aki-6 epidemiology of acute kidney injury · aki-6 epidemiology of transient acute kidney injury 2....

FACULTY OF MEDICINE AND

HEALTH SCIENCES

Academic Year 2011 - 2012

AKI-6 Epidemiology of Acute Kidney Injury

Anne NOBELS

Promotor: Prof. Dr. E. Hoste

Co-promotor: Prof. Dr. J. Kellum (Pittsburg)

Dissertation presented in the 2nd

Master year

in the program of

Master in Medicine

FACULTY OF MEDICINE AND HEALTH SCIENCES

Academic Year 2011 - 2012

AKI-6 Epidemiology of Acute Kidney Injury

Anne NOBELS

Promotor: Prof. Dr. E. Hoste

Co-promotor: Prof. Dr. J. Kellum (Pittsburg)

Dissertation presented in the 2nd

Master year

in the program of

Master in Medicine

“The author and the promotor give the permission to use this thesis for consultation and to

copy parts of it for personal use. Every other use is subject to the copyright laws, more

specifically the source must be extensively specified when using results from this thesis.”

Date

Anne Nobels (student) Prof. Dr. E. Hoste (promotor)

Foreword

This master thesis is the result of two years hard work. I want to thank sincerely all those people who

helped me during this period.

First of all I want to thank my promotor, Prof. Dr. Eric Hoste, for his endless patience, for his critical

view, for his feedback, for all the time he spend on my master thesis, and for the opportunity to work

further on a scientific paper after this master thesis.

I want to thank Prof. Dr. John Kellum and Dr. Nattachai Sisrawat to help me understand the AKI-6

database and the different AKI classifications.

Chris Danneels and Bram Gadeyne, I want to thank for their ICT help and their patience with an

ICTstarter like me. Special thanks to Chris Danneels for writing a program to calculate the duration of

the AKI episodes.

Jonathan De Rudder, I want to thank for his mathematical insight and his recalculation of the CKD-

EPI equitation.

My parents, family and friends I want to thank for their support during this master thesis and my

studies in general.

Table of Contents

1. Abstract ........................................................................................................................................... 1

1.1. Introduction ............................................................................................................................. 1

1.2. Materials and Methods ............................................................................................................ 1

1.3. Results ..................................................................................................................................... 1

1.4. Conclusion ............................................................................................................................... 2

2. Introduction ..................................................................................................................................... 3

3. Materials and methods ..................................................................................................................... 4

3.1. Literature ................................................................................................................................. 4

3.2. Study Design ........................................................................................................................... 4

3.3. Acute Kidney Injury (AKI) ..................................................................................................... 5

3.3.1. RIFLE classification for AKI .......................................................................................... 5

3.3.2. Acute Kidney Injury Network (AKIN) diagnostic and classification system for AKI ... 6

3.3.3. The Kidney Disease Improving Global Outcomes (KDIGO) definition and staging

system for AKI ................................................................................................................................ 6

3.3.4. Baseline serum creatinine concentration ......................................................................... 7

3.3.5. Classification of patients into AKI categories ................................................................. 8

3.4. Transient Acute Kidney Injury ................................................................................................ 8

3.5. Statistical analysis ................................................................................................................... 8

3.6. Presentation of the results ........................................................................................................ 9

4. Results ........................................................................................................................................... 10

4.1. Basic Characteristics of the study population ....................................................................... 10

4.2. Acute Kidney Injury .............................................................................................................. 12

4.3. Outcomes ............................................................................................................................... 14

4.3.1. ICU Mortality ................................................................................................................ 14

4.3.2. Hospital Mortality ......................................................................................................... 16

4.3.3. ICU Length of stay ........................................................................................................ 17

4.3.4. Hospital Length of Stay ................................................................................................. 19

4.4. Transient AKI ........................................................................................................................ 22

4.4.1. Transient AKI defined as ≤3 days of AKI (AKIt3) ....................................................... 22

4.4.2. Transient AKI defined as ≤ 2 days of AKI (AKIt2) ...................................................... 24

4.4.3. Transient AKI defined as ≤1 day of AKI (AKIt1) ........................................................ 26

4.4.4. Comparison of mortality between AKIt1, AKIt2 and AKIt3 ........................................ 28

5. Discussion ..................................................................................................................................... 31

5.1. Prevalence of AKI ................................................................................................................. 31

5.2. Outcomes ............................................................................................................................... 32

5.3. Classifications of AKI ........................................................................................................... 33

5.3.1. AKI and transient AKI prevalence ................................................................................ 34

5.3.2. AKI and transient AKI outcomes .................................................................................. 34

5.4. Strengths and limitations ....................................................................................................... 35

6. Conclusion ..................................................................................................................................... 36

7. Nederlandse samenvatting ............................................................................................................. 37

7.1. Inleiding................................................................................................................................. 37

7.2. Methodologie ......................................................................................................................... 37

7.3. Resultaten .............................................................................................................................. 39

7.4. Besluit .................................................................................................................................... 41

8. References ..................................................................................................................................... 42

1 AKI-6 Epidemiology of Transient Acute Kidney Injury

1. Abstract

1.1. Introduction

Acute Kidney Injury (AKI) is associated with increased mortality, even after correction for covariates

(1). In 2004 the Acute Dialysis Quality Initiative (ADQI) group developed a consensus definition for

AKI, the RIFLE classification (2). Up to two-thirds of all ICU patients will develop AKI defined by

the RIFLE classification (1). In the meantime two modifications of the RIFLE classification were

developed, the AKIN classification (3), and recently the KDIGO classification (4).

Recently, transient AKI or transient azotemia (TA) was defined as AKI lasting for < 72 h (5). Patients

with TA had a significantly higher odds ratio for hospital mortality, and long-term mortality (5).

1.2. Materials and Methods

The AKI-6 TRansient AKI Study (TRAK Study) is a retrospective multicenter international cohort

study. Data were collected by the Acute Kidney Injury 6 study group (AKI-6). AKI-6 is a multicenter,

transatlantic study group of intensivists of 6 centers, 2 centers in the USA, 2 European centers and 2

Australian centers. A total of 11,309 patients admitted on the Intensive Care Unit in the period 2005-

2007 were analyzed. When baseline creatinine was not available, this was calculated by the 4-variable

MDRD (6) or CKD-EPI equation (7). Therefore, AKI patients were classified according to 5 AKI

classifications: RIFLE MDRD, RIFLE CKD-EPI, AKIN, KDIGO MDRD and KDIGO CKD-EPI. We

analyzed 4 clinical outcomes: ICU mortality, hospital mortality, ICU length of stay, and hospital

length of stay. AKI patients and patients without AKI were compared, as well as patients with

transient AKI and patients with a longer AKI episode. We defined transient AKI in three different

ways:

1. Transient AKI with duration of ≤ 3 days of AKI (AKIt3)



1.3. Results

Acute Kidney Injury occurred in 17.8% to 31.0% of the ICU patients according to the AKI

classification used and was associated with worse clinical outcomes. Patients with AKI had a higher


ICU mortality (17.6%-24.0%) compared to the patients without AKI (4.5%-5.5%). There was also

higher hospital mortality in AKI patients (25.5%-32.9%) compared to patients without AKI (7.9%-

9.4%). Patients with AKI had a longer ICU and hospital length of stay compared to patients without

AKI.

Transient AKI occurred frequently. The period prevalence of AKIt3 varied according to the

classification used between 13.9% and 22.7% of ICU patients, the period prevalence of AKIt2 varied

between 8.0% and 19.7%, and the period prevalence of AKIt1 varied between 6.4% and 13.1%. AKIt3

occurred in 65.7% to 78% of AKI patients, AKIt2 in 34.0% to 67.1% and AKIt1 in 28.2% to 42.1%.

Transient AKI (AKIt1, AKIt2 and AKIt3) was associated with a higher ICU and hospital mortality

compared to patients without AKI. There was no difference in mortality between the different transient

AKI definitions, and also not with all AKI.

The duration of an AKI episode was associated with a longer ICU and hospital length of stay. We

couldn’t find an association with ICU mortality. Hospital mortality of patients with AKIt2 and 3 was

lower compared to patients with longer duration of AKI. Patients with AKIt1 had a similar hospital

mortality compared to patients with a longer AKI episode (>1 day).

Comparing the five classification used in this analysis: RIFLE MDRD, RIFLE CKD-EPI, AKIN,

KDIGO MDRD and KDIGO CKD-EPI, differences can be seen in AKI prevalence, duration of the

first AKI episode, clinical outcomes, transient AKI prevalence and transient AKI outcomes.

1.4. Conclusion

In this large multicenter international cohort of ICU patients, AKI was common and related to an

increase of ICU and hospital mortality, and a longer ICU and hospital length of stay. Transient AKI

occurred in up to 2 third of all AKI cases. ICU and hospital mortality was higher in transient AKI

patients compared to patients without AKI, but similar between Transient AKI variants and all AKI.

Compared to AKI with longer duration, most Transient AKI had similar ICU mortality, but lower

hospital mortality. A longer AKI episode was associated with a longer length of stay.

Although the AKI definitions are very similar, there was important variation in prevalence of AKI and

transient AKI, and outcomes among the different AKI definitions.

Duration of AKI should be incorporated in new AKI consensus definitions and used in clinical studies.


2. Introduction

Acute Kidney Injury (AKI) is a common condition in critical ill patients with a significant higher risk

of death. For years there was no consensus definition for AKI, but in the last decade three consensus

definitions were developed using a combination of creatinine and urine output criteria. In 2004 the

Acute Dialysis Quality Initiative (ADQI) group developed the RIFLE classification (2). Up to two-

thirds of all intensive care unit patients will develop AKI defined by the RIFLE classification (1). In

2007 The Acute Kidney Injury Network (AKIN) developed an adaptation of the RIFLE classification

(3). The last definition was developed only a few months ago by the KDIGO group (4). The RIFLE

and KDIGO classification work with a baseline creatinine value. If there is no baseline value available,

the baseline is calculated out of the glomerular filtration rate (GFR) value by the 4-variable

Modification of Diet in Renal Disease (MDRD) equitation (6). In 2009 Levey et al. (7) proposed a

new and more accurate equitation to calculate the GFR, the Chronic Kidney Disease Epidemiology

Collaboration (CKD-EPI) equitation.

Most AKI epidemiology studies examined the relation between morbidity and mortality based on the

maximum RIFLE class. Uchino et al. (5) demonstrated that patients with transient AKI (<72h) had a

significantly higher odds ratio for hospital mortality. Coca et al.(8) demonstrated that the duration of

an postoperative AKI episode is associated with an increased risk of long-term mortality in diabetic

US veterans.

The aim of the TRAK study (AKI-6 Transient AKI Study) was to determine the influence of AKI

duration on outcomes (mortality, length of stay) in an Intensive Care Unit (ICU) population. We

compared different AKI classifications and different ways of calculating baseline creatinine value.


3. Materials and methods

3.1. Literature

Before starting the analyses there was performed a literature study. Articles were found using Pubmed

and following keywords: Acute kidney injury, RIFLE, AKIN, KDIGO, MDRD, CKD-EPI….

References of found articles were also used. These articles were used in the in the introduction and

discussion section of this thesis. An overview of the articles can be found under references. The

references were compiled using “Endnote X5”.

3.2. Study Design

The TRAK study is a retrospective multicenter international cohort study. Data were collected by the

Acute Kidney Injury 6 study group (AKI-6). AKI-6 is a multicenter, transatlantic study group of

intensivists of 6 centers, Dr. J.A. Kellum, University of Pittsburgh Medical Center, (Pittsburgh, PA,

USA), Dr. G. Ognjen, the Mayo Clinic (Rochester, Minnesota, USA), Dr. S Webb, Royal Perth

Hospital (Perth, Australia), Dr. R. Bellomo, Austin Health Center (Melbourne, Australia), Dr. E. Hoste,

Ghent University Hospital (Ghent, Belgium), Dr. C. Ronco and Dr. D. Cruz, Ospedale San Bortolo di

Vicenza (Vicenza, Italy). In the rest of this master thesis the participating centers will be referred as

the cities were they are situated.

In Pittsburg, Rochester, Perth and Ghent every patient admitted on the Intensive Care Unit (ICU) was

registered from 2005 till 2007. In Melbourne and Vicenza patients were registered during a shorter

time period within the same study period. This is the main reason for the unequal patient distribution

in the database.

During the whole ICU stay the following data were recorded: worst serum creatinine concentration,

urine output, treatment with mechanical ventilation, and treatment with renal replacement therapy.

ICU mortality, hospital mortality, ICU length of stay and hospital length of stay, were registered as

outcomes.


To compare serum creatinine values in the different centers, the values had to be recalibrated to

Isotope Dilution Mass Spectrometry reference measurement procedure (IDMS standards). Ghent,

Mayo, Perth and Vicenza were already using the IDMS standards in their lab, so recalibration was not

necessary. For Pittsburg and Melbourne we used the same recalibration formulas as Zavada et al. (9).

Pittsburg:

Austin:

(SCr: Serum creatinine concentration)

3.3. Acute Kidney Injury (AKI)

Acute kidney Injury (AKI) was defined according to the different consensus staging systems for AKI

that have recently been published: the RIFLE criteria (2), AKIN criteria (3) and KDIGO criteria (4).

AKIN and KDIGO are modifications of the RIFLE criteria, therefore the differences between the 3

staging systems are limited on first sight. In all three staging systems, AKI can be staged based on an

increase of serum creatinine concentration or a period of oliguria. As urine output criteria were not

available in the majority of patients, we used only the creatinine criteria for staging and classification

of AKI.

3.3.1. RIFLE classification for AKI

RIFLE is an acronym for three levels of renal dysfunction: Risk, Injury, Failure and two renal

outcomes: Loss and End Stage Kidney Disease. In the TRAK study we only analyzed the renal

dysfunction, not the renal outcomes. The creatinine criteria for the different stages are displayed in

table 1.

Table 1. RIFLE classification for AKI, creatinine criteria

RIFLE Creatinine Criteria

Risk SCr of 1.5 to 1.9 times baseline

Injury SCr of 2.0 to 2.9 times baseline

Failure SCr of 3.0 or more times baseline

Acute on chronic AKI SCr ≥4mg/dl and acute rise ≥0.5 mg/dl

SCr: serum creatinine concentration


3.3.2. Acute Kidney Injury Network (AKIN) diagnostic and classification system for AKI

AKIN defines AKI as an abrupt (within 48u) reduction in kidney function defined as an absolute

increase in serum creatinine of ≥0.3 mg/dl, a 50% increase in serum creatinine or a reduction in urine

output (<0.5 ml/kg/h for more than 6 hours). We used the lowest creatinine value in 48u before the

start of AKI as baseline creatinine value. AKIN classifies AKI patients in 3 stages of severity. In Table

2 the creatinine criteria for this stages are described.

Table 2. Acute Kidney Injury Network (AKIN) diagnostic and classification system for AKI,

creatinine criteria

AKIN Creatinine Criteria

Stage 1 Increase of SCr ≥0.3 mg/dl

or increase of SCr ≥150% to 200%

Stage 2 Increase of SCr ≥200% to 300%

Stage 3 Increase of SCr ≥ 300% (or SCr ≥4 mg/dl and

acute rise ≥0.5mg/dl) or initiation of RRT

SCr: serum creatinine concentration, RRT: Renal Replacement Therapy

3.3.3. The Kidney Disease Improving Global Outcomes (KDIGO) definition and staging

system for AKI

According to KDIGO, AKI is defined as any of the following: increase in serum creatinine by ≥0.3

mg/dl within 48 hours or increase in serum creatinine to ≥1.5 times baseline within 7 days or reduction

of urine output <0.5 ml/kg/h for 6 hours. AKI patients are classified in 3 stages of severity. The

creatinine criteria for these stages are described in table 3.


Table 3. The Kidney Disease Improving Global Outcomes (KDIGO) definition and staging system

for AKI, creatinine criteria

KDIGO Creatinine Criteria

Stage 1 SCr of 1.5 to 1.9 times baseline

or ≥0.3 mg/dl increase

Stage 2 SCr of 2.0 to 2.9 times baseline

Stage 3 SCr of 3.0 times baseline

or initiation of RRT

Acute on chronic AKI SCr of ≥4 mg/dl

SCr: serum creatinine concentration, RRT: Renal Replacement Therapy

In the RIFLE and KDIGO definitions “acute on chronic AKI” is described as a separate AKI stage

(SCr ≥4 mg/dl ± an acute rise of 0.5mg/dl). In the AKIN classification acute on chronic AKI is

considered as a part of stage 3. In the results section we will therefore report on acute on chronic AKI

for RIFLE and KDIGO, while for AKIN we will only report stage 3.

3.3.4. Baseline serum creatinine concentration

The RIFLE and KDIGO classifications use a baseline creatinine value measured before the current

hospitalisation of the patient, for calculation of the increase in serum creatinine concentration. In 69.5%

of the patients this baseline serum creatinine concentration value was unknown.

If there was no baseline creatinine available, the re-expressed 4-variable MDRD (6) and CDK-EPI (7)

equitation were used to calculate a baseline value. In patients who had absence of chronic kidney

disease, we assumed a Glomerular Filtration Rate (GFR) of 75 ml/min (1, 2).

MDRDr:

CKD-EPI:

o κ is 0.7 for females and 0.9 for males

o α is -0.329 for females and -0.411 for males


3.3.5. Classification of patients into AKI categories

As we used for this analysis 3 different classifications for AKI, and 2 estimates for missing baseline

serum creatinine concentrations, we classified patients according to 5 different classifications.

1) RIFLE MDRD: AKI was classified using the RIFLE classification. If there was no baseline

creatinine available the re-expressed 4-variable MDRD was used to calculate a baseline value.

2) RIFLE CKD-EPI: AKI was classified using the RIFLE classification. If there was no baseline

creatinine available the CKD-EPI equitation was used to calculate a baseline value.

3) AKIN: AKI was classified using the AKIN classification. We used the lowest creatinine value

in 48u before the start of AKI as baseline creatinine value.

4) KDIGO MDRD: AKI was classified using the KDIGO classification. If there was no baseline

creatinine available the re-expressed 4-variable MDRD was used to calculate a baseline value.

5) KDIGO CKD-EPI: AKI was classified using the KDIGO classification. If there was no

baseline creatinie available the CKD-EPI equitation was used to calculate a baseline value.

Only the first AKI episode was included in our analysis.

3.4. Transient Acute Kidney Injury

Transient Acute Kidney Injury was defined in three different ways:




3.5. Statistical analysis

To describe the characteristics of the study population MS Access 2010 was used. The number of AKI

episodes per patient and duration of these episodes were calculated using MS Access 2010. Specific

cases were selected and exported to SPSS for further statistical analysis


SPSS Statistics version 19 was used to perform the statistical analysis. Categorical variables are

displayed as number (percentage). To analyze categorical variables we used the Chi-square test.

Continuous variables are displayed as median and 25th and 75

th percentiles. We tested continuous

variables for normality by distribution plots, and compared means using Student’s T-test when

normally distributed, and Kruskall-Wallis test and Mann-Whitney-U test when not. A double sided p-

value <0.05 was considered significant.

3.6. Presentation of the results

Tables were made by MS Word 2010. The bar charts were made by MS Excel 2010.


4. Results

4.1. Basic Characteristics of the study population

The AKI-6 database includes 55,486 patient days and 11,309 patients. Three of the AKI-6 centers

contributed for 79% of the study cohort. Among these centers patient’s inclusion was evenly

distributed. The cohort represents a typical ICU population for a developed country. Two-thirds of

patients were of male gender, median age was 62 years, and more than 80% of patients were

Caucasian. In table 4 the baseline characteristics of the study population are described.

Table 4. Baseline Characteristics of the study population

Baseline Characteristics of the study population

Number of patients per participating center (% of total study population)

Pittsburgh 2974 (26.9%)

Rochester 2852 (25.2%)

Ghent 3044 (26.9%)

Vicenza 267 (2.4%)

Perth 2077 (18.4%)

Melbourne 95 (0.8%)

Number of AKI patients per participating center (% of AKI patients per center) Pittsburgh 923 (31,0%)

Rochester 704 (24,7%)

Ghent 679 (22,3%)

Vicenza 99 (37,1%)

Perth 811 (39,0%)

Melbourne 61 (64,2%)

Patient characteristics (% of study population) Gender

Male 6776 (60%)

Female 4532 (40%)

Median age (in years) 62 (48, 73)

Pittsburgh 61 (48,73)

Rochester 66 (52,77)

Ghent 62 (50,72)

Vicenza 64 (45,74)

Perth 55 (38,70)

Melbourne 62 (45,74)

Race

Caucasian 9536 (84.3%)

Black 450 (4.0%)

Hispanic 572 (5.1%)

Asian 43 (0.4%)

American Indian 10 (0.09%)

Other 149 (1.3%)

Availability of baseline creatinine 3452 (30.5%)

Pittsburgh 155 (5.2%)

Rochester 2794 (98.0%)

Ghent 181 (5.9%)


Vicenza 267 (100%)

Perth 0 (0.0%)

Melbourne 55 (58.0%)


4.2. Acute Kidney Injury

A total of 11,309 patients were classified according to the 5 different classifications for AKI that were

used in this analysis: RIFLE MDRD, RIFLE CKD-EPI, AKIN, KDIGO MDRD and KDIGO CKD-

EPI. We calculated the number of AKI episodes per classification, the number of patients who had 1, 2,

3, 4 or more than 4 AKI episodes and the duration of the first AKI episode. The results are described

in tables 5 and 6.

The KDIGO classification was the most sensitive for detection of AKI, and the AKIN classification

the least sensitive. When defined by RIFLE the use of MDRD resulted in a higher number of AKI

episodes, while with KDIGO, the use of the CKD-EPI equation resulted in a higher number of AKI

episodes detected.

The prevalence of AKI varied according to the classification used between 17.8% and 31.0%.

Table 5. Number of AKI episodes per AKI classification

AKI episode

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN

KDIGO

MDRD

KDIGO

CKD-EPI

Total

episodes

3025 2912 2592 3588 4102

≥1 2663 (23.5%) 2568 (22.7%) 2010 (17.8%) 3204 (28.3%) 3506 (31.0%)

≥2 287 (2.5%) 274 (2.4%) 354 (3.1%) 290 (2.6%) 453 (4.0%)

≥3 59 (0.5%) 52 (0.5%) 114 (1.0%) 61 (0.5%) 96 (0.8%)

≥4 14 (0.1%) 14 (0.1%) 55 (0.5%) 21 (0.2%) 26 (0.2%)

>4 2 (0.02%) 4 (0.04%) 59 (0.5%) 12 (0.1%) 21 (0.2%)

In the majority of AKI patients, the duration of the first AKI episode was 1 or 2 days. So transient AKI

was very common among AKI patients at ICU. There was a greater proportion of AKI patients with

shorter duration of AKI (≤2 days) when classified according to AKIN.


Table 6. Duration of first AKI episode per AKI classification

Duration of

first AKI

episode

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

1 day 763 (28.7%) 728 (28.3%) 806 (40.1%) 999 (31.1%) 1475 (42.1%)

2 days 621 (23.3%) 607 (23.6%) 544 (27.1%) 761 (23.8%) 759 (21.6%)

3 days 374 (14.0%) 363 (14.1%) 221 (11.0%) 397 (12.4%) 343 (9.8%)

4 days 245 (9.2%) 240 (9.3%) 124 (6.2%) 253 (7.9%) 244 (7.0%)

5 days 166 (6.2%) 152 (5.9%) 90 (4.5%) 177 (5.5%) 164 (4.7%)

6 days 99 (3.7%) 100 (3.8%) 38 (1.9%) 118 (3.7%) 116 (3.3%)

7 days 76 (2.8%) 72 (2.8%) 32 (1.6%) 87 (2.7%) 75 (2.1%)

>7 days 320 (12.0%) 306 (11.9%) 155 (7.7%) 412 (12.9%) 330 (9.4%)


4.3. Outcomes

The outcomes we analyzed were Intensive Care Unit Mortality (ICU Mortality), Hospital Mortality,

Intensive Care Unit Length of Stay (ICU Length of Stay) and Hospital Mortality. We compared

patients with and without AKI. AKI patients were classified according to the 5 different AKI

classifications: RIFLE MDRD, RIFLE CKD-EPI, AKIN, KDIGO MDRD and KDIGO CKD-EPI. We

also compared the outcomes of the different AKI stages. Only the first AKI episode was included in

our analyses.

4.3.1. ICU Mortality

Total ICU Mortality was 8.7%. Patients with AKI had a higher ICU mortality (17.6%-24.0%)

compared to the patients without AKI (4.5%-5.5%) (table 7). We found a stepwise increase in

mortality with increasing severity of AKI in all classifications. Patients who experienced acute on

chronic AKI (Fc) had a lower mortality compared to Failure patients, when defined according to the

RIFLE classification. When defined by KDIGO, this difference was less pronounced. Mortality for

stage 1 and 2 patients defined according to AKIN was higher when compared to RIFLE and KDIGO

with similar severity of AKI.

Table 7: ICU mortality of patients without and with AKI, defined according to the different AKI

classifications

ICU Mortality

No AKI

(%)

R/1 (%) I/2 (%) F/3 (%) Fc (%) All AKI (%)

RIFLE

MDRD

438 (5.1) 128 (14.8) 154 (22.8) 173 (33.8) 93 (15.5) 548 (20.7)

RIFLE

CKD-EPI

446 (5.1) 124 (15.5) 158 (24.1) 166 (34.1) 93 (15.5) 541 (21.2)

AKIN 507 (5.5) 198 (20.2) 32 (29.1) 253 (27.5) 483 (24.0)

KDIGO

MDRD

365 (4.5) 155 (13.5) 106 (18.6) 89 (27.5) 272 (23.7) 622 (19.5)

KDIGO

CKD-EPI

373 (4.8) 173 (11.1) 119 (19.8) 51 (25.9) 270 (23.7) 613 (17.6)

R/1: Risk/ Stage 1, I/2: Injury/Stage 2, F/3: Failure/ Stage 3, Fc: Acute on chronic AKI


The P-values of the comparison between the different AKI stages per classification are displayed in

table 8. Patients with AKI had a significant higher mortality compared to patients without AKI,

regardless of severity of AKI. The differences between Risk/Stage 1 and Injury/Stage 2 and

Risk/Stage 1 and Failure/Stage 3 were also significant for all classifications. The difference between

Risk/Stage 1 and Acute on chronic (Fc) was significant when defined according to KDIGO. When

defined according to RIFLE the difference was not significant. For the comparison between

Injury/Stage 2 and Failure/Stage 3, Injury/Stage 2 and Acute on chronic (Fc) and Failure/Stage 3 and

Acute on chronic (Fc) the results were variable. Acute on chronic (Fc) defined according to RIFLE

had lower mortality compared to Failure, while this was not the case when defined according to

KDIGO.

Table 8: P-values for ICU mortality of patients without and with AKI, defined according to the

different AKI classifications

ICU Mortality: P-values

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

No AKI and R/1 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and I/2 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and F/3 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and Fc <0.001 <0.001 <0.001 <0.001

R/1 and I/2 <0.001 <0.001 0.031 0.006 <0.001

R/1 and F/3 <0.001 <0.001 <0.001 <0.001 <0.001

R/1 and Fc 0.716 0.914 <0.001 <0.001

I/2 and F/3 <0.001 <0.001 0.724 0.002 0.072

I/2 and Fc 0.001 <0.001 0.017 0.067

F/3 and Fc <0.001 <0.001 0.161 0.504



4.3.2. Hospital Mortality

Total Hospital Mortality was 13.6%. Hospital mortality showed a similar trend as ICU mortality

among the different severity grades of AKI and definitions. Similar to ICU mortality, we found a

higher mortality in AKI patients (25.5%-32.9%) compared to patients without AKI (7.9%-9.4%) (table

9). There was a stepwise increase in mortality with increasing severity of AKI in all classifications.

Again, we found that patients who suffered from acute on chronic AKI (Fc) had lower hospital

mortality than Failure patients when defined by RIFLE. When defined by KDIGO there was no

significant difference.

Table 9: Hospital mortality of patients without and with AKI, defined according to the different AKI

classifications

Hospital Mortality

No AKI

(%)

R/1 (%) I/2(%) F/3 (%) Fc (%) All AKI (%)

RIFLE

MDRD

748 (8.7) 195 (22.9) 217 (32.6) 223 (43.7) 137 (22.9) 772 (29.4)

RIFLE

CKD-EPI

764 (8.8) 187 (23.3) 218 (33.7) 214 (44.1) 138 (23.0) 757 (29.9)

AKIN 864 (9.4) 277 (28.3) 41 (37.3) 341 (37.2) 659 (32.9)

KDIGO

MDRD

673 (7.9) 226 (19.9) 158 (28.1) 121 (37.5) 380 (33.2) 885 (28.0)

KDIGO

CKD-EPI

640 (8.2) 255 (16.6) 180 (30.4) 70 (35.7) 377 (33.2) 882 (25.5)


In table 10 the p-values for the comparison of the different AKI stages per classification are displayed.

Patients with AKI had a significant higher hospital mortality compared to patients without AKI,

regardless of severity of AKI. The difference between Risk/Stage 1 and Injury/Stage 2 and Risk/Stage

1 and Failure/Stage 3 was significant for all classifications. When defined by KDIGO classification

there was a difference between Risk and Acute on chronic AKI (Fc), while when defined by RIFLE,

the difference was not significant. The difference between Injury/stage 2 and Failure/stage 3 was only

significant when defined by both RIFLE variants and KDIGO MDRD. For both RIFLE variants, the

difference between Injury and Acute on chronic (Fc) and Failure and Acute and chronic (Fc) was

significant. For the other classifications variable results were noticed.


Table 10: P-values for Hospital mortality of patients without and with AKI, defined according to the


Hospital Mortality: P-values

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

No AKI and R/1 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and I/2 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and F/3 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and Fc <0.001 <0.001 <0.001 <0.001

R/1 and I/2 <0.001 <0.001 0.050 <0.001 <0.001

R/1 and F/3 <0.001 <0.001 <0.001 <0.001 <0.001

R/1 and Fc 0.996 0.879 <0.001 <0.001

I/2 and F/3 <0.001 <0.001 0.986 0.004 0.166

I/2 and Fc <0.001 <0.001 0.034 0.240

F/3 and Fc <0.001 <0.001 0.153 0.489


4.3.3. ICU Length of stay

Patients with AKI had a longer ICU length of stay compared to patients without AKI (table 11). In

contrast to mortality, we could not find a stepwise increase with increasing severity of AKI. Patients

with Failure/Stage 3 AKI had even a shorter length of stay than patients with Risk/Stage 1 AKI when

defined by both the RIFLE variants and AKIN. For AKIN the difference was even significant.

Probably this can be explained by the higher mortality associated with Failure. The AKI stage with

the longest length of stay was different for every classification: when defined by RIFLE and KDIGO

MDRD it was Risk/Stage 1. When defined by RIFLE CKD-EPI it was Acute on chronic (Fc). When

defined by AKIN it was Stage 2. When defined by KDIGO CKD-EPI there was no difference between

the different stages.


Table 11: ICU Length of Stay of patients without and with AKI, defined according to the different

AKI classifications

ICU Length of stay

No AKI R/1 I/2 F/3 Fc

RIFLE MDRD 2 (1.7; 4.0) 8 (2.1; 10.0) 5 (2.7; 9.0) 4 (2.1; 8.1) 5 (2.7; 10.0)

RIFLE

CKD-EPI

2 (1.7; 4.0) 4 (2.1; 8.3) 4 (2.6; 9.0) 4 (2.1; 8.1) 5 (2.7; 10.0)

AKIN 2 (1.7; 4.0) 6 (3.6; 12.0) 9 (5.0; 17.1) 5 (7.8; 12.0)

KDIGO

MDRD

2 (1.7; 4.0) 5 (2.6; 10.2) 4 (2.4; 8.0) 4 (2.5; 7.9) 4 (2.1; 9.9)

KDIGO

CKD-EPI

2 (1.7; 4.0) 4 (2.0; 8.2) 4 (2.6; 8.0) 4 (2.0; 7.0) 4 (2.1; 9.6)


The p-values for the comparison of the different AKI stages are displayed in table 12. There was a

significant difference between patients with AKI and patients without AKI for all classifications. Only

for AKIN there were significant results for all AKI stages. For the other classification variable results

were noticed. When defined by RIFLE MDRD there was a significant difference between Risk and

Injury, Risk and Acute on chronic (Fc) and Failure and Acute on chronic (Fc). When defined by

RIFLE CKD-EPI the difference was significant between Risk and Acute on chronic (Fc) and Failure

and Acute on chronic (Fc). When defined by KDIGO MDRD there was a significant difference

between Stage 1 and Stage 2, Stage 1 and Stage 3 and Stage 1 and Acute on chronic (Fc). When

defined by KDIGO CKD-EPI no significant results could be found between the different AKI stages.


Table 12: P-values for ICU Length of Stay of patients without and with AKI, defined according to

the different AKI classifications

ICU Length of stay: P-values

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

No AKI and R/1 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and I/2 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and F/3 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and Fc <0.001 <0.001 <0.001 <0.001

R/1 and I/2 0.016 0.104 <0.001 0.027 0.063

R/1 and F/3 0.504 0.785 <0.001 0.027 0.584

R/1 and Fc 0.002 0.006 0.042 0.085

I/2 and F/3 0.160 0.261 <0.001 0.733 0.068

I/2 and Fc 0.467 0.274 0.673 0.860

F/3 and Fc 0.037 0.031 0.482 0.120


4.3.4. Hospital Length of Stay

Patients with AKI had a longer Hospital Length of Stay compared to patients without AKI (table 13).

Hospital Length of Stay showed similar trends as ICU Length of Stay, namely that we could not

discover a stepwise increase when increasing AKI severity. When defined by both KDIGO variants,

patients with Stage 3 AKI had even a significant longer length of stay compared to Stage 1 AKI

patients. Probably this can be explained by the higher mortality associated with Stage 3. The AKI

stage with the longest Hospital Length of Stay varied among the different classifications. When

defined by both RIFLE variants and KDIGO CKD-EPI it was Acute on chronic (Fc). When defined by

AKIN it were Stage 1 and Stage 3. When defined by KDIGO MDRD it was Stage 1.


Table 13: Hospital Length of Stay of patients without and with AKI, defined according to the


Hospital Length of stay

No AKI (%) R/1 (%) I/2 (%) F/3 (%) Fc (%)

RIFLE

MDRD

10

(6.0; 18.0)

14

(8.0; 26.0)

15

(7.0; 29.0)

14

(7.0; 27.0)

16

(9.0; 32.0)

RIFLE

CKD-EPI

10

(6.0; 18.0)

14

(8.0; 27.0)

15

(7.0; 28.0)

14

(7.0; 26.5)

16

(9.0; 31.8)

AKIN 10

(6.0; 18.0)

17

(10.0; 30.0)

20

(12.0; 41.5)

17

(8.0; 43.0)

KDIGO

MDRD

10

(6.0; 18.0)

15

(9;0; 29.4)

15

(7.8; 26.0)

13

(7.0; 26.0)

15

(7.9; 33.5)

KDIGO

CKD-EPI

10

(6.0; 18.0)

14

(7.1; 26.0)

15

(7.0; 27.0)

12

(6.0; 21.8)

15

(7.9; 29.9)


In table 14 the p-values for comparison of the different AKI stages are displayed. There was always a

significant difference between AKI patients and patients without AKI except for Acute on chronic

when defined by KDIGO CKD-EPI. For the differences between the other AKI stages, the results

were variable. For both RIFLE variants there were significant results for the difference between

Risk/Injury/Failure and Acute on chronic (Fc). For AKIN we found significant results for the

difference between Stage 1 and Stage 2, and Stage 2 and Stage 3. For KDIGO MDRD, significant

results could be found for the difference between Stage 1 and Stage 2, Stage 1 and Stage 3, and Stage

3 and Acute on chronic (Fc). For KDIGO CKD-EPI there were significant results for the difference

between Stage 1 and Stage 3, Stage 2 and Stage 3, and Stage 3 and Acute on chronic (Fc).


Table 14: P-values for Hospital Length of Stay of patients without and with AKI, defined according

to the different AKI classifications

ICU Length of stay: P-values

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

No AKI and R/1 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and I/2 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and F/3 <0.001 <0.001 <0.001 <0.001 <0.001

No AKI and Fc <0.001 <0.001 <0.001 0.135

R/1 and I/2 0.337 0.687 0.042 0.030 0.392

R/1 and F/3 0.270 0.085 0.404 0.001 0.004

R/1 and Fc 0.001 0.002 0.249 0.061

I/2 and F/3 0.075 0.061 0.030 0.193 0.002

I/2 and Fc 0.031 0.015 0.238 0.534

F/3 and Fc <0.001 <0.001 0.018 <0.001



4.4. Transient AKI

One of the important aims of the TRAK study was to investigate the influence of AKI duration on

outcomes in ICU patients. To explore this influence we compared patients with transient AKI and

patients with a longer AKI episode. We defined transient AKI in three different ways:




In table 15 to 23, the period prevalence of transient AKI and the influence of AKI duration on

outcomes are described for the 5 different AKI classifications used in this analysis: RIFLE MDRD,

RIFLE CKD-EPI, AKIN, KDIGO MDRD, KDIGO CKD-EPI.

We also compared the ICU and hospital mortality of the different transient AKI definitions (figure 1, 2

and table 24 and 25).

4.4.1. Transient AKI defined as ≤3 days of AKI (AKIt3)

4.4.1.1. Period prevalence

The period prevalence of AKIt3 varied according to the classification used between 13.9% and 22.7%

of ICU patients (table 15), with KDIGO CKD-EPI as most sensitive, and AKIN as the least sensitive

classification for detecting AKIt3. AKIt3 occurred in the majority of AKI patients during their ICU

stay and varied according to the classification used from 65.7% to 78.1% of AKI patients.

Table 15. Period prevalence of AKIt3, defined according to the different AKI classifications

Period prevalence of AKIt3

AKIt3 RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

N 1751 1690 1570 2158 2571

% ICU 15.5 14.9 13.9 19.1 22.7

% AKI 65.7 65.8 78.1 67.4 73.3

N: number of patients, % ICU: % of all ICU patients, % AKI: % of all AKI patients, defined according to the

different classification.


4.4.1.2. Mortality

When defined by RIFLE MDRD, RIFLE CKD-EPI and KDIGO MDRD, AKIt3 patients had a similar

ICU mortality compared to patients with a longer AKI episode (> 3d) (table 16). When defined by

AKIN and KDIGO CKD-EPI, AKIt3 patients had a significant lower ICU mortality. Hospital

mortality was significantly lower for AKIt3 patients for all AKI classifications (table 16).

Table 16. ICU and hospital mortality of AKIt3 compared with a longer AKI episode (>3 days),

defined according to the different AKI classifications.

ICU Mortality (%) Hospital Mortality (%)

≤3 days >3 days p-value ≤3 days >3 days p-value

RIFLE

MDRD

359 (20.5) 187 (20.6) 0.917 479 (27.5) 294 (32.7) 0.006

RIFLE

CKD-EPI

360 (21.3) 187 (20.5) 0.641 474 (28.2) 283 (32.8) 0.018

AKIN 358 (22.8) 120 (27.3) 0.048 484 (30.9) 174 (39.7) <0.001

KDIGO

MDRD

397 (18.4) 222 (21.2) 0.063 533 (25.0) 351 (33.8) <0.001

KDIGO

CKD-EPI

401 (15.6) 211 (22.7) <0.001 557 (21.8) 325 (35.2) <0.001

4.4.1.3. Length of Stay

Both ICU and hospital length of stay were longer for patients who experienced a longer period of AKI

(>3d) compared to AKIt3 patients (table 17). The results were strongly significant for all AKI

classifications (p<0.001).


Table 17. ICU and hospital length of stay of AKIt3 compared with a longer AKI episode (>3 days),


ICU LOS Hospital LOS


RIFLE

MDRD

3

(2.0;5.3)

8

(5.0;18;0)

<0.001 12

(6.0; 22.0)

22

(14.0; 39.0)

<0.001

RIFLE

CKD-EPI

5

(2.0; 5.5)

8

(5.0; 14.7)

<0.001 12

(6.0; 22;0)

22

(14.0; 40.0)

<0.001

AKIN 5

(2.8; 10.0)

10

(6.4; 19.0)

<0.001 15

(8.0; 29.0)

26

(15.0; 44.0)

<0.001

KDIGO

MDRD

3

(2.0; 6.0)

8

(5.0; 15.0)

<0.001 12

(7.0; 23.0)

21

(13.0; 39.0)

<0.001

KDIGO

CKD-EPI

3

(1.8; 5.8)

7

(4.0; 13.0)

<0.001 12

(6.0; 22.0)

19

(11.0; 36.0)

<0.001

4.4.2. Transient AKI defined as ≤ 2 days of AKI (AKIt2)


Similar to AKIt3, the period prevalence of AKIt2 varied according to the definition used (table 18).

KDIGO CKD-EPI was the most sensitive classification (19.7%), RIFLE MDRD the least sensitive

(8.0%) for detecting AKIt2. AKIt2 occurred in 34.0% to 67.1% of AKI patients.



AKIt2 RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

N 905 1332 1348 1758 2230

% ICU 8.0 11.8 11.9 15.5 19.7

% AKI 34.0 51.9 67.1 54.9 63.6




4.4.2.2. Mortality

AKIt2 patients had a similar ICU mortality compared to patients who experienced a longer AKI

episode (>2d), except when defined by KDIGO CKD-EPI. When defined by AKIN and both KDIGO

variants, AKIt2 patients had a lower hospital mortality. When defined by both RIFLE variants, the

hospital mortality is similar for AKIt2 patients and patients with a longer AKI episode (>2d).

Table 19. ICU and hospital mortality of AKIt2 compared with a longer AKI episode (> 2 days),




RIFLE

MDRD

191 (21.1) 255 (19.9) 0.457 380 (27.7) 393 (31.0) 0.067

RIFLE

CKD-EPI

289 (21.7) 249 (20.2) 0.345 372 (28.1) 385 (31.5) 0.064

AKIN 306 (22.7) 172 (26.1) 0.093 412 (30.6) 246 (37.3) 0.003

KDIGO

MDRD

327 (18.6) 292 (20.2) 0.254 427 (24.5) 457 (31.9) <0.001

KDIGO

CKD-EPI

339 (15.2) 273 (21.5) <0.001 459 (20.7) 423 (33.6) <0.001


Similar to AKIt3, length of stay in the ICU, and in the hospital were longer in patients who

experienced a longer AKI episode (>2) compared to AKIt2 patients (table 20). The results were

strongly significant for all AKI classifications (p<0.001).


Table 20. ICU and hospital length of stay of AKIt2 compared with a longer AKI episode (>2 days),




RIFLE

MDRD

3

(1.9; 5.0)

7

(4.0; 12.7)

<0.001 11

(6.0; 21.0)

19

(11.0; 36.0)

<0.001

RIFLE

CKD-EPI

3

(1.9; 5.0)

7

(4.0; 12.8)

<0.001 11

(6.0; 20.1)

19

(11.0; 36;0)

<0.001

AKIN 5

(2.7; 10.0)

9

(5.0; 16.9)

<0.001 15

(7.8; 28.0)

22

(13.0; 41.8)

<0.001

KDIGO

MDRD

3

(1.9; 6.0)

7

(4.0; 12.7)

<0.001 12

(6.0; 23.0)

19

(11.0; 35.0)

<0.001

KDIGO

CKD-EPI

3

(1.8; 5.8)

7

(4.0; 13.0)

<0.001 12

(6.0; 22.0)

19

(11.0; 36.0)

<0.001

4.4.3. Transient AKI defined as ≤1 day of AKI (AKIt1)


The period prevalence of AKIt1 varied according to the definition used from 6.4% to 13.1% (table 21).

Similar to AKIt3 and AKIt2, KDIGO CKD-EPI was the most sensitive classification for detecting

AKIt1. RIFLE CKD-EPI was the least sensitive classification. AKIt1 occurred in 28.2% to 42.1% of

AKI patients.



AKIt1 RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

N 758 723 805 995 1476

% ICU 6.7 6.4 7.1 8.7 13.1

% AKI 28.5 28.2 40.0 27.7 42.1




4.4.3.2. Mortality

AKIt1 patients had a similar ICU mortality compared to patients who experienced a longer AKI

episode (> 1 day), except when defined by KDIGO CKD-EPI, where AKIt1 patients had a lower ICU

mortality (table 22). Hospital mortality was similar for AKIt1 patients defined by both RIFLE variants

and AKIN compared to patients who had a longer AKI episode (>1 day). When defined by both

KDIGO variants, AKIt1 patients had lower hospital mortality.

Table 22. ICU and hospital mortality of AKIt1 compared with a longer AKI episode (> 1 day),



≤1 day >1 day p-value ≤1 day >1 day p-value

RIFLE

MDRD

169 (22.3) 377 (19.8) 0.160 213 (28.2) 560 (29.7) 0.462

RIFLE

CKD-EPI

167 (23.1) 371 (20.2) 0.104 206 (28.7) 551 (30.2) 0.444

AKIN 198 (24.6) 280 (23.3) 0.499 251 (31.2) 407 (33.9) 0.212

KDIGO

MDRD

197 (19.8) 422 (19.1) 0.661 251 (25.5) 633 (28.9) 0.044

KDIGO

CKD-EPI

223 (15.1) 389 (19.2) 0.002 292 (20.0) 590 (29.3) <0.001


Similar to AKIt3 and AKIt2, patients with a longer AKI episode (>1 day) had a longer ICU and

hospital length of stay compared to AKIt1 patients (table 23). The results were strongly significant for

all classifications (p<0.001).


Table 23. ICU and hospital length of stay of AKIt1 compared with a longer AKI episode (>1 day),



≤1 day >1 day p-value ≤1 day >1 day p-value

RIFLE

MDRD

3

(1.6; 5.0)

5

(3.0; 10.0)

<0.001 10

(5.0; 20.0)

16

(9.0; 31.0)

<0.001

RIFLE

CKD-EPI

3

(1.5; 5.5)

5

(3.0; 5.0)

<0.001 10

(5.0; 20.0)

16

(9.0; 31.0)

<0.001

AKIN 4

(2.1; 9.2)

7

(4.0; 13.7)

<0.001 14

(7.1; 27.0)

19

(11.0; 35.0)

<0.001

KDIGO

MDRD

3

(1.6; 6.0)

5

(3.0; 10.0)

<0.001 12

(6.0; 22.0)

16

(9.0; 31.0)

<0.001

KDIGO

CKD-EPI

3

(1.6; 5.9)

5

(3.0; 10.6)

<0.001 11

(6.0; 22.0)

16

(9.0; 31.0)

<0.001

4.4.4. Comparison of mortality between AKIt1, AKIt2 and AKIt3

4.4.4.1. ICU Mortality

Patients with transient AKI had a higher ICU mortality compared to patients without AKI, even when

AKI only lasted for 1 day (AKIt1) (figure 1). The duration of the transient AKI had no influence on

the ICU mortality. AKIt1, AKIt2 and AKIt3 had a similar ICU Mortality in all AKI classifications,

except when defined according to AKIN.


Figure 1. Comparison of ICU Mortality of patients with and without transient AKI (AKIt1, AKIt2

and AKIt3), defined according to the different AKI classifications.

The p-values for the comparison of ICU Mortality between the different definitions of transient AKI

are displayed in table 24. The ICU Mortality was similar for AKIt1, AKIt2, AKIt3 for almost all

classifications. Only when defined by AKIN there was a significant difference, more specifically there

was a significant difference between AKIt1 and AKIt2 (p=0.042).

Table 24. P-values for the comparison of ICU mortality between AKIt1, AKIt2 and AKIt3.

P-values of ICU Mortality

RIFLE MDRD 0.235

RIFLE CKD-EPI 0.191

AKIN 0.042

KDIGO MDRD 0.147

KDIGO CKD-EPI 0.934

4.4.4.2. Hospital Mortality

Transient AKI patients had a higher hospital mortality compared to patients without AKI, even when

AKI only lasted for 1 day (AKIt1) (figure 1). The duration of the transient AKI had no influence on

the hospital mortality. AKIt1, AKIt2 and AKIt3 had a similar hospital mortality.

0%

5%

10%

15%

20%

25%

30%

RIFLE MDRD RIFLE CKD-EPI AKIN KDIGO MDRD KDIGO CKD-EPI

no AKI

AKIt1

AKIt2

AKIt3

all AKI


Figure 2. Comparison of Hospital Mortality for patients with and without transient AKI (AKIt1,

AKIt2 and AKIt3), defined according to the different AKI classifications.

The p-values for the comparison of Hospital Mortality between the different definitions of transient

AKI are displayed in table 25. The Hospital Mortality was similar for AKIt1, AKIt2, AKIt3 for all

classifications.

Table 25. P-values for the comparison of Hospital mortality between AKIt1, AKIt2 and AKIt3.

P-values of Hospital Mortality

RIFLE MDRD 0.626

RIFLE CKD-EPI 0.651

AKIN 0.554

KDIGO MDRD 0.290

KDIGO CKD-EPI 0.228

0%

5%

10%

15%

20%

25%

30%

35%

RIFLE MDRD RIFLE CKD-EPI AKIN KDIGO MDRD KDIGO CKD-EPI

no AKI

AKIt1

AKIt2

AKIt3

all AKI


5. Discussion

Acute Kidney Injury (AKI) was a common finding in this large cohort of ICU patients, and the period

prevalence varied largely depending the AKI classification used. During ICU stay, 17.8 to 31.0% of

the patients had an episode of AKI. This was associated with worse clinical outcomes such as

increased length of stay and mortality.

Transient AKI was prevalent amongst ICU and AKI patients, and was also associated with a higher

mortality. ICU and hospital mortality of Transient AKI variants (1 to 3 days AKI) were comparable to

that of all AKI. Finally, a longer duration of an AKI episode was associated with a higher mortality

and a longer length of stay compared to transient AKI.

5.1. Prevalence of AKI

In our TRAK study we found an overall AKI prevalence of 17.8-31.0% depending on which

classification was used. The AKI prevalence per classification was: 23.5% for RIFLE MDRD, 22.7%

for RIFLE CKD-EPI, 17.8% for AKIN, 28.3% for KDIGO MDRD and 31.0% for KDIGO CKD-EPI.

The prevalence and incidence of AKI varied among ICU studies, depending on the study population (1,

10). In the NEiHROS-AKI study, the first prospective multicenter study of AKI, 10.8% of the 2164

ICU patients suffered from AKI (11). Thakar et al. (12) found in the Veteran Affairs Hospital ICUs

across the US an overall incidence of AKI of 22% when AKI was defiend by creatinine criteria only.

In the study by Ostermann and Chang (13) AKI occurred in 35.8% of the ICU patients. Bashaw et al.

(14) analyzed AKI by RIFLE using only creatinine values. The incidence of AKI in their ICU

population was 36.1%. Recently Mandelbnaum found an incidence of 57% when AKI was defined by

AKIN criteria (15). Finally, in a study by Hoste et al. (16) in 5,383 ICU patients of University of

Pittsburg Medical Center, AKI occurred in 67% of the patients.

Differences between these cohorts can be explained by differences in the cohort observed (different

patient characteristics or observation period) and differences in the definition for AKI used (creatinine

criteria only, or combination of creatinine and urine output criteria, variant of urine output criteria, …).

A remarkable result was that the AKI prevalence of the Pittsburg cohort in the TRAK study was only

31.0%, which was very low compared to the 67% found by Hoste et al. (16). Several reasons could be

found to explain this difference. Firstly this was a different patient cohort. The Pittsburg cohort from

the Hoste study was from 2000 to 2001, the Pittsburg cohort from the TRAK study was from 2005 to

2007. Secondly the urine output criteria were not included in the TRAK study in contrast to the Hoste

study. Thirdly there was a different method of estimating baseline creatinine. In the study by Hoste et

al. (16) the lowest creatinine value among the hospital admission creatinine, the ICU admission


creatinine or the MDRD creatinine value was used as the baseline value. This could result in an

overestimating of the prevalence of AKI. In the TRAK study the baseline creatinine value was used

when available. When there was no baseline available, the re-expressed 4-variable MDRD or CKD-

EPI equitation were used to calculate a baseline value. This was also suggested by Zavada et al. (9).

They stated that the use of the 4-variable MDRD equitation to calculate baseline creatinine may over-

or underestimate some mild AKI cases, but does not misclassify patients in Injury and Failure.

Whenever possible, recorded creatinine values should be used as a reference of baseline. In a big

cross-sectional analysis, the CKD-EPI creatinine equitation proved to be better than the MDRD

equation, especially at higher GFR, and could replace it for routine clinical use (7). In the TRAK study

small differences were seen between the use of the re-expressed 4 variable MDRD and the CKD-EPI

equitation for calculating a baseline creatinine value. Further analyses will be needed to explore these

differences in more detail.

5.2. Outcomes

Patients with AKI had a higher ICU mortality (17.6%-24.0%) compared to the patients without AKI

(4.5%-5.5%). Similar to ICU mortality we found higher hospital mortality in AKI patients (25.5%-

32.9%) compared to patients without AKI (7.9%-9.4%). AKI patients also had a longer ICU and

hospital length of stay.

Patients in the Risk stage of RIFLE or Stage 1 of AKIN and KDIGO had a significant higher ICU and

hospital mortality and significant longer ICU and hospital length of stay compared to patients without

AKI. This again emphasizes the importance of early AKI detection, AKI treatment and AKI

prevention at ICU.

Transient AKI patients had also a higher ICU and hospital mortality compared to patients without AKI,

even when the AKI episode only lasted for 1 day. Also this result emphasizes the importance of early

AKI detection, AKI treatment and AKI prevention at ICU. There was no difference in mortality

between the different definitions of transient AKI and also not between Transient AKI and all AKI.

The reason for this remained unclear. Further research will be needed to clarify this result.

The longer the duration of AKI, the more impact we found on outcomes. Patients with AKIt3 had

similar ICU mortality, but lower hospital mortality compared to patients with a longer AKI episode

(>3 days). AKIt2 patients had similar ICU mortality compared to patients with a longer AKI episode (>

2 days). But, according to the classification used, AKIt2 patients had similar or lower hospital

mortality compared to patients who experienced a longer AKI episode (>2 days). Finally, patients with


AKIt1 had a similar ICU and hospital mortality compared to patients with a longer AKI episode (>1

day). Transient AKI defined according to the 3 time periods (AKIt3, AKIt2 and AKIt1) was associated

with a significant shorter ICU and hospital length of stay compared to longer AKI episodes.

It was remarkable that transient AKI patients (AKIt3 and AKIt2) had similar ICU mortality, but lower

hospital mortality than patients with longer AKI episodes. A possible explanation for this may be, that

a longer period of AKI could also be associated with greater severity of AKI (more stage 2 or 3

patients), and is therefore a more important modifier of outcome. Also, longer duration of AKI may be

lead to more comorbidity and so impact on outcome. Further analyses will be needed to clarify the

cause of this remarkable result.

In almost all AKI studies the relation between morbidity and mortality was examined based on the

maximum AKI stage. Uchino et al. (5) and Coca et al.(8) demonstrated that the duration of AKI has

also an impact on hospital mortality. Uchino classified patients with an AKI episode of <72h as

transient azotemia (TA). Patients with TA had a significantly higher odds ratio for hospital mortality,

even when lasting only for 24 hours (5).

Coca prospectively studied 35,302 US diabetic veterans undergoing their first noncardiac surgery.

AKI was classified according to the AKIN classification and by duration (short (less than 2 days),

medium (3-6 days) or long (7 days or more)). 17.8% of the patient population suffered from AKI.

Both a higher stage and duration were independently associated with increased risk of long-term

mortality. Within each stage, longer duration of AKI was significantly associated with a graded higher

rate of mortality (8).

The strength of these studies is their large study population. Their major limitation is their limited

external validity. The Uchino study is a single-center study in hospitalized patients and the Coca study

only included US diabetic veterans undergoing their first noncardiac surgery, which can result in a

higher incidence of AKI in the study population.

5.3. Classifications of AKI

Comparing the five classification used in this analysis: RIFLE MDRD, RIFLE CKD-EPI, AKIN,

KDIGO MDRD and KDIGO CKD-EPI, differences could be seen in AKI prevalence, duration of the

first AKI episode, clinical outcomes, transient AKI prevalence and transient AKI outcomes.


5.3.1. AKI and transient AKI prevalence

The KDIGO classification was the most sensitive for identifying AKI, the AKIN classification the

least sensitive. The use of CKD-EPI as a marker for baseline serum creatinine concentration in

patients where this was not available gave various results. When defined by RIFLE, AKI prevalence

decreased when using CKD-EPI, when defined by KDIGO, AKI prevalence increased. The duration of

the first AKI episode also varied according to the classification used. There was a greater proportion of

AKI patients with shorter duration of AKI (≤2 days) when classified according to AKIN.

The prevalence of transient AKI also varied among the different classifications. For the three different

definitions of transient AKI, the prevalence was the highest for KDIGO CKD-EPI. For AKIt3, the

prevalence was the lowest for AKIN. For AKIt2, the prevalence was the lowest for RIFLE MDRD.

For AKIt1, the prevalence was the lowest for RIFLE CKD-EPI.

Using CKD-EPI increased the incidence of transient AKI for the KDIGO classification and gave

various results for the RIFLE classification compared with using MDRD.

The prevalence of transient AKI within AKI patients also differed among the different classifications.

Of all AKI cases, the period prevalence of AKIt3 was 65.7 to 78.1%, of AKIt2 34.0 to 67.1% and of

AKIt12 27.7 to 42.1% according to the classifications used. So transient AKI had a very high

prevalence among AKI patients. Transient AKI also had a high prevalence in ICU patients. AKIt3

occurred in 13.9 to 22.7% of ICU patients according to the AKI classification used. AKIt2 and AKIt1

were still relatively prevalent in this large ICU cohort (AKIt2: 8.0 to 19.7%, and AKIt1: 6.4 to 13.1%

of ICU patients).

5.3.2. AKI and transient AKI outcomes

Although the AKIN and KDIGO classification are modifications of the RIFLE classification and they

only differ in minor details, large differences can be seen in clinical outcomes between the different

classifications. ICU mortality varied from 17.6% to 24.0% among the different classifications, hospital

mortality varied from 25.5% to 32.9% and also ICU and hospital length of stay differed among the

different classifications. The differences between the different AKI stages varied also according to the

classification used.

Also for transient AKI, outcomes varied among the different classifications, except for the ICU and

hospital length of stay, which was significantly shorter in transient AKI patients for all classifications.

For ICU and hospital mortality we found various results for the different classifications.


These findings illustrate the importance of the classification used for AKI when comparing studies.

Similar to findings by Joannidis et al. (17) we found that the AKIN classification was found less

sensitive in this cohort. Also, the use of the more precise CKD-EPI equation for assessment of

baseline creatinine yielded different results compared to the recent golden standard, the MDRD

equation. Further analyses will be needed to explore the cause of this difference in AKI prevalence and

outcomes between the different AKI classifications.

5.4. Strengths and limitations

Our TRAK study had both strengths and limitations. AKI-6 was a multicenter, transatlantic database

containing 11,309 ICU patients from Belgium, Italy, US (2 centers) and Australia (2 centers). It was

also the first study that explored in such great detail duration of AKI and transient AKI. On the other

hand, the TRAK study was a retrospective study with an unequal patient distribution (Ghent, Pittsburg

and Rochester together included more than 75% of the study population). Secondly we did not

incorporate urine output data, which may result in an underestimating of the AKI prevalence. Thirdly

there was no baseline value available for 69.5% of the patients, which may result in a misclassification

and over- or underestimating of AKI prevalence. Fourthly we did not analyze the severity of transient

AKI. Further analyses will be needed to explore this is more detail.


6. Conclusion

In this large multicentric, international cohort of ICU patients, we found that AKI occurred in one fifth

to one-third of ICU patients. Further, transient AKI accounted for two-thirds of AKI cases, and

occurred in 10 to 20% of ICU patients. AKI and transient AKI were related to an increase of ICU and

hospital mortality and a longer ICU and hospital length of stay. ICU mortality was comparable

between AKIt2 and AKIt3 patients, and patients with longer duration of AKI. Hospital mortality was

however lower. AKIt1 had similar ICU and hospital mortality compared to patients with longer AKI

duration. A longer AKI duration was associated with a longer ICU and hospital length of stay.

Different AKI classifications, i.e. the three AKI classifications, RIFLE, AKIN, KDIGO, and the use of

the re-expressed 4-variable MDRD and CKD-EPI equation, resulted in large variations. Further

research will be needed to explore these differences in more detail.

In the future, duration of AKI should be incorporated in new AKI consensus definitions and used in

clinical studies.


7. Nederlandse samenvatting

7.1. Inleiding

Acute nierinsufficiëntie (AKI) is een veel voorkomende problematiek op Intensieve Zorgen (IZ) en is

geassocieerd met een hoger risico op sterfte. Gedurende vele jaren was er geen consensus definitie

voor acute nierinsufficiëntie, maar in de laatste 10 jaar zijn er verschillende ontwikkeld. In 2004

ontwikkelde de Acute Dialysis Quality Initiative (ADQI) groep de RIFLE classificatie (2). Studies

toonden aan dat tot twee derde van de IZ patiënten acute nierinsufficiëntie, gedefinieerd volgens de

RIFLE classificatie, ontwikkelden (1). Ondertussen werden er al twee aanpassingen van de RIFLE

classificatie gepubliceerd. In 2007 ontwikkelde het Acute Kidney Injury Network de AKIN

classificatie (3) en enkele maanden geleden werd de KDIGO classificatie ontwikkeld (4).

Recent werd transiënte acute nierinsufficiëntie door Uchino et. al (5) gedefinieerd als acute

nierinsufficiëntie die minder dan 72 uur duurde. Patiënten met transiënte acute nierinsufficiëntie

hadden een grotere odds ratio voor mortaliteit. Een andere studie van Coca et al. (8) toonde aan dat de

duur van een postoperatieve episode van acute nierinsufficiëntie geassocieerd was met een hogere

mortaliteit bij Amerikaanse veteranen met diabetes mellitus.

Het doel van deze AKI-6 Transiënte nierinsufficiëntie Studie (TRAK Studie) was om de invloed van

de duur van een episode van acute nierinsufficiëntie op mortaliteit en opnameduur te onderzoeken in

een IZ populatie. We hebben de verschillende classificaties voor acute nierinsufficiëntie en de

verschillende manieren om de basis creatinine waarde te berekenen, vergeleken.

7.2. Methodologie

De TRAK Studie is een retrospectieve, multicentrische, internationale cohort studie. De data werden

verzameld met behulp van de AKI-6 studie groep. AKI-6 is een multicentrische, trans-Atlantische

studiegroep met intensivisten van 6 verschillende centra, 2 centra in de Verenigde Staten, 2 Europese

centra en 2 Australische centra. De databank bestond uit 11,309 patiënten die opgenomen waren op IZ

in de periode 2005 tot 2007.

Tijdens het IZ verblijf werden verschillende gegevens geregistreerd: laagste serum creatinine waarde,

urine output, behandeling met mechanische ventilatie en behandeling met niervervangende therapie

(dialyse). Er werden ook verschillende outcomes geregistreerd, namelijk mortaliteit tijdens de opname

op IZ, mortaliteit tijdens de ziekenhuisopname, opnameduur op IZ en opnameduur in het ziekenhuis.


Om de creatinine waarden van de verschillende centra te kunnen vergelijken, werden de waarden

omgezet naar de IDMS standaarden. Vier van de zes centra gebruikten de IDMS methode al in hun lab,

dus daar was geen herberekening nodig. Voor de andere twee centra gebruikten we de formules van

Zavada et al. (9).

Patiënten met acute nierinsufficiëntie werden geclassificeerd volgens de RIFLE, AKIN en KDIGO

classificaties. Door het groot aantal ontbrekende waarden voor de urine output, werden enkel de

creatinine waarden gebruikt. De creatinine waarden voor de verschillende classificaties zijn

weergegeven in tabel 1-3. De RIFLE en KDIGO classificaties gebruikten als basis creatinine waarde

een waarde die bij de patiënt gemeten werd voor de huidige IZ opname. Indien deze waarde niet

gekend was, werd de basis creatinine waarde berekend a.d.h.v. de Glomerulaire Filtratie Snelheid

(GFR). De MDRD met 4 variabelen (gecorrigeerd voor IDMS) (6) en de CKD-EPI formule (7)

werden gebruikt om de basis creatinine waarde te berekenen. Bij patiënten zonder chronische

nierinsufficiëntie zijn we uitgegaan van een GFR van 75 ml/min (1, 2).

De AKIN definitie maakte geen gebruik van een vooraf gemeten basis creatinine. Hier werd de laagste

creatinine waarde in 48u voor het optreden van de acute nierinsufficiëntie gebruikt.

Op deze manier komen we dus tot 5 definities voor acute nierinsufficiëntie die gebruikt werden in

deze studie: RIFLE MDRD, RIFLE CKD-EPI, AKIN, KDIGO MDRD en KDIGO CKD-EPI.

Transiënte acute nierinsufficiëntie werd gedefinieerd op 3 verschillende manieren:

1. Episode van acute nierinsufficiëntie van ≤ 3 dagen (AKIt3)

2. Episode van acute nierinsufficiëntie van ≤ 2 dagen (AKIt2)

3. Episode van acute nierinsufficiëntie van ≤ 1 dag (AKIt1)

Om de karakteristieken van de studie populatie te beschrijven werd er gebruik gemaakt van MS

Access 2010 en SPSS Statistics versie 19. Categorische variabelen werden weergegeven als aantallen

(percentage) en werden geanalyseerd m.b.v. de Chi-kwadraat test. Continue variabelen werden

weergegeven als de mediaan en het 25ste

en 75ste

percentiel. Continue variabelen werden getest op

normale verdeling m.b.v. distributie plots en geanalyseerd m.b.v. de Students’ T-test indien ze

normaal verdeeld waren en m.b.v. de Kruskal-Wallis test en de Mann-Whitney U test indien niet. Een

2-zijdige p-waarde van ≤0.05 werd als significant beschouwd.


7.3. Resultaten

Van alle IZ patiënten hadden 17.8% tot 31.0% acute nierinsufficiëntie (AKI) (tabel 5). De KDIGO

classificatie was de gevoeligste classificatie om AKI te detecteren, de AKIN classificatie de minst

gevoelige. Indien we AKI definieerden volgens RIFLE gaf het gebruik van de MDRD formule de

meeste AKI episodes. Indien we AKI definieerden volgens KDIGO gaf de CKD-EPI formule de

meeste AKI episodes (tabel 5).

In de meerderheid van de AKI patiënten duurde de eerste AKI episode maar 1 of 2 dagen. Dit betekent

dat transiënte acute nierinsufficiëntie zeer veel voorkwam bij patiënten met AKI. Er was een grotere

proportie patiënten met een kortere AKI episode (≤2 dagen) indien AKI gedefinieerd werd volgens de

AKIN criteria (tabel 6).

Patiënten met acute nierinsufficiëntie hadden een hogere IZ mortaliteit (17.6%-24.0%) in vergelijking

met patiënten zonder acute nierinsufficiëntie (4.5%-5.5%). Er was een stapsgewijze toename van de

mortaliteit bij een toename van de ernst van de acute nierinsufficiëntie. De patiënten die acute

bovenop chronische nierinsufficiëntie (Fc) hadden, hadden iets andere kenmerken dan de andere

patiënten (tabel 7). De verschillen tussen de verschillende AKI stadia varieerden naargelang de

classificatie die gebruikt werd (tabel 8).

De ziekenhuismortaliteit toonde dezelfde trends als de IZ mortaliteit, met ook hier een stapsgewijze

toename van de mortaliteit bij ernstigere AKI stadia. Patiënten met acute nierinsufficiëntie hadden een

hogere ziekenhuismortaliteit (25.5%-32.9%) in vergelijking met patiënten zonder acute

nierinsufficiëntie (7.9%-9.4%) (tabel 9). De verschillen tussen de verschillende AKI stadia varieerden

ook hier naargelang de classificatie die gebruikt werd (tabel 10).

Patiënten met acute nierinsufficiëntie hadden een langer verblijf op IZ dan patiënten zonder acute

nierinsufficiëntie. Maar in tegenstelling tot bij de mortaliteit konden we hier geen stapsgewijze trend

waarnemen (tabel 11). Ook hier waren er verschillen tussen de verschillende classificaties (tabel 12).

Ook het verblijf in het ziekenhuis was langer bij patiënten met acute nierinsufficiëntie in vergelijking

met patiënten zonder acute nierinsufficiëntie en ook hier was er geen stapsgewijze trend waar te

nemen (tabel 13). De verschillen tussen de verschillende classificaties worden weergegeven in tabel 14.

Een transiënte episode van acute nierinsufficiëntie van ≤3 dagen (AKIt3) kwam voor in 13.9% tot 22.7%

van de IZ patiënten. De KDIGO CKD-EPI was de meest gevoelige classificatie voor het detecteren


van AKIt3, AKIN de minst gevoelige classificatie. AKIt3 kwam voor bij 65.7% tot 78.1% van de

patiënten met acute nierinsufficiëntie (tabel 15).

AKIt3 patiënten hadden een gelijkaardige IZ mortaliteit in vergelijking met patiënten met een langere

AKI episode (>3 dagen) indien AKI gedefinieerd werd volgens RIFLE MDRD, RIFLE CKD-EPI en

KDIGO MDRD. Indien AKI gedefinieerd werd volgens AKIN en KDIGO CKD-EPI, hadden de

AKIt3 patiënten een significant lagere IZ mortaliteit (tabel 16). Een AKI episode van >3 dagen was

wel geassocieerd met een hogere ziekenhuismortaliteit (tabel 16) en een langer verblijf op IZ en in het

ziekenhuis (tabel 17), en dit voor alle classificaties van AKI.

Een transiënte episode van acute nierinsufficiëntie van ≤2 dagen (AKIt2) kwam voor in 8.0% tot 19.7%

van de IZ patiënten. De KDIGO CKD-EPI was de meest gevoelige classificatie voor het detecteren

van AKIt2, RIFLE MDRD de minst gevoelige classificatie. AKIt2 kwam voor bij 34.0% tot 67.1%

van de patiënten met acute nierinsufficiëntie (tabel 18).

AKIt2 patiënten hadden een gelijkaardige IZ mortaliteit in vergelijking met patiënten met langere AKI

episode (>2 dagen), behalve wanneer AKI gedefinieerd werd volgens KDIGO CKD-EPI (tabel 19).

Indien AKI gedefinieerd werd volgens AKIN en beide KDIGO varianten hadden AKIt2 patiënten een

lagere ziekenhuismortaliteit. Indien AKI gedefinieerd werd volgens beide RIFLE varianten was de

ziekenhuismortaliteit gelijkaardig bij AKIt2 patiënten met en patiënten met een langere AKI episode

(tabel 19). Een AKI episode >2 dagen was geassocieerd met een langer verblijf op IZ en in het

ziekenhuis (tabel 20).

Een transiënte episode van acute nierinsufficiëntie van ≤1 dag (AKIt1) kwam voor in 6.4% tot 13.1%

van de IZ patiënten. Net zoals bij AKIt2 en AKIt3, was KDIGO CKD-EPI de meest gevoelige

classificatie voor het detecteren van AKIt1, RIFLE CKD-EPI was de minst gevoelige classificatie.

AKIt1 kwam voor in 28.2% tot 42.1% van de AKI patiënten (tabel 21).

AKIt1 patiënten hadden een gelijkaardige IZ mortaliteit in vergelijking met patiënten met een langere

AKI episode (>1 dag), behalve wanneer AKI gedefinieerd werd volgens KDIGO CKD-EPI. Indien

AKI gedefinieerd werd volgens de beide KDIGO varianten, hadden AKIt1 patiënten een lagere

ziekenhuissterfte. Indien AKI gedefinieerd werd volgens de beide RIFLE varianten en de AKIN

classificatie, hadden AKIt1 patiënten een gelijkaardige ziekenhuissterfte in vergelijking met patiënten

met een langere AKI episode (>1 dag) (tabel 22). Een AKI episode van >1 dag was geassocieerd met

een langer verblijf op IZ en in het ziekenhuis (tabel 23).


Patiënten met transiënte AKI hadden een hogere IZ en ziekenhuismortaliteit dan patiënten zonder

acute nierinsufficiëntie (figuur 1, 2). Er is geen verschil in mortaliteit tussen de verschillende definities

voor transiënte AKI (tabel 24, 25) en tussen transiënte AKI en de totale AKI mortaliteit (figuur 1,2).

7.4. Besluit

In deze grote multicentrische, internationale cohort studie van IZ patiënten, kwam AKI voor in één

vijfde tot één derde van de IZ patiënten. Transiënte AKI kwam voor in twee derde van de AKI

patiënten en in 10 à 20% van de IZ patiënten. AKI en transiënte AKI waren geassocieerd met een

stijging van de IZ en ziekenhuissterfte en een langere opnameduur op IZ en in het ziekenhuis. De IZ

sterfte was vergelijkbaar tussen AKIt2 en AKIt3 patiënten en patiënten met een langere duur van AKI,

maar ziekenhuissterfte was lager voor AKIt2 en AKIt3 patiënten. AKIt1 patiënten hadden een

gelijkaardige IZ en ziekenhuissterfte vergeleken met patiënten met een langere AKI episode. Een

langere AKI duur was geassocieerd met een langere opnameduur op IZ en in het ziekenhuis.

Er waren verschillen te zien tussen de drie AKI classificaties RIFLE, AKIN en KDIGO en het gebruik

van de 4-variable MDRD en CKD-EPI formule. Verder onderzoek is nodig om deze verschillende

verder uit te klaren.

In de toekomst zou de duur van AKI geïncorporeerd moeten worden in AKI definities en gebruikt

worden in klinische studies.


8. References

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Network: report of an initiative to improve outcomes in acute kidney injury. Critical care.

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risk of death in hospitalized patients. Nephrology, Dialysis, Transplantation. 2010;25(6):1833-9.

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of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized

serum creatinine values. Clinical Chemistry. 2007;53(4):766-72.

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estimate glomerular filtration rate. Annals of Internal Medicine. 2009;150(9):604-12.

8. Coca S, King J, Rosenthal R, Perkal M, Parikh C. The duration of postoperative acute kidney

injury is an additional parameter predicting long-term survival in diabetic veterans. Kidney

international. 2010;78(9):926-33.

9. Zvada J, Hoste E, Cartin Ceba R, Calzavacca P, Gajic O, Clermont G, et al. A comparison of

three methods to estimate baseline creatinine for RIFLE classification. Nephrology, Dialysis,

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Opinion in Critical Care. 2011;17:548-55.

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Prospective Hospital Renal Outcome Survey on Acute Kidney Injury (NEiPHROS-AKI): Targeting

the Problem with the RIFLE Criteria. Clinical journal of the American Society of Nephrology

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12. Thakar CV, Christianson A, Freyberg R, Almenoff P, Render ML. Incidence and outcomes of

acute kidney injury in intensive care units: A Veterans Administration study. Critical care medicine

2009;37(9):2552 -8


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Critical Care Medicine. 2007;35(8):1837-43.

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kidney injury in critically ill patients. Nephrology, Dialysis, Transplantation. 2008;23(5):1569-74.

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9. Attachments

9.1. Number of valids

Table 26. Number of valids per outcome per AKI classification.

Number of Valids

RIFLE

MDRD

RIFLE

CKD-EPI

AKIN KDIGO

MDRD

KDIGO

CKD-EPI

Outcomes

ICU

Mortality

11293 11294 11305 11294 11293

Hospital

Mortality

11223 11224 11236 11226 11225

ICU

Length of Stay

11294 11294 11305 11294 11293

Hospital

Length of Stay

11209 11209 11220 11209 11208

Transient

AKI

ICU

Mortality

2660 2564 2010 3200 3503

Hospital

Mortality

2640 2544 2005 3172 3474

ICU

Length of Stay

2660 2564 2010 3200 3503

Hospital

Length of Stay

2639 2563 2008 3170 3472

9.2. Abbreviation list

AKI Acute Kidney Injury, Acute nierinsufficiënte

GFR Glomerular Filtration Rate

MDRD Modification of Diet in Renal Disease equation

CKD-EPI Chronic Kidney Disease Epidemiology Collaboration equation

TRAK Study AKI-6 Transient AKI Study

ICU Intensive Care Unit

AKI-6 Acute Kidney Injury 6 Study Group

Pittsburg University of Pittsburgh Medical Center

Rochester The Mayo clinic, Rochester

Perth Royal Perth Hospital

Melbourne Austin Health Center, Melbourne

Ghent Ghent University Hospital

Vicenza Ospedale San Bortolo di Vicenza

IDMS Isotope Dilution Mass Spectrometry reference measurement procedure

SCr Serum creatinine concentration

RIFLE RIFLE classifcation for AKI

AKIN Acute Kidney Injury Network diagnostic and classification system for

AKI

KDIGO The Kidney Disease Improving Global Outcomes definition and

staging system for AKI

AKIt3 AKI episode of ≤ 3 days



ICU Mortality Intensive Care Unit Mortality

ICU Length of Stay Intensive Care Unit Length of Stay

R/1 Risk in RIFLE classification / Stage 1in AKIN and KDIGO

classification

I/2 Injury in RIFLE classification /Stage 2 in AKIN and KDIGO

classification

F/3 Failure in RIFLE classification / Stage 3 in AKIN and KDIGO

classification

Fc Acute on chronic AKI

aki-6 epidemiology of acute kidney injury · aki-6 epidemiology of transient acute kidney injury 2....

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