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. 2020 Jan 17;15(1):e0226325. doi: 10.1371/journal.pone.0226325

A systematic review and meta-analysis of acute kidney injury in the intensive care units of developed and developing countries

Fernando de Assis Ferreira Melo 1,*, Etienne Macedo 2, Ana Caroline Fonseca Bezerra 1, Walédya Araújo Lopes de Melo 1, Ravindra L Mehta 2, Emmanuel de Almeida Burdmann 3, Dirce Maria Trevisan Zanetta 4
Editor: Giuseppe Remuzzi5
PMCID: PMC6968869  PMID: 31951618

Abstract

Objectives

Although the majority of the global population lives in developing countries, most of the epidemiological data related to intensive care unit (ICU) acute kidney injury (AKI) comes from developed countries. This systematic review aims to ascertain the methodology of studies on ICU AKI patients in developing and developed countries, to determine whether epidemiological comparisons between these two settings are possible, and to present a summary estimate of AKI incidence.

Methods

A systematic review of published studies reporting AKI in intensive care units (2005–2015) identified in PubMed, LILACS, and IBECs databases was conducted. We compared developed and developing countries by evaluating study methodology, AKI reference serum creatinine definitions, population characteristics, AKI incidence and mortality. AKI incidence was calculated with a random-effects model.

Results

Ninety-two studies were included, one of which reported data from both country categories: 60 from developed countries (1,057,332 patients) and 33 from developing countries (34,539 patients). In 78% of the studies, AKI was defined by the RIFLE, AKIN or KDIGO criteria. Oliguria had 11 different definitions and reference creatinine 23 different values. For the meta-analysis, 38 studies from developed and 18 from developing countries were selected, with similar AKI incidence: 39.3% and 35.1%, respectively. The need for dialysis, length of ICU stay and mortality were higher in developing countries.

Conclusion

Although patient characteristics and AKI incidence were similar in developed and developing countries, main outcomes were worse in developing country studies. There are significant caveats when comparing AKI epidemiology in developed and developing countries, including lack of standardization of reference serum creatinine, oliguria and the timeframe for AKI assessment. Larger, prospective, multicenter studies from developing countries are urgently needed to capture AKI data from the overall population without ICU access.

Introduction

Acute kidney injury (AKI) affects 20 to 50% of intensive care unit (ICU) patients, and it is associated with high mortality, increased ICU length of stay and greater hospitalization cost [1–5]. When renal replacement therapy (RRT) is used, mortality rates can reach up to 80% [2,6].

It is widely accepted that AKI characteristics are different in developed and developing countries due to contrasting socioeconomic patterns, government health expenditures, heath service infrastructure and AKI etiology [7].

Although the vast majority of the global population lives in developing countries, most of the epidemiological data from ICU patients with AKI comes from developed countries. Comparisons of these two different settings are scarce. A multicenter prospective study found higher mortality for ICU AKI patients in developing countries [8], which might be related to an inadequate number of ICU beds in relation to population size and the difficulty of health care access, among other reasons. To determine whether the outcomes in these populations are comparable, it is necessary to evaluate whether there are differences in patient characteristics as well as the methodological aspects among the analyzed studies.

This systematic review covers methodological aspects, including AKI and reference serum creatinine definitions, as well as the main characteristics and outcomes of ICU AKI patients from studies in developed and developing countries. We aim to determine whether epidemiological comparisons between these two country categories are appropriate with the available data and to estimate their AKI incidence using meta-analysis.

Material and methods

Database search

This systematic review was conducted using the recommendations of the “Cochrane Handbook for Systematic Reviews of Interventions” [9] (Fig 1). A systematic electronic search was performed to identify all original studies which might include acute kidney injury patients in intensive care units published from 2005 until 2015, including the keyword terms: “acute kidney injury”, “acute kidney failure”, “acute kidney insufficiency”, “acute renal injury”, “acute renal failure”, “acute renal insufficiency”, “intensive care units”, “critical ill patient and critical ill”. We accessed the PubMed, CENTRAL (Cochrane Controlled Register of Trials), LILACS (Latin American and Caribbean Health Sciences Library), and IBECs (Spanish Bibliographical Index of Health Sciences) databases. The search strategies for each database can be found in S1 File. This search was last updated on July 31, 2015, and the language was limited to English, Spanish, French, Italian and Portuguese. The manuscripts were manually analyzed in order to find additional references. There was no blinding in relation to the author, place of publication, or journal.

Fig 1. Flowchart of study selection.

Fig 1

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The studies were classified into two groups: those from developed and those from developing countries, and they were assigned group membership based on the United Nations classification.

Study selection

An initial eligibility screen of all retrieved titles and abstracts was conducted, and only studies reporting AKI in intensive care units in the 10-year surveyed period were selected for further review. Full-text papers were obtained for inspection of each study that potentially fulfilled the inclusion criteria on the basis of title and/or abstract. The following specific criteria were used for final selection: only studies with adult patients and those with reported epidemiological data. Duplicate articles were identified and eliminated using the Endnoteweb [10] software tool.

The final group of manuscripts was selected by the main author and reviewed by a coauthor. Discordances were solved by consensus using the predefined inclusion and exclusion criteria in accordance with the recommendations of the “Cochrane Handbook for Systematic Reviews of Interventions” [9]. When necessary, a final decision was achieved by consulting a third coauthor.

Data collection process

Two authors performed independent data extraction using standardized data extraction forms.

The following data were retrieved:

  1. Research place and study description: country, study type, length of data collection, number of ICUs, type of ICU, number of patients.

  2. AKI characteristics: incidence, definition, criteria used for definition, timeframe for AKI assessment, percentage of oliguric patients, oliguria definition, reference serum creatinine (SCr) defined as the value used for comparing increased SCr to establish the diagnosis of AKI.

  3. AKI patient characteristics: mean age, gender ratio, previous comorbidities, patient source, severity of illness score.

  4. Outcomes: length of ICU stay, length of hospital stay, frequency of RRT use, type of RRT, mortality.

Statistical analysis

The frequencies of studies were calculated by considering those that assessed the respective data. The number of studies used for each calculation is shown after the presented frequency.

Weighted means and percentages of reported data were estimated using the study population as weight.

The pooled point AKI incidence of developed and developing countries´ studies was estimated for studies that used the RIFLE, AKIN or KDIGO criteria for the AKI definition. All estimates and their 95% confidence intervals (95% CI) were calculated using a random-effects model for descriptive data analysis. Subgroup analyses were conducted with studies grouped by each different criterion for the utilized AKI definition. Heterogeneity and consistency were evaluated using Cochran’s Q and the I2 statistics, respectively. Funnel plots were used to evaluate publication bias. The analysis was performed in Microsoft Excel, using the step-by-step approach constructed by Neyeloff et al. [11] to analyze descriptive data. The pooled AKI incidence of both country groups were compared using the estimated 95% confidence interval.

Results

Of 2,459 potential studies, 1,635 were excluded because they did not assess patients, were duplicates, or had titles and abstracts that were not related to the purpose of this review. Of the remaining 824 studies, 17 were excluded for not meeting the language definitions and 714 were excluded as they did not meet the eligibility criteria. Ninety-two studies were included in the final analysis. One study [8] reported data from both developed and developing countries, and its data was reported in both country categories. As a result, the final analysis consisted of 60 studies presenting data from developed countries and 33 studies with data from developing countries (Fig 1 and Table 1). The 92 studies included in the final analysis can be found in S2 File.

Table 1. Frequency of studies in developed and developing countries with data reported.

Developed countries Developing countries
(N = 60) (N = 33)
Description of studies (n = 93)
    Retrospective 46.7% (28) 42.4% (14)
    Prospective 53.3% (32) 57.6% (19)
Definition of AKI by
    RIFLE 34.4% (20) 39.3% (13)
    AKIN 37.9% (22) 33.3% (11)
    KDIGO 10% (6) 21.2% (7)
    sCr* rise 24.1% (14) 9% (3)
    sCr rise + decreases in     urinary volume 73.2% (41) 78.1% 25
Oliguria definition (n = 81) 81.6% (49) 97% (32)
Reference SCr definition (n = 60) 68.3% (41) 57.5% (19)
Timeframe for AKI diagnosis 58.3% (35) 69.6% (23)
Frequency of AKI > 40% 54.7% (29) 82.1% (23)
AKI etiology described 46.6% (28) 66.6% (22)
Patient characteristics
    > 65 years old 40% (22) 12.1% (4)
    Male frequency > 60% 59.6% (34) 67.8% (19)
    Comorbidities 51.6% (31) 78.7% (26)
    Severity scores
        APACHE II 58.3% (35) 54.5% (18)
        SOFA 25% (15) 18.1% (6)
Outcomes
    Length of ICU stay 71.6% (43) 69.6% (23)
    Length of hospital stay 38.3% (23) 21.2% (7)
    RRT > 30% in AKI patients 13.3% (8) 30.3% (10)
    Mortality 15.9% (7) 56% (14)
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*sCr = serum creatinine

Description of studies

Study design

In both developed and developing countries, the majority of studies were from university hospitals [91.6% (55/60) and 72.7% (24/33), respectively] (Tables 2 and 3).

Table 2. Country and study features description—developed countries.
Author Home country Study type Length of data collection Number of ICUs Type of ICU Number of Patients
Abosaif et al, 2005 England Retrospective 24 1 Mixed 247
Bagshaw et al, 2005 Canada Prospective 36 3 Mixed 5,693
Chawla et al, 2005 USA Prospective 8 1 Mixed 194
Ostermann et al, 2005 England and Germany Retrospective 110 22 Mixed 41,972
Ahlstrom et al, 2006 Finland Prospective 11 2 Mixed 658
Herrera-Gutiérrez et al, 2006 Spain Prospective 8 43 Mixed 15,714
Hoste, 2006 USA Retrospective 12 7 Mixed 5,383
Bagshaw et al, 2007 Australia Prospective 120 20 Mixed 91,254
Cruz et al, 2007 Italy Prospective 3 19 Mixed 2,164
Eachempati et al, 2007 USA Prospective 108 1 Mixed 41,972
Ostermann et al, 2007 England and Germany Retrospective 120 11 Surgery 8,505
Bagshaw et al, 2008 Australia Retrospective 60 57 Trauma 124,088
Bagshaw et al, 2008 Australia Retrospective 60 57 Mixed 120,123
Barrantes et al, 2008 USA Retrospective 12 1 Mixed 471
Lopes et al, 2008 Portugal Retrospective 36 1 Mixed 662
Ostermann et al, 2008 England and Germany Retrospective 123 22 Mixed 23,303
Abelha et al, 2009 Portugal Retrospective 24 1 Mixed 1,166
Andrikos et al, 2009 Italy and Greece Prospective 4 22 Mixed 1,076
Cartin-Ceba et al, 2009 USA Retrospective 42 3 Mixed 11,644
Costantini et al, 2009 USA Retrospective 36 1 Surgery 571
Joannidis et al, 2009 Austria and Portugal Prospective . . . 303 Mixed 16,784
Thakar et al, 2009 USA Retrospective 60 191 Mixed 325,395
Aldawood et al, 2010 Saudi Arabia Retrospective 72 1 Mixed 7,173
Cruz et al, 2010 USA Prospective 6 1 Mixed 301
Elseviers et al, 2010 Belgium Prospective 35 9 Mixed 1,303
Park et al, 2010 Korea Retrospective 6 1 Mixed 378
Clec'h et al, 2011 France Retrospective 149 13 Mixed 8,639
Darmon et al, 2011 France Prospective 5 3 Mixed 203
Garzotto et al, 2011 Italy Prospective 7 10 Mixed 576
Macedo et al, 2011 USA Prospective 2 1 Mixed 75
Macedo et al, 2011 USA Prospective . . . 1 Mixed 317
Mandelbaum et al, 2011 USA Retrospective 72 7 Mixed 14,524
Medve et al, 2011 Hungary Prospective 2 7 Mixed 459
Ostermann et al, 2011 England and Germany Retrospective 123 22 Mixed 22,303
Piccini et al, 2011 Italy Prospective 7 10 Mixed 576
Prowle et al, 2011 Australia, Canada, Japan, USA, Germany, Italy Prospective 1 7 Mixed 239
Clark et al, 2012 Canada Prospective 11 11 Mixed 119
Han et al, 2012 Korea Retrospective 57 1 Mixed 1625
Medve et al, 2012 Hungary Prospective . . . 1 Surgery 265
Odutayo et al, 2012 Canada Prospective 12 5 Mixed 603
Shashaty et al, 2012 USA Retrospective 45 1 Trauma 400
Sigurdsson et al, 2012 Iceland Retrospective 12 2 Mixed 1012
Vaara et al, 2012 Finland Retrospective 23 9 Mixed 30,380
Wohlauer et al, 2012 USA Prospective 192 1 Surgery 2,158
Allegretti et al, 2013 USA Retrospective 44 1 Mixed 863
Alsultan et al, 2013 Saudi Arabia Prospective 36 2 Mixed 2,574
Fuchs et al, 2013 USA Retrospective 80 1 Mixed 12,339
Legrand et al, 2013 France Retrospective 48 1 Surgery 137
Nisula et al, 2013 Finland Prospective 6 10 Mixed 1568
Poukkanen et al, 2013 Finland Prospective 5 1 Infectious diseases 423
Poukkanen et al, 2013 Finland Prospective 5 1 Infectious diseases 918
Doi et al, 2014 Japan Prospective 5 1 Mixed 339
Han et al, 2014 Korea Retrospective 72 1 Mixed 1,883
Linder et al, 2014 Canada Prospective 108 1 Mixed 1,844
Shinjo et al, 2014 Japan Retrospective 60 1 Mixed 2,579
Udy et al, 2014 Australia, Singapore, Hong Kong and Portugal Prospective . . . 4 Mixed 281
Bouchard et al, 2015 Various Prospective 20 9 Mixed 316
Harris et al, 2015 USA Retrospective 12 1 Surgery 624
Rimes-Stigiare et al, 2015 Sweden Prospective 72 41 Mixed 97,782
Vanmassenhove et al, 2015 Belgium Prospective 14 1 Mixed 195
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Table 3. Country and study features description—developing countries.
Author Home country Study type Length of data collection Number of ICUs Type of ICU Number of patients
Mataloun et al, 2006 Brazil Prospective 12 1 Mixed 221
Silva Junior et al, 2006 Brazil Retrospective 48 1 Mixed 381
Chow et al, 2007 Malaysia Prospective 6 1 Mixed 18,697
Daher et al, 2008 Brazil Retrospective 36 1 Infectious diseases 722
Lima et al, 2008 Brazil Retrospective 36 1 Infectious diseases 829
Fernandes et al, 2009 Brazil Prospective 10 1 Mixed 89
Friedericksen et al, 2009 South Africa Retrospective 12 1 Mixed 198
Chang et al, 2010 Taiwan Retrospective 35 1 Mixed 291
Maccariello et al, 2010 Brazil Prospective 18 11 Mixed 244
Balushi et al, 2011 Oman Retrospective 12 1 Mixed 1,373
Ponce et al, 2011 Brazil Prospective 24 1 Mixed 564
Fonseca Ruiz et al, 2011 Colombia Retrospective 24 1 Mixed 794
Samimagham et al, 2011 Iran Retrospective 12 1 Mixed 235
Alves et al, 2012 Brazil Retrospective 15 1 Mixed 204
Chen et al, 2012 Taiwan Prospective 12 1 Mixed 150
Daher et al, 2012 Brazil Prospective 12 1 Mixed 408
Lai et al, 2012 Taiwan Retrospective 101 1 Surgical 634
Wahrhaftig et al, 2012 Brazil Prospective 12 1 Mixed 200
Zhou et al, 2012 China Retrospective 8 5 Mixed 1,036
Dalboni et al, 2013 Brazil Prospective . . . 1 Mixed 303
Levi et al, 2013 Brazil Prospective 12 1 Mixed 190
Silva et al, 2013 Brazil Prospective 20 6 Mixed 366
Singh et al, 2013 India Prospective 17 1 Mixed 1,504
Daher et al, 2014 Brazil Retrospective 99 1 Infectious diseases 253
Luo et al, 2014 China Prospective 6 30 Mixed 3,107
Morales-Buenrostro et al, 2014 Mexico Prospective 3 1 Mixed 56
Peng et al, 2014 China Retrospective 36 1 Infectious diseases 211
Wijewickrama et al, 2014 Sri Lanka Prospective 6 1 Mixed 108
Bentata et al, 2015 Morocco Retrospective 84 1 Obstetric 186
Bouchard et al, 2015 Various Prospective 20 5 Mixed 429
Heegard et al, 2015 Afghanistan Prospective 18 2 Trauma 134
Ralib et al, 2015 Malaysia Prospective 3 1 Mixed 143
Santos et al, 2015 Brazil Prospective 12 1 Mixed 279
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The 92 studies report data from 1,091,871 patients. The number of patients from developed countries was 30 times higher; 1,057,332 vs. 34,539 patients in developed versus developing countries, respectively. Larger cohorts with more than 5,000 patients were more frequent in developed countries [33.3% (20/60)], whereas in developing countries, 87.8% (29/33) of the studies included less than 1,000 patients (Tables 2 and 3). The number of ICUs included in developed countries was significantly higher than in developing countries (990 vs. 86 ICUs). In fact, in developed countries, 41.6% of the studies (25/60) assessed more than five ICUs, while in developing countries, 81.8% of studies (27/33) assessed only one ICU. The majority of studies (82.7%, i.e., 77/93) evaluated patients from ICUs classified as "mixed" (Tables 2 and 3).

Definition of AKI

Both developed and developing country studies frequently used RIFLE, AKIN, KDIGO, as defined or modified (Fig 2). In developed countries, AKIN and RIFLE were the most frequently used criteria [37.9% (22/58) and 34.4%, (20/58), respectively], followed by increased SCr (24.1%, 14/58). In developing countries, RIFLE and AKIN were also more often applied [39.3% (13/33) and 33.3% (11/33), respectively], followed by KDIGO at 21.2% (7/33) (Tables 4 and 5). The majority of studies [73.2% (41/56) in developed countries and 78.1% (25/32) in developing countries] reported using both increases in SCr and decreases in urinary volume for the AKI diagnosis.

Fig 2. Flowchart of AKI definition criteria.

Fig 2

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Footnote: 1 One study contained data from both (developed and developing) country groups, and the respective data were included in each country group for the analysis. 2 Two studies did not mention the criteria used for the definition of IRA.

Table 4. AKI characteristics—developed countries.
Author AKI Frequency (%) AKI definition Criteria used for AKI definition Timeframe for AKI assessment Oliguric patients (%) Oliguria definition Reference creatinine definition
Abosaif et al, 2005 . . . RIFLE Cr . . . . . . < 0.5 ml/kg/h x 6 h Lower Cr on hospital admission
Bagshaw et al, 2005 4.2 Cr rise/Oliguria Cr/Diuresis . . . 77.0 < 500 ml x 24 h . . .
Chawla et al, 2005 18.0 Cr rise/Oliguria Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 48 h . . .
Ostermann et al, 2005 17.9 Cr rise/Oliguria Cr/Diuresis . . . . . . BUN > 8 mmol/l Cr > 120 mmol/l
Ahlstrom et al, 2006 51.9 RIFLE Cr Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h MDRD
Herrera-Gutiérrez et al, 2006 5.7 Cr rise/Oliguria Cr/Diuresis . . . . . . < 400 ml x 24 h . . .
Hoste et al, 2006 67.0 RIFLE Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lower Cr on hospital admission, or MDRD
Bagshaw et al, 2007 5.2 Cr rise/Oliguria Cr/Diuresis . . . . . . . . . . . .
Cruz et al, 2007 10.8 RIFLE Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h MDRD
Eachempati et al, 2007 6.2 Cr rise Cr . . . . . . Cr > 2.4 mg/dl
Ostermann et al, 2007 35.8 RIFLE Cr Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h . . .
Bagshaw et al, 2008 36.1 RIFLE modified Cr/Diuresis Since ICU discharge or death, after 24 h from ICU admission . . . < 35 ml/kg/h MDRD
Bagshaw et al, 2008 36.1/37.1 RIFLE modified/AKIN modified Cr/Diuresis Since ICU discharge or death, after 24 h from ICU admission . . . < 35 ml/kg/h MDRD
Barrantes et al, 2008 42.9 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Lopes et al, 2008 43.8/50.4 RIFLE modified/AKIN modified Cr/Diuresis Until 48 h . . . < 7.2 ml/kg X 24 h MDRD
Ostermann et al, 2008 35.4 Cr rise Cr . . . . . . . . . . . .
Abelha et al, 2009 7.5 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Andrikos et al, 2009 16.0 RIFLE Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Cartin-Ceba et al, 2009 50.0 RIFLE Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h Lower Cr 3 months before ICU admission
Costantini et al, 2009 29.8 AKIN Cr/Diuresis Since ICU discharge or death after 48 h from admission . . . < 0.5 ml/kg/h x 6 h . . .
Joannidis et al, 2009 35.5/28.5 RIFLE/AKIN Cr/Diuresis 7 days . . . < 0.5 ml/kg/h x 6 h MDRD
Thakar et al, 2009 60.8 AKIN modified Cr Since ICU discharge or death . . . . . . Lower Cr 24 h before hospital admission
Aldawood et al, 2010 24.4 . . . . . . Since hospital discharge or death . . . . . . . . .
Cruz et al, 2010 44.0 Cr rise Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lower Cr 3 months before ICU admission or MDRD
Elseviers et al, 2010 . . . Cr rise Cr . . . . . . . . . . . .
Park et al, 2010 41.3 RIFLE Cr/Diuresis 7 days . . . < 0.5 ml/kg/h x 6 h Lower Cr 3 months before hospital admission, or MDRD
Clec’h et al, 2011 32.9 RIFLE Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h MDRD
Darmon et al, 2011 67.0 AKIN Cr/Diuresis 12 hours . . . < 0.5 ml/kg/h x 6 h . . .
Garzotto et al, 2011 42.7 RIFLE Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lower Cr 3 months before ICU admission
Macedo et al, 2011 60.0 AKIN Cr/Diuresis Since ICU discharge or death 55.0 < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Macedo et al, 2011 52.0 AKIN Cr/Diuresis Since hospital discharge or death 47.0 < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Mandelbaum et al, 2011 57.0 AKIN Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h . . .
Medve et al, 2011 24.4 AKIN Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Ostermann et al, 2011 35.4 AKIN Cr/Diuresis Since ICU discharge or death . . . . . . First Cr on ICU admission
Piccini et al, 2011 42.7 RIFLE Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h Lowest Cr 3 months before ICU admission
Prowle et al, 2011 9.6 AKIN modified/ RIFLE modified Cr/Diuresis 4 weeks 38.0 < 0.5 ml/kg Cr before disease or estimated using GRF 75 ml/min
Clark et al, 2012 7.8 AKIN Cr . . . . . . < 0.5 ml/kg/h x 6 h Newest Cr 6 months before ICU admission, or MDRD
Han et al, 2012 57.0 AKIN Cr/Diuresis 7 days . . . < 0.5 ml/kg/h x 6 h Lowest Cr 7 days before hospital admission
Medve et al, 2012 18.1 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Odutayo et al, 2012 26.7 AKIN Cr 90 days . . . < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Shashaty et al, 2012 36.8 AKIN Cr/Diuresis 5 days . . . < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Sigurdsson et al, 2012 21.7 RIFLE . . . . . . . . . < 0.5 ml/kg/h x 6 h Cr 1 year before ICU admission or the lowest after hospital discharge or MDRD
Vaara et al, 2012 26.6 RIFLE Cr Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h Lowest Cr during ICU stay
Wohlauer et al, 2012 2.1 Cr rise Cr Since hospital discharge or death . . . . . . . . .
Allegretti et al, 2013 . . . Cr rise Cr . . . . . . . . . First Cr on ICU admission
Alsultan et al, 2013 65.0 . . . . . . . . . . . . . . . . . .
Fuchs et al, 2013 54.3 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lowest Cr on hospital admission
Legrand et al, 2013 50.3 AKIN Cr/Diuresis 5 days . . . < 0.5 ml/kg/h x 6 h Lowest Cr before ICU admission (time not informed), or MDRD
Nisula et al, 2013 40,5 KDIGO Cr/Diuresis 5 days after 24 h from admission . . . < 0.5 ml/kg/h x 6 h Newest Cr from last year, excluding the last week before ICU admission, or MDRD
Poukkanen et al, 2013 36.2 KDIGO Cr/Diuresis 5 days . . . < 0.5 ml/kg/h x 6 h Newest Cr from last year, excluding the week before ICU admission
Poukkanen et al, 2013 53.2 KDIGO Cr/Diuresis 5 days . . . < 0.5 ml/kg/h x 6 h Lowest Cr 1 year before ICU admission
Doi et al, 2014 38.6 RIFLE Cr . . . . . . < 0.5 ml/kg/h x 6 h Lowest Cr 3 months before ICU admission or MDRD
Han et al, 2014 78.7 KDIGO Cr/Diuresis . . . 31.8 < 0.5 ml/kg/h x 6 h . . .
Linder et al, 2014 57.0 KDIGO Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h Lowest Cr 3 months before ICU admission
Shinjo et al, 2014 29.5/38.4 AKIN/KDIGO Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lowest Cr 3 months before ICU admission
Udy et al, 2014 65.1 Cr rise Cr/Diuresis Since ICU discharge or death, after 48 h from admission . . . . . . . . .
Bouchard et al, 2015 19.1 AKIN Cr/Diuresis 7 days 31.5 < 0.5 ml/kg/h x 6 h Cr from 3 to 12 months before ICU admission
Harris et al, 2015 47.0 RIFLE Cr . . . . . . < 0.5 ml/kg/h x 6 h Lowest Cr 1 year before ICU admission or MDRD
Rimes-Stigiare et al, 2015 5.4 Cr/Oliguria Cr/Diuresis . . . . . . < 400 ml x 24 h . . .
Vanmassenhove et al, 2015 63.0 Cr rise Cr . . . . . . . . . MDRD
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* Cr = serum creatinine

Table 5. AKI characteristics—developing countries.
Author AKI Frequency (%) AKI definition Criteria used for AKI definition Timeframe for AKI assessment Oliguric patients (%) Oliguria definition Reference creatinine definition
Mataloun et al, 2006 19.0 Cr rise Cr Since ICU discharge or death . . . . . . . . .
Silva Junior et al, 2006 33.5 Cr rise Cr . . . . . . < 600 ml x 24 h . . .
Chow et al, 2007 1.1 Oliguria Diuresis . . . . . . < 400 ml x 24 h
Daher et al, 2008 20.3 RIFLE modified Cr/Diuresis Since ICU discharge or death 34.0 < 400 ml x 24 h Lowest Cr on hospital admission, or MDRD
Lima et al, 2008 17.7 RIFLE Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h . . .
Fernandes et al, 2009 . . . ATN-ISS Diuresis Since ICU discharge or death 62.0 < 400 ml x 24 h Lowest Cr on hospital admission
Friedericksen et al, 2009 23.2 Cr rise Cr . . . 50.0 < 400 ml x 24 h Lowest Cr on hospital admission
Chang et al, 2010 . . . RIFLE/AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Maccariello et al, 2010 39.8 RIFLE Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Balushi et al, 2011 0.5 Cr / Oliguria Cr/Diuresis . . . . . . < 500 ml x 24 h . . .
Ponce et al, 2011 25.5 AKIN Cr/Diuresis Since ICU discharge or death 68.5 < 0.5 ml/kg/h x 6 h . . .
Fonseca Ruiz et al, 2011 31.1 AKIN Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h . . .
Samimagham et al, 2011 31.1 AKIN Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h . . .
Alves et al, 2012 11.8 RIFLE modified/AKIN modified Cr/Diuresis Since ICU discharge or death . . . < 400 ml x 6 h Last Cr 6 months before ICU admission or MDRD
Chen et al, 2012 28.7 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Cr on hospital admission
Daher et al, 2012 15.3 RIFLE modified Cr/Diuresis Since ICU discharge or death, after 24 h from admission . . . < 400 ml x 24 h Lowest Cr before hospital admission or MDRD
Lai et al, 2012 . . . RIFLE Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h Last Cr within 1 month to 1 year before admission
Wahrhaftig et al, 2012 36.0 RIFLE modified Cr/Diuresis Since ICU discharge or death . . . < 0.5 ml/kg/h x 6 h Lowest Cr before hospital admission or MDRD
Zhou et al, 2012 34.1 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lowest Cr 2 days before ICU admission
Dalboni et al, 2013 45.6 RIFLE Cr 48 h . . . < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Levi et al, 2013 . . . KDIGO Cr/Diuresis Since ICU discharge or death, after 24 h from admission . . . < 0.5 ml/kg/h x 6 h . . .
Silva et al, 2013 13.3 RIFLE Cr Since ICU discharge or death, after 48 h from admission . . . < 0.5 ml/kg/h x 6 h . . .
Singh et al, 2013 2.2 RIFLE modified Cr/Diuresis Since hospital discharge or death, after 48 h from admission 61.0 < 400 ml x 24 h Lowest Cr on hospital admission
Daher et al, 2014 . . . RIFLE modified Cr/Diuresis Since ICU discharge or death . . . < 400 ml x 24 h Lowest Cr before hospital admission or MDRD
Luo et al, 2014 46.9/38.4/51 RIFLE/AKIN/KDIGO Cr/Diuresis 10 days . . . < 0.5 ml/kg/h x 6 h Lower Cr 3 month before ICU admission
Morales-Buenrostro et al, 2014 30.3 AKIN 30 days . . . < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Peng et al, 2014 47.9 KDIGO Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Wijewickrama et al, 2014 60.2 AKIN Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h . . .
Bentata et al, 2015 34.4 KDIGO Cr/Diuresis 30 days 17.4 < 0.5 ml/kg/h x 6 h First Cr on ICU admission
Bouchard et al, 2015 19.9 AKIN Cr/Diuresis 7 days 26.1 < 0.5 ml/kg/h x 6 h Cr from 3 to 12 months before hospital admission
Heegard et al, 2015 34.3 KDIGO Cr/Diuresis 14 days . . . < 0.5 ml/kg/h x 6 h Cr 1 year before hospital admission or MDRD
Ralib et al, 2015 65.0 KDIGO Cr/Diuresis Since ICU discharge or death, after 48 h from admission 61.0 < 0.5 ml/kg/h x 6 h First Cr on ICU admission, or MDRD
Santos et al, 2015 32.9 KDIGO Cr/Diuresis . . . . . . < 0.5 ml/kg/h x 6 h Lowest Cr before hospital admission
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* Cr = serum creatinine

Oliguria definition

Although the oliguria criteria were reported in the majority of the studies, only 10% of developed and 21.2% of developing country studies reported the frequency of oliguric patients.

The oliguria definition was stated in 81.6% (49/60) of developed country studies and in 97% (32/33) of developing country studies. In five studies from developed countries and two from developing countries, the oliguria definition was not available in the manuscript and was obtained through contact with the researcher by electronic mail. In total, 11 different definitions for oliguria were used. The most frequent was “urinary volume < 0.5 ml/kg/h for 6 h”, which was found in 81.6% (40/49) of developed and in 68.7% (22/32) of developing country studies (Tables 4 and 5 and Fig 2).

Reference serum creatinine definition

The reference SCr definition was available in 68.3% (41/60) of studies in developed countries and 57.5% (19/33) in developing countries. In 12 studies from developed countries and 8 from developing countries, this information was not available in the manuscript, and it was obtained through contact with the researcher. We found 29 different definitions for reference SCr (Tables 4 and 5 and Fig 2), and there was no particular dominant definition.

Timeframe for AKI assessment

The timeframe for AKI diagnosis was available in 58.3% (35/60) of studies in developed countries and 69.6% (23/33) in developing countries. Among those reporting this information, the most used definition for timeframe was “until ICU discharge or death” found in 42.8% (15/35) of developed and in 39.1% (9/23) of developing country studies (Tables 4 and 5).

Incidence and AKI etiology

The incidence of AKI was reported in 91.3% (85/93) of the analyzed studies (Tables 4 and 5). Most studies of both developed (54.7%, 29/53) and developing countries (82.1%, 23/28) reported an AKI incidence up to 40%. According to different AKI definitions, AKI incidence varied from 2.1% [12] to 78.7% [13] in developed countries and from 0.5% [14] to 65% [15] in developing countries.

AKI etiology was described in 46.6% (28/60) of studies from developed countries and in 66.6% (22/33) of studies from developing countries. Sepsis and shock were the most common causes of AKI in both developed and developing countries (see Tables 6 and 7). The frequency of sepsis as the cause of AKI in developed countries ranged from 4.4% [13] to 100% [16], and half of the studies had frequencies greater than 40% (9/18). In developing countries, the frequency of sepsis as a cause of AKI ranged from 2.9% [17] to 100% [18], and 66.7% of the studies reported a frequency greater than 40% (12/18). In developed countries, shock was less frequently reported as a cause of AKI than in developing countries. Only one study reported tropical diseases (leptospirosis) as contributing to AKI etiology (Tables 6 and 7).

Table 6. Characteristics of patients with AKI—developed countries.

Author Median age Male gender (%) AKI etiology Comorbidities Patient location before ICU Severity scores
Abosaif et al, 2005 65 68 Sepsis 41.2% CVD* 41.2%, COPD* 41.2%, CKD* 48.4% Surgery room 47.5%, ward 52.5% APACHE II 22.3/ SAPS II 51.5
Bagshaw et al, 2005 65 62 Shock 15%, drugs 85% CVD 50%, COPD 34.6%, DM* 30%, CKD 18.8% . . . APACHE II 33
Chawla et al, 2005 65 54 . . . CVD 30.4%, DM 36.6%, CKD 18% . . . APACHE II 12.5
Ostermann et al, 2005 61 64 Surgery 59.4%, medical 40.5% . . . Surgery room 57.1%, ward 16.4%, emergency 15.6% APACHE II 14
Ahlstrom et al, 2006 63 . . . . . . . . . APACHE II 22
Herrera-Gutiérrez et al, 2006 59 71 Shock 36.6%, drugs 38.4%, mixed 21.2% CVD 84.7%, COPD 18%, CKD 4.4% Surgery room 18.1%, ward 31.3%, emergency 7.9% APACHE II 22.5/ SOFA 11.9
Hoste et al, 2006 63 49 Sepsis 17.2%, heart failure 33%, neurological 20.7% . . . Surgery room 61.5%, ward 38.3% APACHE II 56 / SOFA 7.8
Bagshaw et al, 2007 64 61 . . . CVD 11.6%, COPD 8.5%, HD* 4.8% Surgery room 49.6%, ward 50.4% APACHE II 16.4
Cruz et al, 2007 64 62 Sepsis 25.6%, shock 38%, drugs 14.5%, contrast 5.6% CVD 58.5%, DM 25.6% Surgery room 27,8%, ward 37.2% . . .
Eachempati et al, 2007 63 60 . . . . . . Surgery room 100% APACHE III 81
Ostermann et al, 2007 61 64 . . . . . . Surgery room 57.1%, ward 16.4%, emergency 15.6% APACHE II 21
Bagshaw et al, 2008 55 16 . . . CVD 17.7%, COPD 9.7%, HD 3% Emergency 100% APACHE II 20.9/APACHE III 71.7
Bagshaw et al, 2008 62 60 Sepsis 27.8% . . . Surgery room 49.7% APACHE II 16.9
Barrantes et al, 2008 67 57 Sepsis 19.4%, respiratory failure 35.2% . . . . . . APACHE II 15
Lopes et al, 2008 59 59 . . . CVD 53.2% Ward 76.4%, others 23.6% SAPS II 46.3
Ostermann et al, 2008 61 61 Surgery 45.7%, medical 54.2 . . . Surgery room 43.1%, ward 24.2, Emergency 18.6% APACHE II 18, SOFA 7
Abelha et al, 2009 64 65 Emergency 33% CVD 46% Emergency 33% APACHE II 13, SAPS II 33
Andrikos et al, 2009 72 67 Sepsis 45.3%, shock 9.4%, Surgery 21.2%, drugs 7.1% CVD 67.5%, DM 32.9% Surgery room 31.8%, ward 38.8%, emergency 20% . . .
Cartin-Ceba et al, 2009 66 54 . . . . . . . . . APACHE III 11.5
Costantini et al, 2009 46 71 Trauma 100% . . . Emergency 100% . . .
Joannidis et al, 2009 63 61 post surgery 34.5%, emergency 65.3% CVD 9.1%, COPD 4.2%, DM 8.5%, HD 3.1% Surgery room 55%, ward 42.2% SOFA 3, SAPS III 47
Thakar et al, 2009 98 . . . CVD 51.6%, COPD 22.1%, DM 28.6%, CKD 3.6%, HD 4.5% Surgery room 22%, ward 45% . . .
Aldawood et al, 2010 60 55 . . . . . . Surgery room 3%, ward 84%, others 13% APACHE II 33
Cruz et al, 2010 64 69 . . . DM 15.6%, CKD 6.6% Surgery room 8.3%, ward 54.6%, emergency 37.1% APACHE II 20/ SOFA 5/SAPS II 45
Elseviers et al, 2010 64 63 Shock 45.5%, drugs 54.5% . . . Surgery room 27.2%, ward 72.8% APACHE II 23.9/ SOFA 9.2
Park et al, 2010 63 63 . . . . . . Surgery room 17.5%, ward 82.5% SOFA 7.4
Clec'h et al, 2011 66 59 . . . CVD 17.9%, COPD 12.9%, HD 6.3%, DM 16.4% Surgery room 10.9%, ward 71.8%, emergency 17.3% APACHE II 19.9/ SOFA 5.3/ SAPS II 50.2
Darmon et al, 2011 61 49 Sepsis 67.5%, shock 19.8%, Drugs 20.7%, CKD 16.3%, contrast 8.9% . . . . . . SAPS II 46
Garzotto et al, 2011 66 59 CVD 12.1%, respiratory failure 27.4%, neurological 17%, trauma 14.4% . . . Surgery room 52.7%, ward 47.3% APACHE 18, SOFA 5, SAPS II 43
Macedo et al, 2011 69 58 Sepsis 47% CVD 70%, DM 30%, CKD 12%, HD 35%, COPD 2.1% … . . .
Macedo et al, 2011 63 Sepsis 18.5%, shock 34.7%, respiratory failure 52%, drugs 18.5% CVD 31.7%, DM 30.5%, HD 17.3% . . . . . .
Mandelbaum et al, 2011 66 58 . . . . . . . . . SOFA 5
Medve et al, 2011 65 56 Sepsis 44%, shock 39%, post operatory 16%, drugs 2% . . . Surgery room 64.3%, ward 35.7%, SOFA 6/ SAPS II 47.5
Ostermann et al, 2011 62 63 . . . . . . Surgery room 38%, ward 30.7%, emergency 14.1%, others 17.2% APACHE II 18/ SOFA 7
Piccini et al, 2011 66 59 CVD 12.1%, respiratory failure 27.4%, neurological 17%, trauma 14.4% . . . Surgery room 52.7%, ward 47.3% APACHE 18, SOFA 5, SAPS II 43
Prowle et al, 2011 59 . . . . . . Surgery room 47.7%, ward 52.3% . . .
Clark et al, 2012 59 66 . . . CVD 55%, COPD 24%, HD 15%, DM 34% Surgery room 41%, ward 45%, emergency 14% APACHE II 27/SOFA 13.4
Han et al, 2012 68 60 Sepsis 4.4%, CVD 36.7%, Tumor 16.9% . . . Ward 97.9% APACHE II 19.4
Medve et al, 2012 67 Sepsis 45.8% . . . Surgery room 100% SOFA 5/ SAPS II 40
Odutayo et al, 2012 65 71 . . . CVD 55%, DM 32% Ward 86%, emergency 6%, Others 8% . . .
Shashaty et al, 2012 40 74 . . . CVD 16.8%, DM 6% Emergency 100% APACHE III 73
Sigurdsson et al, 2012 59 61 Sepsis 26%, shock 46.4%, respiratory failure 35.4%, surgery 35% CVD 46%, DM 14%, COPD 25%, HD 3% . . . APACHE II 23
Vaara et al, 2012 63 63 . . . . . . Surgery room 39.7%, ward 36.7% SOFA 10/ SAPS II 48
Wohlauer et al, 2012 37 74 . . . . . . Surgery room 100% MOF 184
Allegretti et al, 2013 63 . . . CVD 29%, DM 29%, COPD 20%, HD 18% Surgery room 45%, ward 55% Charlson 2
Alsultan et al, 2013 54 . . . CVD 22%, DM 20.9% . . . APACHE II 29.9
Fuchs et al, 2013 63 60 . . . CVD 26%, DM 13%, HD 5% Surgery room 24,3%, ward 75.7% SOFA 8.9/ SAPS I 16.3
Legrand et al, 2013 71 60 . . . CVD 43%; DM 15%; COPD 9%; HD 7% Surgery room 100% SAPS II 57
Nisula et al, 2013 65 65 . . . CVD 77.5%, COPD 10.8%, DM 22.9%, CKD 8.1% Surgery room 39.4%; emergency 82.1% SOFA 9/ SAPS II 42
Poukkanen et al, 2013 64 92 Sepsis 100% CVD 19.6%, DM 5.2% Emergency 96.7% SOFA 9, SAPS II 43
Poukkanen et al, 2013 66 66 Sepsis 31.6% CVD 10.6%, COPD 12%, DM 24.8% Surgery room 24.2%, emergency 97% SAPS II 48, SOFA 11
Doi et al, 2014 66 61 . . . . . . Surgery room 49.6%, ward 50.4% APACHE II 15
Han et al, 2014 68 60 Sepsis 4.6%, CVD 30.8%, post operatory 1.9% DM 12.2%, CKD 8.7% . . . APACHE II 18.4
Linder et al, 2014 61 68 Sepsis 81%, post operatory 27.8% CVD 8.1%, COPD 12.7%, DM 2.6% . . . APACHE II 24.6
Shinjo et al, 2014 63 66 . . . CVD 38.5%, DM 18.4%, COPD 3.5%, HD 3.1% Surgery room 74.3%, ward 13.2%; emergency 12.5% APACHE II 9/SOFA 4/ SAPS II 28
Udy et al, 2014 54 63 . . . . . . Surgery room 44.8%, ward 9.3%; emergency 45.9% IQR 3
Bouchard et al, 2015 62 62 . . . . . . . . . . . .
Harris et al, 2015 59 59 . . . CVD 46%, DM 26% Surgery room 100% APACHE III 66
Rimes-Stigiare et al, 2015 68 60 . . . . . . . . . APACHE II 25/ SAPS II 55
Vanmassenhove et al, 2015 66 67 Sepsis 100% . . . . . . APACHE II 27
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Neurologic etiologies of AKI include polyuria of diabetes insipidus and salt wasting syndrome; CKD refers to AKI on baseline CKD patients. Comorbidities: CVD = cardiovascular disease DM = diabetes mellitus; COPD = chronic obstructive pulmonary disease; HD = hepatic disease; CKD = chronic kidney disease

Table 7. Characteristics of patients with AKI—developing countries.

Author Median age Male gender (%) AKI etiology Comorbidities Patient location before ICU Severity scores
Mataloun et al, 2006 55 46 . . . CVD 35.7%, DM 14% Surgery room 44.3%; ward 27.6%; emergency 28.1% APACHE II 15.2
Silva Junior et al, 2006 50 62 Sepsis 40.6%, shock 48.4%, drugs 21.9% CVD 25.8%, COPD 28.9% . . . . . .
Chow et al, 2007 58 Sepsis 41%, shock 43.6% . . . Surgery room 30.8%, ward 69.2%; obstetrics1% . . .
Daher et al, 2008 45 77 Sepsis 41.5%, shock 40.2%, drugs 10.2% CVD 13%, COPD 19% Clinical ward 100% APACHE II 28
Lima et al, 2008 45 77 Infection 100% CVD 14.2%, HD 40.1% . . . APACHE II 27
Fernandes et al, 2009 56 62 Sepsis 63% CVD 63%, HD 22% Surgery room 44%, ward 51.5%, emergency 45% APACHE II 25.5
Friedericksen et al, 2009 44 61 Sepsis 50%, multiple organ failure 78% CVD 21.7%, DM 19% . . . APACHE II 23.4
Chang et al, 2010 62 70 Sepsis 55% DM 27.5%, HD 42% . . . APACHE II 22.8/ SOFA 9.19
Maccariello et al, 2010 70 Sepsis 74%, shock 75%, contrast 33% CVD 68%, DM 28% Surgery room 19%, ward 13%; emergency 68% SOFA 8.3/ SAPS III 70
Balushi et al, 2011 61 60 Shock 53.6%, drugs 46.4% CVD 53.7%, DM 59.9% . . . . . .
Ponce et al, 2011 57 56 . . . . . . . . . . . .
Fonseca Ruiz et al, 2011 53 53 Sepsis 19.6% CVD 44,6%, DM 18,2% Surgery room 38.2%, ward 57.6%, emergency 4.2% APACHE II 13/SOFA 4/ SAPS II 27
Samimagham et al, 2011 40 71 . . . . . . Surgery room 52.3%, ward 11.1% APACHE II 23.9
Alves et al, 2012 50 45 Sepsis 65% . . . Surgery room 27.9%, ward 67.4%
Obstetrics 4.7%		 SOFA 9.8
Chen et al, 2012 69 75 . . . CVD 73%, DM 61% Ward 100% APACHE II 14
Daher et al, 2012 55 Sepsis 40%, drugs 14%, leptospirosis 12% CVD 24,7%; DM 14,8% Ward 100% . . .
Lai et al, 2012 64 66 . . . CVD 58.4%, DM 28.7% Surgery room 70.7%, emergency 29.3% . . .
Wahrhaftig et al, 2012 66 47 Sepsis 74.2%, shock 17% CVD and DM 99% Surgery room 13.8%, ward 29.7%, emergency 17.3%, others 35.6% APACHEII 13 /SOFA 3
Zhou et al, 2012 59 69 Sepsis 30.6%, respiratory failure 79.9% CVD 36%, DM 12.8% Surgery room 3.7%, ward 79.1%, emergency 7.6%, other 9.6% APACHE III 45.4 / SOFA 5.1
Dalboni et al, 2013 67 66 . . . CVD 39%, DM 18% . . . APACHE II 20
Levi et al, 2013 64 45 Sepsis 46.8%, CVD 42% CVD 46.8%, DM 32.2% Surgery room 30.5%, ward 30.5%, emergency 22.6% APACHE II 15
Silva et al, 2013 57 60 . . . COPD 77,3%, HD 49,2% . . . SAPS III 69.7
Singh et al, 2013 51 0 Sepsis 35.2%, shock 14.2%, drugs 23.5% CVD 13,7%, COPD 23,5% . . . . . .
Daher et al, 2014 46 72 . . . HIV/AIDS 30%, Tuberculosis 12% Ward 100% APACHE II 50
Luo et al, 2014 61 65 Sepsis 32.2 CVD 5.9%, COPD 6.1%, CKD* 6.1%, DM 18.9%, Surgery room 57%, SOFA 6
Morales-Buenrostro et al, 2014 52 54 . . . CVD 16.2%, DM 24.3% Surgery room 21.6%, ward 64,9%, others 10.8% . . .
Peng et al, 2014 52 68 Sepsis 100% . . . . . . APACHE II 20.8
Wijewickrama et al, 2014 48 62 Sepsis 28.7%, shock 12.1% CVD 28%, DM 27% . . . SOFA 9
Bentata et al, 2015 28 Obstetrics
100%		 CVD 19.5%, Emergency 22% . . .
Bouchard et al, 2015 59 63 . . . . . . . . . . . .
Heegard et al, 2015 26 98 Trauma 100% . . . Emergency 100% . . .
Ralib et al, 2015 50 64 . . . CVD 36.4%, DM 28.7% Surgery room 25.2%, ward 74.8% APACHE II 19.4/ SOFA 8.7
Santos et al, 2015 43 66 Sepsis 2.9%, CVD 3.2%, emergency 48.4% DM 12.9% Emergency 48.8% APACHE II 10
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Comorbidities: CVD = cardiovascular disease; DM = diabetes mellitus; COPD = chronic obstructive pulmonary disease; HD = hepatic disease; CKD = chronic kidney disease

Patient characteristics

Age

Almost 40% (22/56) of the studies in developed countries described a mean age above 65 years in AKI patients (ranging from 37 [12] to 72 years [19]), while only 12.1% (4/33) of the studies in developing countries reported an age higher than 65 years in AKI patients (ranging from 26 [20] to 70 years [21]) (Tables 6 and 7). The weighted mean ages were 62.0 and 56.8 years for developed and developing country patients, respectively.

Gender and ethnicity

Male sex was predominant in AKI patients in both groups of countries: 59.6% (34/57) and 67.8% (19/28) of the studies in developed and developing countries, respectively, reported a male frequency above 60%. The weighted male frequencies were 67.1% and 64.5% for developed and developing country patients, respectively.

Only 9.5% (9) of the studies reported the patients’ ethnic background (Tables 6 and 7).

Comorbidities

Comorbidities were assessed in 51.6% (31/60) and 78.7% (26/33) of studies from developed and developing countries, respectively. The most prevalent comorbidities were cardiovascular diseases (CVD), diabetes and chronic respiratory disease.

In developed counties, a CVD frequency greater than 40% was reported in 51.6% (16/31), versus 30.4% (7/23) in developing countries. The weighted CVD frequencies were 41.3% and 32.6% for developed and developing country patients, respectively.

The frequency of diabetes was similar in both groups of countries. In approximately 60% (16/27 in studies of developed and 10/18 of developing countries) of studies, the prevalence of diabetes was over 20% in the studied population (Tables 6 and 7). The weighted diabetes frequencies were 27.3% and 24.5% for developed and developing country patients, respectively.

Severity scores

The most reported severity scores were APACHE II and SOFA. The Apache II score in AKI patients was reported in 32 and 18 studies from developed and developing countries, respectively. The APACHE II score had a similar distribution in the two groups of countries, ranging from 9 [22] to 56 [23] in developed country studies and from 10 [17] to 50 [24] in studies from developing countries. Approximately half of the studies had an APACHE II score up to 20 (16/32) in developed and in developing countries (9/18) (Tables 6 and 7). The weighted APACHE II scores were 18.7 and 21.0 for developed and developing country patients, respectively.

The SOFA score was reported in 21 and 10 studies from developed and developing countries, respectively. The distribution of the SOFA score was similar between groups, ranging from 3 [25] to 13.4 [26] in studies from developed countries and from 3 [27] to 9.8 [28] in developing country studies. In studies where this information was available, a SOFA score over 5 was reported by 71% (15/21) of studies from developed countries and 80% (8/10) of studies in developing countries (Tables 6 and 7). The weighted SOFA scores were 7.6 and 8.2 for developed and developing country patients, respectively.

Patient location before ICU

Most of the AKI patients who were admitted to the ICU came from surgical and clinical wards units. The majority of manuscripts from both developed countries (13/16) and developing countries (9/11) reported that up to 50% of patients with AKI had hospital admission in emergency situations (Tables 6 and 7).

Outcomes

Length of ICU and hospital stay

In developed and in developing countries, 71.6% (43/60) and 69.6% (23/33) of the studies reported the length of ICU stay for AKI patients, which ranged from 1 to 22 days and from 5 to 23 days, respectively. The reported ICU stay was longer than seven days in 38.6% (17/44) and 80% (20/25) of developed and developing country studies, respectively (Tables 8 and 9). The weighted mean ICU stay lengths were 7.2 and 12.2 days for developed and developing country patients, respectively.

Table 8. Outcomes—Developed countries.
Autor ICU stay (days) Hospital stay (days) RRT in ICU AKI patients (%) Type of RRT Mortality in ICU AKI patients (%)
Abosaif et al, 2005 . . . . . . 38.8 C 100% 47.5
Bagshaw et al, 2005 8.1 22 6 C 61%, I 20% 50
Chawla et al, 2005 . . . . . . 37.1 . . .
Ostermann et al, 2005 . . . . . . . . . C 92%, I 7.1% 66.7
Ahlstrom et al, 2006 . . . . . . 7 . . . 16.6
Herrera-Gutiérrez et al, 2006 15.6 19.9 38 . . . 46.8
Hoste et al, 2006 3 16 6 . . .
Bagshaw et al, 2007 4.4 14.2 . . . . . .
Cruz et al, 2007 10 . . . 30.3 C 50.7%, I 14.1% 36.3
Eachempati et al, 2007 16 15.9 19.8 I 100% 45
Ostermann et al, 2007 . . . . . . 12.2 C 80.2%, I 5.2% 28.4
Bagshaw et al, 2008 . . . . . . . . . . . . 16.7
Bagshaw et al, 2008 3.7 14.6 . . . . . . 24.2
Barrantes et al, 2008 3 9 15 . . .
Lopes et al, 2008 8.2 . . . 27.2 . . . 41.3
Ostermann et al, 2008 7 . . . 23 C 93.6%, I 0.4% 31.1
Abelha et al, 2009 2.8 25 . . . . . . 17.2
Andrikos et al, 2009 13 . . . 53.5 C 86%, I 13.2% 64.7
Cartin-Ceba et al, 2009 . . . . . . 19 C 39%, I 61% 20
Costantini et al, 2009 13.6 25 7 . . . 15.9
Joannidis et al, 2009 2.8 . . . . . . . . . 16
Thakar et al, 2009 . . . . . . 4.4 . . .
Aldawood et al, 2010 15 . . . 9 . . . 64
Cruz et al, 2010 7 . . . . . . . . . 17.3
Elseviers et al, 2010 16.4 34.2 49.9 C 42%, I 58% 58
Park et al, 2010 . . . 17.2 . . . . . . 62.8
Clec'h et al, 2011 7 . . . 19 . . .
Darmon et al, 2011 . . . . . . 22.1 . . . 36.7
Garzotto et al, 2011 5 . . . 8 . . . 21.7
Macedo et al, 2011 4 8 6 . . .
Macedo et al, 2011 3 8 . . . . . . 9.5
Mandelbaum et al, 2011 7 16 . . . . . . 12.4
Medve et al, 2011 4.5 13.5 15.1 I 64.8% 39.3
Ostermann et al, 2011 7 . . . . . . . . . 31.1
Piccini et al, 2011 5 . . . 8 . . . 21.7
Prowle et al, 2011 . . . . . . 39 . . . 22.5
Clark et al, 2012 . . . . . . . . . C 77%, I 17%
Han et al, 2012 7 . . . 17 . . .
Medve et al, 2012 6 18 . . . . . . 33.3
Odutayo et al, 2012 . . . . . . 11.8 . . .
Shashaty et al, 2012 . . . . . . . . . . . . 14.9
Sigurdsson et al, 2012 17 . . . 17 . . . 9
Vaara et al, 2012 12.5 . . . 6.8 . . . 29.1
Wohlauer et al, 2012 14 . . . 23 . . .
Allegretti et al, 2013 21 . . . . . . . . . 60.7
Alsultan et al, 2013 . . . . . . 12 . . .
Fuchs et al, 2013 . . . . . . . . . . . . . . .
Legrand et al, 2013 9 . . . . . . . . . 23
Nisula et al, 2013 2.8 9 10.3 . . . . . .
Poukkanen et al, 2013 5.7 16 8 . . . . . .
Poukkanen et al, 2013 4.2 14 . . . . . . . . .
Doi et al, 2014 5 . . . . . . . . . 12
Han et al, 2014 22 . . . 38.4 . . . 67.4
Linder et al, 2014 9.1 23.4 . . . . . . 67.1
Shinjo et al, 2014 1 31 . . . . . . 7.1
Udy et al, 2014 5 . . . . . . . . . 14
Bouchard et al, 2015 5 11 15.5 . . . 27.6
Harris et al, 2015 4.5 19 12 . . . 33
Rimes-Stigiare et al, 2015 . . . . . . 6 . . . 35
Vanmassenhoe et al, 2015 12 . . . 13.8 . . . 23.1
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RRT: renal replacement therapy; C = continuous RRT, I = intermittent RRT

Table 9. Outcomes in developing countries.
Autor ICU stay (days) Hospital stay (days) RRT in ICU AKI patients (%) Type of dialysis Mortality in ICU AKI patients (%)
Mataloun et al, 2006 16.1 . . . 23.8 I 100% 76.2
Silva Junior et al, 2006 17 . . . 32 I 100% 62.5
Chow et al, 2007 13.7 . . . 16.7 P 69.2%, I 15.3% . . .
Daher et al, 2008 11 . . . 35 I 100% 66.6
Lima et al, 2008 12 . . . 35 . . . 64.6
Fernandes et al, 2009 22 22.3 48 C 30%, I 10% 85
Friedericksen et al, 2009 10.8 . . . 17.3 C 25%, I 75% 47.8
Chang et al, 2010 11.4 . . . . . . . . . 60.8
Maccariello et al, 2010 23 29 . . . C 84% 63
Balushi et al, 2011 . . . . . . 60.7 . . .
Ponce et al, 2011 12.9 . . . . . . . . . 62.5
Fonseca Ruiz et al, 2011 8.4 . . . 12.4 C 30.8%, I 69.2% 25.4
Samimagham et al, 2011 10.6 . . . . . . . . . 72.6
Alves et al, 2012 10.7 . . . 2.3 I 100% 29
Chen et al, 2012 . . . . . . . . . . . .
Daher et al, 2012 . . . . . . 68 I 100% 33.6
Lai et al, 2012 . . . . . . . . . . . . . . .
Wahrhaftig et al, 2012 12 . . . . . . 53.3
Zhou et al, 2012 11.6 . . . 63.5 . . . 50
Dalboni et al, 2013 . . . . . . . . . . . . 9
Levi et al, 2013 . . . . . . . . . . . . 63.1
Silva et al, 2013 17 20.5 28.7 C 85.3%, I 14.7% 78.6
Singh et al, 2013 . . . . . . 20.6 . . . 73.5
Daher et al, 2014 . . . . . . 27.6 . . . 62.8
Luo et al, 2014 5 27.4 . . . . . . . . .
Morales-Buenrostro et al, 2014 . . . . . . . . . . . . . . .
Peng et al, 2014 8.5 15.7 . . . . . . . . .
Wijewickrama et al, 2014 11.6 . . . 58.4 I 97.3%; P 2.7% 52.3
Bentata et al, 2015 6.5 . . . . . . . . . 10.2
Bouchard et al, 2015 6 10 30.2 . . . . . .
Heegard et al, 2015 . . . . . . 5.6 . . . 21.7
Ralib et al, 2015 6.4 14.2 25 C 36%, I 58.3% 91
Santos et al, 2015 9.5 . . . 71.7 . . . 33.3
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RRT: renal replacement therapy; C = continuous RRT, I = intermittent RRT; P = peritoneal dialysis

In non-AKI patients, ICU stays longer than 7 days were not reported in developed country studies (0/24) but occurred in 44% (4/9) of studies in developing countries. In developed and developing country studies, 38.3% (23/60) and 21.2% (7/33) of the studies reported the length of hospital stay, which ranged from 8 to 31 days and 10 to 29 days, respectively. Hospital stays were longer than 15 days in 58.3% (14/24) and 66.7% (6/9) of developed and developing country studies, respectively (Tables 8 and 9). In non-AKI patients, the hospital stay was longer than 15 days in 25% (4/16) and 33.3% (1/3) in developed and in developing country studies, respectively. The weighted mean lengths of hospital stay were 15.5 and 23.6 days for developed and developing country patients, respectively.

Renal replacement therapy

Sixty-three percent of the analyzed studies reported the use of renal replacement therapy (RRT) in ICU AKI patients. In developed countries, 21% of the 38 studies with available data referred to the use of RRT in ICU AKI patients as being greater than 30%. In developing countries, 48% of the 21 studies with available data showed that the frequency of RRT use was higher than 30% in ICU AKI patients (Tables 8 and 9). The weighted frequencies of RRT were 8.8% and 23.8% for developed and developing country patients, respectively.

Mortality

Reported ICU mortality in AKI patients was greater in developing country studies. AKI mortality greater than 60% was reported in 15.9% (7/44) of studies from developed countries and 56% from developing countries (14/25) (Tables 8 and 9). The weighted frequencies of mortality were 30.8% and 54.8% for developed and developing country patients, respectively.

Synthesis of AKI incidence

Pooled AKI incidence estimates for developed and developing countries in the meta-analysis are presented in Table 10, according to the AKI definition used. The RIFLE, AKIN or KDIGO criteria for AKI definition was used, as defined, by 39 and 21 studies in developed and developing country studies, respectively. One study in developed countries and 3 in developing countries studies did not report AKI incidence, so 38 and 18 studies, respectively, had an AKI incidence estimation included in the meta-analysis. The pooled estimate of AKI incidence in developed and developing countries is shown in Fig 3. There was a tendency towards a greater incidence in developed countries, although this was not significant. When only prospective studies were analyzed, this tendency disappeared (Table 10).

Table 10. Pooled AKI frequency of developed and developing countries’ studies according to AKI Definition.

Subgroup Country group Studies Patients AKI frequency 95% confidence Test for heterogeneity
(n) (n) (%) interval I2 Index Q Test p-value
RIFLE/AKIN/KDIGO Developed 38 153,846 39.3 34.6–43.9 27.5 0.062
Developing 18 9,174 35.1 28.4–41.9 -15.1 0.612
RIFLE Developed 14 71,954 37.4 30.0–44.8 13.0 0.018
Developing 4 1,742 26.9 15.3–42.0 26.9 0.250
AKIN Developed 18 72,677 36.9 29.5–44.3 22.7 0.185
Developing 8 3,372 30.8 25.5–36.1 42.2 0.097
KDIGO Developed 6 9,215 50.7 38.3–63.1 7.26 0.370
Developing 6 4,060 43.8 34.7–52.8 15.2 0.316
RIFLE/AKIN/KDIGO–Prospective studies Developed 18 29,164 37.4 30.9–43.9 26.4 0.145
Developing 13 6,677 36.2 27.4–44.9 -16.2 0.587
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*Included the studies that used the RIFLE, AKIN or KDIGO definition

Fig 3. Forest plot of AKI incidence.

Fig 3

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Footnote: The studies shown are those that used the RIFLE, AKIN or KDIGO criteria for AKI definition. A) Developed country studies; B) Developing country studies.

Fig 4 shows the funnel plot for both country groups in which individual study frequency of AKI is a function of their sample size with the pooled incidence of studies that used the RIFLE, AKIN or KDIGO criteria for the AKI definition being depicted as a black line. Note that the Fig 4A (developed countries) had a 10-fold greater sample size than Fig 4B (developing countries). The studies with a greater sample size depart from the polled estimated AKI incidence, suggesting the possibility of publication bias or bias resulting from the lack of standardizing reference creatinine, oliguria, and the timeframe for AKI assessment.

Fig 4. Funnel plot of sample size of studies as a function of AKI incidence.

Fig 4

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Footnote: The studies shown are those that used the RIFLE, AKIN or KDIGO criteria for AKI definition. A) Developed country studies; B) Developing country studies. Pooled AKI incidence is depicted as a vertical line.

Discussion

We found a high incidence of AKI in both country categories, and a tendency towards a greater incidence in developed countries. Due to the differences in AKI definitions, timeframe and the types of studied population, the reported incidence varied from 0.5% to 78%.

Our review covered a 10-year period. Thus, different AKI definitions were used for AKI assessment, including the RIFLE, AKIN and KDIGO criteria [29,30,31]. Only two-thirds of the studies reported the definition for reference serum creatinine, with 29 different definitions used, which results in high heterogeneity of AKI incidence estimate [32]. In the most recent AKI definitions (RIFLE, AKIN and KDIGO), the reference SCr is the value observed up to seven days or 48 hours before the SCr increase defining the AKI diagnosis. However, we observed that several studies used as reference SCr values obtained months, or even one year before the AKI episode, which is not consistent with the current AKI definitions. When the reference serum creatinine was not available, the MDRD formula has been used for estimation of the missing SCr value, which is a flawed methodology as it can misdiagnose AKI in CKD patients [12,33,34]. The oliguria definition was more uniform, with recent studies correctly using the RIFLE, AKIN and KDIGO oliguria definitions. The addition of urine output criteria was associated with higher and earlier AKI detection and incidences in critically ill patients [32].

Another important caveat to create a valid comparison between developed and developing countries is the striking differences in the number of studies and the sample sizes. Eighty per cent of the world population lives in developing countries, but only one-third of the studies sample reported data from them, with the majority assessing a single center with a relatively small number of patients [35]. Moreover, approximately half of the studies from developing countries were from Brazil, and only two were from Africa. On the other hand, approximately 40% of developed country studies assessed more than five centers. The sample size from developed countries studies was more than 30-fold greater compared to those from developing countries. There is a clear underrepresentation of developing countries that is probably caused by a lack of health resources and electronic medical records, as well as difficulty in gathering epidemiological data and, consequently, conducting adequate large observational studies. These studies can be more capable to determine the true burden of a disease than trials and more valuable in assessing the incidence and prevalence of the disease [36]. A snapshot of worldwide AKI incidence found more severe AKI presentation in patients from developing countries, which was considered to be due to delay in AKI recognition and treatment, adversely affecting the outcomes [7,37].

The incidence of AKI development in the ICUs was similar in both types of countries, with a numeric tendency to be greater in developed country studies. When only prospective studies were analysed, this tendency disappeared. Developing and developed countries have very distinct healthcare patterns. In developing countries, deficiencies in health structure, long distance from the community to the hospital and poor transportation systems limit patient access to healthcare. Lack of universal health coverage and insufficient funding for the health system imposes significant cost of treatment for the patients and family, including high cost procedures such as ICU and renal replacement therapy [38]. Tropical infectious diseases, animal venoms, natural medicine, abortion and eclampsia are known to be important AKI etiological factors in developing countries [39,40]; however, their incidence was extremely low in the ICU population. This is likely due to the limited number of ICUs, which are located mostly in larger urban cities, as well as inadequate recognition of high-risk AKI patients in the primary health system. Furthermore, difficulty transporting patients due to geographical and economic issues may contribute to this situation [39]. As a consequence, developing country’s ICUs reflect tertiary hospitals and university hospitals mostly from an urban population. Thus, patient characteristics were similar in both types of country. Sepsis and shock were the main causes of AKI in both developed and developing countries, but the frequency of sepsis was approximately 50% greater in developing country studies. In developed country studies, AKI patients were older, which likely reflects higher population longevity, better socioeconomic conditions and more structured health services. Overall, cardiovascular diseases were the most frequently reported comorbidity, although they were more frequent in developed country studies.

AKI was associated with poor outcomes, higher length of stay (LOS) and mortality, which is consistent with other studies [41,42]. In developing country studies, AKI had higher LOS and mortality compared to developed countries, although patients were younger, had less CVD and had similar APACHE II scores. Difficulty accessing health services [39,43] and lack of infrastructure, including ICU beds and human resources for care of the critically ill in these countries [44,45], are probably the cause of worse outcomes in such a low resource setting. It is possible that the patients treated in developing countries are transferred to an ICU at a late stage of disease progression and have a reduced change of recovering [45]. The finding of higher frequency RRT use in developing countries supports this hypothesis.

This systematic review highlighted important caveats for the comparison between ICU AKI epidemiology in developed and developing countries. The vast majority of studies assessed university tertiary hospitals, limiting the generalizability of the results. Different AKI definitions were used over time, and even when the new AKI criteria were used, there is an important lack of standardization for reference serum creatinine. Most of the studies from developing countries were single center. The number of patients and ICUs assessed in developed country studies was greater than 30-fold and 10-fold higher than in developing countries, respectively, highlighting the underrepresentation of developing countries.

Conclusion

AKI incidence was high in both types of countries. Patient characteristics were mostly similar, but outcomes were worse for patients in developing country studies. Despite patient´s similarities, the non-inclusion of secondary hospitals and the differences in the number of studies and sample sizes exemplify the challenge of comparing developing and developed country AKI epidemiology. The widespread application of AKI definitions has made it possible to compare AKI epidemiology across different settings. However, an effort to standardize reference serum creatinine, oliguria and the timeframe for AKI assessment is crucial. There is an urgent need for larger, prospective, multicenter studies that assess broader populations from developing countries.

Supporting information

S1 File. Supplementary material search strategies.

(DOCX)

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S2 File. Supplementary material syst review references.

(DOCX)

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S3 File. PRISMA checklist.

(DOCX)

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Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

This study was funded by the São Paulo Research Foundation, FAPESP (process number 2014/19286-4) and Fundação de Amparo à Pesquisa do Acre, FAPAC.

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Associated Data

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Supplementary Materials

S1 File. Supplementary material search strategies.

(DOCX)

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S2 File. Supplementary material syst review references.

(DOCX)

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S3 File. PRISMA checklist.

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Data Availability Statement

All relevant data are within the paper and its Supporting Information files.

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