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Definition of acute kidney injury (acut

Offic ial reprint from UpToDate

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2010 UpToDate

Definition of acute kidney injury (acute renal failure)

Author
Paul M Palevsky, MD

Section Editor
Gary C Curhan, MD, ScD

Last literature review version 18.3: Setembro 2010 |

2008

Deputy Editor
Alic e M Sheridan, MD
This topic last updated: Outubro 28,

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 extrac ellular volume and electrolytes. The loss of kidney function is most
easily detec ted 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 c reatinine to quantitatively define ARF:
Serum c reatinine 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 func tion: 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 onc e dialysis is initiated. One exception is when the
serum creatinine continues to fall on days when hemodialysis is not performed, indicating
rec overy 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 clinic al
research since it confounds comparisons between studies. Some definitions employed in c linical
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-ac quired 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 serum
creatinine 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 Ac ute 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 ac ute renal failure [3]. Rec ognizing the need for a uniform definition for ARF, the
ADQI group proposed a c onsensus graded definition, called the RIFLE criteria [4]. A modification
of the RIFLE criteria was subsequently proposed by the Ac ute Kidney Injury Network, which
included the ADQI group as well as representatives from other nephrology and intensive care
societies [5-7].
Bec ause of these initiatives, the term acute kidney injury (AKI) was proposed to represent the
entire spec trum of acute renal failure. This topic review will address the c urrent 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 c reatinine 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 dec rease by 25 perc ent or urine
output <0.5 mL/kg per hour for six hours
Injury Twofold increase in the serum creatinine or GFR decrease by 50 percent or urine
output <0.5 mL/kg per hour for 12 hours
Failure Threefold increase in the serum creatinine or GFR decrease by 75 percent or urine
output of <0.5 mL/kg per hour for 24 hours, or anuria for 12 hours
Loss Complete loss of kidney function (eg, need for renal replac ement therapy) for more
than four weeks
ESRD Complete loss of kidney function (eg, need for renal replacement therapy) for more
than three months (figure 1)
The RIFLE criteria c orrelated with prognosis in a number of studies [8-14]. As an example, a
systematic review of 13 studies demonstrated a stepwise increase in the relative risk of death in
patients who met the RIFLE criteria for various stages of AKI [14]. Compared to patients who did
not have AKI, patients in the RIFLE stages of "risk," "injury," and "failure" had increased relative
mortality risks of 2.4 (CI 1.94-2.97), 4.15 (CI 3.14-5.48), and 6.37 (CI 5.14-7.9). Despite
significant heterogeneity among studies, results from most individual reports were qualitatively
similar.
Limitations There are several important shortcomings to the RIFLE criteria:
The "risk," "injury," and "failure" strata are defined by either changes in serum creatinine or
urine output. The assignment of the corresponding changes in serum c reatinine and changes in
urine output to the same strata are NOT based on evidence. In the one assessment of the RIFLE
classification that compared the serum creatinine and urine output criteria, the serum creatinine
criteria were strong predictors of ICU mortality, whereas the urine output criteria did not
independently predict mortality [12]. Thus, if the RIFLE classification is used to stratify risk, it is
important that the c riteria that result in the least favorable RIFLE strata be used [4].
As mentioned above, the change in serum creatinine during acute renal failure does not
directly c orrelate with the actual change in glomerular filtration rate, which alters the
assignment of that patient to a particular RIFLE level. As an example, in a patient with an abrupt
dec line in renal func tion in the setting of severe ARF, the serum creatinine might rise from 1.0 to
1.5 mg/dL (88.4 to 133 micromol/L) on day one, 2.5 mg/dL (221 mic romol/L) on day two, and 3.5
mg/dL (309 micromol/L) on day three. Acc ording to the RIFLE criteria, the patient would progress
from "risk" on day one to "injury" on day two and "failure" on day three, even though the actual
GFR has been <10 mL/min over the entire period. This issue is intrinsic to any assessment of
acute renal failure based upon the serum creatinine level.
It is impossible to calc ulate the change in serum creatinine in patients who present with ARF
but without a baseline measurement of serum c reatinine. The authors of the RIFLE c riteria
suggest back-calculating an estimated baseline serum creatinine concentration using the fourvariable MDRD equation, assuming a baseline GFR of 75 mL/min per 1.73 m2 [4]. However, this
approac h has not been prospec tively validated.
AKIN CRITERIA Given these limitations, a modification of the RIFLE c riteria has been proposed
by the Ac ute Kidney Injury Network. The AKIN proposed both diagnostic criteria for ARF and a
staging system that was based on the RIFLE c riteria [5-7]. In addition, the term ac ute kidney
injury (AKI) was proposed to represent the entire spec trum of acute renal failure.
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Diagnostic criteria The proposed diagnostic criteria for ARF are an abrupt (within 48 hours)
absolute inc rease in the serum c reatinine conc entration of 0.3 mg/dL (26.4 mic romol/L) from
baseline, a percentage increase in the serum creatinine c onc entration of 50 perc ent, 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 inc rease 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 48
hours is based upon data that showed that poorer outcomes were associated with small c hanges
in the creatinine when the rise in creatinine was observed within 24 to 48 hours [16,17].
Two additional c aveats were proposed by the AKIN group:
The diagnostic c riteria 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, acc ording to the current definition, AKI would still be used to
describe the patient with acute urinary tract obstruction and an ac ute 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 c lassification or staging system for ARF is c omprised 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
outc omes.
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 c linical trials.
Ultimately these definitions are likely to be replaced by more sensitive and spec ific biomarkers of
renal injury.
CLINICAL UTILITY The RIFLE and AKIN criteria have helped to focus attention that
dec rements in renal function that result in small changes in serum creatinine c onc entration are
associated with signific ant c linical consequences. However, the precise c linical 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 c riteria have greatest utility in epidemiologic studies and in defining
consistent inclusion criteria and/or endpoints for c linical studies. Their utility at the bedside is
less clear and it seems likely that they will eventually be replac ed at least in part by sensitive
and specific 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 ac ute renal failure is highly appropriate. Just as ac ute 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 ac ute 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 elec trolytes. (See 'Introduction' above.)

Although the loss of kidney function is most easily detec ted by measurement of the serum
creatinine, several problems are assoc iated with the use of this measure to quantitatively define
ARF, particularly the lack of consensus in the quantitative definition. (See 'Introduc tion' above.)
The Acute Dialysis Quality Initiative (ADQI) has proposed a graded definition of ARF c alled
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 correc tion of
volume status and obstruc tive causes of ARF prior to classific ation. (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 c oncentration 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 c riteria 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 'Clinic al utility' above.)

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REFERENCES
1. Mehta, RL, Chertow, GM. Acute renal failure definitions and classific ation: time for change?
J Am Soc Nephrol 2003; 14:2178.
2. Hou, SH, Bushinsky, DA, Wish, JB, et al. Hospital-acquired renal insufficiency: a prospective
study. Am J Med 1983; 74:243.
3. Ronco, C, Kellum, JA, Mehta, R. Ac ute dialysis quality initiative (ADQI). Nephrol Dial
Transplant 2001; 16:1555.
4. Bellomo, R, Ronco, C, Kellum, JA, et al. Acute renal failure - definition, outc ome measures,
animal models, fluid therapy and information technology needs: the Sec ond International
Consensus Conferenc e 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, Warnoc k, DG, Mehta, RL, et al. Improving outc omes from acute kidney injury:
report of an initiative. Am J Kidney Dis 2007; 50:1.
7. Molitoris, BA, Levin, A, Warnoc k, DG, et al. Improving outc omes from acute kidney injury. J
Am Soc Nephrol 2007; 18:1992.
8. Ali, T, Khan, I, Simpson, W, et al. Inc idenc e 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 ac ute
renal 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 are
associated with hospital mortality in c ritically ill patients: a cohort analysis. Crit Care 2006;
10:R73.
11. Kuitunen, A, Vento, A, Suojaranta-Ylinen, R, Pettil, V. Ac ute 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. Ac ute kidney injury in the intensive care unit ac cording to
RIFLE. Crit Care Med 2007; 35:1837.
14. Ricc i, Z, Cruz, D, Ronco, C. The RIFLE criteria and mortality in ac ute kidney injury: A
systematic 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 c reatinine
predict 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. A
comparison of the RIFLE and AKIN criteria for ac ute 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 and

urine output. The criteria that leads to the worst classification should be
used. Note that RIFLE-F is present even if the increase in SCrt is <3
fold so long as the new SCrt is 4.0 mg/dL (350 mcmol/L) in the
setting of an acute increase of at least 0.5 mg/dL (44 mcmol/L). The
designation RIFLE-FC should be used in this case to denote "acute-onchronic" disease. Similarly when RIFLE-F classification is reached by urine
output criteria, a designation of RIFLE-FO should be used to denote
oliguria. The shape the figure denotes the fact that more patients (high
sensitivity) will be included in the mild category, including some without
actually having renal failure (less specificity). In contrast, at the bottom,
the criteria are strict and therefore specific, but some patients will be
missed. Reproduced with permission from: 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:B204. Copyright
2004 BioMed Central Ltd.

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Classification/staging system for acute kidney injury*

Stage

Serum creatinine criteria

Urine output
criteria

Increase in serum creatinine of more than or equal to 0.3

mg/dL (26.4 mircomol/L) or increase to more than or equal
to 150 to 200 percent (1.5- to 2-fold) from baseline

Less than 0.5

mL/kg per hour
for more than 6
hours

Increase in serum creatinine to more than 200 to 300

percent (>2- to 3-fold) from baseline

Less than 0.5

mL/kg per hour
for more than 12
hours

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

Less than 0.3

mL/kg per hour
for 24 hours or
anuria for 12
hours

* 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 recent
data 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 w ide 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 of
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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