The Association Between Urine Output,
Creatinine Elevation, and Death
Milo Engoren, MD, Michael D. Maile, MD, MS, Michael Heung, MD,
Elizabeth S. Jewell, MS, Christie Vahabzadeh, MD, Jonathan W. Haft, MD, and
Sachin Kheterpal, MD
Departments of Anesthesiology, Internal Medicine, and Cardiothoracic Surgery, University of Michigan, Ann Arbor; and Department
of Anesthesiology, Beaumont Health Center, Royal Oak, Michigan
Background. Acute kidney injury can be defined by a
fall in urine output, and urine output criteria may be
more sensitive in identifying acute kidney injury than
traditional serum creatinine criteria. However, as
pointed out in the Kidney Disease Improving Global
Outcome guidelines, the association of urine output
with subsequent creatinine elevations and death is
poorly characterized. The purpose of this study was to
determine what degrees of reduced urine output are
associated with subsequent creatinine elevation and
death.
Methods. This was a retrospective cohort study of adult
patients (age ‡18 years) cared for in a cardiovascular
intensive care unit after undergoing cardiac operations in
a tertiary care university medical center. All adult pa-
tients who underwent cardiac operations and were not
receiving dialysis preoperatively were studied. The
development of acute kidney injury was defined as an
increase in creatinine of more than 0.3 mg/dL or by more
than 50% above baseline by postoperative day 3.
A cute kidney injury (AKI) occurs commonly in inten-
sive care unit (ICU) patients, affecting 11% to 57% of
patients depending on the patient population, the
severity of AKI, and the definition [1–5]. AKI is associated
with increased death and ICU and hospital lengths of stay
[1]. Improved understanding of AKI has been hampered
by lack of a uniform definition and a tendency of studies
to focus on more severe disease such as AKI requiring
renal replacement therapy [1].
The development of consensus criteria for AKI defini-
tion and staging based on changes in serum creatinine
(AKI-Cr) or urine output (UO; AKI-UO) has been an
important advance [2, 3, 6]. The use of Cr values for the
diagnosis of AKI in these guidelines is well supported
because increases are associated with increased death [7].
However, although the measurement of UO in the ICU is
almost de rigueur, the clinical importance of changes in
UO is less well understood.
Accepted for publication July 11, 2016.
Address correspondence to Dr Engoren, Department of Anesthesiology,
University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109;
email: engorenm@med.umich.edu.
Ó 2016 by The Society of Thoracic Surgeons
Published by Elsevier
Results. Acute kidney injury developed in 1,061 of
4,195 patients (25%). Urine output had moderate discrim-
ination in predicting subsequent acute kidney injury
(C statistic [ .637 ± .054). Lower urine output and longer
duration of low urine output were associated with greater
odds of developing acute kidney injury and death.
Conclusions. We found that there is similar accuracy in
using urine output corrected for actual, ideal, or adjusted
weight to discriminate future acute kidney injury by
creatinine elevation and recommend using actual weight
for its simplicity. We also found that low urine output is
associated with subsequent acute kidney injury and that
the association is greater for lower urine output and for
low urine output of longer durations. Low urine output
(<0.2 mL $ kg–1 $ h–1), even in the absence of acute
kidney injury by creatinine elevation, is independently
associated with mortality.
(Ann Thorac Surg 2016;-:-–-)
Ó 2016 by The Society of Thoracic Surgeons
Possible explanations for the lack of research in this
area include difficulties in collecting these data and con-
cerns about how to interpret UO in the settings of diuretic
medications, variable hydration state, and the presence of
urinary obstruction [8]. Despite such limitations, UO re-
mains an important, readily available clinical measure
that provides an opportunity to identify AKI before
changes in Cr become apparent. In fact, the effect of UO
on AKI diagnosis and staging was specifically identified
as an area in need of research in recent Kidney Disease
Improving Global Outcomes (KDIGO) guidelines, which
state, “The influence of urinary output criteria on AKI
staging needs to be further investigated. Influence of . . .
differing weights (actual, ideal body weight, lean body
mass) should be considered. Also, it is currently not
known how urine volume criteria should be applied
The Supplemental Table and Figures can be
viewed in the online version of this article [http://dx.
doi.org/10.1016/j.athoracsur.2016.07.036] on http://
www.annalsthoracicsurgery.org.
0003-4975/$36.00
http://dx.doi.org/10.1016/j.athoracsur.2016.07.036
2 ENGOREN ET AL Ann Thorac Surg
URINE OUTPUT AND CREATININE ELEVATION 2016;-:-–-

(e.g., average vs. persistent reduction for the period
specified) [9].”
Although there is overlap, a discordance frequently
exists between patients diagnosed with AKI-Cr and AKI-
UO. In these situations, whether AKI-Cr and AKI-UO
have different or similar prognoses is unclear [6, 10–12].
Several recent studies have shown that AKI-UO is asso-
ciated with increased death [13–15]. However, two of
these studies each only examined a single threshold of
low UO (<7.2 mL $ kg–1 $ day–1 [13] and <500 mL/day
[15]), and one required Cr exceeding 3.5 mg/dL to define
AKI [15] and were thus unable to establish a threshold or
dose-dependency between AKI-UO and AKI-Cr and be-
tween AKI-UO and death. None of the studies evaluated
whether the effect of different types of weight (actual,
ideal, or adjusted) should be used to adjust UO. Indeed, a
more comprehensive examination of the prognostic effect
of AKI-UO requires a large database with complete UO
and follow-up data.
The purposes of this study were to determine (1) what
type of weight (actual, ideal, or adjusted) should be used
to adjust for hourly UO, (2) what, if any, level of UO is a
harbinger of AKI-Cr, and (3) is AKI-UO associated with
death in patients after cardiac operations?
The occurrence of low UO (<0.5 mL $ kg–1 $ h–1) was
investigated by a member of the ICU team. If low UO was
thought to be from hypovolemia, based on physical ex-
amination and central and systemic blood pressures, a
fluid bolus of albumin or crystalloid was given. Hetas-
tarches were not used. If sufficient anemia (hematocrit of
w25% at the start of the study, decreasing to 20% by the
end of the study) was present, red blood cell transfusion
would be given. If the low UO was thought to be related
to low cardiac output, a fluid bolus would be given if
there was associated hypovolemia, otherwise an inotrope
would be added or increased. If associated with hypo-
tension (mean arterial pressure <60 to 65 mm Hg) and a
normal or elevated cardiac output, then depending on
presumed volume status, a fluid bolus or a vasopressor
would be used. Finally, if low UO was present despite
Table 2. Characteristics of Patients With and Without Acute
Kidney Injurya
AKI—Yes AKI—No
(n ¼ 1,061) (n ¼ 3,134)
Characteristic No. % No. % p Value

Male 710 67 2,073 66 0.673

Patients and Methods Hypertension 777 73 1,973 63 <0.001
Diabetes mellitus 264 25 625 20 <0.001
Study Population
Cerebrovascular 129 12 299 10 0.018
This single-center retrospective study was approved by disease
the Institutional Review Board, which waived informed Stroke 73 7 140 5 0.003
consent because it was an analysis of deidentified data Peripheral vascular 94 9 194 6 0.004
and performed in accordance with the ethical standards disease
laid down in the 1964 Declaration of Helsinki and its later Type of operation <0.001
amendments. All adult (age
18 years) patients who un- CABG only 95 9 488 16 <0.001
derwent cardiac operations between January 1, 2006, and CABG and valve 85 8 190 6 0.073
December 31, 2011, and were not receiving dialysis pre- Valve only 239 23 798 26 0.029
operatively were studied. Patients with chronic kidney
Aortic only 80 8 231 7 0.746
disease were included.
Aortic and valve 488 46 1,160 37 <0.001
All patients received general anesthesia and were and/or CABG
routinely monitored with arterial catheters. Almost all Other 6 0.6 11 0.4 0.486
patients received hypothermic cardiopulmonary bypass. Chronic lung disease <0.001
In the ICU, pulmonary artery catheters were continued
None 865 82 2702 86 <0.001
until the patient was liberated from mechanical ventila-
Mild 110 10 264 8 0.061
tion and on no more than low-dose inotropes or vaso-
Moderate 48 5 103 3 0.131
pressors. Arterial catheters were generally continued
Severe 38 4 65 2 0.008
until just before ICU discharge.
Race <0.001
White 895 84 2,790 89 <0.001
Table 1. Patients Meeting Kidney Disease Improving Global Black 111 10 141 4 <0.001
Outcomes Creatinine Criteria for Acute Kidney Injury by the Other 49 5 174 6 0.268
Start of Postoperative Days 1, 2, and 3 or on Any Day
Mean SD Mean SD
Day 1 Day 2 Day 3 Any Day
KDIGO No. No. No. No. Age, y 63 14 61 14 <0.001
No 3,738 3,388 3,545 3,134 Height, cm 172 11 172 11 0.779
Stage 1 416 658 507 851 Ejection fraction .53 .15 .55 .14 0.008
Stage 2 38 108 100 138 Preoperative creatinine, 1.2 0.4 1.0 0.3 <0.001
mg/dL
Stage 3 3 41 53 72
a
Missing data: age (n ¼ 1), height (n ¼ 9), and ejection fraction (n ¼ 144).
KDIGO ¼ Kidney Disease Improving Global Outcomes Creatinine
Criteria. AKI ¼ acute kidney injury; CABG ¼ coronary artery bypass grafting.
Ann Thorac Surg ENGOREN ET AL 3
2016;-:-–- URINE OUTPUT AND CREATININE ELEVATION

Fig 1. Urine output threshold and acute kidney injury. Heat map shows adjusted odds ratios of developing at least Kidney Disease Improving
Global Outcomes stage 1 acute kidney injury by creatinine criteria based on urine output meeting the hourly threshold averaged (A) over the several
hours (mean) or (B) below that value for all hours (consecutive). Each box shows the odds ratio (95% confidence interval) and the number of
patients who developed acute kidney injury by creatinine/the number of patients whose urine output met the threshold value for that many hours.
The red outline shows boxes where the odds ratio is statistically significant.

adequate hemodynamics and volume status, a loop
diuretic (furosemide, 20 to 80 mg intravenous push, or
bumetanide, 1 to 2 mg intravenous push) would be given.
Data Collection
Patient demographics, preoperative comorbidities, and
type of cardiac operation were recorded. Laboratory data
were collected from the preoperative period through
postoperative day 7 and accessed from the data ware-
house, an electronic repository of patient information. In
the ICU, UO was routinely measured hourly until the
bladder catheter was removed and recorded in the elec-
tronic medical record (Centricity; GE Healthcare IT,
Barrington, IL). Bladder catheters were maintained until
the patient was liberated from mechanical ventilation,
hemodynamically stable without vasopressors or
inotropes, and hourly UO was no longer necessary.
Catheters and hourly UOs were collected for at least 24
hours in 69% of patients and for at least 48 hours in 25%
of patients. When clinical symptoms were suggestive of
urinary retention, such as prior urinary clots and a
sudden decrease in UO, catheters were flushed and irri-
gated, as necessary.
Outcomes
AKI was explored using both Cr-based and UO-based
criteria. AKI-Cr was defined using KDIGO criteria
(stage 1: >0.3 mg/dL increase in Cr or >50% increase,
stage 2: >100% increase, stage 3: >200% increase) using
the highest Cr value by the morning of postoperative day
3. The last preoperative Cr value was used as the baseline.
For multivariable analyses, the different stages of AKI-Cr
4 ENGOREN ET AL
URINE OUTPUT AND CREATININE ELEVATION
Fig 1. (Continued).
were collapsed into one group as the dependent variable.
UOs were summed for each day for all possible hourly
intervals (1, 2, 3, . , 11, 12) and adjusted by weight. To
answer the first question of which weight to use, we
applied three different patient weights (kg): (1) actual; (2)
ideal, calculated as height (cm)  [0.9 – 88], if male, or
height (cm)  [0.9 – 92], if female; and (3) adjusted,
calculated as ideal body weight þ 0.4  [actual weight –
ideal weight]. We used nine different volume thresholds
for UO (0.1, 0.2, ., 0.9 mL $ kg–1 $ h–1). This produced
108 UO-time interval combinations for each of the three
weight definitions.
Death was defined using The Society of Thoracic Sur-
geons definition of death within 30 days of the operation
or longer if the patient was still hospitalized from the
index operation.
We next analyzed UO based on thresholds, as KDIGO
and prior Risk, Injury, Failure, Loss, End-Stage (RIFLE)
Ann Thorac Surg
2016;-:-–-
and Acute Kidney Injury Network (AKIN) definitions all
used thresholds to define AKI-UO [9, 16, 17]. To answer
the second question of how urine volume criteria should
be applied (eg, average vs persistent reduction for the
period specified), UOs were determined two different
ways: by consecutive hours (all UOs for those hours were
less than the specified threshold) and mean (although the
hourly UO could be greater than the threshold, the mean
UO over the hours was less than the specified threshold).
A patient who had at least one episode of UO below the
weight-adjusted threshold for the time period was
deemed to have met the threshold for that day. If the time
period extended across midnight, the partial time period
before midnight was analyzed as part of the prior day,
and the total time period was analyzed as part of the
succeeding day.
To ensure a directional association between UO and the
subsequent development of AKI-Cr, once AKI-Cr
Ann Thorac Surg ENGOREN ET AL 5
2016;-:-–- URINE OUTPUT AND CREATININE ELEVATION

developed, all further UOs were censored and not
included in the models for AKI-Cr. The sensitivity and
specificity of each UO-time interval combination were
determined, and receiver operator characteristic curves (C
statistic, a measure of discrimination) were created with
KDIGO stage 1 or worse as the dependent variable of
interest.
UO thresholds are the traditional way of defining AKI-
UO but may produce a false dichotomy at the threshold
[8, 9, 16]. For example, if the hourly threshold is 0.5 mL/kg,
then a patient whose UO is 0.45 mL/kg is considered the
same as a patient whose hourly UO is 0.1 mL/kg and
different from one whose hourly UO is 0.55 mL/kg. We
therefore also analyzed the association between AKI-UO
and AKI-Cr with death using 30 different UO-time com-
binations, comprising 5 hourly UO ranges (<0.2, 0.2 to
< 0.4, 0.4 to < 0.6, 0.6 to < 0.8, and 0.8 to 0.9 mL/kg) and 6
time intervals (1 or 2, 3 or 4, 5 or 6, 7 or 8, 8 or 10, and 11 or
12 hours). To maintain statistical power, all levels of AKI-Cr
were collapsed into one stage (KDIGO stage 1 or greater).
The association between AKI and death (the third
question) was determined using binary logistic regres-
sion, adjusted for age, height, type of operation, ejection
fraction, baseline creatinine, and comorbidities with 95%
confidence intervals (CIs) that excluded 1 and a p of less
than 0.05 denoting statistical significance. No adjustment
was made for multiple outcomes [18]. All statistics were
done with R software (R Foundation, Vienna, Austria).
prominent with longer durations. These general relation-
ships were observed when examining UO by consecutive
hours or mean hours (Fig 1).
Patients with AKI were more likely to have longer times
of mechanical ventilation and ICU and hospital stays
(Table 3). One hundred-twenty patients (2.8%) died. After
adjustment for demographics, comorbidities, baseline
creatinine, and type of operation, lower UO thresholds for
longer times were significantly associated with death
(Fig 2). Results were similar for UO being continuously
below the threshold for all hours in the time period and
for the UO averaged over the time period being below the
threshold.
When we analyzed the data, not by thresholds but by
ranges, we found that lower UO and longer times of low
UO were both associated with the subsequent develop-
ment of AKI-Cr. Even short durations (1 or 2 hours) were
associated with approximately a 35% to 120% increase in
the ORs of AKI-Cr (Supplemental Fig 1). As the duration
of low UO progressively increased, the ORs of developing
AKI-Cr progressively increased, particularly for UO of
less than 0.2 or 0.2 to 0.4 mL $ kg–1 $ h–1. Despite low UO
being associated with AKI-Cr, after adjustment for other
factors, only UO below 0.2 mL $ kg–1 $ h–1 was inde-
pendently associated with increased risk of death, and
this risk increased with increasing duration of low UO
(Supplemental Fig 2).

Comment
Results
We have performed one of the largest studies to date
KDIGO stage 1 or greater AKI-Cr developed in 1,061 of
examining the prognostic effect of declines in UO and
4,195 patients (25%) within 3 days of their operation
relationship to AKI as defined by Cr-based criteria. Using
(Table 1). These patients were older, were more likely to
a large database of patients undergoing cardiac opera-
have comorbidities, and had lower ejection fractions
tions, we have described the clinical effect of several
(Table 2). The discriminatory ability of UO to predict AKI-
different approaches to applying AKI-UO definitions. In
Cr was similar between actual (C statistic ¼ .637  .054),
ideal (.623  .058), and adjusted (.631  .060) body weight.
Although discrimination improved with successive days Table 3. Outcomes
after the operation for all types of weights and both
continuous and mean UO, there was little difference AKI—Yes AKI—No
(n ¼ 1,061) (n ¼ 3,134)
when analyzed by weight type within body mass index
category (Supplemental Table 1). Outcome No. % No, % p Value
After adjustment for factors in Table 2, all UO thresholds
Prolonged ventilation 412 39 287 9 <0.001
(adjusted by actual weights) examined (up to 0.9 mL $ kg–1 $
Deep sternal wound 5 0.5 8 0.3 0.335
h–1) for any length of time were associated with increased infections
odds of developing AKI-Cr compared with patients whose
Reoperation for bleeding 63 6 45 1 <0.001
UO remained above 0.9 mL $ kg–1 $ h–1 (Fig 1). In general, a
Readmission to ICU 185 17 551 18 0.926
trend toward increasing risk for AKI was noted with
Readmission to hospital 163 15 429 14 0.185
increasing duration of UO within each threshold category
(horizontal left to right trend in Fig 1). However, this rela- Median IQR Median IQR
tionship was modest at higher UO thresholds (0.6 to 0.9 mL
$ kg–1 $ h–1) and became more pronounced only at lower Total ventilator 18 7–57 6 4–14 <0.001
time, h
UO thresholds. For example, the adjusted odds ratio (OR)
Length of stay
for AKI at a UO of 0.1 mL $ kg–1 $ h–1 ranged from
ICU, h 114 66–195 51 28–90 <0.001
2.355 (95% CI, 1.77 to 3.135) for a duration of 1 hour to
36.99 (95% CI, 4.38 to 312.24) for a duration of 12 hours. Postoperative, d 10 7–15 6 5–8 <0.001
Similarly, for any given duration, the risk of AKI generally Total hospital, d 12 7–21 7 5–11 <0.001
increased with lower UO threshold (vertical top to bottom AKI ¼ acute kidney injury; ICU ¼ intensive care unit; IQR ¼
trend in Fig 1). Once again, this relationship was most interquartile range.
6 ENGOREN ET AL Ann Thorac Surg
URINE OUTPUT AND CREATININE ELEVATION 2016;-:-–-

Fig 2. Urine output threshold and acute death. Heat map shows adjusted odds ratios of dying based on urine output meeting the hourly threshold
averaged (A) over the several hours (mean) or (B) below that value for all hours (consecutive). Each box shows the odds ratio (95% confidence
interval) and the number of patients who died/the number of patients whose urine output met the threshold value for that many hours. The red
outline shows boxes where the odds ratio is statistically significant.

general, declining UO was associated with developing
AKI-Cr, but only extreme drops in UO (by threshold or
by longer duration) were associated with increased death.
Our findings have several practical implications.
Importantly, we found that there is similar discrimi-
nation in using UO corrected for actual, ideal, or adjusted
body weight. This did not vary when we stratified by
three levels of obesity (Supplemental Table 1). For
simplicity, we therefore recommend using actual weight.
Low UO was associated with subsequent rise in creati-
nine levels. UO of less than 0.5 mL $ kg–1 $ h–1 for 6 or 12
hours was associated with an increased risk of developing
AKI-Cr (Fig 1) but not of dying (Fig 2). However, as the
UO threshold became lower (eg, <0.3 mL $ kg–1 $ h–1),
the association between UO and death became significant
and progressively increased the longer UO remained
below that threshold. Although UO thresholds are part of
the KDIGO, AKIN, and RIFLE definitions for AKI,
threshold values may produce a false similarity between
dissimilar values (eg, 0.1 and 0.45) and suggest a false
separation between similar values (eg, 0.48 and 0.52). A 0.5
mL $ kg–1 $ h–1 threshold includes 0.1 and 0.45 and their
average outcome is compared with the average outcome
of all values exceeding 0.5. To avoid this problem, we
repeated the analyses dividing UO into ranges instead of
thresholds. This found a time-dependent association be-
tween UO and AKI-Cr: short times of profoundly low UO
were associated with AKI-Cr, whereas at higher levels of
UO, longer time periods were required to develop
AKI-Cr. UO below 0.2 or between 0.2 and 0.4 mL $ kg–1 $
h–1 was associated with increased odds of developing
AKI-Cr, with the ORs progressively increasing the longer
UO remained in these ranges. This suggests that low UO
acts as an early predictor of AKI-Cr and that if in-
terventions are beneficial in preventing AKI-Cr, the
physician has varying times to intervene depending on the
Ann Thorac Surg
2016;-:-–-
Fig 2. (Continued).
severity of the low UO. Although higher levels of UO were
associated with the subsequent development of AKI-Cr,
the ORs were generally in the range of 1.5 to 2.0 and did
not vary appreciably with duration.
Our findings that threshold values of UO are associated
with AKI-Cr is similar to that of Prowle and colleagues
[12], who in a study of 239 patients found that UO below
0.5 mL $ kg–1 $ h–1 was associated with subsequent AKI-
Cr, although they did not find an association between
duration of oliguria and AKI-Cr. This may relate to
different patient populations (after cardiac operations in
our study vs mixed medical and surgical ICU in theirs),
different creatinine elevations to define AKI-Cr (0.3
mg/dL or 50% rise vs 0.5 mg/dL), or their limited power
with only 239 patients [12]. However, our findings extend
theirs by analyzing the data by ranges instead of just
thresholds. This allowed us to better relate the amount
and time of low UO to both AKI-Cr and to death. Our
findings that low UO is independently associated with
ENGOREN ET AL 7
URINE OUTPUT AND CREATININE ELEVATION
death are similar to two other studies [14, 15]. However,
our study differs by analyzing UO ranges and not just
thresholds. This better allows us to determine the effect of
different levels of low UO.
Current consensus AKI definitions use a UO threshold
of 0.5 mL $ kg–1 $ h–1 for 6 hours to diagnose the earliest
stage of AKI. In our study, this threshold was associated
with a nearly 80% increased risk for developing AKI
based on Cr criteria (adjusted OR, 1.79; 95% CI, 1.37 to
2.33) but not with a significant risk of death (adjusted OR,
1.21; 95% CI, 0.63 to 2.33; Fig 1). Conversely, an observed
UO of 0.1 mL $ kg–1 $ h–1 for just 2 hours was associated
with both a significant increased risk of subsequently
meeting AKI by Cr-based criteria (adjusted OR, 3.22; 95%
CI, 3.44 to 4.45) and death (adjusted OR, 2.93; 95% CI, 1.37
to 6.28). These findings reinforce the sensitive nature of
extreme drops in UO in identifying patients at risk for
poor outcomes, even within only a few hours. Impor-
tantly, these early hours may be a critical time to
8 ENGOREN ET AL
URINE OUTPUT AND CREATININE ELEVATION
intervene and alter the prognosis of AKI in patients. Yet,
current guidelines require a minimum of 6 hours of
decreased UO to make a diagnosis of AKI. Our results
suggest that additional criteria—focusing on more severe
drops in UO for even short durations—may be
warranted.
An early study showed that the glomerular filtration
rate is preserved in fasted, dehydrated individuals until
the UO falls to approximately 0.35 to 0.5 mL/min (21 to
30 mL/h) [18]. Below this value, the glomerular filtration
rate falls linearly until anuria and no filtration are
reached. Although we found that AKI-Cr developed in
38% (after 1 hour)—59% (after 12 hours) of patients with
a UO below 0.3 mL $ kg–1 $ h–1 (21 mL/h for a 70-kg
person)—AKI-Cr did not develop in 41 (62%). This
suggests that AKI may have developed (we just did not
measure Cr at the right time), but that UO and filtration
increased sufficiently enough by the time of the next Cr
measurement so that Cr had recovered to below that
required for AKI-Cr or that these patient are able to
concentrate their urine to a greater extent as found by
Chelsey in his 14 patients [18]. Further study is needed
to clarify this point.
Limitations
Our study has several limitations. First, this was a single-
center study in patients undergoing cardiac operations
and may not be generalizable to other centers or other
populations, particularly nonsurgical patients, where the
mechanisms of oliguria and AKI may be different. In
particular, patients undergoing cardiopulmonary bypass
are typically administered large quantities of fluids, have
a generalized inflammatory state leading to extravasation
of fluid and an increase in extravascular water, and may
be intravascularly depleted despite the positive fluid
balance [19].
Second, we are limited on not knowing the fluid bal-
ances, hemodynamic management, blood transfusions,
and diuretic medications that may affect both UO and Cr
elevations. Studies will be needed to clarify the effects of
these interventions and management strategies on renal
function and outcome.
Third, despite an overall large database, many different
categories examined had relatively few patients, limiting
the statistical power. This highlights the challenges
associated with formally studying the effect of different
UO criteria.
Strengths
This study has several strengths. First, the use of the
electronic medical record enabled us to collect hourly
UOs for more than 4,000 patients.
Second, by analyzing UO as a threshold and as discrete
ranges, we were able to show that although traditional
thresholds of AKI-UO (<0.5 mL $ kg–1 $ h–1 for 6 or for
12 hours) are associated with the subsequent develop-
ment of AKI-Cr and with death, the analysis by ranges
shows that this association is driven mostly by the more
severe levels of oliguria.
Ann Thorac Surg
2016;-:-–-
Conclusions
The recent KDIGO AKI guidelines identified several key
topics for investigation specifically related to UO criteria
for diagnosing AKI. Using a large, single-center database
of cardiac surgical patients, we answered three of them in
this study. First, there is no significant difference in pre-
dictive accuracy of adjusting UO by ideal, adjusted, or
actual weight and recommend using actual weight for its
simplicity. Second, low UO below 0.4 mL $ kg–1 $ h–1
was associated with subsequent AKI-Cr with the risk
increasing for longer durations and lower UO. Third, only
UO below 0.2 mL $ kg–1 $ h–1 was independently asso-
ciated with increased death and this risk increased with
longer duration. As a whole, these findings support the
prognostic significance of UO for both renal outcomes
and death and provide further clarity regarding these
relationships.
This study was performed at the University of Michigan and was
supported by departmental and institutional funds.
References
1. Fonseca Ruiz NJ, Castro DP, Guerra AM, Saldarriaga FM,
Hernandez JD. Renal injury study in critical ill patients in
accordance with the new definition given by the Acute
Kidney Injury Network. J Crit Care 2011;26:206–12.
2. Cruz DN, Bolgan I, Perazella MA, et al. North East Italian
Prospective Hospital Renal Outcome Survey on Acute
Kidney Injury (NEiPHROS-AKI): targeting the problem
with the RIFLE criteria. Clin J Am Soc Nephrol 2007;2:
418–25.
3. Sigurdsson MI, Vesteinsdottir IO, Sigvaldason K,
Helgadottir S, Indridason OS, Sigurdsson GH. Acute kidney
injury in intensive care units according to RIFLE classifica-
tion: a population-based study. Acta Anaesthesiol Scand
2012;56:1291–7.
4. Case J, Khan S, Khalid R, Khan A. Epidemiology of acute
kidney injury in the intensive care unit. Crit Care Res Pract
2013;2013:479730.
5. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of
acute kidney injury in critically ill patients: the multinational
AKI-EPI study. Intensive Care Med 2015;41:1411–23.
6. Han SS, Kang KJ, Kwon SJ, et al. Additional role of urine
output criterion in defining acute kidney injury. Nephrol
Dial Transplant 2012;27:161–5.
7. Lassnigg A, Schmidlin D, Mouhieddine M, et al. Minimal
changes of serum creatinine predict prognosis in patients
after cardiothoracic surgery: a prospective cohort study. J Am
Soc Nephrol 2004;15:1597–605.
8. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury
Network: report of an initiative to improve outcomes in acute
kidney injury. Crit Care 2007;11:R31.
9. Kidney Disease: Improving Global Outcomes (KDIGO)
Acute Kidney Injury Work Group. KDIGO clinical practice
guideline for acute kidney injury. Kidney Int Suppl 2012;2:
1–138.
10. Wlodzimirow KA, Abu-Hanna A, Slabbekoorn M,
Charmuleau RA, Schultz MJ, Bouman CS. A comparison of
RIFLE with and without urine output criteria for acute kidney
injury in critically ill patients. Crit Care 2012;16:R200.
11. Cerda J. Oliguria: an earlier and accurate biomarker of acute
kidney injury? Kidney Int 2011;80:699–701.
12. Prowle JR, Liu YL, Licari E, et al. Oliguria as predictive
biomarker of acute kidney injury in critically ill patients. Crit
Care 2011;15:R172.
Ann Thorac Surg
2016;-:-–-
13. Macedo E, Malhotra R, Bouchard J, Wynn SK, Mehta RL.
Oliguria is an early predictor of higher mortality in critically
ill patients. Kidney Int 2011;80:760–7.
14. Mandelbaum T, Lee J, Scott DJ, et al. Empirical relationships
among oliguria, creatinine, mortality, and renal replacement
therapy in the critically ill. Intensive Care Med 2013;39:414–9.
15. Teixeira C, Garzotto F, Piccinni P, et al. Fluid balance and
urine volume are independent predictors of mortality in
acute kidney injury. Crit Care 2013;17:R14.
16. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P,
Acute Dialysis Quality Initiative Workgroup. Acute renal
ENGOREN ET AL 9
URINE OUTPUT AND CREATININE ELEVATION
failure—definition, outcome measures, animal models, fluid
therapy and information technology needs: the Second In-
ternational Consensus Conference of the Acute Dialysis
Quality Initiative (ADQI). Crit Care 2004;8:R204–12.
17. Perneger TV. What’s wrong with Bonferroni adjustments.
BMJ 1998;316:1236–8.
18. Chelsey LC. Renal excretion at low urine volumes and the
mechanism of oliguria. J Clin Invest 1938;17:591–7.
19. Hamada Y, Kawachi K, Tsunooka N, Nakamura Y, Takano S,
Imagawa H. Capillary leakage in cardiac surgery with cardio-
pulmonary bypass. Asian Cardiovasc Thorac Ann 2004;12:193–7.