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Epidemiology of Acute Kidney Injury

Jorge Cerda,* Norbert Lameire, Paul Eggers, Neesh Pannu, Sigehiko Uchino,
Haiyan Wang, Arvind Bagga,** and Adeera Levin
*Division of Nephrology, Albany Medical College, Albany, New York; Department of Internal Medicine, University
Hospital Ghent, Ghent, Belgium; Kidney and Urology Epidemiology, National Institute of Diabetes and Digestive and
Kidney Disease, National Institutes of Health, Bethesda, Maryland; Division of Nephrology, University of Alberta,
Edmonton, Alberta, Canada; Department of Emergency and Critical Care Medicine, Saitama Medical Center, Saitama,
Japan; The First Hospital Institute of Nephrology, Beijing University, Beijing, China; **Division of Pediatric
Nephrology, All India Institute of Medical Sciences, New Delhi, India; and Division of Nephrology, University of
British Columbia, Vancouver, British Columbia, Canada
Background and objectives: The worldwide incidence of acute kidney injury is poorly known because of underreporting,
regional disparities, and differences in definition and case mix. New definitions call for revision of the problem with unified
criteria.
Design, setting, participants, & measurements: This article reports on the research recommendations of an international
multidisciplinary committee, assembled to define a research agenda on acute kidney injury epidemiology using a modified
three-step Delphi process.
Results: Knowledge of incidence and risk factors is crucial because it drives local and international efforts on detection and
treatment. Also, notable differences exist between developing and developed countries: Incidence seems higher in the former,
but underreporting compounded by age and gender disparities makes available data unreliable. In developing countries,
incidence varies seasonally; incidence peaks cause critical shortages in medical and nursing personnel. Finally, in developing
countries, lack of systematic evaluation of the role of falciparum malaria, obstetric mechanisms, and hemolytic uremic
syndrome on acute kidney injury hampers efforts to prevent acute kidney injury.
Conclusions: The committee concluded that epidemiologic studies should include (1) prospective out- and inpatient studies
that measure incidence of community and hospital acute kidney injury and postacute kidney injury chronic kidney disease;
(2) incidence measurements during seasonal peaks in developing and developed countries; and (3) whenever available, use of
reliable existing administrative or institutional databases. Epidemiologic studies using standardized definitions in community and institutional settings in developing and underdeveloped countries are essential first steps to achieving early detection
and intervention and improved patient outcomes.
Clin J Am Soc Nephrol 3: 881-886, 2008. doi: 10.2215/CJN.04961107

he incidence rate of acute kidney injury (AKI) around


the world is not well known (13). Recent studies in the
United States (4,5) and Spain (6) have shown incidences
varying between an average of 23.8 cases per 1000 discharges
(4) with an 11% yearly increase between 1992 and 2001, to an
increase from 61 to 288 per 100,000 population between 1988
and 2002 (5). More recently, Ali et al. (7) reported a high
incidence of 1811 cases of AKI per million population during
2003. The relatively wide disparity in reported incidence rates
and the increasing frequency of the condition raise concerns as
to the real magnitude of the problem. In addition to a real

Published online ahead of print. Publication date available at www.cjasn.org.


Correspondence: Dr. Jorge Cerda, Division of Nephrology, Albany Medical College and Capital District Renal Physicians, 62 Hackett Boulevard, Albany, NY
12209. Phone: 518-434-2244; Fax: 518-434-4659; E-mail: cerdaj@mail.amc.edu
Copyright 2008 by the American Society of Nephrology

increase in worldwide incidence, large differences in the definition of AKI and case mix likely underlie such differences.
It is recognized that the epidemiology of AKI in developing
countries differs from that of the developed world in many
important ways (8 16). Whereas in developed regions elderly
patients predominate (4,5), in developing countries, AKI is a
disease of the young (14,17,18) and children (19,20), in whom
volume-responsive prerenal mechanisms are common (21
24). Although overall mortality seems to be lower than in
developed countries (2528), this finding is not true across all
age groups: In these regions, AKI affects predominantly the
young and children and mortality is high (29,30).
The difficulties of defining the incidence of AKI are especially
notable when one searches for data on developing countries
(8,13,15,16,25,3133), the place of residence of more than 50% of
the worlds population. No nationwide collection systems are
available, and data from isolated centers are not based on the
ISSN: 1555-9041/3030881

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Clinical Journal of the American Society of Nephrology

current AKI definition. Reports from Kuwait (8) reported an


incidence of 4.1 per 100,000 population per year; Anochie et al.
(31) in Nigeria reported an incidence of 11.7 cases of AKI per
year in children in a hospital that serves more than 1 million
children; in a tertiary care center in north India, the reported
incidence was 20 cases per 1000 pediatric admissions (29).
Among adult patients from South Africa, Seedat (25,34) reported an incidence of 20 cases per year per million population;
in Brazil, Noronha et al. (10) reported an incidence of 7.9 cases
per 1000 hospital admissions, and in North India, Jha and
Chugh (33) reported a yearly incidence of 6.4 per 1000 admissions.
New definitions of AKI (3537) make it again necessary to
revisit this issue with unified criteria. Such new measurements
will help us to understand the magnitude of the problem and
enable meaningful comparisons between different centers and
geographic regions. Previous articles have reviewed the status
of this rapidly changing field (13). A recent systematic review
described the similarities and differences in incidence, cause,
pathophysiology, and public health implications of AKI in
developed and developing regions (16). This article aims to
build on such a review of existing knowledge and present a
research agenda to begin to address the multiple areas of uncertainty in the epidemiology of AKI. This is the first time a
multidisciplinary group including representatives from the
main national and international societies of nephrology and
critical care gathers to elaborate such a research agenda. The
group understands that only by obtaining accurate knowledge
on the epidemiology of AKI using contemporary diagnostic
criteria can the problem acquire the necessary visibility that
will enable the development of new initiatives. Such initiatives
will be essential to move us forward in the field, decrease the
worldwide incidence of AKI, and improve patient outcomes
(36,38).
As long as AKI remains underreported, it will not be addressed properly. In developing countries, the most common
causes of AKI are frequently associated with volume-responsive prerenal (39,40), obstetric (41), infectious (42,43), or toxic
(25,44) mechanisms; thus, inexpensive, simple interventions
such as education on oral rehydration (29,45), improved crosscultural interaction with traditional healers (46), change in obstetric management policies (47,48), or management of infection
(49) may result in a dramatic reduction in the incidence and
severity of AKI (29,42,45 49). Given that in developing countries the costs of renal replacement therapies are prohibitively
high (17,50 52), prevention is often the only realistic way to
decrease its severe impact on morbidity and mortality. Although inexpensive, such interventions will not be carried on
until the problem reaches political visibility and achieves institutional and organizational support (16).

Materials and Methods


For the purposes of defining a research agenda in the context of the
epidemiology of AKI, we used a modified Delphi process. This is
described in detail by Kellum et al. (53) in this issue. Briefly, the
three-step modified Delphi procedure included a literature review
phase, focused group interactions with presentations to the entire com-

Clin J Am Soc Nephrol 3: 881-886, 2008

mittee, and a final ranking phase during which the research agenda
was developed.

Literature Review and Synthesis


We conducted a systematic review of the literature using the following databases: Medline (1966 through August 2006), EMBASE (1980
through 2006, week 36), CINAHL (1982 through August 2006), and
PubMed. Articles in any language were considered. The purpose of the
review was to identify key unanswered questions. A secure internet
Web site was set up with FTP capability; group members were able to
upload and download full-text articles, and through a number of
iterative steps, a series of clinical questions were developed.

Work Group Deliberations


After reviewing the literature and establishing a global perspective
on the problem, discussions were undertaken within the work group
regarding key knowledge gaps and recommendations for research that
would improve the understanding of AKI worldwide. An organizational framework for AKI was introduced and discussed (Figure 1). In
addition, recognizing that AKI commonly precedes or aggravates
chronic kidney disease (CKD) (20,54 60), a schematic view of the
natural history of AKI was developed (Figure 2).

Results
Global Perspectives
Local conditions in developing countries make underreporting an important problem (1,16). It is improbable that incidence
rates are so much lower in these regions than in developed
countries. The most likely explanation for the seemingly lower
incidence of AKI is that the majority of patients who develop
AKI never make it to large reporting centers: The condition is
underrecognized, distances are enormous, and the costs of
transportation and lost wages are prohibitive (3). Delayed referral as a result of transportation difficulties and traditional
cultural mores is still a formidable problem in many regions of
the world (61) associated with significantly worse outcomes, as
seen among children with hemolytic uremic syndrome in India
(30).
Gender disparities in seeking medical attention make available reports even more unreliable. Thus, in certain regions in
Africa and India, boys are more than twice as likely as girls to
be taken by their parents to see medical personnel (62 66).
Gender disparity is also expressed in the development of AKI
after septic abortion (41,67). In some African countries, the
problem has unfortunately worsened (41) despite nationwide
efforts.
In developing countries even at large centersthe availability of medical and nursing personnel is limited. This limitation becomes even more critical during seasonal variations in
incidence (10,68 70). For example, during the monsoon season
in Southeast Asia, the incidence of AKI may increase by 18 to
24% as a result of the increase in new cases of malaria, leptospirosis, acute gastroenteritis, and dysentery (71).
The causes and risk factors for AKI in developing countries
may be different from those in developed countries. Although
prerenal or toxic mechanisms predominate, specific etiologies
are important.

Clin J Am Soc Nephrol 3: 881-886, 2008

Epidemiology of Acute Kidney Injury

883

The incidence of acute glomerulonephritis, both primary and secondary to infecCOMPLICATIONS


tious diseases appears to be higher than in
developed countries. Thus, in south-east
Anatolia, Turkey, acute glomerulonephritis
causes more than 60% of childhood cases of
AKI (72), and is an important cause of AKI
in northern Africa (7375) Potential reasons
NORMAL
INCREASED
KIDNEY
DECREASED
DEATH
DAMAGE
are multiple, including access to care (leadRISK
FAILURE
GFR
ing to late and therefore severe presentation), diagnostic testing capabilities and
perhaps a true incidence difference. This is
an important research question that warrants further study.
ANTECEDENTS
Malaria represents an especially imporINTERMEDIATE STAGE
tant problem (16). There is an upsurge in
AKI
worldwide malarial incidence (76,77). In InOUTCOMES
dia, for example, the overall yearly incidence is 13 to 17.8% of malarial cases (43).
Figure 1. Conceptual model of acute kidney injury (AKI).
Incidence is increasing in Africa, India,
Thailand, and New Guinea (42). As its
worldwide incidence increases, so are the
intervention, including appropriate antimalarial treatment and
complications of severe falciparum malaria, including AKI (78). renal replacement therapy, is associated with improved surEach year, 300 million people contract the disease, which will vival and recovery of kidney function among patients with AKI
be responsible for more than 1 million yearly deaths in Africa as a result of severe falciparum malaria (79,80).
alone (49,77). It is estimated that in 1% of cases (3000,000/yr), a
combination of parasite and host factors will lead to severe Specific Problems in Children
malaria, jaundice, and AKI (42,78), a complication associated
Although the majority of causes of AKI in children around
with 45% mortality (78); in areas of endemic malaria, the inci- the world are secondary to volume-responsive mechanisms,
dence of AKI may be 4% of malarial cases (42). Worldwide, including acute diarrheal losses and renal hypoperfusion after
the incidence of AKI as a result of malaria varies between 0.6 major surgery and secondary to systemic sepsis (81 83), other
and 60% of malarial cases, depending on the region (43). Early conditions have shown an increased frequency in certain reINSULT

1 - FULL RECOVERY

2 - AKI TO CKD

RENAL FUNCTION

100

3 - ACUTE-ON-CHRONIC
KIDNEY DISEASE
4 - AKI TO ESRD

gions of the world. Thus, hemolytic uremic syndrome (HUS) is


the chief cause of CKD and ESRD in children in Argentina (84)
and in northern India (85), where it has increased in frequency
in comparison with previous surveys (45). Whereas in Argentina the mortality associated with HUS has decreased from 10
to 3% (84), in India, it remains high (up to 59% [29]), attributed
often to late referral of patients (30). An additional complication
to longitudinal incidence comparisons is that some diseases
virtually did not exist a few years ago; thus, HUS was very
uncommon in south and southeast Asia before the 1970s but
has since then become one of the most important causes of AKI
in children of that region (29). Follow-up studies of patients
suggest that of the patients who have AKI and are successfully
discharged from the hospital, a significant proportion may
show features of CKD, including low GFR, hypertension, and
proteinuria (20,84).

The Elderly and Complex Patients

0
TIME

Figure 2. Natural history of AKI. Patients who develop AKI may


experience (1) complete recovery of renal function, (2) development of progressive chronic kidney disease (CKD), (3) exacerbation of the rate of progression of preexisting CKD; or (4)
irreversible loss of kidney function and evolve into ESRD.

Although it is widely known that the elderly and those with


multiple medical conditions are at increased risk for AKI
(4,5,86), the measurement of this risk is inaccurate, especially in
outpatient situations. It remains unclear whether the underlying condition(s) increases susceptibility or whether those patients are more likely to be exposed to important initiating
factors for AKI.

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Clinical Journal of the American Society of Nephrology

Clin J Am Soc Nephrol 3: 881-886, 2008

Research Recommendations

Conclusions

Key research studies to evaluate incidence and risk factors


are crucial. Knowledge of the magnitude of the problem will
drive local and international efforts to detect and treat the
problem as early as possible. The scarcity or absence of data
makes it unlikely that the problem will be addressed by local,
regional, and worldwide organizations such as the Pan American Health Organization and the World Health Organization
in a strong, consistent manner. Accurate knowledge of the
epidemiology of AKI in developing countries will have powerful preventive and treatment effects (18,29,30,45,80,87); conversely, complex technical questions on renal replacement therapies may, for the time being, largely remain less relevant to
this population (51,52).

AKI is a worsening problem, but its true incidence is unknown. From a worldwide perspective, there is a clear need to
understand the epidemiology of AKI more accurately. Use of
standardized definitions and descriptions of existing at-risk
and high-risk populations, both in community and institutional
settings in developing and underdeveloped countries, are the
first steps to improve outcomes.

Epidemiology of AKI in Developing and Developed


Countries
There is a need for a variety of epidemiologic studies to
acquire new knowledge about the incidence of AKI. Although
data collected from surveys, administrative data sets, post hoc
analysis of clinical trials, or review of existing laboratory or
clinical databases have important methodologic limitations, it is
clear that without attempts to quantify the true burden of
illness using standardized definitions, improved understanding and outcomes will not be possible.
Establishing the True Incidence in Different Locations.
Studies using the new definition of AKI can be instrumented in
a prospective manner, such as measuring the incidence of AKI
in emergency departments to measure community-acquired
AKI and among hospital inpatients to measure hospital and
intensive care unitacquired AKI. Such measurements can then
be followed up longitudinally for 3, 6, and 12 mo to ascertain
the natural history of the problem and to measure the importance of AKI as a cause of CKD (see Figure 2). In developing
countries, where community-acquired AKI occurs in the rural
setting and rarely reaches the hospital, different regional data
collection techniques will be necessary to ensure accurate measurement of incidence.
Unique situations that may facilitate knowledge acquisition
include data collection during periods of presumed increased
incidence, such as during monsoon season in Southeast Asia
(68,70) or the rainy season in South America (10,88). If local
resources are used, then such studies would not be costly and
could be obtained in a short period of time. Local innovations
in this regard would enable acquisition of data at small cost.
Establishing True Incidence in Different Locations/Situations. In developed countries, use of currently existing administrative or institution databases whenever available will
help to establish the prevalence of abnormal kidney function at
the time of admission to hospitals or emergency departments
and the occurrence of changes in renal function during hospitalization. Collecting information about populations at risk
(e.g., elderly patients in nursing homes during influenza season
or before and after vaccination) would also enable more precise
estimates of the burden of illness. Such databases are rarely
available (32,41,89) in developing countries.

Disclosures
None.

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