RIFLE and AKIN classifications for acute kidney injury: a critical and comprehensive review
Mục Lục
Abstract
In May 2004, a new classification, the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification, was proposed in order to define and stratify the severity of acute kidney injury (AKI). This system relies on changes in the serum creatinine (SCr) or glomerular filtration rates and/or urine output, and it has been largely demonstrated that the RIFLE criteria allows the identification of a significant proportion of AKI patients hospitalized in numerous settings, enables monitoring of AKI severity, and is a good predictor of patient outcome. Three years later (March 2007), the Acute Kidney Injury Network (AKIN) classification, a modified version of the RIFLE, was released in order to increase the sensitivity and specificity of AKI diagnosis. Until now, the benefit of these modifications for clinical practice has not been clearly demonstrated.
Here we provide a critical and comprehensive discussion of the two classifications for AKI, focusing on the main differences, advantages and limitations.
Introduction
Over the last few decades, more than 35 different definitions have been used to define acute kidney injury (AKI) [1]. Many of those definitions were complex; however, the more commonly used were based on urine output (UO) and/or serum creatinine (SCr) criteria. An increase in basal SCr of at least 44.2 μmol/L (0.5 mg/dL), a decrease in Cr clearance of at least 50% or the need for renal replacement therapy (RRT) were the most frequent definitions used for AKI in clinical practice [2]. Where UO has been used to define AKI, it is generally considered that a value less than 400–500 mL/day could be an indicator.
Multiple definitions for AKI have obviously led to a great disparity in the reported incidence of AKI making it difficult or even impossible to compare the various published studies focusing on AKI [3–7]. Therefore, it became crucial to establish a consensual and accurate definition of AKI that could ideally be used worldwide.
The RIFLE classification
In May 2002, the Acute Dialysis Quality Initiative (ADQI) group for the study of AKI, composed of nephrologists and intensivists, came together over 2 days in a conference in Vicenza (Italy), with the purpose of defining AKI. From this conference, the consensual RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification for AKI definition emerged, which was published in May 2004 in Critical Care [8].
The ADQI group considered that the ideal AKI definition would have to accomplish the following criteria: easy clinical applicability, sensitivity and specificity, consider baseline SCr variations and also consider the ‘acute-on-chronic’ phenomenon (which means the occurrence of an acute insult over a chronically injured renal function causing its deterioration). This definition should classify AKI according to its severity (mild versus severe) and its timing of occurrence (precocious versus late AKI). By fulfilling these criteria, this classification should allow the detection of patients whose kidney function was slightly affected (high sensitivity but low specificity) as well as patients with severe kidney function deterioration (high specificity with diminishing sensitivity).
The RIFLE classification (Table 1) is based on SCr and UO determinants, and considers three severity classes of AKI (Risk, Injury and Failure), according to the variations in SCr and/or UO, and two outcome classes (loss of kidney function and end-stage kidney disease). The patient should be classified using the criteria (SCr and/or UO) which leads to the worst classification (maximum RIFLE), for instance, if a patient was in the Risk class according to the UO but in the Injury class according to SCr variation, then the worst criteria (SCr) should be used for classifying the severity of AKI in this patient.
Table 1.
Class
.
GFR
.
UO
.
Risk ↑ SCr × 1.5 or ↓ GFR >25% <0.5 mL/kg/h × 6 h Injury ↑ SCr × 2 or ↓ GFR >50% <0.5 mL/kg/h × 12 h Failure ↑ SCr × 3 or ↓ GFR >75% or if baseline SCr ≥353.6 μmol/L(≥4 mg/dL) ↑ SCr >44.2 μmol/L(>0.5 mg/dL) <0.3 mL/kg/h × 24 h or anuria × 12 h Loss of kidney function Complete loss of kidney function >4 weeks End-stage kidney disease Complete loss of kidney function >3 months Class
.
GFR
.
UO
.
Risk ↑ SCr × 1.5 or ↓ GFR >25% <0.5 mL/kg/h × 6 h Injury ↑ SCr × 2 or ↓ GFR >50% <0.5 mL/kg/h × 12 h Failure ↑ SCr × 3 or ↓ GFR >75% or if baseline SCr ≥353.6 μmol/L(≥4 mg/dL) ↑ SCr >44.2 μmol/L(>0.5 mg/dL) <0.3 mL/kg/h × 24 h or anuria × 12 h Loss of kidney function Complete loss of kidney function >4 weeks End-stage kidney disease Complete loss of kidney function >3 months
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Table 1.
Class
.
GFR
.
UO
.
Risk ↑ SCr × 1.5 or ↓ GFR >25% <0.5 mL/kg/h × 6 h Injury ↑ SCr × 2 or ↓ GFR >50% <0.5 mL/kg/h × 12 h Failure ↑ SCr × 3 or ↓ GFR >75% or if baseline SCr ≥353.6 μmol/L(≥4 mg/dL) ↑ SCr >44.2 μmol/L(>0.5 mg/dL) <0.3 mL/kg/h × 24 h or anuria × 12 h Loss of kidney function Complete loss of kidney function >4 weeks End-stage kidney disease Complete loss of kidney function >3 months Class
.
GFR
.
UO
.
Risk ↑ SCr × 1.5 or ↓ GFR >25% <0.5 mL/kg/h × 6 h Injury ↑ SCr × 2 or ↓ GFR >50% <0.5 mL/kg/h × 12 h Failure ↑ SCr × 3 or ↓ GFR >75% or if baseline SCr ≥353.6 μmol/L(≥4 mg/dL) ↑ SCr >44.2 μmol/L(>0.5 mg/dL) <0.3 mL/kg/h × 24 h or anuria × 12 h Loss of kidney function Complete loss of kidney function >4 weeks End-stage kidney disease Complete loss of kidney function >3 months
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The temporal pattern of the SCr and/or UO variation is also relevant for defining AKI: the deterioration of renal function must be sudden (1–7 days) and sustained (persisting >24 h).
This definition can easily be applied when the baseline SCr is known; however, in a significant number of patients baseline SCr is unknown; in these cases, if there is no history of chronic kidney disease (CKD), baseline SCr should be calculated using the Modification of Diet in Renal Disease (MDRD) [9] equation, assuming a baseline glomerular filtration rate (GFR) of 75 mL/min/1.73m2.
Strengths and limitations of the RIFLE classification
Strengths of the RIFLE classification
RIFLE has been largely validated in terms of determining the incidence of AKI and its prognostic stratification in several settings of hospitalized patients [10–26].
In these studies, RIFLE facilitated the identification of a large proportion of AKI patients and there was an independent and stepwise increase in mortality as AKI severity increased; RIFLE also exhibited a good prognostic accuracy in terms of mortality (Table 2). Furthermore, it has been shown that the RIFLE enables monitoring of the progression of AKI severity during hospitalization and RIFLE classes are strongly associated with increased lengths of stay, RRT requirement, renal function recovery and discharge from hospital to a care facility [11–14, 26].
Table 2.
Setting
.
N
.
Design
.
Criteria
.
Incidence (%)
.
Mortality (%/relative risk)
.
AUROC
.
Hospital Uchino et al. [
10] 20.126 Retrospective, single-centre Cr, GFR
No AKI (82)
R (9)
I (5)
F (4) Hospital mortality
No AKI (4.4)
R (15.1/2.5)
I (29.2/5.4)
F (41.1/10.1) NS ICU Hoste et al. [
11] 5.383 Retrospective, multi-centre Cr, UO
No AKI (33)
R (28)
I (27)
F (12) Hospital mortality
No AKI (5.5)
R (8.8/1.0)
I (11.4/1.4)
F (26.3/2.7) NS Ostermann and Chang [
12] 41.972 Retrospective, multi-centre GFR
No AKI (64)
R (17)
I (11)
F (8) Hospital mortality
No AKI (8.4)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) 0.897 Cruz et al. [
13] 2.164 Prospective, multi-centre Cr, UO
No AKI (89)
R (2)
I (4)
F (5) ICU mortality
No AKI (NS)
R (20/1.0)
I (29/2.2)b
F (48.5/4.9)b NS Bagshaw et al. [
14] 120.123 Retrospective, multi-centre Cr, UO
No AKI (64)
R (16)
I (14)
F (6) Hospital mortality
No AKI (8.9)
R (17.9 /1.6)
I (27.7 /2.5)
F (33.2/3.2) 0.810 Cardiac surgery Heringlake et al. [
15] 29.623 Prospective, multi-centre Cr
No AKI (84)
R (9)
I (5)
F (2) Hospital mortality
No AKI (NS)
R (NS)
I (NS)
F (NS) NS Kuitunen et al. [
16] 813 Prospective, single-centre Cr, UO
No AKI (81)
R (11)
I (3)
F (5) 90-day mortality
No AKI (0.9)
R (8.0/NS)
I (21.4/NS)
F (32.5/NS) 0.824 Lin et al. [
17] 46 Retrospective, single-centre Cr, UO
No AKI (22)
R (15)
I (39)
F (24) Hospital mortality
No AKI (25)
R (57/5.3)
I (72/10.4)
F (100/Infinity) 0.868 Aortic arch surgery Arnaoutakis et al. [
18] 267 Retrospective, single-centre Cr, GFR
No AKI (52)
R (20)
I (12)
F (16) 30-day mortality
No AKI (3)
R (9/NS)
I (12/NS)
F (38/NS) NS Cirrhosis Jenq et al. [
19] 134 Prospective, single-centre Cr, UO
No AKI (40)
R (12)
I (5)
F (43) Hospital mortality
No AKI (32.1)
R (68.8/4.7)
I (71.4/5.3)
F (94/38.8) 0.837 Liver Transplantation O’Riordan et al. [
20] 94 Retrospective, single-centre 359
No AKI (NS)
R (NS)
I (11.1)
F (25.7) 30-day mortality
No AKI (NS)
R (NS)
I (8.8/NS)
F (23.7/2.8) NS 1-year mortality
No AKI (NS)
R (NS)
I (23.5/NS)
F (52.5/2.6) NS Sepsis Lopes et al. [
21] 182 Retrospective, single-centre NS
No AKI (62)
R (6)
I (12)
F (20) 60-day mortality
No AKI (9.6)
R (27.3/NS)
I (28.6/NS)
F (55/3.6) 0.750 Chen et al. [
22] 121 Retrospective, single-centre Cr
No AKI (44)
R (26)
I (16)
F (20) Hospital mortality
No AKI (34)
R (40.0/1.3)
I (73.7/5.4)
F (76.5/6.3) 0.678 Burn Lopes et al. [
23] 126 Retrospective, single-centre NS
No AKI (64)
R (14)
I (9)
F (13) Hospital mortality
No AKI (6)
R (11.1/5.6)
I (63.6/6.2)
F (75/NS) 0.834 HIV Lopes et al. [
24] 97 Retrospective, single-centre NS
No AKI (53)
R (12)
I (9)
F (26) 60-day mortality
No AKI (23.5)
R (50/NS)
I (66.6/5.1)
F (72/4.6) 0.732 Trauma Bagshaw et al. [
25] 9449 Retrospective, multi-centre Cr, UO
No AKI (81.9)
R (9.4)
I (7.2)
F (1.5) Hospital mortality
No AKI (7.8)
R (16/1.7)
I (15.9/1.9)
F (24.7/2.3) NS HCT Lopes et al. [
26] 82 Retrospective, single-centre Cr, GFR
No AKI (46)
R (13)
I (24)
F (17) 5-year mortality
No AKI (32.9)
R (44.4/1.62)
I + F (66.7/1.64) NS Setting
.
N
.
Design
.
Criteria
.
Incidence (%)
.
Mortality (%/relative risk)
.
AUROC
.
Hospital Uchino et al. [
10] 20.126 Retrospective, single-centre Cr, GFR
No AKI (82)
R (9)
I (5)
F (4) Hospital mortality
No AKI (4.4)
R (15.1/2.5)
I (29.2/5.4)
F (41.1/10.1) NS ICU Hoste et al. [
11] 5.383 Retrospective, multi-centre Cr, UO
No AKI (33)
R (28)
I (27)
F (12) Hospital mortality
No AKI (5.5)
R (8.8/1.0)
I (11.4/1.4)
F (26.3/2.7) NS Ostermann and Chang [
12] 41.972 Retrospective, multi-centre GFR
No AKI (64)
R (17)
I (11)
F (8) Hospital mortality
No AKI (8.4)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) 0.897 Cruz et al. [
13] 2.164 Prospective, multi-centre Cr, UO
No AKI (89)
R (2)
I (4)
F (5) ICU mortality
No AKI (NS)
R (20/1.0)
I (29/2.2)b
F (48.5/4.9)b NS Bagshaw et al. [
14] 120.123 Retrospective, multi-centre Cr, UO
No AKI (64)
R (16)
I (14)
F (6) Hospital mortality
No AKI (8.9)
R (17.9 /1.6)
I (27.7 /2.5)
F (33.2/3.2) 0.810 Cardiac surgery Heringlake et al. [
15] 29.623 Prospective, multi-centre Cr
No AKI (84)
R (9)
I (5)
F (2) Hospital mortality
No AKI (NS)
R (NS)
I (NS)
F (NS) NS Kuitunen et al. [
16] 813 Prospective, single-centre Cr, UO
No AKI (81)
R (11)
I (3)
F (5) 90-day mortality
No AKI (0.9)
R (8.0/NS)
I (21.4/NS)
F (32.5/NS) 0.824 Lin et al. [
17] 46 Retrospective, single-centre Cr, UO
No AKI (22)
R (15)
I (39)
F (24) Hospital mortality
No AKI (25)
R (57/5.3)
I (72/10.4)
F (100/Infinity) 0.868 Aortic arch surgery Arnaoutakis et al. [
18] 267 Retrospective, single-centre Cr, GFR
No AKI (52)
R (20)
I (12)
F (16) 30-day mortality
No AKI (3)
R (9/NS)
I (12/NS)
F (38/NS) NS Cirrhosis Jenq et al. [
19] 134 Prospective, single-centre Cr, UO
No AKI (40)
R (12)
I (5)
F (43) Hospital mortality
No AKI (32.1)
R (68.8/4.7)
I (71.4/5.3)
F (94/38.8) 0.837 Liver Transplantation O’Riordan et al. [
20] 94 Retrospective, single-centre 359
No AKI (NS)
R (NS)
I (11.1)
F (25.7) 30-day mortality
No AKI (NS)
R (NS)
I (8.8/NS)
F (23.7/2.8) NS 1-year mortality
No AKI (NS)
R (NS)
I (23.5/NS)
F (52.5/2.6) NS Sepsis Lopes et al. [
21] 182 Retrospective, single-centre NS
No AKI (62)
R (6)
I (12)
F (20) 60-day mortality
No AKI (9.6)
R (27.3/NS)
I (28.6/NS)
F (55/3.6) 0.750 Chen et al. [
22] 121 Retrospective, single-centre Cr
No AKI (44)
R (26)
I (16)
F (20) Hospital mortality
No AKI (34)
R (40.0/1.3)
I (73.7/5.4)
F (76.5/6.3) 0.678 Burn Lopes et al. [
23] 126 Retrospective, single-centre NS
No AKI (64)
R (14)
I (9)
F (13) Hospital mortality
No AKI (6)
R (11.1/5.6)
I (63.6/6.2)
F (75/NS) 0.834 HIV Lopes et al. [
24] 97 Retrospective, single-centre NS
No AKI (53)
R (12)
I (9)
F (26) 60-day mortality
No AKI (23.5)
R (50/NS)
I (66.6/5.1)
F (72/4.6) 0.732 Trauma Bagshaw et al. [
25] 9449 Retrospective, multi-centre Cr, UO
No AKI (81.9)
R (9.4)
I (7.2)
F (1.5) Hospital mortality
No AKI (7.8)
R (16/1.7)
I (15.9/1.9)
F (24.7/2.3) NS HCT Lopes et al. [
26] 82 Retrospective, single-centre Cr, GFR
No AKI (46)
R (13)
I (24)
F (17) 5-year mortality
No AKI (32.9)
R (44.4/1.62)
I + F (66.7/1.64) NS
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Table 2.
Setting
.
N
.
Design
.
Criteria
.
Incidence (%)
.
Mortality (%/relative risk)
.
AUROC
.
Hospital Uchino et al. [
10] 20.126 Retrospective, single-centre Cr, GFR
No AKI (82)
R (9)
I (5)
F (4) Hospital mortality
No AKI (4.4)
R (15.1/2.5)
I (29.2/5.4)
F (41.1/10.1) NS ICU Hoste et al. [
11] 5.383 Retrospective, multi-centre Cr, UO
No AKI (33)
R (28)
I (27)
F (12) Hospital mortality
No AKI (5.5)
R (8.8/1.0)
I (11.4/1.4)
F (26.3/2.7) NS Ostermann and Chang [
12] 41.972 Retrospective, multi-centre GFR
No AKI (64)
R (17)
I (11)
F (8) Hospital mortality
No AKI (8.4)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) 0.897 Cruz et al. [
13] 2.164 Prospective, multi-centre Cr, UO
No AKI (89)
R (2)
I (4)
F (5) ICU mortality
No AKI (NS)
R (20/1.0)
I (29/2.2)b
F (48.5/4.9)b NS Bagshaw et al. [
14] 120.123 Retrospective, multi-centre Cr, UO
No AKI (64)
R (16)
I (14)
F (6) Hospital mortality
No AKI (8.9)
R (17.9 /1.6)
I (27.7 /2.5)
F (33.2/3.2) 0.810 Cardiac surgery Heringlake et al. [
15] 29.623 Prospective, multi-centre Cr
No AKI (84)
R (9)
I (5)
F (2) Hospital mortality
No AKI (NS)
R (NS)
I (NS)
F (NS) NS Kuitunen et al. [
16] 813 Prospective, single-centre Cr, UO
No AKI (81)
R (11)
I (3)
F (5) 90-day mortality
No AKI (0.9)
R (8.0/NS)
I (21.4/NS)
F (32.5/NS) 0.824 Lin et al. [
17] 46 Retrospective, single-centre Cr, UO
No AKI (22)
R (15)
I (39)
F (24) Hospital mortality
No AKI (25)
R (57/5.3)
I (72/10.4)
F (100/Infinity) 0.868 Aortic arch surgery Arnaoutakis et al. [
18] 267 Retrospective, single-centre Cr, GFR
No AKI (52)
R (20)
I (12)
F (16) 30-day mortality
No AKI (3)
R (9/NS)
I (12/NS)
F (38/NS) NS Cirrhosis Jenq et al. [
19] 134 Prospective, single-centre Cr, UO
No AKI (40)
R (12)
I (5)
F (43) Hospital mortality
No AKI (32.1)
R (68.8/4.7)
I (71.4/5.3)
F (94/38.8) 0.837 Liver Transplantation O’Riordan et al. [
20] 94 Retrospective, single-centre 359
No AKI (NS)
R (NS)
I (11.1)
F (25.7) 30-day mortality
No AKI (NS)
R (NS)
I (8.8/NS)
F (23.7/2.8) NS 1-year mortality
No AKI (NS)
R (NS)
I (23.5/NS)
F (52.5/2.6) NS Sepsis Lopes et al. [
21] 182 Retrospective, single-centre NS
No AKI (62)
R (6)
I (12)
F (20) 60-day mortality
No AKI (9.6)
R (27.3/NS)
I (28.6/NS)
F (55/3.6) 0.750 Chen et al. [
22] 121 Retrospective, single-centre Cr
No AKI (44)
R (26)
I (16)
F (20) Hospital mortality
No AKI (34)
R (40.0/1.3)
I (73.7/5.4)
F (76.5/6.3) 0.678 Burn Lopes et al. [
23] 126 Retrospective, single-centre NS
No AKI (64)
R (14)
I (9)
F (13) Hospital mortality
No AKI (6)
R (11.1/5.6)
I (63.6/6.2)
F (75/NS) 0.834 HIV Lopes et al. [
24] 97 Retrospective, single-centre NS
No AKI (53)
R (12)
I (9)
F (26) 60-day mortality
No AKI (23.5)
R (50/NS)
I (66.6/5.1)
F (72/4.6) 0.732 Trauma Bagshaw et al. [
25] 9449 Retrospective, multi-centre Cr, UO
No AKI (81.9)
R (9.4)
I (7.2)
F (1.5) Hospital mortality
No AKI (7.8)
R (16/1.7)
I (15.9/1.9)
F (24.7/2.3) NS HCT Lopes et al. [
26] 82 Retrospective, single-centre Cr, GFR
No AKI (46)
R (13)
I (24)
F (17) 5-year mortality
No AKI (32.9)
R (44.4/1.62)
I + F (66.7/1.64) NS Setting
.
N
.
Design
.
Criteria
.
Incidence (%)
.
Mortality (%/relative risk)
.
AUROC
.
Hospital Uchino et al. [
10] 20.126 Retrospective, single-centre Cr, GFR
No AKI (82)
R (9)
I (5)
F (4) Hospital mortality
No AKI (4.4)
R (15.1/2.5)
I (29.2/5.4)
F (41.1/10.1) NS ICU Hoste et al. [
11] 5.383 Retrospective, multi-centre Cr, UO
No AKI (33)
R (28)
I (27)
F (12) Hospital mortality
No AKI (5.5)
R (8.8/1.0)
I (11.4/1.4)
F (26.3/2.7) NS Ostermann and Chang [
12] 41.972 Retrospective, multi-centre GFR
No AKI (64)
R (17)
I (11)
F (8) Hospital mortality
No AKI (8.4)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) 0.897 Cruz et al. [
13] 2.164 Prospective, multi-centre Cr, UO
No AKI (89)
R (2)
I (4)
F (5) ICU mortality
No AKI (NS)
R (20/1.0)
I (29/2.2)b
F (48.5/4.9)b NS Bagshaw et al. [
14] 120.123 Retrospective, multi-centre Cr, UO
No AKI (64)
R (16)
I (14)
F (6) Hospital mortality
No AKI (8.9)
R (17.9 /1.6)
I (27.7 /2.5)
F (33.2/3.2) 0.810 Cardiac surgery Heringlake et al. [
15] 29.623 Prospective, multi-centre Cr
No AKI (84)
R (9)
I (5)
F (2) Hospital mortality
No AKI (NS)
R (NS)
I (NS)
F (NS) NS Kuitunen et al. [
16] 813 Prospective, single-centre Cr, UO
No AKI (81)
R (11)
I (3)
F (5) 90-day mortality
No AKI (0.9)
R (8.0/NS)
I (21.4/NS)
F (32.5/NS) 0.824 Lin et al. [
17] 46 Retrospective, single-centre Cr, UO
No AKI (22)
R (15)
I (39)
F (24) Hospital mortality
No AKI (25)
R (57/5.3)
I (72/10.4)
F (100/Infinity) 0.868 Aortic arch surgery Arnaoutakis et al. [
18] 267 Retrospective, single-centre Cr, GFR
No AKI (52)
R (20)
I (12)
F (16) 30-day mortality
No AKI (3)
R (9/NS)
I (12/NS)
F (38/NS) NS Cirrhosis Jenq et al. [
19] 134 Prospective, single-centre Cr, UO
No AKI (40)
R (12)
I (5)
F (43) Hospital mortality
No AKI (32.1)
R (68.8/4.7)
I (71.4/5.3)
F (94/38.8) 0.837 Liver Transplantation O’Riordan et al. [
20] 94 Retrospective, single-centre 359
No AKI (NS)
R (NS)
I (11.1)
F (25.7) 30-day mortality
No AKI (NS)
R (NS)
I (8.8/NS)
F (23.7/2.8) NS 1-year mortality
No AKI (NS)
R (NS)
I (23.5/NS)
F (52.5/2.6) NS Sepsis Lopes et al. [
21] 182 Retrospective, single-centre NS
No AKI (62)
R (6)
I (12)
F (20) 60-day mortality
No AKI (9.6)
R (27.3/NS)
I (28.6/NS)
F (55/3.6) 0.750 Chen et al. [
22] 121 Retrospective, single-centre Cr
No AKI (44)
R (26)
I (16)
F (20) Hospital mortality
No AKI (34)
R (40.0/1.3)
I (73.7/5.4)
F (76.5/6.3) 0.678 Burn Lopes et al. [
23] 126 Retrospective, single-centre NS
No AKI (64)
R (14)
I (9)
F (13) Hospital mortality
No AKI (6)
R (11.1/5.6)
I (63.6/6.2)
F (75/NS) 0.834 HIV Lopes et al. [
24] 97 Retrospective, single-centre NS
No AKI (53)
R (12)
I (9)
F (26) 60-day mortality
No AKI (23.5)
R (50/NS)
I (66.6/5.1)
F (72/4.6) 0.732 Trauma Bagshaw et al. [
25] 9449 Retrospective, multi-centre Cr, UO
No AKI (81.9)
R (9.4)
I (7.2)
F (1.5) Hospital mortality
No AKI (7.8)
R (16/1.7)
I (15.9/1.9)
F (24.7/2.3) NS HCT Lopes et al. [
26] 82 Retrospective, single-centre Cr, GFR
No AKI (46)
R (13)
I (24)
F (17) 5-year mortality
No AKI (32.9)
R (44.4/1.62)
I + F (66.7/1.64) NS
Open in new tab
Originally, the RIFLE criteria was established to standardize the definition and stratification of AKI severity. Several studies, however, have determined the ability of the RIFLE in predicting mortality using the area under the receiver operating characteristic (AUROC) curve, and some of them have inclusively compared it with other general or specific scoring systems [16, 17, 21, 23, 24, 27, 28]. Taking into account that the RIFLE relies only on renal function it would be conceivable that the RIFLE prognostic capacity was inferior to that of other general scores (i.e. Acute Physiology and Chronic Health Evaluation, Simplified Acute Pathophysiology Score). However, RIFLE has proven to be an important tool in predicting patient outcome and, furthermore, seems to have increased the prognostic ability of those general scores usually employed in the intensive care unit (ICU).
Limitations of the RIFLE classification
Despite its clinical use, the RIFLE classification has a number of important limitations. First, baseline SCr is necessary to define and classify AKI; this baseline value is frequently unknown in clinical practice. In this situation, the ADQI work group [8] propose estimating the baseline SCr using the MDRD equation [9], assuming a baseline GFR of 75 mL/min/1.73m2. In CKD patients, baseline SCr determined assuming a GFR of 75 mL/min/1.73m2 has a low correlation with the real value of SCr and results in an overestimation of AKI incidence [29]. Second, the MDRD formula has been validated in CKD patients with stable renal function, not in AKI patients. Third, in several of the studies previously mentioned, only SCr was used to define and stage AKI [12, 15, 20]. In CKD patients, compared with patients with previously normal renal function, the percentage increase in SCr used to define AKI generally occurs later and, thus, defining AKI using only the SCr criteria could diminish the sensitivity of AKI diagnosis in CKD patients [30]. Moreover, determination of renal function using SCr has several other limitations as listed below:
Fourth, decrease in the UO is sensitive and frequent in AKI; however, it also has some important limitations in defining and staging AKI [33]:
Fifth, the aetiology of AKI and the requirement for RRT are not considered in the RIFLE classification. In two studies that evaluated ICU patients with AKI requiring continuous RRT, the RIFLE classification showed less acuity in predicting mortality [35, 36]. One possible explanation for this phenomenon is that in both the studies, the clinical severity of patients was so high that it could not allow RIFLE to discriminate mortality according to AKI severity (i.e. between the three classes).
-
The endogenous production and serum release of Cr are variable, and it is influenced by multiple factors, namely age, gender, diet, and muscle mass;
-
10 to 40% of Cr elimination is performed by tubular secretion [31] and this mechanism is amplified as the GFR diminishes, thus, overestimating renal function in AKI patients;
-
many medications inhibit tubular secretion of Cr (i.e. trimethoprim, cimetidine), causing a temporary increase in SCr;
-
various factors can interfere with SCr determination (i.e. acetoacetate accumulated in diabetic ketoacidosis can interfere with the alkaline picrate method), causing a false elevation in SCr [32];
-
Cr is a marker of renal function, and not of renal lesion.
-
Sensitivity and specificity of UO can be significantly changed by the use of diuretics, and this issue is not specifically considered in the RIFLE classification;
-
the UO can only be determined in patients with a bladder catheter in place, which, despite being common in ICU patients, is not frequent in other hospitalized patients;
-
It is possible that the predictive ability of UO could be inferior to that of SCr, which can explain the difference in terms of mortality between the same classes defined by each one of those criteria, observed in studies that utilized both criteria to define and classify AKI [11, 13, 34]. The capacity of the RIFLE (using both criteria) to predict mortality can be more stable than the ability of this classification employing only SCr [13], which corroborates the clinical utility of using simultaneously both criteria as proposed by the ADQI work group [8].
Finally, the RIFLE classification does not provide any information regarding the origin of the renal lesion (i.e. cellular or subcellular levels), as opposed to several biomarkers of AKI recently identified and studied. Furthermore, the limitations of the conventional renal function markers (Cr and UO) can be overwhelmed with the utilization of those new biomarkers. In fact, various urinary and serum markers of AKI have been identified and described [37], such as neutrophil gelatinase-associated lipocalin, interleukin-18 and the kidney injury molecule-1. These biomarkers start to elevate soon in AKI (1–3 days before the increase in SCr), and do exhibit a great sensitivity and specificity in AKI diagnosis, a good correlation with RRT requirement, as well as with mortality, in several settings, namely in the post-operative period of cardiac surgery [38, 39], in ICU patients [40] and in the contrast-induced nephropathy in children undergoing coronary angiography [41]. In renal transplantation, it has been shown that these biomarkers also have a good correlation with the cold ischaemic time, the maximum value of SCr in the post-transplantation period and the requirement for RRT, and are good predictors of acute tubular necrosis and long-term renal graft function [42, 43, 44].
It must also be emphasized that the RIFLE criteria has only has only evaluated in a minority (<2%) of patients included in prospective studies. This major concern certainly did limit the analysis of other clinical or laboratory variables with prognostic impact on the epidemiology of AKI.
The Acute Kidney Injury Network (AKIN) classification
In September 2005, in a meeting in Amsterdam a new classification of AKI was proposed by the Acute Kidney Injury Network (AKIN) working group composed of nephrologists, critical care physicians and other physicians specialized in AKI. The AKIN classification (Table 3) was published in March 2007 in Critical Care [45], and it is a later version of the RIFLE classification with some modifications: the diagnosis of AKI is only considered after achieving an adequate status of hydration and after excluding urinary obstruction; the AKIN classification only relies on SCr and not on GFR changes; baseline SCr is not necessary in the AKIN classification, and it requires at least two values of SCr obtained within a period of 48 h; AKI is defined by the sudden decrease (in 48 h) of renal function, defined by an increase in absolute SCr of at least 26.5 μmol/L (0.3 mg/dL) or by a percentage increase in SCr ≥50% (1.5× baseline value), or by a decrease in the UO (documented oliguria <0.5 mL/kg/h for more than 6 h); Stage 1 corresponds to the risk class, but it also considers an absolute increase in SCr ≥26.5 μmol/L (0.3 mg/dL); Stages 2 and 3 correspond to injury and failure classes, respectively; Stage 3 also considers patients requiring RRT independently of the stage (defined by SCr and/or UO) they are in at the point of RRT initiation; the two outcome classes (loss of kidney function and end-stage kidney disease) were removed from the classification.
Table 3.
Stage
.
SCr
.
UO
.
1 ↑ SCr ≥26.5 μmol/L (≥0.3 mg/dL) or ↑SCr ≥150 a 200% (1.5 a 2×) <0.5 mL/kg/h (>6 h) 2 ↑ SCr >200 a 300% (>2 a 3×) <0.5 mL/kg/h (>12 h) 3b ↑ SCr >300% (>3×) or if baseline SCr ≥353.6 μmol/L (≥4 mg/dL) ↑SCr ≥44.2 μmol/L (≥0.5 mg/dL) <0.3 mL/kg/h (24 h) oranuria (12 h) Stage
.
SCr
.
UO
.
1 ↑ SCr ≥26.5 μmol/L (≥0.3 mg/dL) or ↑SCr ≥150 a 200% (1.5 a 2×) <0.5 mL/kg/h (>6 h) 2 ↑ SCr >200 a 300% (>2 a 3×) <0.5 mL/kg/h (>12 h) 3b ↑ SCr >300% (>3×) or if baseline SCr ≥353.6 μmol/L (≥4 mg/dL) ↑SCr ≥44.2 μmol/L (≥0.5 mg/dL) <0.3 mL/kg/h (24 h) oranuria (12 h)
Open in new tab
Table 3.
Stage
.
SCr
.
UO
.
1 ↑ SCr ≥26.5 μmol/L (≥0.3 mg/dL) or ↑SCr ≥150 a 200% (1.5 a 2×) <0.5 mL/kg/h (>6 h) 2 ↑ SCr >200 a 300% (>2 a 3×) <0.5 mL/kg/h (>12 h) 3b ↑ SCr >300% (>3×) or if baseline SCr ≥353.6 μmol/L (≥4 mg/dL) ↑SCr ≥44.2 μmol/L (≥0.5 mg/dL) <0.3 mL/kg/h (24 h) oranuria (12 h) Stage
.
SCr
.
UO
.
1 ↑ SCr ≥26.5 μmol/L (≥0.3 mg/dL) or ↑SCr ≥150 a 200% (1.5 a 2×) <0.5 mL/kg/h (>6 h) 2 ↑ SCr >200 a 300% (>2 a 3×) <0.5 mL/kg/h (>12 h) 3b ↑ SCr >300% (>3×) or if baseline SCr ≥353.6 μmol/L (≥4 mg/dL) ↑SCr ≥44.2 μmol/L (≥0.5 mg/dL) <0.3 mL/kg/h (24 h) oranuria (12 h)
Open in new tab
These modifications were based on the cumulative evidence that even small increases in SCr are associated with a poor outcome, and in the extreme variability of resources and of the indications to start RRT exhibited in different countries and hospitals [7, 46, 47].
It has been shown that the AKIN classification, like the RIFLE classification, allowed the identification and stratification of AKI in a large proportion of hospitalized patients and was independently associated with the outcome [34, 48–56]. In fact, patients with AKI had higher in-hospital mortality and longer lengths of stay, and AKI survivors were more likely to be discharged to an extended care facility.
The AKIN classification could theoretically improve the RIFLE criteria sensitivity and specificity, although the advantages of the RIFLE modifications have not been proven. In fact, the AKIN classification compared with the RIFLE classification did not exhibit a better prognostic acuity in terms of in-hospital mortality, although it enabled the identification of more AKI patients [34, 50–56] (Table 4).
Table 4.
Setting
.
.
.
Incidence and categorization of AKI (%)
.
Mortality (%/relative risk)
.
AUROC
.
.
N
.
Design
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
ICU Bagshaw et al. [
50] 120.123 Retrospective,multi-centre AKI (any class) (36.1)
R (16.2)
I (13.6)
F (6.3) AKI (any stage) (37.1)
Stage 1 (18.1)
Stage 2 (10.1)
Stage 3 (8.9) Hospital mortality
No AKI (8.9)
AKI (any class) (24.2/3.3)
R (17.9/2.2)
I (27.7/3.9)
F (33.2/5.1) Hospital mortality
No AKI (8.5)
AKI (any stage) (24.5/3.1)
Stage 1 (18.5/2.1)
Stage 2 (28.1/4.2)
Stage 3 (32.6/5.7) 0.660 0.670 Lopes et al. [
34] 662 Retrospective,single-centre AKI (any class) (33.8)
R (14.7)
I (11)
F (18.1) AKI (any stage) (50.4)
Stage 1 (21.1)
Stage 2 (10.1)
Stage 3 (19.2) Hospital mortality
No AKI (11)
AKI (any class) (41.3/2.8)
R (30.9/2.7)
I (32.8/2.0)
F (55/3.6) Hospital mortality
No AKI (8.5)
AKI (any stage) (39.8/3.6)
Stage 1 (30.7/3.5)
Stage 2 (32.8/2.7)
Stage 3 (53.5/3.6) 0.733 0.750 Lassnigg et al. [
51] 7.241 Prospective,multi-centre AKI (any class) (3.0)
R (2.2)
I (0.6)
F (0.2) AKI (any stage) (8.2)
Stage 1 (6.4)
Stage 2 (0.04)
Stage 3 (1.8) 30-day mortality
No AKI (3.6)
AKI (any class) (27.5/NS)
R (29/NS)
I (19/NS)
F (33/NS) 30-day mortality
No AKI (2.8)
AKI (any stage) (23.1/NS)
Stage 1 (16.4/NS)
Stage 2 (66.7/NS)
Stage 3 (38.2/NS) NS NS Joannidis et al. [
52] 16.784 Retrospective,multi-centre AKI (any class) (35.5)
R (7.6)
I (11.1)
F (16.8) AKI (any stage) (28.5)
Stage 1 (7.5)
Stage 2 (7.2)
Stage 3 (13.8) Hospital mortality
No AKI (13.6)
AKI (any class)(36.5/ NS)
R (29.2/1.4)
I (32.3/1.9)
F (42.6/3.0) Hospital mortality
No AKI (15.9)
AKI (any stage) (36.4/NS)
Stage (1 34.5/2.0)
Stage (2 29/1.9)
Stage (3 41.2/3.0) NS NS Ostermmann et al. [
53] 41.172 Retrospective,multi-centre AKI (any class) (35.9)
R (17.2)
I (11)
F (7.6) AKI (any stage) (35.4)
Stage 1 (19.1)
Stage 2 (3.8)
Stage 3 (12.5) Hospital mortality
No AKI (NS)
AKI (any class)
(36.1/NS)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) Hospital mortality
No AKI (NS)
AKI (any stage) (40.4/NS)
Stage 1 (29.9/0.98)
Stage 2 (35.8/1.1)
Stage 3 (57.9/2.01) 0.897 0.840 Cardiac surgery Haase et al. [
54] 282 Prospective,single-centre AKI (any class) (45.80
R (30.1)
I (12.1)
F (3.5) AKI (any stage) (44.7)
Stage 1 (33.7)
Stage 2 (6.7)
Stage 3 (4.3) Hospital mortality
No AKI (0)
AKI (any class) (4.7/NS)
R (1.2/NS)
I (8.8/NS)
F (20/NS) Hospital mortality
No AKI (0)
AKI (any stage) (4.8/NS)
Stage 1 (1.1/NS)
Stage 2 (0/NS)
Stage 3 (41.7/NS) 0.910 0.940 Englberger et al. [
55] 4.836 Retrospective,single-centre AKI (any class) (18.9)
R (14.8)
I (3.5)
F (0.64) AKI (any stage) (26.3)
Stage 1 (23.6)
Stage 2 (1.2)
Stage 3 (1.5) Hospital mortality
No AKI (0.64)
AKI (any class) (7/4.5)
R (3.8/NS)
I (18.3/NS)
F (19.4/NS) Hospital mortality
No AKI (0.53)
AKI (any stage) (7.7/5.3)
Stage 1 (2.6/NS)
Stage 2 (12.3/NS)
Stage 3 (44.6/NS) 0.800 0.820 Robert et al. [
56] 24.747 Prospective,single-centre AKI (any class) (31.2)
R (21.7)
I (5.9)
F (3.6) AKI (any stage) (29.9)
Stage 1 (22.9)
Stage 2 (3.4)
Stage 3 (3.6) Hospital mortality
No AKI (1.4)
AKI (any class)
(9.8/NS)
R (3.3/2.40)
I (11.1/8.9)
F (36.4/40.9) Hospital mortality
No AKI (1.3)
AKI (any stage) (9.1/NS)
Stage 1 (4.1/3.2)
Stage 2 (14.2/12.4)
Stage 3 (36.8/43.8) 0.780 0.790 Setting
.
.
.
Incidence and categorization of AKI (%)
.
Mortality (%/relative risk)
.
AUROC
.
.
N
.
Design
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
ICU Bagshaw et al. [
50] 120.123 Retrospective,multi-centre AKI (any class) (36.1)
R (16.2)
I (13.6)
F (6.3) AKI (any stage) (37.1)
Stage 1 (18.1)
Stage 2 (10.1)
Stage 3 (8.9) Hospital mortality
No AKI (8.9)
AKI (any class) (24.2/3.3)
R (17.9/2.2)
I (27.7/3.9)
F (33.2/5.1) Hospital mortality
No AKI (8.5)
AKI (any stage) (24.5/3.1)
Stage 1 (18.5/2.1)
Stage 2 (28.1/4.2)
Stage 3 (32.6/5.7) 0.660 0.670 Lopes et al. [
34] 662 Retrospective,single-centre AKI (any class) (33.8)
R (14.7)
I (11)
F (18.1) AKI (any stage) (50.4)
Stage 1 (21.1)
Stage 2 (10.1)
Stage 3 (19.2) Hospital mortality
No AKI (11)
AKI (any class) (41.3/2.8)
R (30.9/2.7)
I (32.8/2.0)
F (55/3.6) Hospital mortality
No AKI (8.5)
AKI (any stage) (39.8/3.6)
Stage 1 (30.7/3.5)
Stage 2 (32.8/2.7)
Stage 3 (53.5/3.6) 0.733 0.750 Lassnigg et al. [
51] 7.241 Prospective,multi-centre AKI (any class) (3.0)
R (2.2)
I (0.6)
F (0.2) AKI (any stage) (8.2)
Stage 1 (6.4)
Stage 2 (0.04)
Stage 3 (1.8) 30-day mortality
No AKI (3.6)
AKI (any class) (27.5/NS)
R (29/NS)
I (19/NS)
F (33/NS) 30-day mortality
No AKI (2.8)
AKI (any stage) (23.1/NS)
Stage 1 (16.4/NS)
Stage 2 (66.7/NS)
Stage 3 (38.2/NS) NS NS Joannidis et al. [
52] 16.784 Retrospective,multi-centre AKI (any class) (35.5)
R (7.6)
I (11.1)
F (16.8) AKI (any stage) (28.5)
Stage 1 (7.5)
Stage 2 (7.2)
Stage 3 (13.8) Hospital mortality
No AKI (13.6)
AKI (any class)(36.5/ NS)
R (29.2/1.4)
I (32.3/1.9)
F (42.6/3.0) Hospital mortality
No AKI (15.9)
AKI (any stage) (36.4/NS)
Stage (1 34.5/2.0)
Stage (2 29/1.9)
Stage (3 41.2/3.0) NS NS Ostermmann et al. [
53] 41.172 Retrospective,multi-centre AKI (any class) (35.9)
R (17.2)
I (11)
F (7.6) AKI (any stage) (35.4)
Stage 1 (19.1)
Stage 2 (3.8)
Stage 3 (12.5) Hospital mortality
No AKI (NS)
AKI (any class)
(36.1/NS)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) Hospital mortality
No AKI (NS)
AKI (any stage) (40.4/NS)
Stage 1 (29.9/0.98)
Stage 2 (35.8/1.1)
Stage 3 (57.9/2.01) 0.897 0.840 Cardiac surgery Haase et al. [
54] 282 Prospective,single-centre AKI (any class) (45.80
R (30.1)
I (12.1)
F (3.5) AKI (any stage) (44.7)
Stage 1 (33.7)
Stage 2 (6.7)
Stage 3 (4.3) Hospital mortality
No AKI (0)
AKI (any class) (4.7/NS)
R (1.2/NS)
I (8.8/NS)
F (20/NS) Hospital mortality
No AKI (0)
AKI (any stage) (4.8/NS)
Stage 1 (1.1/NS)
Stage 2 (0/NS)
Stage 3 (41.7/NS) 0.910 0.940 Englberger et al. [
55] 4.836 Retrospective,single-centre AKI (any class) (18.9)
R (14.8)
I (3.5)
F (0.64) AKI (any stage) (26.3)
Stage 1 (23.6)
Stage 2 (1.2)
Stage 3 (1.5) Hospital mortality
No AKI (0.64)
AKI (any class) (7/4.5)
R (3.8/NS)
I (18.3/NS)
F (19.4/NS) Hospital mortality
No AKI (0.53)
AKI (any stage) (7.7/5.3)
Stage 1 (2.6/NS)
Stage 2 (12.3/NS)
Stage 3 (44.6/NS) 0.800 0.820 Robert et al. [
56] 24.747 Prospective,single-centre AKI (any class) (31.2)
R (21.7)
I (5.9)
F (3.6) AKI (any stage) (29.9)
Stage 1 (22.9)
Stage 2 (3.4)
Stage 3 (3.6) Hospital mortality
No AKI (1.4)
AKI (any class)
(9.8/NS)
R (3.3/2.40)
I (11.1/8.9)
F (36.4/40.9) Hospital mortality
No AKI (1.3)
AKI (any stage) (9.1/NS)
Stage 1 (4.1/3.2)
Stage 2 (14.2/12.4)
Stage 3 (36.8/43.8) 0.780 0.790
Open in new tab
Table 4.
Setting
.
.
.
Incidence and categorization of AKI (%)
.
Mortality (%/relative risk)
.
AUROC
.
.
N
.
Design
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
ICU Bagshaw et al. [
50] 120.123 Retrospective,multi-centre AKI (any class) (36.1)
R (16.2)
I (13.6)
F (6.3) AKI (any stage) (37.1)
Stage 1 (18.1)
Stage 2 (10.1)
Stage 3 (8.9) Hospital mortality
No AKI (8.9)
AKI (any class) (24.2/3.3)
R (17.9/2.2)
I (27.7/3.9)
F (33.2/5.1) Hospital mortality
No AKI (8.5)
AKI (any stage) (24.5/3.1)
Stage 1 (18.5/2.1)
Stage 2 (28.1/4.2)
Stage 3 (32.6/5.7) 0.660 0.670 Lopes et al. [
34] 662 Retrospective,single-centre AKI (any class) (33.8)
R (14.7)
I (11)
F (18.1) AKI (any stage) (50.4)
Stage 1 (21.1)
Stage 2 (10.1)
Stage 3 (19.2) Hospital mortality
No AKI (11)
AKI (any class) (41.3/2.8)
R (30.9/2.7)
I (32.8/2.0)
F (55/3.6) Hospital mortality
No AKI (8.5)
AKI (any stage) (39.8/3.6)
Stage 1 (30.7/3.5)
Stage 2 (32.8/2.7)
Stage 3 (53.5/3.6) 0.733 0.750 Lassnigg et al. [
51] 7.241 Prospective,multi-centre AKI (any class) (3.0)
R (2.2)
I (0.6)
F (0.2) AKI (any stage) (8.2)
Stage 1 (6.4)
Stage 2 (0.04)
Stage 3 (1.8) 30-day mortality
No AKI (3.6)
AKI (any class) (27.5/NS)
R (29/NS)
I (19/NS)
F (33/NS) 30-day mortality
No AKI (2.8)
AKI (any stage) (23.1/NS)
Stage 1 (16.4/NS)
Stage 2 (66.7/NS)
Stage 3 (38.2/NS) NS NS Joannidis et al. [
52] 16.784 Retrospective,multi-centre AKI (any class) (35.5)
R (7.6)
I (11.1)
F (16.8) AKI (any stage) (28.5)
Stage 1 (7.5)
Stage 2 (7.2)
Stage 3 (13.8) Hospital mortality
No AKI (13.6)
AKI (any class)(36.5/ NS)
R (29.2/1.4)
I (32.3/1.9)
F (42.6/3.0) Hospital mortality
No AKI (15.9)
AKI (any stage) (36.4/NS)
Stage (1 34.5/2.0)
Stage (2 29/1.9)
Stage (3 41.2/3.0) NS NS Ostermmann et al. [
53] 41.172 Retrospective,multi-centre AKI (any class) (35.9)
R (17.2)
I (11)
F (7.6) AKI (any stage) (35.4)
Stage 1 (19.1)
Stage 2 (3.8)
Stage 3 (12.5) Hospital mortality
No AKI (NS)
AKI (any class)
(36.1/NS)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) Hospital mortality
No AKI (NS)
AKI (any stage) (40.4/NS)
Stage 1 (29.9/0.98)
Stage 2 (35.8/1.1)
Stage 3 (57.9/2.01) 0.897 0.840 Cardiac surgery Haase et al. [
54] 282 Prospective,single-centre AKI (any class) (45.80
R (30.1)
I (12.1)
F (3.5) AKI (any stage) (44.7)
Stage 1 (33.7)
Stage 2 (6.7)
Stage 3 (4.3) Hospital mortality
No AKI (0)
AKI (any class) (4.7/NS)
R (1.2/NS)
I (8.8/NS)
F (20/NS) Hospital mortality
No AKI (0)
AKI (any stage) (4.8/NS)
Stage 1 (1.1/NS)
Stage 2 (0/NS)
Stage 3 (41.7/NS) 0.910 0.940 Englberger et al. [
55] 4.836 Retrospective,single-centre AKI (any class) (18.9)
R (14.8)
I (3.5)
F (0.64) AKI (any stage) (26.3)
Stage 1 (23.6)
Stage 2 (1.2)
Stage 3 (1.5) Hospital mortality
No AKI (0.64)
AKI (any class) (7/4.5)
R (3.8/NS)
I (18.3/NS)
F (19.4/NS) Hospital mortality
No AKI (0.53)
AKI (any stage) (7.7/5.3)
Stage 1 (2.6/NS)
Stage 2 (12.3/NS)
Stage 3 (44.6/NS) 0.800 0.820 Robert et al. [
56] 24.747 Prospective,single-centre AKI (any class) (31.2)
R (21.7)
I (5.9)
F (3.6) AKI (any stage) (29.9)
Stage 1 (22.9)
Stage 2 (3.4)
Stage 3 (3.6) Hospital mortality
No AKI (1.4)
AKI (any class)
(9.8/NS)
R (3.3/2.40)
I (11.1/8.9)
F (36.4/40.9) Hospital mortality
No AKI (1.3)
AKI (any stage) (9.1/NS)
Stage 1 (4.1/3.2)
Stage 2 (14.2/12.4)
Stage 3 (36.8/43.8) 0.780 0.790 Setting
.
.
.
Incidence and categorization of AKI (%)
.
Mortality (%/relative risk)
.
AUROC
.
.
N
.
Design
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
RIFLE
.
AKIN
.
ICU Bagshaw et al. [
50] 120.123 Retrospective,multi-centre AKI (any class) (36.1)
R (16.2)
I (13.6)
F (6.3) AKI (any stage) (37.1)
Stage 1 (18.1)
Stage 2 (10.1)
Stage 3 (8.9) Hospital mortality
No AKI (8.9)
AKI (any class) (24.2/3.3)
R (17.9/2.2)
I (27.7/3.9)
F (33.2/5.1) Hospital mortality
No AKI (8.5)
AKI (any stage) (24.5/3.1)
Stage 1 (18.5/2.1)
Stage 2 (28.1/4.2)
Stage 3 (32.6/5.7) 0.660 0.670 Lopes et al. [
34] 662 Retrospective,single-centre AKI (any class) (33.8)
R (14.7)
I (11)
F (18.1) AKI (any stage) (50.4)
Stage 1 (21.1)
Stage 2 (10.1)
Stage 3 (19.2) Hospital mortality
No AKI (11)
AKI (any class) (41.3/2.8)
R (30.9/2.7)
I (32.8/2.0)
F (55/3.6) Hospital mortality
No AKI (8.5)
AKI (any stage) (39.8/3.6)
Stage 1 (30.7/3.5)
Stage 2 (32.8/2.7)
Stage 3 (53.5/3.6) 0.733 0.750 Lassnigg et al. [
51] 7.241 Prospective,multi-centre AKI (any class) (3.0)
R (2.2)
I (0.6)
F (0.2) AKI (any stage) (8.2)
Stage 1 (6.4)
Stage 2 (0.04)
Stage 3 (1.8) 30-day mortality
No AKI (3.6)
AKI (any class) (27.5/NS)
R (29/NS)
I (19/NS)
F (33/NS) 30-day mortality
No AKI (2.8)
AKI (any stage) (23.1/NS)
Stage 1 (16.4/NS)
Stage 2 (66.7/NS)
Stage 3 (38.2/NS) NS NS Joannidis et al. [
52] 16.784 Retrospective,multi-centre AKI (any class) (35.5)
R (7.6)
I (11.1)
F (16.8) AKI (any stage) (28.5)
Stage 1 (7.5)
Stage 2 (7.2)
Stage 3 (13.8) Hospital mortality
No AKI (13.6)
AKI (any class)(36.5/ NS)
R (29.2/1.4)
I (32.3/1.9)
F (42.6/3.0) Hospital mortality
No AKI (15.9)
AKI (any stage) (36.4/NS)
Stage (1 34.5/2.0)
Stage (2 29/1.9)
Stage (3 41.2/3.0) NS NS Ostermmann et al. [
53] 41.172 Retrospective,multi-centre AKI (any class) (35.9)
R (17.2)
I (11)
F (7.6) AKI (any stage) (35.4)
Stage 1 (19.1)
Stage 2 (3.8)
Stage 3 (12.5) Hospital mortality
No AKI (NS)
AKI (any class)
(36.1/NS)
R (20.9/1.4)
I (45.6/1.9)
F (56.8/1.6) Hospital mortality
No AKI (NS)
AKI (any stage) (40.4/NS)
Stage 1 (29.9/0.98)
Stage 2 (35.8/1.1)
Stage 3 (57.9/2.01) 0.897 0.840 Cardiac surgery Haase et al. [
54] 282 Prospective,single-centre AKI (any class) (45.80
R (30.1)
I (12.1)
F (3.5) AKI (any stage) (44.7)
Stage 1 (33.7)
Stage 2 (6.7)
Stage 3 (4.3) Hospital mortality
No AKI (0)
AKI (any class) (4.7/NS)
R (1.2/NS)
I (8.8/NS)
F (20/NS) Hospital mortality
No AKI (0)
AKI (any stage) (4.8/NS)
Stage 1 (1.1/NS)
Stage 2 (0/NS)
Stage 3 (41.7/NS) 0.910 0.940 Englberger et al. [
55] 4.836 Retrospective,single-centre AKI (any class) (18.9)
R (14.8)
I (3.5)
F (0.64) AKI (any stage) (26.3)
Stage 1 (23.6)
Stage 2 (1.2)
Stage 3 (1.5) Hospital mortality
No AKI (0.64)
AKI (any class) (7/4.5)
R (3.8/NS)
I (18.3/NS)
F (19.4/NS) Hospital mortality
No AKI (0.53)
AKI (any stage) (7.7/5.3)
Stage 1 (2.6/NS)
Stage 2 (12.3/NS)
Stage 3 (44.6/NS) 0.800 0.820 Robert et al. [
56] 24.747 Prospective,single-centre AKI (any class) (31.2)
R (21.7)
I (5.9)
F (3.6) AKI (any stage) (29.9)
Stage 1 (22.9)
Stage 2 (3.4)
Stage 3 (3.6) Hospital mortality
No AKI (1.4)
AKI (any class)
(9.8/NS)
R (3.3/2.40)
I (11.1/8.9)
F (36.4/40.9) Hospital mortality
No AKI (1.3)
AKI (any stage) (9.1/NS)
Stage 1 (4.1/3.2)
Stage 2 (14.2/12.4)
Stage 3 (36.8/43.8) 0.780 0.790
Open in new tab
Strengths and limitations of the AKIN classification
The AKIN classification is a modified version of the RIFLE classification; therefore, their strengths and limitations are very similar to those aforementioned for the RIFLE. The AKIN classification has, however, some additional benefits and limitations related to the modifications introduced to the RIFLE classification.
Strengths of the AKIN classification
First, the AKI definition is only considered after an adequate status of hydration is achieved. Therefore, the AKIN classification, unlike RIFLE, adds important aetiological information. Second, the AKIN classification is based on SCr and not on GFR changes. Third, the AKIN classification does not need baseline SCr to define AKI, although it requires at least two SCr determinations within 48 h.
Limitations of the AKIN classification
First, the AKIN classification does not allow the identification of AKI when SCr elevation occurs in a time frame higher than 48 h. Second, Stage 3 of the AKIN classification includes three diagnostic criteria (Cr, UO and RRT requirement), and the extreme variability in the beginning and cessation of RRT as well as in RRT modality used and in the dose of dialysis among different physicians, hospitals and countries could significantly limit the prognostic acuity of this classification, particularly of Stage 3.
Which classification should we use in clinical practice?
The extensive number of publications focusing on the RIFLE and AKIN classifications are demonstrative and they are widely accepted by the medical community. There remains, however, some heterogeneity in the utilization of the criteria defining and classifying AKI, such as the use (or non-use) of UO and baseline SCr, and of the estimated GFR instead of the variation in SCr.
The Kidney Disease Improving Global Outcomes work group recently combined the RIFLE and AKIN classifications in order to establish one classification of AKI for practice, research and public health. Therefore, AKI has been defined as an increase in SCr ≥0.3 mg/dL (≥26.5 μmol/L) within 48 h; or an increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days or a urine volume of <0.5 mL/kg/h for 6 h. Furthermore, AKI has been staged in severity according to the AKIN criteria (Table 3). 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 requiring an acute increase of ≥0.5 mg/dL (≥44 µmol/L) over an unspecified time period, it instead require that the patient first achieve the creatinine-based change specified in the definition [either ≥0.3 mg/dL (≥26.5 µmol/L) within a 48-h 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 [57]. The integration of the new biomarkers of AKI into the clinical classification could increase the sensitivity and specificity of AKI diagnosis, overwhelming some of the limitations of the traditional markers of kidney function, such as Cr and UO [58].
Conflict of interest statement
None declared.
References
1
Kellum
JA
Levin
N
Bouman
C
Developing a consensus classification system for acute renal failure
,
Curr Opin Crit Care
,
2002
, vol.
8
(pg.
509
–
514
)
, vol.(pg.
2
Thadhani
R
Pascual
M
Bonventre
JV
Acute renal failure
,
N Engl J Med
,
1996
, vol.
334
(pg.
1448
–
1460
)
, vol.(pg.
3
Schaefer
JH
Jochimsen
F
Keller
F
Outcome prediction of acute renal failure in medical intensive care
,
Intensive Care Med
,
1991
, vol.
17
(pg.
19
–
24
)
, vol.(pg.
4
Brivet
FG
Kleinknecht
DJ
Loriat
P
Acute renal failure in intensive care units—causes, outcome, and prognostic factors of hospital mortality: a prospective, multicenter study
,
Crit Care Med
,
1996
, vol.
24
(pg.
192
–
198
)
, vol.(pg.
5
Liano
F
Pascual
J
Madrid Acute Renal Failure Study Cluster. Epidemiology of acute renal failure: a prospective, multicenter, community-based study
,
Kidney Int
,
1996
, vol.
50
(pg.
811
–
818
)
, vol.(pg.
6
Silvester
W
Bellomo
R
Cole
L
Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia
,
Crit Care Med
,
2001
, vol.
29
(pg.
1910
–
1915
)10.1001/jama.1997.03550190064046
, vol.(pg.
7
Chertow
GM
Burdick
E
Honour
M
Acute kidney injury, mortality, length of stay, and costs in hospitalized patients
,
J Am Soc Nephrol
,
2005
, vol.
16
(pg.
3365
–
3370
)10.1016/S1470-2045(08)70179-7
, vol.(pg.
8
Bellomo
R
Ronco
C
Kellum
JA
Palevsky P and the ADQI workgroup. 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
, vol.
8
pg.
R204
10.1016/S1470-2045(07)70246-2
, vol.pg.
9
Manjunath
G
Sarnak
MJ
Levey
AS
Prediction equations to estimate glomerular filtration rate: an update
,
Curr Opin Nephrol Hypertens
,
2001
, vol.
10
(pg.
785
–
792
)
, vol.(pg.
10
Uchino
S
Bellomo
R
Goldsmith
D
An assessment of the RIFLE criteria for acute renal failure in hospitalized patients
,
Crit Care Med
,
2006
, vol.
34
(pg.
1913
–
1917
)
, vol.(pg.
11
Hoste
EA
Clermont
G
Kersten
A
RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis
,
Crit Care
,
2006
, vol.
10
pg.
R73
, vol.pg.
12
Ostermann
M
Chang
RW
Acute kidney injury in the intensive care unit according to RIFLE
,
Crit Care Med
,
2007
, vol.
35
(pg.
1837
–
1843
)
, vol.(pg.
13
Cruz
DN
Bolgan
I
Perazella
MA
North East Italian Prospective Hospital Renal Outcome Survey on acute kidney injury (NEiPHROS-AKI): targeting the problem with the RIFLE criteria
,
Clin J Am Soc Nephrol
,
2007
, vol.
2
(pg.
418
–
425
)10.1046/j.1525-1497.2003.20220.x
, vol.(pg.
14
Bagshaw
SM
George
C
Dinu
I
A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients
,
Nephrol Dial Transplant
,
2008
, vol.
23
(pg.
1203
–
1210
)
, vol.(pg.
15
Heringlake
M
Knappe
M
Vargas Hein
O
Renal dysfunction according to the ADQI-RIFLE system and clinical practice patterns after cardiac surgery in Germany
,
Minerva Anestesiol
,
2006
, vol.
72
(pg.
645
–
654
)10.1093/jnci/djp409
, vol.(pg.
16
Kuitunen
A
Vento
A
Suojaranta-Ylinen
R
Acute renal failure after cardiac surgery: evaluation of the RIFLE classification
,
Ann Thorac Surg
,
2006
, vol.
81
(pg.
542
–
546
)10.1001/jama.1994.03510400075038
, vol.(pg.
17
Lin
CY
Chen
YC
Tsai
FC
RIFLE classification is predictive of short-term prognosis in critically ill patients with acute renal failure supported by extracorporeal membrane oxygenation
,
Nephrol Dial Transplant
,
2006
, vol.
21
(pg.
2867
–
2873
)
, vol.(pg.
18
Arnaoutakis
GJ
Bihorac
A
Martin
TD
RIFLE criteria for acute kidney injury in aortic arch surgery
,
J Thorac Cardiovasc Surg
,
2007
, vol.
134
(pg.
1554
–
1560
)
, vol.(pg.
19
Jenq
CC
Tsai
MH
Tian
YC
RIFLE classification can predict short-term prognosis in critically ill cirrhotic patients
,
Intensive Care Med
,
2007
, vol.
33
(pg.
1921
–
1930
)
, vol.(pg.
20
O’Riordan
A
Wong
V
McQuillan
R
Acute renal disease, as defined by the RIFLE criteria, post-liver transplantation
,
Am J Transplant
,
2007
, vol.
7
(pg.
168
–
176
)
, vol.(pg.
21
Lopes
JA
Jorge
S
Resina
C
Prognostic utility of RIFLE for acute renal failure in patients with sepsis
,
Crit Care
,
2007
, vol.
11
pg.
408
, vol.pg.
22
Chen
YC
Jenq
CC
Tian
YC
Rifle classification for predicting in-hospital mortality in critically ill sepsis patients
,
Shock
,
2009
, vol.
31
(pg.
139
–
145
)
, vol.(pg.
23
Lopes
JA
Jorge
S
Neves
FC
An assessment of the RIFLE criteria for acute renal failure in severely burned patients
,
Nephrol Dial Transplant
,
2007
, vol.
22
pg.
285
, vol.pg.
24
Lopes
JA
Fernandes
J
Jorge
S
An assessment of the RIFLE criteria for acute renal failure in critically ill HIV-infected patients
,
Crit Care
,
2007
, vol.
11
pg.
401
, vol.pg.
25
Bagshaw
SM
George
C
Gibney
RT
A multi-center evaluation of early acute kidney injury in critically ill trauma patients
,
Ren Fail
,
2008
, vol.
30
(pg.
581
–
589
)
, vol.(pg.
26
Lopes
JA
Gonçalves
S
Jorge
S
Contemporary analysis of the influence of the acute kidney injury after reduced intensity conditioning haematopoietic cell transplantation on long-term survival
,
Bone Marrow Transplant
,
2008
, vol.
42
(pg.
619
–
626
)
, vol.(pg.
27
Abosaif
NY
Tolba
YA
Heap
M
The outcome of acute renal failure in the intensive care unit according to RIFLE: model application, sensitivity, and predictability
,
Am J Kidney Dis
,
2005
, vol.
46
(pg.
1038
–
1048
)
, vol.(pg.
28
Ahlström
A
Kuitunen
A
Peltonen
S
Comparison of 2 acute renal failure severity scores to general scoring systems in the critically ill
,
Am J Kidney Dis
,
2006
, vol.
48
(pg.
262
–
268
)
, vol.(pg.
29
Bagshaw
SM
Uchino
S
Cruz
D
A comparison of observed versus estimated baseline creatinine for determination of RIFLE class in patients with acute kidney injury
,
Nephrol Dial Transplant
,
2009
, vol.
24
(pg.
2739
–
2744
)
, vol.(pg.
30
Waikar
SS
Bonventre
JV
Creatinine kinetics and the definition of acute kidney injury
,
J Am Soc Nephrol
,
2009
, vol.
20
(pg.
672
–
679
)
, vol.(pg.
31
Shemesh
O
Golbetz
H
Kriss
JP
Limitations of creatinine as a filtration marker in glomerulopathic patients
,
Kidney Int
,
1985
, vol.
28
(pg.
830
–
838
)
, vol.(pg.
32
Molitch
ME
Rodman
E
Hirsch
CA
Spurious serum creatinine elevations in ketoacidosis
,
Ann Intern Med
,
1980
, vol.
93
(pg.
280
–
281
)
, vol.(pg.
33
Hoste
EA
Kellum
JA
Acute kidney injury: epidemiology and diagnostic criteria
,
Curr Opin Crit Care
,
2006
, vol.
12
(pg.
531
–
537
)
, vol.(pg.
34
Lopes
JA
Fernandes
P
Jorge
S
Acute kidney injury in intensive care unit patients: a comparison between the RIFLE and the Acute Kidney Injury Network classifications
,
Crit Care
,
2008
, vol.
12
pg.
R110
, vol.pg.
35
Bell
M
Liljestam
E
Granath
F
Optimal follow-up time after continuous renal replacement therapy in actual renal failure patients stratified with the RIFLE criteria
,
Nephrol Dial Transplant
,
2005
, vol.
20
(pg.
354
–
360
)
, vol.(pg.
36
Maccariello
E
Soares
M
Valente
C
RIFLE classification in patients with acute kidney injury in need of renal replacement therapy
,
Intensive Care Med
,
2007
, vol.
33
(pg.
597
–
605
)
, vol.(pg.
37
Venkataraman
R
Kellum
JA
Defining acute renal failure: the RIFLE criteria
,
J Intensive Care Med
,
2007
, vol.
22
(pg.
187
–
193
)
, vol.(pg.
38
Mishra
J
Dent
C
Tarabishi
R
Neutrophil gelatinase associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery
,
Lancet
,
2005
, vol.
365
(pg.
1231
–
1238
)
, vol.(pg.
39
Parikh
CR
Mishra
J
Thiessen-Philbrook
H
Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery
,
Kidney Int
,
2006
, vol.
70
(pg.
199
–
203
)
, vol.(pg.
40
Parikh
CR
Abraham
E
Ancukiewicz
M
Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit
,
J Am Soc Nephrol
,
2005
, vol.
16
(pg.
3046
–
3052
)
, vol.(pg.
41
Hirsch
R
Dent
C
Pfriem
H
NGAL is an early predictive biomarker of contrast induced nephropathy in children
,
Pediatr Nephrol
,
2007
, vol.
22
(pg.
2089
–
2095
)
, vol.(pg.
42
Parikh
CR
Jani
A
Melnikov
VY
Urinary interleukin-18 is a marker of human acute tubular necrosis
,
Am J Kidney Dis
,
2004
, vol.
43
(pg.
405
–
414
)
, vol.(pg.
43
Parikh
CR
Jani
A
Mishra
J
Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation
,
Am J Transplant
,
2006
, vol.
6
(pg.
1639
–
1645
)
, vol.(pg.
44
Zhang
P
Rothblum
L
Han
WK
Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury
,
Kidney Int
,
2008
, vol.
73
(pg.
608
–
614
)
, vol.(pg.
45
Mehta
RL
Kellum
JA
Shah
SV
Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury
,
Crit Care
,
2007
, vol.
11
pg.
R31
, vol.pg.
46
Levy
EM
Viscoli
CM
Horwitz
RI
The effect of acute renal failure on mortality. A cohort analysis
,
JAMA
,
1996
, vol.
275
(pg.
1489
–
1494
)
, vol.(pg.
47
Lassnigg
A
Schmidlin
D
Mouhieddine
M
Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study
,
J Am Soc Nephrol
,
2004
, vol.
15
(pg.
1597
–
1605
)
, vol.(pg.
48
Barrantes
F
Feng
Y
Ivanov
O
Acute kidney injury predicts outcomes of non-critically ill patients
,
Mayo Clin Proc
,
2009
, vol.
84
(pg.
410
–
416
)
, vol.(pg.
49
Barrantes
F
Tian
J
Vazquez
R
Acute kidney injury criteria predict outcomes of critically ill patients
,
Crit Care Med
,
2008
, vol.
36
(pg.
1397
–
1403
)
, vol.(pg.
50
Bagshaw
SM
George
C
Bellomo
R
for the ANZICS Database Management Committee. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients
,
Nephrol Dial Transplant
,
2008
, vol.
23
(pg.
1569
–
1574
)
, vol.(pg.
51
Lassnigg
A
Schmid
ER
Hiesmayr
M
Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?
,
Crit Care Med
,
2008
, vol.
36
(pg.
1129
–
1137
)
, vol.(pg.
52
Joannidis
M
Metnitz
B
Bauer
P
Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database
,
Intensive Care Med
,
2009
, vol.
35
(pg.
1692
–
1702
)
, vol.(pg.
53
Ostermann
M
Chang
RW
Challenges of defining acute kidney injury
,
QJM
,
2011
, vol.
104
(pg.
237
–
243
)
, vol.(pg.
54
Haase
M
Bellomo
R
Matalanis
G
A comparison of the RIFLE and Acute Kidney Injury Network classifications for cardiac surgery-associated acute kidney injury: a prospective cohort study
,
J Thorac Cardiovasc Surg
,
2009
, vol.
138
(pg.
1370
–
1376
)
, vol.(pg.
55
Englberger
L
Suri
RM
Li
Z
Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery
,
Crit Care
,
2011
, vol.
15
pg.
R16
, vol.pg.
56
Robert
AM
Kramer
RS
Dacey
LJ
Cardiac surgery-associated acute kidney injury: a comparison of two consensus criteria
,
Ann Thorac Surg
,
2010
, vol.
90
(pg.
1939
–
1943
)
, vol.(pg.
57
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group
KDIGO Clinical Practice Guideline for Acute Kidney Injury
,
Kidney Int
,
2012
, vol.
2
Suppl
(pg.
S1
–
138
)
, vol.(pg.
58
Cruz
DN
Ricci
Z
Ronco
C
Clinical review: RIFLE and AKIN—time for reappraisal
,
Crit Care
,
2009
, vol.
13
pg.
211
, vol.pg.
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