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Improving outcomes of acute kidney injury:

report of an initiative
Bruce A Molitoris*, Adeera Levin, David G Warnock, Michael Joannidis, Ravindra L Mehta, John A Kellum,
Claudio Ronco and Sudhir V Shah on behalf of the Acute Kidney Injury Network working group

S U M M A RY INTRODUCTION
Acute kidney injury (AKI) is a common clinical
Acute kidney injury (AKI) is a complex disorder comprising several
problem defined by an abrupt (within 48 h)
etiological factors and occurring in multiple settings. The disorder has a
increase in serum creatinine, resulting from
variety of clinical manifestations that range from minimal elevation in
an injury or insult that causes a functional
serum creatinine level to anuric renal failure. We describe the formation
of a multidisciplinary collaborative network focused on AKI. This Acute
or structural change in the kidney. Recent
Kidney Injury Network has proposed uniform standards for diagnosing epi­demiological studies have detected wide
and classifying AKI. These proposed standards will need to be validated in varia­tion in etiologies of, and risk factors asso-
future studies, a process that will be facilitated by the Acute Kidney Injury ciated with, AKI.1–4 This condition increases
Network, which offers a forum that encourages acquisition of knowledge to hospital mortality rates, which further worsen if
improve patient outcomes. dialysis is required.1–4 There is emerging recog-
nition of the fact that even minor, short-term
keywords acute renal failure, clinical trials, definitions, diagnosis, staging
changes in serum creatinine are associated with
Review criteria increased mortality.5–9 Other important conse-
The PubMed database was searched for articles relevant to the definition, diagnosis quences of AKI are progression of pre-existing
and classification of acute kidney injury and acute renal failure. chronic kidney disease and even development of
end-stage renal disease.10–12
A major limitation in improving outcomes
of AKI has been the lack of common standards
for diagnosis and classification of the condition.
Recognizing that future clinical and translational
research into AKI will require the development
BA Molitoris is Director of the Division of Nephrology in the Department of multidisciplinary collaborative networks of
of Medicine, Indiana University, Indianapolis, IN, USA. A Levin is Professor
investigators, a group representing members
of Medicine in the Division of Nephrology, Director of the Kidney Function
Clinic, St Paul’s Hospital, and Co-Director of the Clinical Investigation of the Acute Dialysis Quality Initiative,13 and
Program, University of British Columbia, Vancouver, BC, Canada. nephrology and critical care societies, recently
DG Warnock is Director of the Division of Nephrology in the Department established the Acute Kidney Injury Network
of Medicine, University of Alabama, Birmingham, AL, USA. M Joannidis is (AKIN)14 in order to facilitate international,
Director of the Medical Intensive Care Unit in the Department of Internal interdisciplinary and intersociety collaboration
Medicine, Medical University of Innsbruck, Innsbruck, Austria. RL Mehta that will ensure progress is made in the field of
is Professor of Clinical Medicine in the Department of Medicine, University AKI. The fundamental goal of AKIN is to ensure
of California San Diego Medical Center, San Diego, CA, USA. JA Kellum the best outcomes for patients with, and those at
is Professor in the Department of Critical Care Medicine, University of risk of developing, AKI. The first AKIN confer-
Pittsburgh, Pittsburgh, PA, USA. C Ronco is Head of the Department of
Nephrology, Dialysis and Transplantation, San Bortolo Hospital, Vicenza, ence, held in Amsterdam, The Netherlands, in
Italy. SV Shah is Professor of Internal Medicine and Director of the Division September 2005 (see Box 1 for a list of partici-
of Nephrology, University of Arkansas for Medical Sciences, and Chief of pants), focused on developing uniform stan-
the Renal Section, Medical Service, John L McClellan Memorial Veterans dards for the definition and classification of
Hospital, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. AKI. Key recommendations are summarized
below (the complete report has been published
Correspondence
*Indiana University School of Medicine, R2, Room 202, 950 West Walnut Street, Indianapolis,
in Critical Care14).
IN 46202, USA
bmolitor@iupui.edu Uniform Standards for Definition
and Classification of AKI
Received 17 May 2007 Accepted 6 June 2007
www.nature.com/clinicalpractice
Previous studies have used an assortment of
doi:10.1038/ncpneph0551 definitions for AKI, including those based on

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Box 1 Members of the AKIN working group. Box 2 Proposed diagnostic criteria for AKI.
Arvind Bagga An abrupt (within 48 h) reduction in kidney function
Aysin Bakkaloglu defined as an absolute increase in serum creatinine
Joseph V Bonventre level of ≥ 26.4 μmol/l (0.3 mg/dl) OR a percentage
Emmanuel A Burdmann increase in serum creatinine level of ≥50% (1.5-
Yipu Chen fold from baseline) OR a reduction in urine output
Prasad Devarajan (documented oliguria of <0.5 ml/kg/h for >6 h).
Vince D’Intini These criteria should be applied in the context
Geoff Dobb of the clinical presentation and following adequate
Charles G Durbin Jr fluid resuscitation when applicable. Permission
Kai-Uwe Eckardt obtained from BioMed Central © Mehta RL et al.
Claude Guerin (2007) Crit Care 11: R31.
Stefan Herget-Rosenthal
Eric Hoste
Michael Joannidis
John A Kellum
Ashok Kirpalani for use in clinical practice (several kidney-specific
Andrea Lassnigg biomarkers are being developed).16
Jean-Roger Le Gall Selection of the absolute criteria for diagnosing
Adeera Levin AKI that are presented in Box 2 was based on
Raul Lombardi evidence that even small changes in serum creati­
William Macias
nine are associated with adverse outcomes in a
Constantine Manthous
Ravindra L Mehta
variety of settings. These changes are asso­ciated
Bruce A Molitoris with both short-term increases in morbidity
Claudio Ronco and mortality, and with longer-term outcomes
Miet Schetz (e.g. 1-year mortality). The co­efficient of varia-
Frederique Schortgen tion of serum creatinine levels measured using
Sudhir V Shah modern analysis methods is relatively small;
Patrick SK Tan therefore, changes of 26.4 μmol/l (0.3 mg/dl)
Haiyan Wang or more are unlikely to be the result of assay
David G Warnock
error.17 Urine output was included as a diag-
Steve Webb
nostic criterion because in intensive care patients
it often portends renal dysfunction before the
onset of changes in serum creatinine level;
hydration state, use of diuretics and presence
changes in serum creatinine, absolute levels of of obstruction can, however, influence urine
serum creatinine, changes in urine output or volume. A time constraint of 48 h for diagnosis
blood urea nitrogen concentrations, or the need was proposed to ensure that the process being
for dialysis. The wide variation in definitions has diagnosed is acute and representative of events
made it difficult to compare information across within a clinically relevant period.
studies and populations.15 The diagnostic criteria Table 1 shows the staging system for AKI that
for AKI that were proposed by AKIN are shown is proposed by AKIN. The system is intended
in Box 2 and are based on three considera­tions. to define the degree of renal dysfunction at the
Firstly, the definition of AKI should be based on time of diagnosis, and to facilitate tracking of
parameters that are readily obtainable worldwide, the course of the disease over time. The RIFLE
and needs to be broad enough to accommodate (Risk, Injury, Failure, Loss, End-stage renal
variations in clinical presentation between age disease) criteria13 utilize changes in serum creati-
groups, locations and clinical situations. Secondly, nine and urine output to characterize three levels
serum creatinine and urine output are two of renal dysfunction. The staging system proposed
measures commonly used to reflect renal function; here retains the emphasis on changes in serum
however, they are both influenced by factors other creatinine and urine output, and corresponds
than glomerular filtration rate, and do not provide to the ‘Risk’, ‘Injury’ and ‘Failure’ categories of
information about the nature and site of kidney the RIFLE classification, with the Stage 1 criteria
injury. Finally, there is currently a lack of sensitive representing the new diagnostic criteria for AKI.
and specific markers of kidney injury available The ‘Loss’ and ‘End-stage renal disease’ cate­gories

440 nature clinical practice NEPHROLOGY MOLITORIS ET AL. august 2007 vol 3 no 8

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Table 1 Proposed classification/staging system for acute kidney injury, based on modification of RIFLE criteria.
Stage Serum creatinine criteria Urine output criteria
1 Increase of ≥26.4 μmol/l (0.3 mg/dl) OR to 150–200% of baseline <0.5 ml/kg/h for >6 h
(1.5–2.0-fold)
2 Increase to >200–300% of baseline (>2–3-fold) <0.5 ml/kg/h for >12 h
3a Increase to >300% of baseline (>3-fold; or serum creatinine <0.3 ml/kg/h for 24 h OR
≥354 μmol/l [4.0 mg/dl] with an acute rise of at least 44 μmol/l anuria for 12 h
[0.5 mg/dl])
Only one criterion (creatinine or urine output) needs to be fulfilled to qualify for a stage. aPatients who receive renal replacement
therapy are considered to have met the criteria for Stage 3, irrespective of the stage that they are in at the time of commencement
of renal replacement therapy. Permission obtained from BioMed Central © Mehta RL et al. (2007) Crit Care 11: R31.

of the RIFLE system were removed from the
staging system as they are outcomes of AKI itself.
The proposed diagnostic (Box 2) and staging
(Table 1) criteria for AKI are designed to facili-
tate acquisition of knowledge and to validate the
emerging concept that small alterations in kidney
function contribute to adverse outcomes. AKIN
recognizes that these criteria might be overly
sensitive; accordingly, there could be an increase
in the number of false-positive diagnoses, such
that some patients who receive a diagnosis of AKI
will not have the disease. It is evident that these
criteria will require evaluation and validation,
and eventually amendment, as new biomarkers
emerge that might more accurately detect AKI.16
are essential to facilitating the dissemination
of knowledge, clarifying clinical practice and
enhancing research. The group described the
five key elements that should be addressed by
the professional communities involved in the
care of patients with AKI.14 These are evaluation
of the global epidemiology of AKI, delineation
of clinically meaningful outcomes, development
and implementation of strategies to improve
outcomes, promotion of research studies to
enhance knowledge, and assessment of the
effectiveness of these collaborative approaches.
A follow-up conference was held in Vancouver
in 2006 and the results will be published soon.

International Collaborative KEY POINTS

Network
Establishment of an international collaborative
research network could facilitate acquisition
of evidence through well-designed and well-
conducted clinical trials, dissemination of infor-
mation via multidisciplinary joint conferences and
publications, and translation of knowledge from
preclinical research. AKIN proposed to further
develop their collaborative effort on the basis of
four main principles. First, identifying the key
roles of each of the current participating societies
and groups to allow retention of their indi­vidual
identities and strengths, while exploiting oppor-
tunities for collaboration. Second, defining the
scope of collaboration. Third, determining
and developing the infrastructure needed for
the collaborative network. Fourth, identifying
unifying principles and initial projects that would
form the basis of ongoing collaboration.14
CONCLUSIONS
The AKIN conference attendees recognized
that collaborative and integrated joint meetings
■ The large numbers of etiologies and risk
factors associated with acute kidney injury
(AKI) have led to the ad hoc development of a
wide range of definitions of this condition
■ The lack of common standards for diagnosis
and classification of AKI has hampered
study of the condition and improvement of
patient outcomes
■ At their first meeting in September 2005,
members of the Acute Kidney Injury
Network (AKIN) working group proposed
new standards based on RIFLE criteria and
recognition of the fact that small changes in
serum creatinine level are associated with
increased mortality
■ The common standards for diagnosis and
classification of AKI proposed by AKIN will
require validation
■ AKIN recommends that a broader
international collaborative network be
established to facilitate progress in AKI
research, dissemination of knowledge, and
implementation of standards of patient care

august 2007 vol 3 no 8 MOLITORIS ET AL.  nature clinical practice NEPHROLOGY 441

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Acknowledgments
In order to encourage
dissemination of the
information set out in this
paper, it is freely accessible
on the Nature Clinical
Practice Nephrology
website, and will also be
published in the American
Journal of Kidney
Diseases, Clinical Journal
of the American Society of
Nephrology, Journal
of the American Society of
Nephrology, and Kidney
International. This article
has not been formally
peer-reviewed.
Competing interests
The authors declared no
competing interests.
442 nature clinical practice NEPHROLOGY
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