ANALYTIC REVIEWS
Defining Acute Renal Failure:
The RIFLE Criteria
Ramesh Venkataraman, MD
John A. Kellum, MD
Acute renal failure is common among critically ill patients
and carries significant morbidity and mortality. The
reported incidence and the attributed morbidity and mor-
tality of acute renal failure vary widely, largely owing to
the use of a wide variety of definitions for acute renal fail-
ure. Until recently, no consensus existed about how to best
define, characterize, and study acute renal failure. This
lack of a standard definition has been a major impediment
to the progress of clinical and basic research in this field.
This review outlines some of the physiologic principles
that may help us better understand and define acute renal
failure and describes the RIFLE criteria (an acronym com-
prising Risk, Injury, and Failure; and Loss, and End-stage
kidney disease), a recent consensus method of defining
and stratifying acute renal failure. Also discussed are many
of the challenges and controversies associated with achiev-
ing consensus and developing a classification for acute
renal dysfunction.
Key words: acute renal failure, definitions, RIFLE criteria
Acute Renal Failure:
Failure of Definitions
Acute renal failure (ARF) is generally defined as an
abrupt and sustained decline in the renal function
that leads to an accumulation of nitrogenous waste
products and uremic toxins. More than 35 different
definitions have been used in the literature, how-
ever, creating much confusion and making compar-
isons difficult [1,2]. Despite the many definitions
From The CRISMA (Clinical Research, Investigation, and Systems
Modeling of Acute Illness) Laboratory, Department of Critical
Care Medicine, University of Pittsburgh, Pittsburgh, PA.
Received May 8, 2006, and in revised form Aug 29, 2006.
Accepted for publication Sep 4, 2006.
Address correspondence to John A. Kellum, MD, Room 608
Scaife Hall, The CRISMA Laboratory, Department of Critical Care
Medicine, University of Pittsburgh, 3550 Terrace St, Pittsburgh,
PA 15261, or e-mail: kellumja@ccm.upmc.edu.
Venkataraman R, Kellum JA. Defining acute renal failure: the
RIFLE criteria. J Intensive Care Med. 2007;22:187-193.
DOI: 10.1177/0885066607299510
Copyright © 2007 Sage Publications
used in clinical trials, no consensus exists about
what functions of the kidney should be assessed,
what variables should be used to define ARF, and
how different degrees of renal dysfunction should
be described and quantified [2]. The failure to have
a standard case definition has made it difficult to
interpret the results of clinical trials, develop prog-
nostic scores, and thereby, has significantly hin-
dered clinical and scientific progress in this field.
Current Challenges and Limitations
The standard definition of ARF as “an abrupt sus-
tained decline in renal function” is regrettably sub-
jective and unclear about what abrupt (how fast),
sustained (how long), or decline (how much) really
mean. It is also unclear which specific functions of
the kidney have to be altered to qualify as ARF. In
general, definitions of ARF need to be based on
commonly accepted principles of physiology, clini-
cal course, histopathology, and prognosis. One
might argue that although the kidney has numerous
functions, including fluid and solute excretion,
electrolyte and acid-base regulation, erythropoiesis,
and endocrine functions, only functions that are
very specific to the kidney and are routinely and
easily measured at the bedside are good candidates
for defining variables. Only 2 functions of the kidney
meet these criteria: urine production and excretion
of nitrogenous wastes. Thus, clinicians and researchers
have loosely defined ARF as an abrupt and sus-
tained decrease in glomerular filtration or urine out-
put, or both.
Even if agreement exists on what functions of
the kidney should be used to define ARF, several
terms, including abrupt, sustained, and decrease,
still need to be quantified better. The inherent
problem of quantifying each of these variables is
that the selection of any arbitrary cutoff value might
compromise the sensitivity or specificity of the def-
inition [1]. In addition, ARF is not a dichotomous
variable; hence, the use of a dichotomous classifi-
cation system (ARF present or absent) will always
187
Venkataraman and Kellum

lead to some milder forms (poor sensitivity) being Table 1. Estimated Baseline Creatinine
missed or some patients being included who never
Men, mg/dL Women, mg/dL
really had the condition at all (poor specificity).
(μmol/L) (μmol/L)
Finally, the natural history of ARF often begins with
mild signs and progresses to more severe. Clinicians Age (years) Black Other Black Other
may be interested in detecting early ARF even when
20-24 1.5 (133) 1.3 (115) 1.2 (106) 1.0 (88)
they are primarily interested in the severe form.
25-29 1.5 (133) 1.2 (106) 1.1 (97) 1.0 (88)
Because of these reasons, the perfect quantitative
30-39 1.4 (124) 1.2 (106) 1.1 (97) 0.9 (80)
definition for ARF is difficult to develop and will 40-54 1.3 (115) 1.1 (97) 1.0 (88) 0.9 (80)
likely never exist. 55-65 1.3 (115) 1.1 (97) 1.0 (88) 0.8 (71)
>65 1.2 (106) 1.0 (88) 0.9 (80) 0.8 (71)
Estimated glomerular filtration rate = 75 mL/(min ⋅ 1.73 m2) =
Patients With Unknown 186 × (serum creatinine) − 1.154 × (age) − 0.203 × (0.742 if
Baseline Renal Function female) × (1.210 if black) = exp(5.228 – 1.154 × In(serum crea-
tinine) − 0.203 × In(Age) − (0.299 if female) + (0.192 if black).
From Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute
Changes in serum creatinine level from baseline
Dialysis Quality Initiative Workgroup. Acute renal failure⎯
reflect changes in the glomerular filtration rate (GFR) definition, outcome measures, animal models, fluid therapy and
and renal function. However, when baseline GFR is information technology needs: the Second International Consensus
not known, it will be impossible to accurately deter- Conference of the Acute Dialysis Quality Initiative (ADQI) Group.
mine the degree of decline in renal function. One Crit Care. 2004;8:R204-R212. Used with permission.
option is to calculate a theoretic baseline serum cre-
atinine value assuming a normal GFR [3]. A normal
GFR of approximately 75 to 100 mL/(min ⋅ 1.73 m2)
can be assumed by normalizing the GFR to the body Existing Markers to Define Acute Renal
surface area [4], and thus, a change from baseline Failure and Their Limitations
can be estimated for a given patient. Finally, the sim-
plified modification of diet in renal disease (MDRD) Clinically available markers potentially useful in
formula provides a robust estimate of GFR relative to defining ARF include serum blood urea nitrogen
the serum creatinine value based on age, race, and (BUN) and creatinine, urine output, creatinine clear-
sex [5,6] (Table 1). All of these approaches, however, ance (CrCl), and other markers of tubular injury.
assume normal baseline renal function and are Most of these markers, although easily available
bound to misclassify some patients. and clinically relevant, may not be a true reflection
of renal function in critically ill patients.
The excretion of water-soluble solutes and urine
Acute-on-Chronic Renal Failure production are the result of glomerular filtration,
and clinicians have generally equated these func-
If a patient has known or unknown preexisting tions of the kidney to the GFR. As a result, most
renal dysfunction, defining acute-on-chronic renal definitions of ARF use an indirect estimate of GFR
failure becomes a difficult proposition. First, the (serum creatinine), solute clearance (BUN), and/or
MDRD equation cannot be used to predict baseline urine output over time (eg, 500 mL over 24 hours
serum creatinine and GFR. Second, the patient’s [7-9]; however, such a thought process is flawed
starting position in the spectrum and progression of both physiologically and conceptually.
renal dysfunction will be more advanced. Hence,
the relative decrease in renal function required by a
given patient with preexisting renal dysfunction to Glomerular Filtration Rate
reach any given cutoff value of serum creatinine
used to define ARF is smaller. Changes in serum cre- The GFR varies widely as a function of normal
atinine from baseline in these patients thus do not physiology and disease [10], and baseline GFR does
truly reflect the degree, rate, and severity of renal not necessarily correspond to the extent of the
injury. It seems that either a different set of criteria functioning renal mass [11]. Without knowing what
will be needed in patients with preexisting renal the maximal GFR (renal reserve) would be in a
dysfunction or some absolute creatinine criteria will given patient, measurements of GFR will not yield
need to be integrated into the classification system. an accurate estimate of the global renal function

188 Journal of Intensive Care Medicine 22(4); 2007


[12]. However, GFR and estimates thereof, such as
CrCl and serum creatinine level, remain useful mea-
sures for assessing renal function. For example, a
GFR of less than 30 mL/(min ⋅ 1.73 m2) will denote
severe renal dysfunction in most patients, corre-
sponding to stage 4 in chronic kidney disease.
A GFR of less than 10 to 15 mL/(min ⋅ 1.73 m2) usu-
ally requires dialysis, again in patients with chronic
disease [13].
Blood Urea Nitrogen
and Serum Creatinine
Blood urea nitrogen is a nonspecific indicator of
renal function and a poor surrogate for GFR [14]
and will not be discussed further in this review. In
a critically ill patient, BUN can vary independently
of the renal function for a multitude of reasons,
including gastrointestinal bleeding, steroid adminis-
tration, and nutritional status. Thus, changes in
BUN do not reliably convey the degree of uremia
in any given patient.
Serum creatinine, however, is much more spe-
cific at assessing renal function than BUN, and most
ARF definitions use some cutoff value of serum cre-
atinine. Several noteworthy studies have found an
inverse relationship between serum creatinine
levels and outcomes in ARF [9,15-17]. The expla-
nation for this finding may be because several
extrarenal factors such as muscle mass, volume of
distribution for creatinine, creatinine production,
and liver function can significantly alter serum cre-
atinine in critically ill patients, and caution must be
used in interpreting serum creatinine values alone
as a marker for ARF.
Furthermore, as GFR decreases, tubular secre-
tion of creatinine increases, leading to relatively
smaller rises in serum creatinine [3]. Serum creati-
nine levels can thus underestimate the degree of
renal dysfunction⎯or overestimate the GFR⎯during
the evolution of ARF.
Finally, although changes in serum creatinine
reflect changes in GFR [18], an estimate of GFR
based on the serum creatinine value is valid only at
steady state, and no single creatinine value corre-
sponds to a given GFR across all patients. Because by
definition ARF is not a steady state, GFR estimates
based on serum creatinine values are not accurate
and lead to falsely high GFR estimations. For the
purposes of determining if renal function is stable,
or getting worse or better, monitoring serum creati-
nine alone is very adequate.
Journal of Intensive Care Medicine 22(4); 2007
Definitions for ARF
Creatinine Clearance
The 24-hour CrCl is used in clinical practice as a sur-
rogate marker of renal function; however, a 24-hour
urine collection period delays the availability of the
result and increases the potential for collection errors.
Recent studies have compared 12-hour CrCl [19] and
2 × 2-hour CrCl [20] and have found them to be just
as accurate as the standard 24-hour CrCl to assess
renal function. Once validated in larger studies, 2-hour
CrCls may serve as a good bedside estimate of renal
function. However, like serum creatinine, CrCl does
not reflect the true GFR in nonsteady states such
as ARF; in fact, CrCl usually overestimates the GFR.
As the GFR decreases, tubular creatinine secretion
increases, resulting in a smaller rise in serum creati-
nine [3]. Creatinine excretion is consequently greater
than the filtered load, leading to an overestimation of
GFR [21]. For this reason, serum creatinine will under-
estimate GFR during the evolution of ARF. Other
accurate methods of determining GFR, such as inulin
clearance, are generally not practical or feasible for
the bedside clinician.
Urine Output
Urine output is the most commonly measured and
monitored parameter for renal function in the critical
care setting. Patients with oliguric ARF have a poorer
prognosis compared with nonoliguric ARF. Although
urine output is very sensitive to renal hemodynam-
ics, and changes in urine output often occur before
other biochemical changes are seen, severe renal
failure can occur despite adequate or even excess
urine output (so-called nonoliguric renal failure). In
a critically ill but volume-repleted and hemodynam-
ically stable patient, low urine output can serve as a
sensitive clinical marker for the development of ARF
and has a good positive predictive value. However,
because urine output can be nonspecifically increased
by interventions in the intensive care unit (ICU) and
because renal failure can occur despite good urine
output, its negative predictive value is rather poor
(ie, the presence of good urine output does not
exclude renal dysfunction).
Several important caveats thus have to be con-
sidered and understood when urine output is used
as a clinical marker for ARF in the ICU:
1. Although decreased urine output may point
toward the onset of renal dysfunction in an
adequately resuscitated patient, the degree of
189
Venkataraman and Kellum
oliguria does not necessarily correlate with the
severity of renal injury.
2. The urine output in many circumstances contin-
ues to be adequate despite onset and progression
of renal dysfunction (ie, nonoliguric renal failure).
3. Multiple interventions in the ICU, including
diuretics, dopamine, and solute diuresis with
mannitol, can lead to a disproportionately
higher urine output compared with the severity
of renal failure.
4. Initiation of dialysis can lead to decreases in
urine output without necessarily implying
worsening renal function.
5. Nonoliguric renal failure has a better prognosis
than oliguric renal failure, but the use of diuret-
ics to increase urine output does not seem to
alter the prognosis [22] and might even result in
harm [23,24].
Markers of Renal Tubular Injury
Several serum and urinary markers, such as neu-
trophil gelatinase-associated lipocalin (NGAL) [25],
kidney injury molecule-1 (KIM-1) [26], cysteine-
rich protein 61 [27], spermidine/spermine N(1)-
acetyltransferase [28], cystatin C [29], and urine
interleukin-18 (IL-18) [30,31], have been identified
as potential markers of early tubular injury.
Of these markers, cystatin C has been evaluated
most extensively. Cystatin C is a nonglycosylated
protein that is produced at a constant rate by nucle-
ated cells. It is found in relatively high concentra-
tions in many body fluids, and its low molecular
weight (13.3 kDa) and positive charge at physio-
logic pH levels facilitate its glomerular filtration. It
is later reabsorbed and almost completely catabo-
lized in the proximal renal tubule. Because of its
constant rate of production, its serum concentration
is therefore determined by glomerular filtration.
Corticosteroids [32] and thyroid dysfunction [33] can
affect cystatin C levels, but its concentration is unaf-
fected by infections, liver disease, and inflammatory
disease. For these reasons, cystatin C has the poten-
tial to be a useful marker in detecting ARF.
Villa et al [34] conducted an evaluation of serum
cystatin C concentration as a real-time marker of
ARF in critically ill patients and demonstrated that
cystatin C correlated better with GFR than creati-
nine and was diagnostically superior to creatinine
(area under the curve [AUC] for cystatin C, 0.927;
95% confidence interval [CI], 86.1-99.4; AUC for cre-
atinine, 0.694; 95% CI, 54.1-84.6) [34].
Herget-Rosenthal et al [35] evaluated early detec-
tion of ARF by cystatin C and showed that the
increase in blood levels of this marker significantly
190
preceded that of creatinine [35]. Moreover, according
to the R, I, and F criteria of RIFLE, cystatin C detected
renal dysfunction 2 days earlier than did creatinine.
It also predicted the long-term need for renal
replacement therapy (RRT) for ARF moderately well.
A subsequent study evaluated serum cystatin C as
a marker of renal function in ARF and its power in
predicting the survival rate of ARF patients [29]. Serum
cystatin C, plasma creatinine, and plasma urea levels
were measured in 202 patients on admission to the
ICU, daily during the first 3 days, and 5 to 7 times a
week during the rest of their ICU stay. This study
found that serum cystatin C showed excellent positive
predictive value for ARF in critical illness; however, it
was not clinically useful in predicting mortality.
Investigators using a genome-wide interrogation
strategy have identified NAGL, which over-expresses
proteins in the kidney after ischemia [36,37], as 1 of
the most strikingly up-regulated genes. Mishra et al
[25] conducted a small clinical study of 71 children
undergoing cardiopulmonary bypass. Serial urine and
blood samples were analyzed by Western blots and
enzyme-linked immunosorbent assay for NGAL expres-
sion. Multivariate analysis showed that the amount of
NGAL in urine at 2 hours after cardiopulmonary
bypass was the most powerful independent predictor
of acute renal injury. The study also revealed that for
the concentration of NGAL in the urine at 2 hours, the
area under the receiver-operating characteristic curve
was 0.998, sensitivity was 1.00, and specificity was
0.98 for a cutoff value of 50 μg/L.
The type 1 transmembrane protein KIM-1 has an
immunoglobulin and mucin domain, and its
expression is markedly up-regulated in the proxi-
mal tubule in the postischemic kidney in rat mod-
els. Han et al [26] evaluated the expression of KIM-1
in a pilot study of 6 patients with biopsy-proven
acute tubular necrosis. They found extensive
expression of KIM-1 in proximal tubule cells in
biopsy specimens from all patients with confirmed
acute tubular necrosis. Moreover, when adjusted
for age, gender, length of time delay between the
initial insult, and sampling of the urine, a 1-unit
increase in normalized KIM-1 was associated with a
greater than 12-fold (odds ratio, 12.4; 95% CI, 1.2-119)
risk for the presence of acute tubular necrosis.
Interleukin-18 has been shown to be an important
mediator of inflammation. Urine IL-18 levels have been
shown to increase in patients with acute tubular
necrosis, both in animal models and human studies
[30,31]. In humans, IL-18 was shown to have a sen-
sitivity and specificity of more than 90% for the diag-
nosis of established kidney injury [31]. In this study, on
multivariable analysis, the urine IL-18 concentration
was an independent predictor of mortality.
Journal of Intensive Care Medicine 22(4); 2007

Large trials evaluating the usefulness of various
biomarkers for early detection of ARF in patients
are lacking; however, biomarkers theoretically could
be important in the diagnosis and management of
ARF. Currently available serum markers for other
disease processes such as troponin-I and brain
natriuretic peptide have correlated fairly well with
the degree of the underlying disease. Serum brain
natriuretic peptide levels also trend down with ade-
quate response to therapy. Theoretically, serial
measurement of a biomarker could potentially help
clinicians pick up early disease and follow the
response to treatment once disease is advanced.
With ongoing research, such a biomarker for ARF is
perhaps not too far off in the future. Further
research exploring the value of biomarkers in terms
of prognosticating in patients with ARF (both sur-
vival and renal recovery) will also be necessary.
RIFLE Criteria
Based on these principles, in an effort to encom-
pass the entire range of acute abnormalities in renal
function, the term acute renal dysfunction (ARD)
was used by the Acute Dialysis Quality Initiative
(ADQI) group, an international, interdisciplinary
collaboration (www.adqi.net). Later, the term acute
kidney injury (AKI) was proposed by the Acute
Kidney Injury Network (AKIN) as an alternative.
The ADQI workgroup considered the definition of
ARD/AKI to require the following features:
• ease of use and clinical applicability;
• high sensitivity and specificity for different pop-
ulations and research questions;
• consideration of creatinine change from baseline;
and
• implementation of classifications for acute-on-
chronic renal disease.
This group then formulated a multilevel classifi-
cation system (RIFLE), in which a wide range of dis-
ease spectra can be included [12]. The RIFLE defines
3 grades of increasing severity of ARD as risk (R),
injury (I), and failure (F) as well as the 2 outcome
variables of loss (L) and end-stage kidney disease (E).
A unique feature of the RIFLE classification is that it
provides for 3 grades of severity of ARD based on
urine output or changes in the serum creatinine
value from the baseline condition, whichever is
more severe (Figure 1). For example, a patient who
has no urine output for 12 hours will be classified as
RIFLE-F, irrespective of what the serum creatinine
is. The 2 clinical outcomes of loss and end-stage
Journal of Intensive Care Medicine 22(4); 2007
Definitions for ARF
renal disease in RIFLE criteria are separated to
acknowledge the important adaptations that occur
in end-state renal disease that are not seen in
patients with ARF. Persistent ARF is defined as a
need for RRT for more than 4 weeks, whereas end-
stage renal disease is defined as the need for RRT
for more than 3 months.
Although RIFLE criteria use both creatinine and
urine output, differences between oliguric and nono-
liguric ARF likely exist. Moreover, oliguria in ARF can
occur independent of the degree of renal dysfunc-
tion, multiple mechanisms lead to oliguria, and more
than 1 mechanism may exist in any given patient.
One limitation of the RIFLE criteria is that it
purely denotes the different severities of ARF without
providing any insight into the pathophysiology of
increased serum creatine or oliguria, or both. Patients
with similar ARF severities according to RIFLE crite-
ria but with different pathophysiologic mechanisms
could have different outcomes. For example, patients
with decreased urine output and increased serum
creatinine caused by urinary obstruction have a
much better outcome compared with patients with
similar levels of derangement caused by septic shock.
The RIFLE classification also uses urine output as 1
of its variables to classify the degree of ARF.
Validating RIFLE Criteria
Several investigators have already applied the
RIFLE criteria to the clinical evaluation of ARF.
Cystatin C has recently been shown to presage var-
ious stages of renal dysfunction defined by the
RIFLE criteria [35]. Hoste et al [38] prospectively
analyzed data from 5313 patients and found the
clinical severity of the RIFLE criteria to correlate
well with increasing mortality. A recent single-center
study evaluated the RIFLE criteria in 183 patients
and concluded that RIFLE classification can improve
the ability of established ICU scoring systems such
as Acute Physiology And Chronic Health Evaluation
(APACHE)–II and Simplified Acute Physiology Score
(SAPS)–II in predicting the outcome of ICU patients
with ARF [39].
Recently, Kuitunen et al [40] used RIFLE criteria
to determine the incidence of postoperative renal
dysfunction in 813 patients after cardiac surgery
and its association with mortality. They demon-
strated that RIFLE criteria were comparable with the
change in plasma creatinine and change in esti-
mated GFR in discriminating 90-day mortality (AUC
for RIFLE criteria, 0.824). In this study, multivariate
logistic regression analysis showed the RIFLE criteria
191
Venkataraman and Kellum

GFR Criteria Urine Output Criteria

Increased SCreat x 1.5 or UO < 0.5 mL/kg/h
GFR decrease > 25% x6h
Risk
High
Increased SCreat x 2
Sensitivity
UO < 0.5 mL/kg/h
or GFR decrease > 50%
Injury x 12 h

Increased SCreat x 3 UO < 0.3 mL/kg/h

ria
GFR decrease 75%, x 24 h or

Oligu
Failure or SCreat? 4 mg/dL Anuria x 12 h
Acute rise ≥ 0.5 mg/dL
High
Persistent ARF = complete loss
Specificity
Loss
of kidney function > 4 weeks
End-Stage Kidney Disease
ESKD (> 3 months)

Fig 1. The RIFLE classification (risk, injury, failure, loss, end-stage kidney disease [EKSD]) scheme for acute renal fail-
ure (ARF). The classification system includes separate criteria for serum creatinine (SCreat) and urine output (UO). The
criteria that lead to the worst possible classification should be used. Note that RIFLE-F is present even if the increase in
serum creatinine is less than 3-fold so long as the new serum creatinine value is ≥4.0 mg/dL (350 μmol/L) in the setting
of an acute increase of at least 0.5 mg/dL (44 μmol/L). The shape of the figure denotes the fact that more patients (high
sensitivity) will be included in the mild category, including some without actually having renal failure (less specificity).
In contrast, at the bottom, the criteria are strict and therefore specific, but some patients will be missed. GFR = glomeru-
lar filtration rate. From Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative Workgroup.
Acute renal failure⎯definition, outcome measures, animal models, fluid therapy and information technology needs: the
Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:
R204-R212. Used with permission.

were also effective in discriminating 90-day mortality,

whereas changes in plasma creatinine and/or esti-
mated GFR were not.
Two recent studies have also sought to deter-
mine whether RIFLE criteria can aid in risk predic-
tion among patients receiving RRT. Bell et al [41]
evaluated the association between mortality and
RIFLE classification in 207 patients receiving con-
tinuous RRT at a university hospital in Sweden [41].
They demonstrated that when continuous RRT was
started in patients with a more severe RIFLE cate-
gory (RIFLE-F and RIFLE-L), their 30-day mortality
was significantly higher (>50%) compared with
those stated at a RIFLE-I or RIFLE-R (<25%). Abosaif
et al [39] showed that the use of RIFLE improved
calibration and discrimination of scores for APACHE
and SAPS-II for 183 patients with AKI on ICU admis-
sion. Thus, the application of RIFLE criteria has
been demonstrated to be a valuable prognostic tool
in a number of different settings.
Conclusions
It is clear that lack of a standardized classification
system has hindered advancement of clinical
research in the prevention and treatment of ARF.
Existing definitions of ARF have major limitations.
There is currently no accurate, easily available mea-
sure of GFR (renal function) in ARF. Traditional sur-
rogate measures such as serum creatinine have
shown limited correlation with GFR. No good
method to differentiate mild from moderate or
severe renal dysfunction currently exists. Several
serum and urine markers of tubular injury are being
studied; although promising, they are not yet ready
for clinical use.
Underlying pathophysiologic principles of ARF
should be used to guide the development of defin-
itions of ARF. The RIFLE criteria are the first inter-
national, interdisciplinary criteria for the classification
of ARF. The criteria have now been prospectively

192 Journal of Intensive Care Medicine 22(4); 2007


validated both in and out of the ICU. Developing a
robust consensus classification system for ARF is
the first step in ensuring improvements in clinical
research leading to improved patient outcomes.
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