J Vet Intern Med 2012;26:500–505
Prognostic Factors and a Prognostic Index for Cats with Acute
Kidney Injury
Y.-J. Lee, J.P.-W. Chan, W.-L. Hsu, K.-W. Lin, and C.-C. Chang
Background: The clinical manifestations of acute kidney injury (AKI) range from mild to fatal in cats; however, prognosis factors have been rarely studied.
Hypothesis/Objectives: To find the clinical factors significantly correlated with the outcome among cats with AKI and
to develop a simple prognostic index.
Animals: Seventy cats with AKI were recruited.
Methods: Demographic and clinicopathological data obtained from 70 cats with AKI were retrospectively collected.
Student’s t-test or Mann–Whitney U-test and Pearson chi-square test or Fisher’s exact were applied to determine the factors associated with survival in cats with AKI. Using logistic regression, the statistically significant factors associated with
prognosis were identified and a new prediction model was generated.
Results: The overall case fatality rate was 64% (45/70). The results showed that nonsurviving cats had significantly
lower levels of PCV, WBC, RBC, LDH and albumin, a lower albumin/globulin ratio, lower blood glucose, and a reduced
body temperature, as well as being older. Serum urea and creatinine concentrations were not statistically significant as
prognostic factors, but a decrease in these 2 variables in 3 days was significantly related to a reduction in death. A summary prognostic index including body temperature and LDH and albumin concentrations had area under the receiveroperating characteristic curve (AUROC) for predicting death of 0.86 (P < .05) and a cut-off value of 0.82, a sensitivity of
77% and a specificity of 90%.
Conclusions: The prognosis in cats with AKI is quite different from that found for human and dogs.
Key words: Case-fatality rate; Death; Feline; Outcome; Renal failure.
cute kidney injury (AKI), which is characterized
by a sudden decrease in renal function and a loss
of capacity to regulate fluids and electrolytes, excrete
wastes and concentrating urine,1 is an important disease in both human and veterinary medicine. Case
fatality rate due to AKI is relatively high among
humans (50% despite dialysis)2,3 as well as among
dogs (60%).4,5 The clinical manifestations of AKI
range from mild to fatal. In such circumstances, prognostic factors that are able to predict death and prevent
disease progression are important to manage AKI.
The survival rate for AKI is not only determined by
renal dysfunction but also is related to the presence of
other complications.6 In humans with AKI, factors
associated with death include age,7,8 gender,8 oliguria,8,9 sepsis,9,10 a low concentration of albumin,11 fluid
overload,12 and an increase in serum creatinine.13–15
However, in dogs with AKI, death is associated with
an increase in serum creatinine,4,16 hypocalcemia,
proteinuria,4 a higher phosphorus concentration,16 and
A
Abbreviations:
From the Department of Veterinary Medicine (Lee, Chan), the
Veterinary Medical Teaching Hospital (Lee, Lin), and
the
Graduate Institute of Microbiology and Public Health (Hsu,
Chang), College of Veterinary Medicine, National Chung-Hsing
University, Taichung, Taiwan (Hsu, Chang). The work was
carried out in Veterinary Medical Teaching Hospital, National
Chung-Hsing University, Taichung, Taiwan.
Corresponding author: Chao-chin Chang, DVM, MS, PhD, 250
Kuo Kuang Road, Graduate Institute of Microbiology and Public
Health, National Chung Hsing University, Taichung 402, Taiwan;
e-mail: [email protected]
greater age.5 Therefore, these factors could be considered concurrently to evaluate the prognosis of AKI in
cats.
Despite its importance in feline medicine, reports
exploring AKI in cats are rare. Previous studies have
mostly been case reports17 or studies based on the
cases with a single cause.18,19 In these circumstances,
the prognostic factors related to AKI in cats have been
largely ignored. To our knowledge, only a single retrospective study of 32 cats with intrinsic AKI has
attempted to explore the risk factors in cats associated
with AKI.20
In the previous study,20 the poor prognostic factors for cats with AKI consisted of elevated serum
potassium and bicarbonate concentrations together
with a reduction in albumin concentration.20 These
prognosis variables in cats are quite different from
those described for dogs4 and humans.13 Additionally,
Submitted September 16, 2011; Revised January 4, 2012;
Accepted February 29, 2012.
Copyright © 2012 by the American College of Veterinary Internal
Medicine
10.1111/j.1939-1676.2012.00920.x
A/G
ALT
AST
AUROC
BT
CK
DCr
DSUN
Hb
IQR
LDH
ROC
SE
SUN
WBC
albumin/globulin
alanine aminotransferase
aspartate transaminase
area under the receiver operating characteristic curve
body temperature
creatine kinase
decrease in concentration of creatinine in 3 days
decrease in concentration of SUN in 3 days
hemoglobin
interquartile ranges
lactate dehydrogenase
receiver operating characteristic curve
standard error
serum urea nitrogen
white blood cell
Kidney Disease in Cats
the etiology and management of AKI seem to differ
from one geographic region to another, which might
affect prognostic factors. Therefore, in-depth studies
are needed to obtain further information that might be
helpful when carrying out clinical evaluations on cats
with AKI.
The objective of this study was to evaluate the
demographic and clinicopathological factors that
might be related to the outcome of AKI in cats when
the cat presents at an animal hospital. After these significant factors have been identified, they can be used
to develop a summary prognostic index to help with
the clinical evaluation of cats with AKI.
Material and Methods
Study Population
The studied individuals with AKI were selected from cats that
had attended the Veterinary Medical Teaching Hospital of the
National Chung-Hsing University from 1998 to 2006. The retrospective dataset was collected using medical records. To identify
cats with AKI, cases with an elevated serum creatinine concentration (>2 mg/dL) and serum urea nitrogen (SUN) (>35 mg/dL)
were recruited as suspected AKI cases. However, cats post renal
or chronic kidney diseases were then excluded. The cats with any
urinary obstructive disease, such as calculi in the urinary tract,
rupture of urinary bladder, cystitis or feline lower urinary tract
disease, were considered postrenal failure cases. Furthermore,
cases with one of following clinical signs, persistent azotemia (a
clinical history more than 14 days), chronic polyuria, polydipsia
or small kidneys, were determined to be chronic kidney disease
cases. Besides, through ultrasonic images, cats with suspected
renal mass, but finally classified as neoplastic disease or feline
infectious peritonitis (FIP), were excluded in this study.
Data Collection
Demographic information was obtained from the medical
records and included age, sex, body weight, and BT. Clinical
pathological data were collected, including Hb, PCV, WBC,
serum creatinine, SUN, SUN/creatinine ratio, AST, ALT, LDH,
CK, albumin, A/G ratio, calcium, phosphorus, glucose, serum
potassium, sodium, and chloride. Clinical symptoms such as
vomiting, diarrhea, anorexia, oliguria/auria, and the duration of
hospitalization were also recorded. Additionally, the decrease in
SUN (DSUN) and creatinine (DCr) in 3 days was calculated.
Statistical Analysis
Variable data with a normal distribution that were assessed by
Shapiro-Wilk test were expressed as means with standard deviation (SD) to show data variation. The Student’s t-test was used
to compare mean values between 2 groups. Non-normally distributed continuous data were reported as medians, the limits of the
overall range and were statistically analyzed by the Mann–
Whitney U-test. Categorical data were reported as proportions
and the proportional difference between groups were evaluated
by Pearson chi-square test or Fisher’s exact test as appropriate.
Univariate logistic regression analysis was applied first to determine the possible risk factors associated with death due to AKI.
After these significant factors were verified, multiple logistic
regression analysis using backward selection at the chosen critical
level (P < .05) was then carried out to incorporate these factors
into the model and generate the best equation for predicting
501
death. The best equation was used to calculate log odds and
was used as the summarized prognostic index to predict death
due to AKI. A receiver operating characteristic (ROC) curve
was constructed using the relationship between the prognostic
index and death due to AKI. The area under the receiver
operating characteristic curve (AUROC) was calculated to evaluate the diagnostic performance of the prognostic index. For
all analyses, values of P .05 were considered statistically
significant. All analyses were performed with commercial software, namely SPSS version 16 for Windows (SPSS Company,
Chicago, IL).
Results
Data from 70 cats, identified using the inclusion and
exclusion criteria, were analyzed. The 20-day case
fatality rate was 64% (45/70). Compared with the AKI
cats in the survival group, the nonsurvival (death)
group cats were significantly older (median: 2 years
versus 6 years old). There was no significant difference
between these 2 groups with regard to the body
weight. Body temperature was lower in nonsurvival
group (median of survivors: 38.2°C; median of nonsurvivors: 37.3°C). No other clinical signs were associated
with death due to AKI in cats (Table 1).
In terms of clinical pathological factors, the nonsurvival group had significant lower values for PCV (50%
in survivors versus 43.3% in nonsurvivors), WBC
(26700 cells/lL in survivors versus 17700 cells/lL in
nonsurvivors), RBC (10.7% in survivors versus 8.0%
in nonsurvivors), LDH (439 IU/L in survivors versus
252.5 IU/L in nonsurvivors), albumin (4.2 g/dL in survivors versus 3.6 g/dL in nonsurvivors), A/G ratio
(1.26 in survivors versus 1.05 in nonsurvivors) and
blood glucose (198 g/dL in survivors versus 147 g/dL
in nonsurvivors) (Table 2). However, the values for
SUN (194 mg/dL in survivors versus 238 mg/dL in
nonsurvivors; P = .14), serum creatinine (6.6 mg/dL in
survivors versus 9.5 mg/dL in nonsurvivors; P = .07)
and electrolytes (calcium, phosphorus, sodium, potassium and chloride), as well as the SUN/creatinine
ratio, among the nonsurvival group were not signifi-
Table 1. Characteristics and clinical signs in the survival and nonsurvival groups of cats with acute kidney
injury in this study at time of first examination.
Variable
Survival
Group
2 (2) (n = 15)
3.3 (1.3)b
(n = 25)
38.2 (2.2)b
(n = 24)
Sex (male) (%) 64 (n = 26)
Vomiting (%)
52 (n = 25)
Diarrhea (%)
8 (n = 25)
Age (year)
Body weight
(Kg)
BT (oC)
a
b
Nonsurvival
Group
6 (4) (n = 33)
2.9 (1.5)b
(n = 40)
37.3 (2)b
(n = 31)
63.6 (n = 44)
37.1 (n = 35)
5.7 (n = 35)
b
P Valuea
<.001
.19
<.05
.98
.25
.73
Analysis of variance for continuous variables and chi-squared
test for categorical variables.
b
Median (interquartile range).
502
Lee et al
Table 2. Laboratory values at time of first examination for the survival and nonsurvival groups of cats with acute
kidney injury.
Variable
Hbb (g/dL)
PCVa (%)
WBCa (lL)
RBCa (106/lL)
SUNa (mg/dL)
Creatininea (mg/dL)
SUN/Creatinine ratioa
ASTa (U/L)
ALTa (U/L)
LDHa (IU/L)
CKa (mg/dL)
Albuminb (g/dL)
A/G ratiob
Calciumb (mg/dL)
ALPa
Phosphorusb (mg/dL)
Chloridea (mEq/L)
Glucosea (g/dL)
Total proteinb (g/dL)
Sodiuma
Potassiuma (mEq/L)
DSUN
DCreatinine
Survival Group
14.9 (2.9);
50 (28–70);
26700 (7900–45900);
10.74 (5.9–14.3);
193.5 (36.3–313.3);
6.6 (2.0–29.8);
23.1 (9–93.2);
39 (17.8–271);
56.1 (18.2–287.9);
439 (152–1774);
559 (121–6354);
4.2 (0.8);
1.26 (0.3);
9.2 (1.0);
36 (13–190);
14 (5.9);
101.2 (82–160);
198 (120–309);
7.6 (1.1);
144.1 (130–198);
4.2 (3.1–9.9);
159.6 (79.6–273);
5.2 (1.8–7.5);
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
P Value**
Nonsurvival Group
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
21
21
21
21
25
25
25
21
21
21
21
21
21
10
21
10
15
20
22
15
14
22
22
12.1 (3.1);
43.25(29–63);
17700 (4200–74400);
8.0 (4.8–18.2);
238.2(93–400.6);
9.5 (2.0–33.5);
21.7 (5.7–107.3);
53 (12–249);
56 (13.7–581.5);
252.5 (51–1153);
368 (48–4477);
3.6 (0.7);
1.05 (0.3);
9.2 (1.8);
27 (11–219);
15 (5.7);
114 (88–156);
147 (32–375);
7.3 (1.3);
150 (116–199);
4.6 (1.5–10);
52.9 (30.7–203);
1.3 (1.5–27.5);
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
44
44
44
44
45
45
45
41
41
42
42
42
42
27
42
28
25
43
42
25
24
16
15
.06
<.05
<.05
<.05
.14
.07
.97
.47
.9
<.05
.26
<.005
<.05
.82
.651
.504
.09
<.005
.28
.14
.77
<.05
<.05
a
Data are median (the limit of overall range) and compared by Mann–Whitney U test.
Data are mean (SD) and compared by Student’s t-test.
**
P < .05 is considered significant.
ALT Alanine aminotransferase, AST Aspartate transaminase, SUN Blood urea nitrogen, CK Creatinine kinase, Hb Hemoglobin,
LDH Lactate dehydrogenase, PCV Packed cell volume, WBC White blood cells.
b
cantly different from those of members of the survival
group.
After univariate analysis, higher levels of BT, PCV,
RBC, glucose, and albumin, as well as a higher A/G
ratio, were negatively associated with death in cats
with AKI, while age was positively associated (all
P < .05). Additionally, both DSUN and DCr had significantly predictive ability in terms of future survival,
as it was found that a greater decrease in SUN and
creatinine concentrations over 3 days were related to a
reduced odds ratio of death due to AKI (Table 3).
Further analysis of the data by multiple logistic
regression with backward selection was then carried
out. Factors of BT, albumin, and LDH were selected
as the most appropriate variables to incorporate in the
model to predict death due to AKI (Table 4).
Table 3. Results of the univariate analysis of variables to identify those variables that are significantly
associated with case fatality rate (P < .05) in 70 cats
with acute renal injury, of which 44 died during this
study.
Variable
Body temperature
Age (year)
PCV
RBC
Glucose
Creatinine
SUN
Albumin
A/G
DSUNa
Dcreatininea
Odds Ratio
95% CI
P Value*
0.588
1.05
0.904
0.786
0.995
1.059
1.004
0.287
0.117
0.990
0.734
0.380–0.907
1.149–1.955
0.895–0.99
0.941–0.989
0.991–0.999
0.988–1.135
0.999–1.009
0.125–0.657
0.020–0.697
0.981–0.998
0.566–0.953
.016
.03
.021
.040
.023
.108
.102
.003
.018
.019
.020
Log (odds of death) ¼ 34:753 0:675 ðBTÞ
1:904 ðalbuminÞ
0:03 ðLDHÞ
P < .05 is considered significant.
DSUN and Dcreatinine represent the decreases in SUN and
creatinine over 3 days, respectively.
CI, confidence interval.
Based on this equation, the log odds was calculated
for each study individual to generate a summarized
prognostic index for cats with AKI. A higher log odds
value indicates a higher probability of death. Using
this index to determine risk of future death due to
AKI, the AuROC was 0.860 ± 0.026. It was further
determined that using this index, a cut-off value of
0.822 had a sensitivity of 77% and a specificity of
90% when determining future death among cats with
AKI (Fig 1).
*
a
Kidney Disease in Cats
Table 4. The best prediction model determined by
multiple logistic regression analysis using backward
selection.
Variable
Body temperature
Albumin
LDH
aOR (95% CI)
P Value
0.509 (0.296–0.875)
0.149 (0.042–0.531)
0.997 (0.994–1.000)
.015
.003
.024
aOR, adjusted odds ratio; CI, confidence interval.
1.0
0.8
Sensitivity
0.6
0.4
0.2
0.0
0.0
0.2
0.4
0.6
0.8
1.0
1- Specificity
Fig 1. Receiver operator curve (ROC) analysis of the summarized prognostic index that was developed in this study. The
index was calculated on the basis of the equation of 34.753–
0.675*(BT)–1.904*(albumin)–0.03*(LDH). The area under the
ROC was 0.860 ± 0.026. Using a cut-off point of 0.822, the sensitivity was 77% and the specificity was 90%.
Discussion
In this study, a summary prognostic index for predicting survival among cats with AKI was obtained by
multiple logistic regression analysis. This method has
been widely applied to study the prognosis of various
different diseases.21 This study showed that lower BT,
concentration of serum albumin or LDH activity are
useful predictors of death in cats with AKI. The values
for these indices, when the survival and nonsurvival
groups were considered, are also significantly different.
Furthermore, when BT, serum albumin, and LDH
were considered concurrently, there was a good predictive value for the prognosis of cats with AKI. Using
this information, it was possible to develop a summary
prognostic index, and a cut-off value of 0.822 was
demonstrated to have high sensitivity (77%) and specificity (90%) when predicting future risk of death
among cats with AKI.
Lower BT values have been reported to be related
to chronic kidney disease,22 but have been seldom considered as a prognosis factor for AKI. Nevertheless, in
503
the present study, BT had a significant predictive value
among cats with AKI. It is well known that the kidney
plays a role in thermogenesis, and that nephrectomized
animals have lower core temperature23; in these circumstances, it is quite probable that hypothermia
might occur due to renal disease. Additionally, in an
experimental study, hypothermia has been found to
induce ultrastructural changes in renal tubular cells
and these changes were similar to acute tubular necrosis.24 Therefore, a low body temperature might result
from renal injury and may then lead to further renal
functional deficiencies.
In a previous study,20 a decrease in serum albumin
increased the odds of death in the cats with acute
kidney injury. However, in our study, the concentration of albumin and the A/G ratio in the survival
and nonsurvival groups were not significantly lower
than the normal reference value, indicating that
hyperalbuminemia might be a result of dehydration
among the cats with AKI. Dehydration hemodynamically decreases glomerular filtration rate and this in
turn results in prerenal azotemia, and such injury
can be resolved by correcting the hydration status.19
Nevertheless, prolonged dehydration can cause renal
tubular necrosis and exacerbate the kidney injury.25
Although an elevation of the SUN/creatinine ratio
can be used to evaluate prerenal azotemia,26 there
was no significant difference in SUN/creatinine ratio
between surviving and nonsurviving cats with AKI
in our study. However, the case clinical information
in this study was derived from historical medical
records and therefore the magnitude or the duration
of any dehydration, as well as any prerenal factors
that might affect each cat, could not be accurately
accessed.
In this study, the mean and median LDH activity
for the survival and nonsurvival groups were significantly higher than the normal reference value. Notably, previous studies have suggested that a high
activity of serum LDH might reflect renal tubular
damage27 or a renal infarct.28 LDH was a prognostic
factor of a good outcome in this study. As LDH
comes from different organs and contained several
types of isoenzymes,29 the total serum LDH activity
might not be specific to renal disease. Nevertheless,
the reason why cats suffering AKI having a high
serum LDH are more likely to survive requires further
investigation.
The case fatality rate of cats with AKI was 64% in
our study, which is higher than the previous reports
for humans,3 cats (47%),20 and dogs.4,5 Nevertheless,
such a high case fatality rate means that it is important that there is an early identification of prognostic
factors when cats suffer from AKI. Six cats with auria
died within 3 days of hospitalization in our study
(data not shown). The most common causes of AKI in
cats have been shown to be related nephrotoxicoses,20
possibly through exposure of antibiotics,17,19 ingestion
of lily,18,20 nonsteroid anti-inflammatory medicine
(NSAID)20 and ethylene glycol.20 Unfortunately, most
of the causes remain unknown in this study, due to
504
Lee et al
the incomplete history taking or owner’s ignorance.
Nevertheless, only 2 cats were with NSAID treatment
and 1 cat received antibiotics according to the clinical
history. Future studies need to take the information
into consideration for constructing a more applicable
model of prognosis.
Different treatments might result in diversity of clinical outcomes. In this study, all the cats were treated
with fluid therapy intravenously to correct the hydration status, electrolytes and acid-base balance. Additionally, the clinical assessments of mucous membrane
capillary refill time, heart and respiratory rate, and
body weight were utilized to adjust the fluid rate.
Diuretics were used during auria or oliguria status.
Oliguria was defined as urine production less than
6.5 mL/kg/day and the urine output was approximately measured by litter box weight. Nevertheless,
quantitative urine output is an important risk factor in
relation to acute kidney injury in both human9 and
veterinary medicines.8 In the current standard managements of AKI, monitoring fluid ins and outs by a
urinary catheter and serial monitoring of central
venous pressure (CVP) are suggested to facilitate
safety of fluid administration and lower the fertility
rate of AKI in cats.30 Unfortunately, the precise urine
output and CVP of each cat could not be obtained
as these works are not routinely conducted in our
hospital. Therefore, their impact on AKI prognosis
could not be evaluated. In the future, it is important
that the current model needs to take this clinical
management factor into account for better prognosis
evaluation.
Conventionally, elevation of SUN and creatinine
(azotemia) are considered the key prognostic factors
of human and canine AKI. In this study, the results
suggested that neither SUN nor creatinine is
increased when a cat suffers death from AKI, which
is consistent with a previous report.20 However, the
above variables should not be neglected because consistently decreased concentrations of SUN and creatinine in 3 days were found to be associated with a
lower case fatality rate in this study. The deliberate
monitoring of serum SUN and creatinine may therefore be useful when assessing prognosis among cats
with AKI.
Geriatric cats had a higher case fatality rate from
AKI in this study. Similar results had been reported in
dogs5 and humans.13 Oxidative stress can result in
geriatric arterioles, which in turn might result in a
decline in the renal glomerular filtration rate (GFR)30;
subsequent to this, the pathological stress from AKI
might cause further deterioration in renal function.
Based on this, elderly cats with AKI should be
cautiously treated.
Renal failure might induce hyperglycemia via insulin
resistance, which can then lead to stress hyperglycemia.31 Interestingly, in the present study, the blood
glucose concentration of the survival cats was higher
than that of the nonsurvival ones. The serum glucose
concentration increased in parallel with the chance of
survival. This might be associated with stress hypergly-
cemia as a result of struggling by the cats.32 It can be
hypothesized that cats in a better physical condition
are able to struggle harder, which might contribute to
higher serum glucose, although the exact mechanism
needs further study.
This work found that both the survival and nonsurvival groups had elevated leukocyte counts. Notably,
the leukocyte count in the survival group was significantly higher than in the nonsurvival group. The
increase in leukocytes might be associated with a poor
prognosis.33 Despite its complexity, the activation and
suppression of the uremia-related immune response
have been proposed to be related to AKI. In the
acute-phase response, infection or massive tissue damage can lead to an increase in leukocytes. However,
immune mediators, such as cytokines, protease, prostaglandins, and uremic toxin, might interfere with leukocyte production.34 In such circumstances, it is difficult
to interpret the severity of AKI in cats merely examining leukocyte concentrations.
In the present study, PCV, RBC, glucose, and the
A/G ratio were significantly related to death due to
AKI in cats by univariate analysis. However, after
multivariate analysis with backward selection, these
factors were excluded and only BT, albumin, and
LDH were selected as the best variables to incorporate
in a model predicting death due to AKI. These exclusions can be explained by the fact that albumin probably represents the state of dehydration and that the
roles of PCV, RBC, glucose, and the A/G ratio would
be similar. Therefore, to prevent collinearity in the
multivariate model, only albumin needed to be incorporated into the final model.
In conclusion, a method of evaluating the outcome
of AKI at an early stage allows the veterinarian to
plan appropriate medical management for cats with
AKI. This study pinpoints several prognostic factors
and has developed a new summary prognostic index
that was modeled using the multiple logistic regression
approach. Of major importance, SUN and serum creatinine concentration cats with AKI was not included
in this index as it was not statistically useful for prognosis. Nevertheless, as different etiologies of AKI are
known to have different prognoses, the cats with AKI
in this study might not be representative of the cases
treated elsewhere. Therefore, the current model would
still need to be further evaluated in the other populations. As a whole, our results are a step forward in
predicting the outcome of cats with AKI, and the summary index should be a useful tool to veterinarians in
the future.
Acknowledgments
The authors thank Professor M-L Wong (National
Chung-Hsing University) for his critical reading and
Professor T-H. Hsu (National Chung-Hsing University) for his kind permission to use the data from the
Veterinary Medical Teaching Hospital, National
Chung Hsing University.
This study was not supported by any grants.
Kidney Disease in Cats
References
1. Schrier RW, Wang W, Poole B, et al. Acute renal failure:
Definitions, diagnosis, pathogenesis, and therapy. J Clin Invest
2004;114:5–14.
2. Silvester W, Bellomo R, Cole L. Epidemiology, management, and outcome of severe acute renal failure of critical illness
in Australia. Crit Care Med 2001;29:1910–1915.
3. Liano F, Pascual J. Outcomes in acute renal failure. Semin
Nephrol 1998;18:541–550.
4. Vaden SL, Levine J, Breitschwerdt EB. A retrospective
case-control of acute renal failure in 99 dogs. J Vet Intern Med
1997;11:58–64.
5. Behrend EN, Grauer GF, Mani I, et al. Hospital-acquired
acute renal failure in dogs: 29 cases (1983–1992). J Am Vet Med
Assoc 1996;208:537–541.
6. Druml W. Acute renal failure is not a “cute” renal failure!
Intensive Care Med 2004;30:1886–1890.
7. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure
in critically ill patients: A multinational, multicenter study.
JAMA 2005;294:813–818.
8. Mehta RL, Pascual MT, Gruta CG, et al. Refining predictive models in critically ill patients with acute renal failure. J Am
Soc Nephrol 2002;13:1350–1357.
9. Neveu H, Kleinknecht D, Brivet F, et al. Prognostic factors
in acute renal failure due to sepsis. Results of a prospective multicentre study. The French Study Group on Acute Renal Failure.
Nephrol Dial Transplant 1996;11:293–299.
10. Chertow GM, Soroko SH, Paganini EP, et al. Mortality
after acute renal failure: Models for prognostic stratification and
risk adjustment. Kidney Int 2006;70:1120–1126.
11. Mahajan S, Tiwari S, Bharani R, et al. Spectrum of acute
renal failure and factors predicting its outcome in an intensive
care unit in India. Ren Fail 2006;28:119–124.
12. Payen D, de Pont AC, Sakr Y, et al. A positive fluid balance is associated with a worse outcome in patients with acute
renal failure. Crit Care 2008;12:R74.
13. Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis 2002;39:930–936.
14. Coritsidis GN, Guru K, Ward L, et al. Prediction of acute
renal failure by “bedside formula” in medical and surgical intensive care patients. Ren Fail 2000;22:235–244.
15. Chawla LS, Abell L, Mazhari R, et al. Identifying critically ill patients at high risk for developing acute renal failure: A
pilot study. Kidney Int 2005;68:2274–2280.
16. Lee Y-J, Chang C-C, Chan JP-W, et al. Prognosis of
acute kidney injury in dogs using RIFLE (Risk, Injury, Failure,
Loss and End-stage renal failure)-like criteria. Veterinary Record
2011;168:264.
17. Mealey KL, Boothe DM. Nephrotoxicosis associated
with topical administration of gentamicin in a cat. J Am Vet
Med Assoc 1994;204:1919–1921.
18. Langston CE. Acute renal failure caused by lily ingestion
in six cats. J Am Vet Med Assoc 2002;220:49–52, 36.
505
19. Gookin JL, Riviere JE, Gilger BC, et al. Acute renal failure in four cats treated with paromomycin. J Am Vet Med Assoc
1999;215:1821–1823, 1806.
20. Worwag S, Langston CE. Acute intrinsic renal failure in
cats: 32 cases (1997–2004). J Am Vet Med Assoc 2008;232:728–
732.
21. Skrifvars MB, Pettila V, Rosenberg PH, et al. A multiple
logistic regression analysis of in-hospital factors related to survival at six months in patients resuscitated from out-of-hospital
ventricular fibrillation. Resuscitation 2003;59:319–328.
22. Fine A, Penner B. The protective effect of cool dialysate is
dependent on patients’ predialysis temperature. Am J Kidney Dis
1996;28:262–265.
23. Lutaif NA, Rocha EM, Veloso LA, et al. Renal contribution to thermolability in rats: Role of renal nerves. Nephrol Dial
Transplant 2008;23:3798–3805.
24. Tveita T, Johansen K, Lien AH, et al. Morphologic
changes in tubular cells from in situ kidneys following experimental hypothermia and rewarming. Apmis 2005;113:13–20.
25. Lameire N. The pathophysiology of acute renal failure.
Crit Care Clin 2005;21:197–210.
26. Medaille C, Trumel C, Concordet D, et al. Comparison of
plasma/serum urea and creatinine concentrations in the dog: A 5year retrospective study in a commercial veterinary clinical
pathology laboratory. J Vet Med A Physiol Pathol Clin Med
2004;51:119–123.
27. Koyama Y, Miyazato T, Tsuha M, et al. Does the high
level of lactate dehydrogenase predict renal function and outcome after renal transplantation from non-heart-beating cadaver
donors? Transplant Proc 2000;32:1604–1605.
28. Korzets Z, Plotkin E, Bernheim J, et al. The clinical
spectrum of acute renal infarction. Isr Med Assoc J 2002;4:781–
784.
29. Huijgen HJ, Sanders GT, Koster RW, et al. The clinical
value of lactate dehydrogenase in serum: A quantitative review.
Eur J Clin Chem Clin Biochem 1997;35:569–579.
30. Lamb EJ, O’Riordan SE, Delaney MP. Kidney function
in older people: Pathology, assessment and management. Clin
Chim Acta 2003;334:25–40.
31. Laluha P, Gerber B, Laluhova D, et al. [Stress hyperglycemia in sick cats: A retrospective study over 4 years]. Schweiz
Arch Tierheilkd 2004;146:375–383.
32. Rand JS, Kinnaird E, Baglioni A, et al. Acute stress
hyperglycemia in cats is associated with struggling and increased
concentrations of lactate and norepinephrine. J Vet Intern Med
2002;16:123–132.
33. Reddan DN, Klassen PS, Szczech LA, et al. White blood
cells as a novel mortality predictor in haemodialysis patients.
Nephrol Dial Transplant 2003;18:1167–1173.
34. Kaysen GA, Eiserich JP. Characteristics and effects of
inflammation in end-stage renal disease. Semin Dial 2003;16:438–
446.