (AKIN) and others [3-5]. These criteria are outlined in the table (table 1).

The KDIGO guidelines define AKI as follows [1]:

●Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours, or

●Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days, or

●Urine volume <0.5 mL/kg/hour for six hours

The KDIGO criteria allow for correction of volume status and obstructive causes of AKI prior to classification. Before diagnosing and classifying AKI, one should assess and optimize volume status and exclude obstruction. This is based upon AKIN criteria, on which the KDIGO definition is based. The AKIN state that these criteria should be used in the context of the clinical presentation and following adequate fluid resuscitation, when applicable, and that use of the urine output criteria alone requires exclusion of urinary tract obstruction or other easily reversible causes of reduced urine output. (See "Evaluation of acute kidney injury among hospitalized adult patients".)

The timeframe for an absolute increase in serum creatinine of ≥0.3 mg/dL is retained from the AKIN definition (48 hours), while the timeframe for a ≥50 percent increase in serum creatinine reverted to the seven days originally included in the Acute Dialysis Quality Initiative (ADQI) RIFLE criteria.

The RIFLE and AKIN definitions are shown in the table (table 1).

STAGING CRITERIA — Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, AKI is staged as follows:

●Stage 1 – Increase in serum creatinine to 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L), or reduction in urine output to <0.5 mL/kg/hour for 6 to 12 hours.

●Stage 2 – Increase in serum creatinine to 2.0 to 2.9 times baseline, or reduction in urine output to <0.5 mL/kg/hour for ≥12 hours.

●Stage 3 – Increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 micromol/L), or reduction in urine output to <0.3 mL/kg/hour for ≥24 hours, or anuria for ≥12 hours, or the initiation of kidney replacement therapy, or, in patients <18 years, decrease in estimated glomerular filtration rate (eGFR) to <35 mL/min/1.73 m².

The KDIGO criteria differ from the RIFLE classification in that the KDIGO criteria only utilize changes in serum creatinine and urine output, not changes in GFR for staging, with the exception of children under the age of 18 years, for whom an acute decrease in eGFR to <35 mL/min/1.73 m² is included in the criteria for stage 3 AKI.

As with the RIFLE and Acute Kidney Injury Network (AKIN) staging systems, KDIGO suggested that patients be classified according to criteria that result in the highest (ie, most severe) stage of injury.

LIMITATIONS — There are a number of limitations to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI [6-9]. These limitations also apply to the older criteria (such as RIFLE and Acute Kidney Injury Network [AKIN]) that also rely solely on changes in creatinine or urine output.

●Many etiologies cause AKI – A major flaw is that the criteria do not distinguish between the multiple etiologies that cause AKI. It is incorrect to treat AKI as a single disease, particularly grouping together hemodynamic causes (ie, "prerenal AKI") and acute tubular necrosis. To address this, the KDIGO guidelines specified that patients with AKI be evaluated promptly to determine cause [1]. Such evaluation is critical for patient care since reversible causes of AKI (such as obstruction) require specific interventions.

In addition, different causes of AKI are associated with different long-term outcomes and prognoses, which is not always addressed in studies that utilize AKI criteria.

Finally, from a research perspective, the development of therapeutic interventions requires the addition of etiologic or anatomic diagnoses to the criteria [9].

●Use of urine output to define AKI – Another important issue is the use of urine output as a sole criterion for AKI. The KDIGO criteria define stages by change in either serum creatinine or urine output. (See 'Diagnostic criteria' above.)

However, using urine output to define or stage AKI is not based on robust evidence. In one assessment of the RIFLE classification, which compared the serum creatinine and urine output criteria, the serum creatinine criteria were strong predictors of intensive care unit (ICU) mortality, whereas the urine output criteria did not independently predict mortality [10]. Brief durations of oliguria may just reflect insufficient volume resuscitation [7].

Other studies, however, have suggested that urine output is predictive of mortality [11,12], and one study even suggested that urine output may be a more sensitive marker for AKI than serum creatinine [13].

One study suggests that risks of death or kidney replacement therapy were highest when both the serum creatinine and urine output criteria were met [14]. However, although the criteria include both creatinine and urine output, in practice, the urine output is often omitted from studies [6].

Until this issue is resolved, it is reasonable to use the criteria that result in the least favorable strata assignment, as suggested in the Acute Dialysis Quality Initiative (ADQI) group [2] and affirmed by KDIGO [1].

●Determination of baseline creatinine – The determination of a baseline creatinine for individual patients is a third limitation. It is impossible to calculate the change in serum creatinine in patients who present with AKI but who do not have a baseline measurement of serum creatinine.

The authors of the RIFLE criteria had initially suggested back-calculating an estimated baseline serum creatinine concentration using the four-variable Modification of Diet in Renal Disease (MDRD) equation, assuming a baseline glomerular filtration rate (GFR) of 75 mL/min/1.73 m² [2]. However, this approach has been demonstrated to result in significant misclassification [6] and should not be utilized.

The European Renal Best Practice (ERBP) group recommended that the first documented serum creatinine be used as the baseline, rather than using historical values (ie, prior to the acute illness) or a calculated value based on a presumed baseline GFR of 75 mL/min [6]. However, the initial hospital creatinine value may already be elevated above the patient's usual baseline if the onset of AKI occurred prior to hospital admission. Creatinine production may also be reduced in the setting of acute illness, leading to an artifactual fall in admission serum creatinine [15]. Changes in volume of distribution of creatinine as the result of volume overload may also depress baseline creatinine values and blunt the rise in creatinine concentration during AKI. Some experts have suggested that an average of creatinine values measured 7 to 365 days prior to hospitalization best approximates the true baseline creatinine value [16].

Even when a baseline creatinine is available, relying on small changes in serum creatinine for the diagnosis of AKI may be associated with a high rate of misdiagnosis, especially in patients with a baseline serum creatinine ≥1.5 mg/dL [17].

A more global concern raised by the Kidney Disease Outcomes Quality Initiative (KDOQI) work group is that the use of a definition based upon a biomarker, such as serum creatinine, or a variable, such as urine output, may result in a marked increase in the number of nephrology consultations, which would provide uncertain benefit to the patient [7]. As noted by an accompanying editorial to the KDOQI commentary, discretion is required to determine the clinical significance of a diagnosis of AKI [18].

UTILITY IN EPIDEMIOLOGIC STUDIES — The Kidney Disease: Improving Global Outcomes (KDIGO) criteria have greatest utility in epidemiologic studies and in defining consistent inclusion criteria and/or endpoints for clinical studies [7,8]. The severity of AKI stage is correlated with mortality risk and intensive care unit (ICU) and hospital length of stay [10,19-31].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Acute kidney injury (The Basics)")

SUMMARY

●Definition of acute kidney injury (AKI) – AKI refers to the abrupt decrease in kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. The term AKI has replaced acute renal failure (ARF), reflecting the recognition that smaller decrements in kidney function are associated with increased morbidity and mortality. (See 'Introduction' above.)

A consensus definition and criteria for AKI has been sequentially developed. The Kidney Disease: Improving Global Outcomes (KDIGO) AKI Workgroup definition and staging system is the preferred definition:

•Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours, or

•Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days, or

•Urine volume <0.5 mL/kg/hour for six hours

●Staging of AKI – Using the KDIGO criteria, AKI is staged as follows:

•Stage 1 – Increase in serum creatinine to 1.5 to 1.9 times baseline, or increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromol/L), or reduction in urine output to <0.5 mL/kg/hour for 6 to 12 hours.

•Stage 2 – Increase in serum creatinine to 2.0 to 2.9 times baseline, or reduction in urine output to <0.5 mL/kg/hour for ≥12 hours.

•Stage 3 – Increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 micromol/L), or reduction in urine output to <0.3 mL/kg/hour for ≥24 hours, or anuria for ≥12 hours, or the initiation of kidney replacement therapy, or, in patients <18 years, decrease in estimated glomerular filtration rate (eGFR) to <35 mL/min/1.73 m². (See 'Staging criteria' above.)

●Limitations – The AKI definition does not distinguish between the multiple etiologies that can cause AKI. Other limitations include the use of urine output as a sole criterion for AKI, which has not been conclusively validated, and difficulty determining baseline kidney function among patients who have not had recent creatinine measurement. (See 'Limitations' above.)