3 definition of acute kidney injury (acute renal failure)

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Official reprint from UpToDate

www.uptodate.com

2010 UpToDate

AuthorPaul M Palevsky, MD

Section EditorGary C Curhan, MD, ScD

Deputy EditorAlice M Sheridan, MD

Definition of acute kidney injury (acute renal failure)

Last literature review version 18.3:Setembro 2010 | This topic last updated:Outubro 28,

2008

INTRODUCTION Acute renal failure (ARF) has traditionally been defined as the abrupt loss of

kidney function that results in the retention of urea and other nitrogenous waste products and in

the dysregulation of extracellular volume and electrolytes. The loss of kidney function is most

easily detected by measurement of the serum creatinine which is used to estimate the

glomerular filtration rate (GFR).

Three problems are associated with the use of the serum creatinine to quantitatively define ARF:

Serum creatinine does not accurately reflect the GFR in a patient who is not in steady state.

In the early stages of severe acute renal failure, the serum creatinine may be low even though

the actual (not estimated) GFR is markedly reduced since there may not have been sufficient

time for the creatinine to accumulate. (See "Assessment of kidney function: Serum creatinine;

BUN; and GFR".)

Creatinine is removed by dialysis. As a result, it is usually not possible to assess kidney

function by measuring the serum creatinine once dialysis is initiated. One exception is when the

serum creatinine continues to fall on days when hemodialysis is not performed, indicat ingrecovery of renal function.

Numerous epidemiologic studies and clinical trials have used different cut-off values for serum

creatinine to quantitatively define ARF [1].

The lack of consensus in the quantitative definition of ARF, in particular, has hindered clinical

research since it confounds comparisons between studies. Some definitions employed in clinical

studies have been extremely complex with graded increments in serum creatinine for different

baseline serum creatinine values [1,2]. As an example, in a classic study of the epidemiology of

hospital-acquired acute renal failure, ARF was defined as a 0.5 mg/dL increase in serum

creatinine if the baseline serum creatinine was 1.9 mg/dL, an 1.0 mg/dL increase in serumcreatinine if the baseline serum creatinine was 2.0 to 4.9 mg/dL, and a 1.5 mg/dL increase in

serum creatinine if the baseline serum creatinine was 5.0 mg/dL [2].

The Acute Dialysis Quality Initiative (ADQI) was created by a group of expert intensivists and

nephrologists to develop consensus and evidence based guidelines for the treatment and

prevention of acute renal failure [3]. Recognizing the need for a uniform definition for ARF, the

ADQI group proposed a consensus graded definition, called the RIFLE criteria [4]. A modification

of the RIFLE criteria was subsequently proposed by the Acute Kidney Injury Network, which

included the ADQI group as well as representatives from other nephrology and intensive care

societies [5-7].

Because of these initiatives, the term acute kidney injury (AKI) was proposed to represent the

entire spectrum of acute renal failure. This topic review will address the current definitions of

acute renal failure, particularly the RIFLE c riteria and the AKIN modifications.

RIFLE CRITERIA The RIFLE criteria consists of three graded levels of injury (Risk, Injury, and

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Failure) based upon either the magnitude of elevation in serum creatinine or urine output, and

two outcome measures (Loss and End-stage renal disease). The RIFLE strata are as follows [4]:

Risk 1.5-fold increase in the serum creatinine or GFR decrease by 25 percent or urine

output


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Diagnostic criteria The proposed diagnostic criteria for ARF are an abrupt (within 48 hours)

absolute increase in the serum creatinine concentration of 0.3 mg/dL (26.4 micromol/L) from

baseline, a percentage increase in the serum creatinine concentration of 50 percent, or oliguria

of less than 0.5 mL/kg per hour for more than six hours (table 1).

The latter two of these criteria are identical to the RIFLE "risk" criteria. The addition of an

absolute change in serum creatinine of 0.3 mg/dL is based on epidemiologic data that have

demonstrated an 80 percent increase in mortality risk associated with changes in serum

creatinine concentration of as little as 0.3 to 0.5 mg/dL [15]. Including a time constraint of 48hours is based upon data that showed that poorer outcomes were associated with small changes

in the creatinine when the rise in creatinine was observed within 24 to 48 hours [16,17].

Two additional caveats were proposed by the AKIN group:

The diagnostic criteria should be applied only after volume status had been optimized

Urinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic

criterion.

A flaw with the last caveat is that, according to the current definition, AKI would still be used to

describe the patient with acute urinary tract obstruction and an acute increase in serum

creatinine. It is not clear whether the AKIN modifications to RIFLE have substantively changed

the classification of patients with AKI or improved its ability to predict hospital mortality [18].

Staging system The classification or staging system for ARF is comprised of three stages of

increasing severity, which correspond to risk (stage 1), injury (stage 2), and failure (stage 3) of

the RIFLE criteria. Loss and ESRD are removed from the staging system and defined as

outcomes.

The clinical applicability of these staging systems is uncertain. However, they will likely have

some utility in standardizing the definitions for epidemiologic studies and for establishing inclusion

criteria and endpoints for clinical trials.

Ultimately these definitions are likely to be replaced by more sensitive and specific biomarkers of

renal injury.

CLINICAL UTILITY The RIFLE and AKIN criteria have helped to focus attention that

decrements in renal function that result in small changes in serum creatinine concentration are

associated with significant c linical consequences. However, the precise clinical utility of these

criteria is uncertain. There is also an inherent confusion within these criteria as to whether

prerenal and obstructive etiologies of ARF are subsumed in or are external to the definition of

AKI.

We believe that these criteria have greatest utility in epidemiologic studies and in defining

consistent inclusion criteria and/or endpoints for clinical studies. Their utility at the bedside is

less clear and it seems likely that they will eventually be replaced at least in part by sensitive

and spec ific biomarkers of renal tubular injury. The use of such biomarkers, analogous to troponin

as a marker of myocardial injury, will permit development of a new paradigm for classifying acute

kidney injury that is not solely dependent upon serum creatinine or other functional markers.

We do believe that adoption of the term acute kidney injury (AKI) to replace the older

terminology of acute renal failure is highly appropriate. Just as acute lung injury is used to

describe acute pulmonary injury that has not progressed to overt organ failure, we believe that

AKI is more representative of the full spectrum of acute kidney dysfunction.

SUMMARY

Acute renal failure (ARF) has traditionally been defined as the abrupt loss of kidney function

resulting in the retention of urea and other nitrogenous waste products and in the dysregulation




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of extracellular volume and electrolytes. (See 'Introduction'above.)

Although the loss of kidney function is most easily detected by measurement of the serum

creatinine, several problems are associated with the use of this measure to quantitatively define

ARF, particularly the lack of consensus in the quantitative definition. (See 'Introduction'above.)

The Acute Dialysis Quality Initiative (ADQI) has proposed a graded definition of ARF called

the RIFLE criteria. The Acute Kidney Injury Network (AKIN) modified the RIFLE criteria in order to

include less severe ARF, to impose a time constraint of 48 hours, and to allow for correction of

volume status and obstructive causes of ARF prior to c lassification. (See 'Rifle criteria'above

and 'AKIN criteria'above.) These criteria have their greatest utility in epidemiologic studies.

The AKIN proposed the term acute kidney injury (AKI) to represent the entire spectrum of

acute renal failure. The proposed diagnostic criteria are an abrupt (within 48 hours) absolute

increase in the serum creatinine concentration of 0.3 mg/dL (26.4 micromol/L) from baseline, a

percentage increase in the serum creatinine concentration of 50 percent, or oliguria of less

than 0.5 mL/kg per hour for more than six hours. These criteria will likely be revised, and possibly

replaced, as biomarkers of tubular injury are developed. (See 'Diagnostic criteria'above.)

We agree that adoption of the term acute kidney injury to replace the older terminology of

acute renal failure is highly appropriate. AKI better represents the full spectrum of acute kidney

dysfunction. (See 'Clinical utility'above.)

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REFERENCES

1. Mehta, RL, Chertow, GM. Acute renal failure definitions and classification: time for change?

J Am Soc Nephrol 2003; 14:2178.

2. Hou, SH, Bushinsky, DA, Wish, JB, et al. Hospital-acquired renal insufficiency: a prospectivestudy. Am J Med 1983; 74:243.

3. Ronco, C, Kellum, JA, Mehta, R. Acute dialysis quality initiative (ADQI). Nephrol Dial

Transplant 2001; 16:1555.

4. Bellomo, R, Ronco, C, Kellum, JA, et al. Acute renal failure - definition, outcome measures,

animal models, fluid therapy and information technology needs: the Second International

Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;

8:R204.

5. Mehta, RL, Kellum, JA, Shah, SV, et al. Acute Kidney Injury Network: report of an initiative

to improve outcomes in acute kidney injury. Crit Care 2007; 11:R31.

6. Levin, A, Warnock, DG, Mehta, RL, et al. Improving outcomes from acute kidney injury:report of an initiative. Am J Kidney Dis 2007; 50:1.

7. Molitoris, BA, Levin, A, Warnock, DG, et al. Improving outcomes from acute kidney injury. J

Am Soc Nephrol 2007; 18:1992.

8. Ali, T, Khan, I, Simpson, W, et al. Incidence and outcomes in acute kidney injury: a

comprehensive population-based study. J Am Soc Nephrol 2007; 18:1292.

9. Uchino, S, Bellomo, R, Goldsmith, D, et al. An assessment of the RIFLE criteria for acuterenal failure in hospitalized patients. Crit Care Med 2006; 34:1913.

10. Hoste, EA, Clermont, G, Kersten, A, et al. RIFLE criteria for acute kidney injury areassociated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006;

10:R73.11. Kuitunen, A, Vento, A, Suojaranta-Ylinen, R, Pettil, V. Acute renal failure after cardiac

surgery: evaluation of the RIFLE classification. Ann Thorac Surg 2006; 81:542.

12. Cruz, DN, Bolgan, I, Perazella, MA, et al. North East Italian Prospective Hospital Renal

Outcome Survey on Acute Kidney Injury (NEiPHROS-AKI): targeting the problem with the




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RIFLE Criteria. Clin J Am Soc Nephrol 2007; 2:418.

13. Ostermann, M, Chang, RW. Acute kidney injury in the intensive care unit according toRIFLE. Crit Care Med 2007; 35:1837.

14. Ricci, Z, Cruz, D, Ronco, C. The RIFLE criteria and mortality in acute kidney injury: Asystematic review. Kidney Int 2008; 73:538.

15. Chertow, GM, Burdick, E, Honour, M, et al. Acute kidney injury, mortality, length of stay,and costs in hospitalized patients. J Am Soc Nephrol 2005; 16:3365.

16. Lassnigg, A, Schmidlin, D, Mouhieddine, M, et al. Minimal changes of serum creatininepredict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am

Soc Nephrol 2004; 15:1597.

17. Levy, MM, Macias, WL, Vincent, JL, et al. Early changes in organ function predict eventual

survival in severe sepsis. Crit Care Med 2005; 33:2194.

18. Bagshaw, SM, George, C, Bellomo, R, ANZICS Database Management, Committe. Acomparison of the RIFLE and AKIN criteria for acute kidney injury in c ritically ill patients.

Nephrol Dial Transplant 2008; 23:1569.




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GRAPHICS

Proposed classification scheme for acute renal failure

The classification system includes separate criteria for creatinine andurine output. The criteria that leads to the worst classification should beused. Note that RIFLE-F is present even if the increase in SCrt is


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Classification/staging system for acute kidney injury*

Stage Serum creatinine criteriaUrine output

criteria

1 Increase in serum creatinine of more than or equal to 0.3mg/dL (26.4 mircomol/L) or increase to more than or equalto 150 to 200 percent (1.5- to 2-fold) from baseline

Less than 0.5mL/kg per hourfor more than 6hours

2 Increase in serum creatinine to more than 200 to 300percent (>2- to 3-fold) from baseline

Less than 0.5mL/kg per hourfor more than 12hours

3 Increase in serum creatinine to more than 300 percent (>3-fold) from baseline (or serum creatinine of more than orequal to 4.0 mg/dL [354 micromol/L] with an acuteincrease of at least 0.5 mg/dL [44 micromol/L])

Less than 0.3mL/kg per hourfor 24 hours oranuria for 12hours

* Modified from RIFLE (Risk, Injury, Failure, Loss , and End-stage kidney disease) criteria. The

staging system proposed is a highly sensitive interim staging system and is based on recentdata indicating that a small change in serum creatinine influences outcome. The diagnostic

criteria should only be applied after volume status has been optimized. Only one criterion

(creatinine or urine output) has to be fulfilled to qualify for a stage.

200 to 300 percent increase = 2- to 3-fold increase.

Given wide variation in indications and timing of initiation of renal replacement therapy (RRT),

individuals who receive RRT are considered to have met the criteria for stage 3 irrespective o f

the stage they are in at the time of RRT.Reproduced with permission from: Mehta, RL, Kellum,JA, Shah, SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in

acute kidney injury. Crit Care 2007; 11:R31. Copyright 2007 BioMed Central Ltd.




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