Creatinine Dog

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
163
II. Metabolism of Creatinine in the Dog . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .163
A. Alimentary supply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .163
B. Biosynthesis of creatine and creatinine . . . . . . . . . . . . . . . . . . . . . . . . .163
C. Urinary elimination of creatinine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
III. Plasma Creatinine Measurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
A. Preanalytical factors of variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
1. Specimen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
2. Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
3. Effect of food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
B. Analytical techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
1. Jaffs reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .164
2. Enzymatic reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
C. Reference intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
D. Interindividual factors of variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
1. Sex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
2. Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
3. Weight/muscle mass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
4. Housing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
E. Intraindividual factors of variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
1. Season . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
2. Biological rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
3. Site of blood sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .165
4. Hydration state . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
5. Physical effort . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
F. Effects of drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
1. Damage to the kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
2. Altered renal hemodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
3. Extracellular dehydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .166
IV. Pathologic Variations in Plasma Creatinine Concentration . . . . . . . . . . . . .166
A. Relationship between plasma creatinine and GFR . . . . . . . . . . . . . . .166
B. Effects of experimental reduction of GFR . . . . . . . . . . . . . . . . . . . . . . .167
C. Diagnostic efficiency of plasma creatinine for diagnosis
of chronic renal failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .167
D. Clinical disorders causing increased plasma creatinine
concentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .167
1. Primary renal disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .167
2. Secondary renal disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .167
3. Congenital or familial renal disease . . . . . . . . . . . . . . . . . . . . . .167
4. Urinary tract obstruction or rupture . . . . . . . . . . . . . . . . . . . . . .167
E. Clinical disorders causing decreased plasma creatinine
concentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .168
V. Creatinine Clearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .168
A. Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .168
1. Endogenous creatinine clearance . . . . . . . . . . . . . . . . . . . . . . . .169
2. Exogenous creatinine clearance . . . . . . . . . . . . . . . . . . . . . . . . . .169
B. Analytical variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
C. Reference values . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
D. Interindividual factors of variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
1. Sex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
2. Body weight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
3. Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
4. Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
E. Intraindividual factors of variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
1. Biological rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
2. Hydration state . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
3. Effect of food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
4. Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
F. Pathologic and toxicologic variations . . . . . . . . . . . . . . . . . . . . . . . . . . .171
VI. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
VII. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
Page 162 Veterinary Clinical Pathology Vol. 32 / No. 4 / 2003
Creatinine in the Dog: A Review
J. P. Braun, H. P. Lefebvre, A. D. J. Watson
Creatinine is the analyte most frequently measured in human and veterinary clinical chemistry laboratories as an indirect measure
of glomerular filtration rate (GFR). Although creatinine metabolism and the difficulties of creatinine measurement have been re-
viewed in human medicine, similar reviews are lacking in veterinary medicine. The aim of this review is to summarize information
and data about creatinine metabolism, measurement, and diagnostic significance in the dog. Plasma creatinine originates from the
degradation of creatine and creatine phosphate, which are present mainly in muscle and in food. Creatinine is cleared by glomeru-
lar filtration with negligible renal secretion and extrarenal metabolism, and its clearance is a good estimate of GFR. Plasma and
urine creatinine measurements are based on the nonspecific Jaff reaction or specific enzymatic reactions; lack of assay accuracy
precludes proper interlaboratory comparison of results. Preanalytical factors such as age and breed can have an impact on plasma
creatinine (P-creatinine) concentration, while many intraindividual factors of variation have little effect. Dehydration and drugs
mainly affect P-creatinine concentration in dogs by decreasing GFR. P-creatinine is increased in renal failure, whatever its cause,
and correlates with a decrease in GFR according to a curvilinear relationship, such that P-creatinine is insensitive for detecting mod-
erate decreases of GFR or for monitoring progression of GFR in dogs with severely reduced kidney function. Low sensitivity can be
obviated by determining endogenous or exogenous clearance rates of creatinine. A technique for determining plasma clearance fol-
lowing IV bolus injection of exogenous creatinine and subsequent serial measurement of P-creatinine does not require urine col-
lection and with additional studies may become an established technique for creatinine clearance in dogs. (Vet Clin Pathol.
2003;32:162-179)
2003 American Society for Veterinary Clinical Pathology
Key Words: Clearance, creatinine, dog, renal disease
From the Dpartement des Sciences Biologiques et Fonctionnelles & UMR 181 ENV-INRA Physiopathologie & Toxicologie Exprimentales, Ecole Na-
tionale Vtrinaire, Toulouse Cedex 3, France (Braun, Lefebvre); and the Faculty of Veterinary Science, The University of Sydney, NSW, Australia (Wat-
son). Corresponding author: JP Braun, Dpartement des Sciences Biologiques et Fonctionnelles & UMR 181, Ecole Nationale Vtrinaire, 23 Chemin
des Capelles, 31076 - Toulouse Cedex 3, France (jp.braun@envt.fr).
2003 American Society for Veterinary Clinical Pathology
Review Article
Introduction
Plasma creatinine is the analyte most frequent-
ly measured in human and veterinary clinical
chemistry laboratories as an indirect measure
of glomerular filtration rate (GFR). Some re-
views have dealt with creatinine metabolism
and the difficulties of its measurement in hu-
man medicine.
1-5
In veterinary clinical chem-
istry such reviews are not available, although
summarized information can be found in general text-
books.
6-10
The aim of this review is to summarize infor-
mation and data about the metabolism, measurement,
and diagnostic significance of creatinine in the dog.
a
Metabolism of Creatinine in the Dog
Creatinine is a small molecule (molecular mass 113 dal-
tons) produced by cyclization from creatine phosphate
and creatine (Figure 1). It is highly water soluble (~750
mmol/L, ~85 g/L). Creatine and creatinine originate
mainly from biosynthesis from the amino acids glycine,
arginine, and methionine and partly from alimentary
supply.The latter is more important in carnivores than in
other animals due to the high concentration of creatine
and, to a lesser degree, creatinine in meat.
Alimentary supply
Creatine concentration is high in meat, whereas creati-
nine concentration is about 10 times lower, with values of
30-45 mol/g and 2-4 mol/g, respectively, in raw beef.
11
About 20 to 65% of creatine is transformed to creatinine
by cooking. In commercial food, creatine and creatinine
concentrations are much lower, generally in the 0.5-2.0
mol/g range.
11
Biosynthesis of creatine and creatinine
The first step of the main route of
creatine biosynthesis (Figure 2)
takes place in the kidney, where
transamidination from arginine to
glycine produces guanidinoac-
etate (= glycocyamine). The mito-
chondrial enzyme, arginine:gly-
cine amidinotransferase (AGAT),
is retroinhibited and repressed by
creatine, thus regulating creatine
production. Although AGAT exists
in the liver of some mammals,
such as cattle and humans, it is not detected in canine
liver. N-methylation of guanidinoacetate is catalyzed by
guanidinoacetate methyltransferase (GAMT), using
methyl groups donated by S-adenosylmethionine, lead-
ing to production of creatine, which has no known func-
tion in hepatocytes. Creatine is distributed by blood to
the rest of the body and via a Na
+
/Cl
-dependent trans-
porter penetrates brain and muscle cells where it is re-
versibly phosphorylated to creatine phosphate by crea-
tine kinase. Skeletal muscle contains about 95% of total
body creatine. Plasma creatine filtered by renal
glomeruli undergoes renal tubular reabsorption, so that
urine creatine elimination is weak, except after oral load-
ing.
3,5,6
Creatinine is the product of the spontaneous, irre-
versible, nonenzymatic, internal dehydration of creatine
and dephosphorylation of creatine phosphate. This con-
version to creatinine occurs at an almost constant rate
and affects about 2% of the total pool of body creatine
daily. Endogenous production of creatinine has been es-
timated as 380 45 mol/kg/d in healthy Beagle dogs
having a GFR (mean SD) of 3.3 0.23 mL/min/kg, plas-
ma creatinine (P-creatinine) concentration of 80 12
mol/L, and daily urine creatinine (dU-creatinine) out-
put of 425 45 mol/kg/d.
12
Endogenous creatinine pro-
duction was lower (300 27 mol/kg/d) in dogs with a
60% experimental reduction of renal mass, but was not
correlated clearly with reduced body mass.
12
In humans
with chronic renal failure, it has been reported that some
Braun, Lefebvre, Watson
Vol. 32 / No. 4 / 2003 Veterinary Clinical Pathology Page163
a
All concentrations are expressed in SI units. To convert from SI to conventional units for creatinine concentration, use the calculation: 1 mol/L =
0.113 mg/L = 0.0113 mg/dL; for reverse conversions, use: 1 mg/L = 8.85 mol/L; 1 mg/dL = 88.5 mol/L.
Creatine Phosphate Creatine Creatinine
Figure 1. Structures of creatine phosphate, creatine, and creatinine.
Figure 2. Reactions of creatine and creatinine biosynthesis. AGAT indicates arginine:glycine
amidinotransferase; GAMT, guanidinoacetate methyltransferase; CK, creatine kinase.
creatinine diffuses into the intestine, where it is hy-
drolyzed to creatine, which is partly reabsorbed and
partly degraded by the intestinal flora and excreted in fe-
ces. This process seems to be negligible in dogs, since
more than 95% of administered creatinine is recovered
in urine within 24 hours
12,13
; however, it cannot be ex-
cluded in advanced renal failure.
After endogenous production or exogenous admin-
istration, creatinine diffuses into the total body water
compartment. Its volume of distribution has been vari-
ably estimated as 400-500 mL/kg
13-15
and, more recently,
as 600 mL/kg in healthy dogs and dogs with surgical re-
nal reduction.
12,16
Creatinine has also been found in peri-
toneal fluid, where its concentration was low (<80
mol/L),
17,18
synovial fluid,
19
bronchoalveolar lavage flu-
id,
20
and aqueous and vitreous humors, where its con-
centration was about twice that in serum.
21
Urinary elimination of creatinine
Creatinine in plasma is freely filtered by glomeruli so
that its concentration in glomerular filtrate is the same
as that in plasma. Creatinine is weakly secreted in renal
proximal tubules in dogs,
22-24
especially in males,
25
but
this is of negligible significance,
12,16
even in males with
chronic renal failure (CRF).
26
As the input of creatinine into plasma depends
mainly on muscle mass, urinary elimination of creatinine
is constant over time. In the dog, it was reported various-
ly that there was no difference in creatinine elimination
according to sex
27,28
or that it was higher in males than in
females.
29,30
Urine creatinine (U-creatinine) concentra-
tion did not differ between day and night,
27
but U-creati-
nine was increased
28
or was not increased
30
after meals.
Interindividual variations of U-creatinine are very large,
even in urine collected for 24 hours.
31-33
Total U-creatinine
excretion differs greatly according to studies, with means
ranging from 170 to 425 mol/kg/d.
12,28,29,31,32
These differ-
ences may be due to food composition, as dogs fed a
meat-based diet (31.4% protein) eliminated more creati-
nine than dogs fed a casein-based diet (10.4% pro-
tein),
34,35
but probably also are due to differences in the
accuracy of creatinine measurement (see below). Varia-
tion in U-creatinine concentration is even larger, mainly
due to changes in urine dilution/concentration, and
ranges from 4.7 to 42.0 mmol/L.
27,31,33,36
Plasma Creatinine Measurement
Preanalytical factors of variation
Specimen. Creatinine concentration is about 5-10 mol/L
higher in serum than in plasma of the same animal
(range of values 100-120 mol/L).
37
Stability. In whole blood with or without anticoagu-
lant, creatinine concentration progressively increased at
room temperature, by up to 35% on the 4th day,
37,38
whereas it was stable at 4C.
38
In serum or heparinized
plasma creatinine concentration was stable for up to 4
days at room temperature
37
and up to 3 months at 20C,
and it increased moderately afterwards.
39
Creatinine de-
creased by more than 25% at 20C in serum after 1
month and in EDTA plasma after 1 day.
40
Long-term sta-
bility of creatinine is better with storage at 70C.
39
Effect of food. P-creatinine is increased for the first
few hours and remains increased for up to 12 hours after
meals of raw or cooked meat.
41,42
Following ingestion of
commercial food of undetermined creatine/creatinine
content, increases,
43,44
decreases,
42,45
or no change
46
in P-
creatinine have been reported. Oral loading with crea-
tine for 2-4 weeks caused a dose-dependent increase in
P-creatinine.
47,48
Interindividual differences in postprandial changes
in P-creatinine were significant.
43,44
Postprandial de-
creases in P-creatinine were attributed to protein-in-
duced increases in GFR.
49
The quality and amount of
protein in dog food have no effect on fasting P-creatinine
in healthy dogs and dogs with CRF.
34,50-56
In dogs with ex-
perimental CRF, P-creatinine was unchanged or lower in
dogs fed 3-fatty acids than in dogs fed 6-polyunsatu-
rated fatty acids.
57,58
Analytical techniques
P-creatinine has been measured for many years by the
nonspecific Jaff reaction, which is being replaced pro-
gressively by specific enzymatic techniques that give val-
ues approximately 20 mol/L lower.
44,59,60
Enzymatic tech-
niques have not been validated for canine plasma, but
with human samples they were reported to be more ac-
curate and to allow better interlaboratory compar-
isons.
61,62
Such comparisons remain potentially mislead-
ing
63-65
as, although the creatinine determination in clin-
ical practice is nearly 100 years old, there still is much de-
bate regarding its accuracy.
61
In a recent study in human
clinical pathology, it was reported that inaccuracy in P-
creatinine measurement was as high as 17% around the
upper limit of the reference interval (120 mol/L) and
could reach 30% at higher concentrations.
65
Jaffes reaction. This method is based on the formation
of a yellow-orange chromogen by the action of picrate
ions on creatinine at alkaline pH. The Jaff reagent (pi-
crate ion) also acts on many other substances such as
bilirubin, lipids, and acetoacetate, which cause a nega-
tive bias, and acetone and glucose, which cause a posi-
tive bias.
66,67
Jaffs reaction overestimates P-creatinine
by up to 45% in healthy dogs. Interferences from these
noncreatinine chromogens vary from dog to dog, and,
Creatinine in the Dog
therefore, a correction factorcannot be applied to con-
vert Jaff creatinine measurements to true creatinine
concentration. Interferences are progressively less in
dogs with renal failure, as true creatinine concentration
increases.
68
Hemoglobin interference is negligible at
concentrations
_<
16 g/L.
69
Because interfering substances
are proportionately less abundant in urine than in plas-
ma, results of U-creatinine measurements by Jaffs re-
action were reported not to be overestimated
68
or only
moderately so by an average of 6%.
59
Enzymatic reactions. These methods are based on the
use of creatinine amidohydrolase (= creatininase, EC
3.5.2.10) or of creatinine iminohydrolase (= creatinine
deiminase, EC 3.5.4.21) (Figure 3). Interferences are lim-
ited to bilirubin at concentrations
_>
50 mol/L.
67
Reference intervals
The value of reported P-creatinine reference intervals in
dogs is highly questionnable. Many textbooks report
normal ranges, with no indication of the characteristics
of the population or assay method used. This may ac-
count for the remarkably large overall range of values re-
ported, from 35 to 250 mol/L, including some intervals
that do not even overlap.
70
It is thus recommended not to
use data or thresholds indicated in the literature, but to
compare results with the reference interval of the labo-
ratory or analyzer used.
Interindividual factors of variation
Sex. There is little or no effect of sex on P-creatinine in
dogs, whatever the age.
71-74
Age. Published data regarding the effect of age on P-
creatinine are conflicting. In most studies P-creatinine
decreased in the first days of life, and then was stable up
to 2 months or increased moderately up to 1 year.
75-78
P-
creatinine was stable
72,76
or increased moderately
79
in
adult dogs up to 8-10 years of age, then it decreased,
whereas body weight (BW) remained unchanged (Figure
4).
80,81
No difference was observed in P-creatinine be-
tween dogs aged 0.5-5.0 and 6.0-13.5
years
82
or between dogs less than 1
year old and more than 9 years old.
83
Weight/muscle mass. In new-
borns, P-creatinine was higher in
large dog breeds.
75
In adults P-crea-
tinine increased with the BW of
dogs,
33,43,84
and U-creatinine did as
well,
33
but interindividual variability
was high. P-creatinine was higher in
Greyhounds and other sight
hounds than in other breeds.
85,86
P-
creatinine was reported to be lower
in some cachectic dogs, although no original study is
available.
87
Housing. P-creatinine was moderately higher (5-15
mol/L) in dogs living outside than in kenneled dogs, al-
though their weight and food intake were similar.
88,89
Intraindividual factors of variation
Season. P-creatinine was slightly higher in summer and
autumn than in winter and spring in laboratory Bea-
gles.
90
Biological rhythms. A circadian rhythm was observed
in fasting animals with a moderate increase in P-creati-
nine at 3 PM,
91
whereas others observed no change over
the whole day.
12,46
In dogs sampled at the same time of
the day, an 18% difference was observed between the
peak (acrophase) in midspring to midsummer and the
trough in winter; monthly and weekly rhythmic compo-
nents also were observed.
92
A circadian rhythm also was
observed for U-creatinine, probably mainly due to meals
(Figure 5).
28
Site of blood sampling. P-creatinine was moderately
higher in samples obtained from the jugular vein than
those from the cephalic vein by a mean value of 5
mol/L, which is much lower than the interindividual
variability in samples obtained from the same site.
93
Vol. 32 / No. 4 / 2003 Veterinary Clinical Pathology Page 165
Figure 3. Enzymatic reactions used to measure creatinine concentration.
Figure 4. Variation of P-creatinine according to age in male (o) and
female () dogs; data from Fukuda.
80
Age (years)
0 2 4 6 8 10 12 14
P
-
C
r
e
a
t
i
n
i
n
e

(
m
o
l
/
L
)
80
75
70
65
60
55
50
45
40
35
30
Creatinine amidohydrolase = creatininase (EC 3.5.2.10)
creatinine + H
2
O creatine (creatininase)
creatine + H
2
O urea + sarcosine (creatinase)
sarcosine + H
2
O + O
2
formaldehyde + glycine + H
2
O
2
(sarcosine oxidase)
or
creatine + ATP creatine phosphate + ADP (creatine kinase)
ADP + phosphoenolpyruvate pyruvate + ATP (pyruvate kinase)
pyruvate + NADH,H
+
acetate + NAD
+
(lactate dehydrogenase)
Creatinine iminohydrolase (EC 3.5.4.21)
creatinine + H
2
O N-methylhydantoin + NH
3
Hydration state. Dehydration caused increases of P-
creatinine only when it was greater than 5%.
45
Changes
in P-creatinine were not proportional to dehydration and
showed large interindividual variability.
94
Physical effort. It was reported that P-creatinine was
unchanged in sled dogs after very long races
95
or de-
creased by ~10% in untrained Beagles 8-10 hours after
running for 1 hour.
96
P-creatinine was also decreased in
the 30 minutes following sprints (14-28 km) in well-
trained sled dogs and increased following the same ef-
fort during abatement of training.
97
On the contrary, P-
creatinine was reported to increase about 50% after ex-
haustive exercise in sled dogs.
98
During training, P-crea-
tinine was reported to be unchanged
99
or to be decreased
by a mean of 33%.
97,100
In Greyhounds, P-creatinine was
slightly increased (by ~20 mol/L) after races and re-
mained so for at least 1 hour.
101,102
P-creatinine was mod-
erately increased in dogs after searching for drugs.
82
Effects of drugs
Most drugs affect P-creatinine by reducing GFR through
one of 3 mechanims.
Damage to the kidney. Gentamicin has been reported
to cause no or moderate increases in P-creatinine,
103,104
except when severe damage occurred,
105-108
especially in
dogs with pre-existing renal failure.
109
Similar effects
were observed with platinum derivatives,
110-115
oxytetra-
cycline,
116
high-dose netilmicin and tobramicin (>50
mg/kg for 2 weeks),
117
amphotericin B,
118
calcif-
erol and its derivatives,
119-121
ivermectin in one
case,
122
trimethoprim-sulfadiazine,
123
and
methoxyflurane plus flunixin.
124
Altered renal hemodynamics. Moderate and
transient increases in P-creatinine were ob-
served after treatment with morphine, oxymor-
phone, ketoprofen, carprofen, ketorolac, and
butorphanol
125,126
; others observed no increase
with piroxicam
127
and carprofen.
128
The an-
giotensin-converting enzyme (ACE) inhibitors
captopril and benazepril caused moderate in-
creases in P-creatinine,
129,130
whereas enalapril
had the same effects as a placebo
131-133
or also
caused moderate increases.
134
Cyclosporin
135
and insulin-like growth factor-1 (IGF1)
136
also
caused moderate increases in P-creatinine, but
cyclosporin was reported to have no effect on P-
creatinine in another case.
137
Paradoxically,
growth hormone treatment, which induces an
increase of IGF1, caused a moderate decrease
in P-creatinine.
138
Extracellular dehydration. Prerenal kidney
insufficiency caused by furosemide in dogs
with heart failure,
130
digoxin,
74
and intraperi-
toneal administration of iodinated povidone-iodine
139
were reported to cause increases of P-creatinine.
Glucocorticoids
140
caused a moderate decrease of P-
creatinine in normal dogs, but not in dogs with hypoad-
renocorticism.
141
Ethionine also has been reported to
cause a moderate decrease of P-creatinine.
142
The mech-
anisms by which glucocorticoids and ethionine affect P-
creatinine are unknown.
Pathologic Variations in P-Creatinine
Relationship between P-creatinine and GFR
When P-creatinine and GFR were determined indepen-
dently (ie, not by endogenous creatinine clearance), the
relationship was hyperbolic,
143-145
exponential,
53,146-148
or
curvilinear
149
(Figure 6). A similar relationship can also
be derived from GFR measured by exogenous creatinine
clearance.
150
The shape of the curve and the dispersion of values
have several consequences. At both ends, a large varia-
tion of one variable corresponds to a very small change
in the other, which means that a reduction of GFR from
3.5 to 2.5 mL/min/kg has little effect on P-creatinine and
that a large decrease of P-creatinine from 500 to 300
mol/L (5.7 to 3.4 mg/dL) corresponds to only a minor
increase in GFR. Interindividual variations are so large
that the same P-creatinine concentration can correspond
to normal or reduced GFR.
Time of Day (h)
0 4 8 12 16 20 24
U
-
C
r
e
a
t
i
n
i
n
e

(
m
o
l
/
k
g
/
4
h
)
60
55
50
45
40
Time of Day (h)
0 4 8 12 16 20 24
U
-
C
r
e
a
t
i
n
i
n
e

(
m
m
o
l
/
L
)
15
10
5
Figure 5. Circadian variations of U-creatinine (total amount excreted per 4
hours and concentration) in canine urine (meals at 8 and 20 h) in male (o) and
female () Beagle dogs.
28
Effects of experimental reduction of GFR
Reduction of renal function by surgery or by injection of
microspheres produces a simultaneous increase in P-
creatinine and decrease in creatinine clearance. The ef-
fects are more intense during the first days, then com-
pensatory hypertrophy of the remaining kidney tissue
causes a decrease and stabilization of P-creatinine,
151-154
which is not attributable to the reduction in muscle mass
of the dogs(Figure 7).
153
For instance, a reduction of renal
mass by 3/4 to 7/8 caused a 1.5- to 2-fold increase in P-
creatinine
109,155-157
and a simultaneous decrease in mean
creatinine clearance from 3.5 to 1.3 mL/min/kg
109
; about
a 60% reduction of kidney mass caused a 2-fold increase
in P-creatinine,
12,158
and a 50% reduction of renal mass
produced no change in P-creatinine for 4 years, regard-
less of the amount of protein in the diet, in dogs aged 7
years at the beginning of the study.
159
Diagnostic efficiency of P-creatinine for diagnosis
of chronic renal failure
The diagnostic efficiency of increases in P-creatinine for
the diagnosis of CRF has been evaluated in only one
study,
144
the criterion for CRF being GFR 2 mL/min/kg
(Table 1). If the predictive values of positives (PVP) and
negatives (PVN) are calculated from these data, it can be
observed that the diagnostic efficiency of P-creatinine is
relatively limited. For instance, at the 150 mol/L (1.7
mg/dL) threshold, a pretest probability of .5 leads to a
PVP of .86 and a PVN of .76 (Figure 8). It is generally con-
sidered that at least ~75% of nephrons must be nonfunc-
tional before P-creatinine is increased above the upper
limit of the reference interval.
P-creatinine is efficient for monitoring the progres-
sion of CRF
160
or the efficiency of a treatment, eg, he-
modialysis
161
; the critical difference has been estimated
to be 35 mol/L (0.4 mg/dL) in the range of normalval-
ues.
162
In dogs with CRF, P-creatinine increased progres-
sively with time, but interindividual variability was
marked, and in some dogs P-creatinine was a poor pre-
dictor of change in GFR.
163
Time of death can be estimat-
ed from the point where the regression line of 1/P-crea-
tinine vs. time intercepts the time axis.
160
P-creatinine is more efficient than plasma urea con-
centration for the diagnosis of CRF.
148
In dogs with spon-
taneous or surgically-induced CRF, the correlation be-
tween plasma concentrations of urea and creatinine was
reported to be high
89,149,164-167
or low.
168
P-creatinine varia-
tions correlated well with the concentration of plasma
cystatin C, a small protein that is eliminated only by
glomerular filtration.
43,169-171
In human medicine, equations are proposed to esti-
GFR (mL/min/kg)
0 1 2 3 4
P
-
C
r
e
a
t
i
n
i
n
e

(
m
o
l
/
L
)
1100
1000
900
800
700
600
500
400
300
200
100
0
Time (weeks)
P
-
C
r
e
a
t
i
n
i
n
e

(
m
o
l
/
L
)
Figure 6. Variations of P-creatinine according to GFR in healthy dogs
and dogs with chronic renal failure. Larger dots, experimental data
from 75 dogs in which GFR was estimated by the clearance of in-
ulin or of iodine
143,146,147
; smaller dots, GFR estimated by exogenous
creatinine clearance.
145
Figure 7. Variations in P-creatinine in dogs with experimental
chronic renal failure (surgery at time 0) fed a maintenance diet (,
44% protein) or reduced protein diets (o, 8.2%; , 17.2%).
152,153
300.0
250.0
200.0
150.0
100.0
50.0
0.0
Table 1. Sensitivity and specificity of P-creatinine at different thresh-
olds for the diagnosis of chronic renal failure (GFR
_<
2 mL/min/kg) in
the dog. The reference interval for the method used in this study was
124 28 mol/L (range 71-193) (data from Gleadhill
144
).
Threshold Plasma Creatinine Concentration (mol/L)
>110 >130 >150 >170
Sensitivity 0.95 0.84 0.72 0.58
Specificity 0.46 0.60 0.89 0.97
0 8 16 24 32 40
mate GFR from P-creatinine, sex, and age. In the dog, an
equation relating GFR and 1/P-creatinine was calculated
but not advocated to derive GFR from P-creatinine: GFR
= 227(1/P-creatinine) [recalculated from the original
data to accommodate SI units: P-creatinine as mol/L,
GFR as mL/min/kg], with a 95% confidence interval of
0.5 mL/min/kg.
145
This equation is very similar to the one
calculated from data of Westhoff et al
146,147
and Haller et
al
143
: GFR = 246(1/P-creatinine) 0.1.
Clinical disorders causing increased P-creatinine
P-creatinine is increased in both acute and chronic renal
failure, whatever the cause, but one cannot differentiate
between them.
172,173
More or less severe increases in P-
creatinine have been reported in various percentages of
dogs with urinary disorders.
Primary renal disease. P-creatinine is increased in pri-
mary renal diseases such as amyloidosis,
160,174
polycystic
disease,
175
glomerulosclerosis,
160
and postoperative ure-
mic crisis,
176
and in intoxications by sodium arsenate,
177
citrinin,
178
sodium fluoride,
179
and vitamin D and its
analogs.
180,181
P-creatinine was reported to decrease pro-
gressively after kidney grafts
182
and to be increased dur-
ing rejection episodes, when very high concentrations
could occur (>800 mol/L).
183-187
Secondary renal disease. Underlying disorders causing
secondary renal disease and subsequent increases in P-
creatinine include babesiosis,
166,188,189
leishmaniasis,
190-194
leptospirosis,
195-198
borreliosis,
199-200
trypanosomiasis,
201,202
heartworm disease,
203
encephalitozoonosis,
204
malignant
histiocytosis,
205
pyometra,
206-209
experimental intestinal
obstruction,
210
gastric dilatation/torsion,
211
diabetes mel-
litus,
212,213
and hypercalcemia caused by hyperparathy-
roidism
214
or lymphoma.
215
The magnitude of increase in
P-creatinine differed greatly according to the severity of
the underlying disorder.
Congenital or familial renal disease. Progressive in-
creases of P-creatinine were observed in young dogs
with congenital or familial renal disease, including
Samoyeds with hereditary nephritis,
216,217
Bernese
Mountain dogs with congenital renal dysplasia,
218
Soft-
coated Wheaten Terriers,
219,220
Bull Terriers and Samoyeds
with a condition resembling Alport syndrome,
221,222
New-
foundland dogs with glomerulosclerosis,
223
Cocker
Spaniels with familial nephropathy
,224
and Greyhounds
with glomerular vasculopathy.
225
Idiopathic increases in
P-creatinine also have been observed in different groups
of dogs up to 3 years of age.
226,227
P-creatinine was mod-
erately increased in 4 of 10 dogs with Fanconi syn-
drome.
228
Urinary tract obstruction or rupture. Ureteral obstruc-
tions
161
and bladder rupture
18
result in increased P-crea-
tinine. In the latter, creatinine concentration was higher
in peritoneal fluid than plasma, allowing identification of
the fluid as urine.
Clinical disorders causing decreased P-creatinine
A moderate decrease in P-creatinine was reported in
80% of dogs with portosystemic shunts
229
or dogs with a
surgically placed portocaval shunt,
230
whereas it was un-
changed in dogs after surgical portocaval anastomosis
associated with periarterial neurectomy.
.231
A decrease
also was noted in early babesiosis.
232
Creatinine Clearance
Because the input of creatinine into plasma is almost
constant over time and creatinine is excreted by glom-
erular filtration with only negligible renal tubular secre-
tion or extrarenal metabolism, urine creatinine clearance
is almost equal to GFR (see a critical review in animals by
Reder et al
233
). This may also be true for plasma creati-
nine clearance.
12
Techniques
Creatinine clearance, ie, the volume of plasma cleared of
creatinine per minute, can be evaluated in several ways
Figure 8. Predictive values of positives (PVP) and of negatives (PVN)
of P-creatinine for the diagnosis of chronic renal failure in the dog
according to pretest probability and thresholds of decision (in
mol/L), calculated from data from Gleadhill.
144
PVP and PVN are the
conditional probabilities that an animal testing positive/negative at a
given threshold of decision is truly diseased/nondiseased according
to the pretest probability that the animal had/did not have the dis-
ease for which the test was used.
Pretest Probability
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
P
V
P

(
)

/

P
V
N

(
-
-
)
1.00
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
(see a general discussion by Heiene and Moe
234
).
Endogenous creatinine clearance. Endogenous clear-
ance is determined by measuring both the total amount
of endogenous creatinine eliminated in urine over a pe-
riod of time and the P-creatinine. The determination of
endogenous creatinine clearance requires measurement
of both plasma and urine creatinine concentrations and
the exact volume of urine eliminated over periods of
time ranging from 20 min to 24 h, depending on the
method.
235,236
Exogenous creatinine clearance. The clearance of ex-
ogenous creatinine can be evaluated after administration
of a precisely known amount of creatinine by bolus SC,
IM, or IV or during IV infusion of creatinine. It can also
be determined from repeated P-creatinine measurement
after IV administration (Figure 9).
12
Analytical variability
It has been reported that results of endogenous creati-
nine clearance were lower than those of urine/plasma
exogenous creatinine clearance when creatinine concen-
trations were measured by Jaffs reaction. This likely oc-
curred because the overestimation of P-creatinine is pro-
portionately lower after exogenous infusion of creati-
nine,
59,237
unless assay methods unaffected by interfering
substances were used, such as enzymatic procedures.
59,68
Results of urine/plasma exogenous creatinine
clearance do not depend on P-creatinine when
values range from 220 to 430 mol/L
237
or when
administered doses range from 40 to 160 mg/kg.
12
Exogenous urine/plasma creatinine clear-
ance is almost equal to urinary inulin clearance,
which is the reference method for GFR determi-
nation
12,59,237-239
and to the clearances of other trac-
ers of GFR:
99m
Tc-DTPA (diethylaminopen-
taacetic acid),
240
iohexol,
241,242 51
Cr-EDTA,
84
and io-
thalamate.
12
Exogenous clearance is moderately
lower than inulin clearance at low urine volumes
of <20 L/min/kg.
243
Repeatability of creatinine clearance mea-
surements was estimated to be good to fair, as
the 95% confidence interval of the difference be-
tween repeated measurements ranged from 2.9
to 2.7 mL/min/kg
244
or was 13.0 12.6%.
16
Proce-
dures involving urine collection are more chal-
lenging because they require either indwelling
catheterization of the bladder and rinsing proce-
dures or the use of metabolic cages, in which
spillage or contamination may occur. The plasma
clearance technique has the advantage of not re-
quiring the fastidious collection of urine and may
become, as data on additional dogs with wide
ranges of GFR are accumulated, an established
technique for creatinine clearance in dogs.
Reference values
Values of creatinine clearance are generally expressed as
mL/min/kg, which may not be optimal because it has
been demonstrated that GFR (urinary inulin clearance
as mL/min/kg) was a decreasing function of BW in
healthy dogs,
143
and variability of urine creatinine clear-
ance expressed per square meter was lower than when
expressed per kg BW
245
or was identical in dogs less than
20 kg BW.
246
However, BW can be measured accurately,
whereas corporal surface is calculated. The main results
of a previous review
209
of creatinine clearance are pre-
sented in Table 2.
Interindividual factors of variation
Substantial interindividual differences have been ob-
served.
247
Sex. Creatinine clearance was the same in males and
females.
237
Body weight. A positive correlation was observed be-
tween the weight of a dog and endogenous creatinine
clearance (mL/min/dog).
84
Age. Creatinine clearance has not been reported in
very young puppies, although inulin clearance increased
Figure 9. Determination of plasma exogenous creatinine clearance. Plasma
exogenous creatinine clearance is calculated from the exact IV dose delivered
and the area under the curve (AUC) of P-creatinine vs. time: Creatinine clear-
ance = dose/ AUC.
12
Dose is known from injection (eg, 272 mol/kg). AUC is
calculated as the sum of the areas of each individual trapezoid making up the
total area [eg, shaded area in figure: 416 mol/L and 300 mol/L at 60 and
120 min, respectively; the area of the trapezoid is: (120 60)(416 +300) / 2
= 21,480 min.mol/L; sum of 8 trapezoids: 127,435 min.mol/L]. Thus, crea-
tinine clearance = 272/127,435 = 0.0021 L/min/kg = 2.1 mL/min/kg.
Time (min)
0 200 400 600
P
-
C
r
e
a
t
i
n
i
n
e

(
a
t

t
i
m
e

t
i
-

b
a
s
a
l

c
o
n
c
e
n
t
r
a
t
i
o
n
)
(
m
o
l
/
L
)
2000
1500
1000
500
0
Table 2. Reported endogenous and exogenous creatinine clearance measurements in dogs.
Endogenous Creatinine Clearance
Animals
Clearance Technique
Special Conditions Mean SD Reference

25 dogs, 2045 determinations over 7 years 94 36 mL/min/m
2
247
7 dogs 86 4 mL/min/m
2
68
6 adult F Beagle dogs, 5.7-12.7 kg 2 times 24 h, metabolic cage, no food 2.9 0.23* mL/min/kg 155
5-6 M/F Beagle dogs, 9.3-3.5 kg 3 times 20 min Dehydrated 2.15 0.09* mL/min/kg 238
Euhydrated 2.66 0.14* mL/min/kg
Hyperhydrated 2.94 0.12* mL/min/kg
3 M + 3 F Beagle dogs, 2.8 0.4 kg 48 h, metabolic cage 9 wks old 4.05 0.61 mL/min/kg 248
13 wks old 4.43 0.51 mL/min/kg
27 wks old 2.49 0.10 mL/min/kg
10 dogs, 0.5-8 yrs old, 5-35 kg 24 h, metabolic cage 3.12 0.85 mL/min/kg 249
Not specified 24 h, metabolic cage 2.96 0.48 mL/min/kg 237
36 F dogs, 6-12 mos old, 7-11 kg 24 h, metabolic cage 3.77 0.77 mL/min/kg 250
57.6 9.3 mL/min/m
2
9 M + 2 F dogs 24 h, metabolic cages 2.34 0.83* mL/min/kg 59
10 dogs 2 times 20 min 48.3 9.5 mL/min/m
2
251
26 M dogs, 18.1 7.5 kg 20 min 2.93 0.96 mL/min/kg 252
60.6 21.9 mL/min/m
2
30 M + 18 F dogs, 22 2.6 kg 2 times 30 min 4.10 0.14* mL/min/kg 244
11 M + 12 F dogs, 7-13 kg 6 times 4 h 2.6 0.6 mL/min/kg 28
7 M + 9 F dogs 6 times 4 h 2.6 0.7 mL/min/kg 32
Exogenous Creatinine Clearance
Animals
Clearance Technique
Special Conditions Mean SD Reference

6 F Beagle dogs, 9.5-17.5 mos old Water loading, IV constant infusion, 4.35 0.26 mL/min/kg 245
3 times 10 min 94.6 3.95 mL/min/m
2
3 M + 28 F dogs, 7-8 yrs old Bolus + IV constant infusion 18% protein diet 3.25 0.23* mL/min/kg 153
35% protein diet 3.12 0.16* mL/min/kg
5 M + 5 F dogs, 7.7-20.4 kg SC, 100 mg/kg, 3 times 20 min 4.08 0.50 mL/min/kg 237
8 F dogs, 12.0-17.5 kg PO, 8.8 mmol in 50 mL water, 14 mmol Na/kg food 4.89 0.83 mL/min/kg 243
3 times 20 min after 1 h 2 mmol Na/kg food 4.13 0.51 mL/min/kg
8 M + 22 F dogs, 14.8 4.5 kg IV, 88 mg/kg, 3 times 30 min 3.45 0.7 mL/min/kg 16
5-6 M/F Beagle dogs, 9.3-13.5 kg IV, 875 mg Dehydrated 2.78 0.06* mL/min/kg 238
Euhydrated 3.64 0.10* mL/min/kg
Hyperhydrated 4.14 0.20* mL/min/kg
6 M Beagle dogs, 9.4-14.0 kg 24 h, metabolic cage 40 mg/kg 2.5 0.42 mL/min/kg 12
80 mg/kg 3.0 0.37 mL/min/kg
160 mg/kg 3.4 0.70 mL/min/kg
Determination from plasma 40 mg/kg 3.0 0.44 mL/min/kg
80 mg/kg 2.9 0.31 mL/min/kg
160 mg/kg 3.0 0.52 mL/min/kg
* Variance is expressed as standard error rather than SD.
M indicates male; F, female; IV, intravenous; PO, per os; SC, subcutaneous.
progressively during the first 2 months of life.
248,253
Crea-
tinine clearance steadily decreased (by approximately
50%) in puppies aged 2 to 7 months, when values were
approximately the same as in adults.
254
Clearance did not
change over 4 years in 7 to 8-year-old dogs fed an 18% or
35% protein diet.
159
Nutrition. Creatinine clearance was lower in dogs
with reduced renal function fed low-protein diets than in
dogs fed high-protein diets
228
or was reported to be un-
affected by dietary protein content
52,54
or by the source of
proteins
255
in healthy dogs and dogs with renal failure.
Creatinine clearance decreased in dogs with renal re-
duction fed 6-fatty acids and not in dogs fed 3-
polyunsaturated fatty acids.
57,58,256
Creatinine clearance
was about 15% higher in dogs receiving 14 mmol sodi-
um/kg food than in dogs receiving 2 mmol/kg.
243
Intraindividual factors of variation
Biological rhythms. Urinary creatinine clearance is rela-
tively stable over time as repeated measurements for 6
years in the same female dogs had a 95% confidence in-
terval of 18 mL/min/m
2
and repeated measurements
for 4 consecutive days had a coefficient of variation of
10%.
50,247
There was no circadian variation of creatinine
clearance.
28,32
Hydration state. Exogenous and endogenous creati-
nine clearances were lower (~15%) in 10%-dehydrated
than in normally hydrated dogs, in which it was lower
(~15%) than in hyperhydrated dogs (dogs given 30 mL/kg
oral water).
238
Effect of food. Creatinine clearance was the same in
fed (~45% protein) and unfed dogs, except in 3 cases
where clearance was increased by 10%.
257
It was moder-
ately higher in the 4 hours following a morning meal.
28,32
Anesthesia. Creatinine clearance was approximately
1/3 lower in dogs anesthetized with thiopental/halo-
thane than in awake dogs.
250
Pathologic and toxicologic variations
In remnant kidney models, creatinine clearance was de-
creased and then progressively increased and stabilized
as compensatory hypertrophy of the remaining neph-
rons occurred.
Creatinine clearance was reduced by approximately
20% following repeated urography with iothalamate.
251
It
was also decreased in dogs treated with cisplatin,
112,113
amphotericin B,
118
and gentamicin.
103
Creatinine clear-
ance was reported to be very low just after renal trans-
plantation, then to progressively increase as animals re-
covered, or to remain low if animals experienced rejec-
tion.
258
Creatinine clearance was decreased by approxi-
mately 1/4 in dogs injected with endothelin-1.
259
Creatinine clearance was reported to be low in dogs
poisoned by sodium arsenate
177
and in pyometra
206
and
hypercalcemia of malignancy.
215
It also was reported to
be unchanged after adenoviral delivery of genes into the
kidneys.
260
Summary
Plasma creatinine concentration is the best routine indi-
rect marker of GFR in dogs. However, analytical meth-
ods, age, body weight, and timing of meals can signifi-
cantly affect results and should be taken into account
when interpreting results, especially when vaues ap-
proach the lower and upper limits of reference intervals.
Creatinine clearance is a better indicator of GFR than P-
creatinine, but its measurement should be limited to sit-
uations in which history, physical examination, and rou-
tine biochemical results are ambiguous.
References
1. Spencer K. Analytical reviews in clinical biochemistry: the es-
timation of creatinine. Ann Clin Biochem. 1986;23:1-25.
2. Houot O. Creatinine. In: Siest G, Henny J, Schiele F, eds.
Rfrences en biologie clinique. Amsterdam, Elsevier; 1990:233-
260.
3. Narayanan S, Appleton HD. Creatinine: a review. Clin Chem.
1980;26:1119-1126.
4. Perrone RD, Madias NE, Lewey AS. Serum creatinine as an in-
dex of renal function: new insights into old concepts. Clin
Chem. 1992;38:1933-1953.
5. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metab-
olism. Physiol Rev. 2000;80:1107-1203.
6. Finco DR. Kidney function. In: Kaneko JJ, Harvey JW, Bruss
ML, eds. Clinical Biochemistry of Domestic Animals. 5th ed. San
Diego, CA: Academic Press; 1997:441-484.
7. Finco DR. Evaluation of renal functions. In: Osborne CA, Fin-
co DR, eds. Canine and Feline Nephrology and Urology. Balti-
more, MD: Williams & Wilkins; 1995:216-229.
8. DiBartola SP. Clinical approach and laboratory evaluation of
renal disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Vet-
erinary Internal Medicine. 5th edition. Philadelphia, PA: WB
Saunders; 2000;1600-1614.
9. Bush BM. Interpretation of Laboratory Results for Small Animal
Clinicians. Oxford: Blackwell Scientific; 1991:234-238.
10. Duncan JR, Prasse KW, Mahaffey EA. Veterinary Laboratory
Medicine, Clinical Pathology. 3rd ed. Ames, IA: Iowa State Uni-
versity Press; 1994:179-181.
11. Harris RC, Lowe JA, Warnes K, Orme CE.The concentration of
creatine in meat, offal and commercial dog food. Res Vet Sci.
1997;62:58-62.
12. Watson ADJ, Lefebvre HP, Concordet D, et al. Plasma exoge-
nous creatinine clearance test in dogs: comparison with other
methods and proposed limited sampling strategy. J Vet Intern
Med. 2002;16:22-33.
13. Greenberg J, Schwartz IL, Spinner M, Silver L, Starr N. Ap-
parent volumes of distribution of p-aminohippurate and cre-
atinine in the dog. Am J Physiol. 1952;168:86-92.
14. Sapirstein LA, Vidt DG, Mandel MJ, Hanusek G. Volume of
distribution of intravenously injected creatinine in the dog.
Am J Physiol. 1955;181:330-336.
15. Schloerb PR. Total body water distribution of creatinine and
urea in nephrectomized dogs. Am J Physiol. 1960;199:661-665.
16. Labato MA, Ross LA. Plasma disappearance of creatinine as a
renal function test in the dog. Res Vet Sci. 1991;50:253-258.
17. Bjorling DE, Latimer KS, Rawlings CA, Kolata RJ, Crowe DT.
Diagnostic peritoneal lavage before and after abdominal
surgery in dogs. Am J Vet Res. 1983;44:816-820.
18. Burrows CF, Bove KC. Metabolic changes due to experimen-
tally induced rupture of the canine urinary bladder. Am J Vet
Res. 1974;35:1083-1088.
19. Damyanovich AZ, Staples JR, Marshall KW. 1H NMR investi-
gation of changes in the metabolic profile of synovial fluid in
bilateral canine osteoarthritis with unilateral joint denerva-
tion. Osteoarthritis Cartilage. 1999;7:165-172.
20. Maden M, Altunok V, Birdane FM, Aslan V, Nizamlioglu M.
Specific enzyme activities in bronchoalveolar lavage fluid as
an aid to diagnosis of tracheobronchitis and bronchopneumo-
nia in dogs. Res Vet Sci. 2001;71:141-145.
21. Hanna PE, Bellamy JEC, Donald A. Postmortem eyefluid
analysis in dogs, cats and cattle as an estimate of antemortem
serum chemistry profiles. Can J Vet Res. 1990;54:487-494.
22. OConnell JMB, Romeo JA, Mudge GH. Renal tubular secre-
tion of creatinine in the dog. Amer J Physiol. 1962;203:985-990.
23. Shannon JA, Jolliffe N, Smith HW.The excretion of urine in the
dog. VI. The filtration and secretion of creatinine. Am J Physiol.
1932;102:534-550.
24. Swanson RE, Hakim AA. Stop-flow analysis of creatinine ex-
cretion in the dog. Am J Physiol. 1962;203:980-984.
25. Robinson T, Harbison M, Bove KC. Influence of reduced re-
nal mass on tubular secretion of creatinine in the dog. Am J Vet
Res. 1974;35:487-491.
26. Finco DR, Brown SA, Crowell WA, Barsanti JA. Exogenous cre-
atinine clearance as a measure of glomerular filtration rate in
dogs with reduced renal mass. Am J Vet Res. 1991;52:1029-1032.
27. McCaw DL, Knapp DW, Hewett JE. Effect of collection time
and exercise restriction on the prediction of urine protein ex-
cretion, using urine protein/creatinine ratio in dogs. Am J Vet
Res. 1985; 46:1665-1669.
28. Uechi M, Terui H, Nakayama T, Mishina M, Wakao M, Taka-
hashi M. Circadian variation of urinary enzymes in the dog. J
Vet Med Sci. 1994;56:849-854.
29. Grtner K, Reulecke W, Hackbarth H, Wollnik F. Zur Ab-
hngigkeit von Muskelmasse und Korpergrsse im Vergleich
von Maus, Ratte, Kaninchen, Hund, Mensch und Pferd [Com-
parison of the regression between muscle mass and body
weight in the mouse, rat, rabbit, dog, human and horse]. Dtsch
Tierrztl Wschr. 1987;94:52-53.
30. Jergens AE, McCaw DL, Hewett JE. Effects of collection time
and food consumption on the urine protein/creatinine ratio in
the dog. Am J Vet Res. 1987;48:1106-1109.
31. Barsanti JA, Finco DR. Protein concentration in urine of nor-
mal dogs. Am J Vet Res. 1979;40:1583-1588.
32. Uechi M, Uechi H, Nakayama T, Wakao Y, Takahashi M. The
variation of excretory urinary glycyl-prolyl dipeptidyl
aminopeptidase in dogs. Res Vet Sci. 1997;63:97-99.
33. Center SA, Wilkinson E, Smith CA, Lewis RM. 24-hour urine
protein/creatinine ratio in dogs with protein-losing nephro-
pathies. J Am Vet Med Assoc. 1985;187:820-824.
34. Bartges JW, Osborne CA, Felice LJ, et al. Diet effect on activi-
ty product ratios of uric acid, sodium urate, and ammonium
urate in urine formed by healthy Beagles. Am J Vet Res.
1995;56:329-333.
35. Bartges JW, Osborne CA, Felice LJ, Unger LK, Chen M. Influ-
ence of allopurinol and two diets on 24-hour urinary excre-
tions of uric acid, xanthine, and ammonia by healthy dogs. Am
J Vet Res. 1995;56:595-599.
36. Iversen L, Petersen TK, Koch J, Hoier R, Jensen AL. Urinens
creatinindhold som indledende klinisk patologisk markor for
Cushings syndrom hos hunde [Application of urinary creati-
nine concentration to the initial clinical pathological examina-
tion of dogs suspected of having hyperadrenocorticism]. Dan-
sk Vet Tidsskr. 1997;80:778-781.
37. Thoresen SI, Havre GN, Morberg H, Mowinckel P. Effects of
storage time on chemistry results from canine whole blood,
serum and heparinized plasma. Vet Clin Pathol. 1992;31:88-94.
38. Fontaine M, Hamelin N, Paradis M. Stabilit des paramtres
plasmatiques sanguins en fonction du temps, des conditions
dentreposage et de transport chez le chien [Effects of time,
storage conditions and mailing on the stability of canine blood
parameters]. Med Vet Quebec. 1986;16:157-164.
39. Thoresen SI, Tverdal A, Havre GN, Morberg H. Effects of stor-
age time and freezing temperature on clinical chemical para-
meters from canine serum and heparinized plasma. Vet Clin
Pathol. 1995;24:129-133.
40. Fernandes ST, Teixeira MN, Santos ES. Influencia da tempara-
tura e do tempo de armazenamento nas dosagens bioquimi-
cas de ureia e creatininina em soro ou plasma caninos [Effect
of temperature and storage time on urea and creatinine mea-
surement in canine seum or plasma]. Arq Bras Med Vet Zootec.
2001;53:648-651.
41. Watson ADJ, Church DB. Postprandial increase in plasma cre-
atinine concentration in dogs fed cooked meat. Aust Vet J. 1980;
56:463.
42. Watson ADJ, Church DB, Fairburn AJ. Postprandial changes in
plasma urea and creatinine concentrations in dogs. Am J Vet
Res. 1981;42:1878-1880.
43. Perxachs A. Cystatine C plasmatique chez le chien. Etude prlimi-
naire [Thse Doctorat Vtrinaire]. Toulouse: Universit Paul
Sabatier; 2000.
44. Evans GO. Post-prandial changes in canine plasma creatinine.
J Small Anim Pract. 1987;28:311-315.
45. English PB, Filippich LJ, Thompson HL. Clinical assessment of
renal function in the dog with a reduction in nephron number.
Aust Vet J. 1980;56:305-312.
46. Epstein ME, Barsanti JA, Finco DR, Cowgill IM. Postprandial
changes in plasma urea nitrogen and plasma creatinine con-
centrations in dogs fed commercial diets. J Am Anim Hosp As-
soc. 1984;20:779-782.
47. Lowe JA, Murphy M, Nash V. Changes in plasma and muscle
creatine concentration after increases in supplementary di-
etary creatine in dogs. J Nutr. 1998;128:2691S-2693S.
48. Harris RC, Lowe JA. Absorption of creatine from meat or oth-
er dietary sources by the dog. Vet Rec. 1995;137:595.
49. OConnor WJ, Summerhill RA. The effects of a meal of meat
on glomerular filtration rate in dogs at normal urine flows. J
Physiol (Lond). 1976;256:81-91.
50. Bove KC, Kronfeld DS, Ramberg C, Goldschmidt M. Long-
term measurement of renal function in partially nephrec-
tomized dogs fed 56, 27 or 19% protein. Invest Urol. 1979;16:378-
384.
51. Bove KC. High dietary protein intake does not cause pro-
gressive renal failure in dogs after 75% nephrectomy or aging.
Semin Vet Med Surg Small Anim. 1992;7:227-236.
52. Hansen B, DiBartola SP, Chew DJ, Brownie C, Nagode L. Clin-
ical and metabolic findings in dogs with chronic renal failure
fed two diets. Am J Vet Res. 1992;53:326-334.
53. Polzin DJ, Osborne CA, Hayden DW, Stevens JB. Effects of a
modified protein diet in dogs with chronic renal failure. J Am
Vet Med Assoc. 1983;183:980-986.
54. Polzin DJ, Osborne CA, Lilich JP. Effects of dietary
protein/phosphate restriction in normal dogs and dogs with
chronic renal failure. J Small Anim Pract. 1991;32:289-295.
55. Polzin DJ, Osborne CA, Stevens JB, Hayden DW. Influence of
modified protein diets on electrolyte, acid base, and divalent
ion balance in dogs with experimentally induced chronic re-
nal failure. Am J Vet Res. 1982;43:1978-1986.
56. Polzin DJ, Osborne CA, Stevens JB, Hayden DW. Influence of
modified protein diets on the nutritional status of dogs with
induced chronic renal failure. Am J Vet Res. 1983;44:1694-1702.
57. Brown SA, Brown CA, Crowell WA, et al. Effects of polyunsat-
urated fatty acid supplementation in early renal insufficiency
in dogs. J Lab Clin Med. 2000;135:275-286.
58. Brown SA, Brown CA, Crowell WA, et al. Beneficial effects of
chronic administration of dietary omega-3 polyunsaturated
fatty acids in dogs with renal insufficiency. J Lab Clin Med.
1998;131: 447-455.
59. Finco DR, Tabaru H, Brown SA, Barsanti JA. Endogenous cre-
atinine clearance measurement of glomerular filtration rate in
dogs. Am J Vet Res. 1993;53:1575-1578.
60. Jung K, Wesslau C, Priem F, Schreiber G, Zubek A. Specific
creatinine determination in laboratory animals using the new
enzymatic test kit creatinine-PAP. J Clin Chem Clin Biochem.
1987;25:356-361.
61. Blijenberg BG, Brouwer HJ, Kuller TJ, Leeneman R, van
Leeuwen CJM. Improvements in creatinine methodology: a
critical assessment. Eur J Clin Chem Clin Biochem. 1994;32:529-
537.
62. Blijenberg BG, Brouwer RJ, Baadenhuiksen H, Boerma GJM.
Creatinine and surveys: an assessment. Eur J Clin Chem Clin
Biochem. 1995;33:855-858.
63. Whelton A, Watson AJ, Rock RC. Nitrogen metabolites and re-
nal function. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of
Clinical Chemistry. 2nd ed. Philadelphia, PA: WB Saunders;
1994:1513-1575.
64. Hanser AM, Hym B, Michotey O, et al. Comparaison des
mthodes de dosage de la cratinine srique [Comparison of
methods for serum creatinine measurement]. Ann Biol Clin.
2001;59:737-742.
65. Lawson N, Lang T, Broughton A, Prinsloo P,Turner C, Marenah
C. Creatinine assays: time for action? Ann Clin Biochem. 2002;
39:599-602.
66. Jacobs RM, Lumsden JH, Grift E. Effects of bilirubinemia, he-
molysis, and lipemia on clinical chemistry analytes in bovine,
canine, equine, and feline sera. Can Vet J. 1992;33:605-608.
67. Jacobs RM, Lumsden JH, Taylor JA, Grift E. Effects of interfer-
ents on the kinetic Jaff reaction and an enzymatic colorimet-
ric test for serum creatinine concentration determination in
cats, cows, dogs and horses. Can J Vet Res. 1991;55:150-154.
68. Balint P, Visy M. True creatinine and pseudocreatinine in
blood plasma of the dog. Acta Physiol Hung. 1965;28:265-272.
69. ONeill SL, Feldman BF. Hemolysis as a factor in clinical
chemistry and hematology of the dog. Vet Clin Pathol.
1989;18:58-68.
70. Lefebvre HP, Watson ADJ, Toutain PL, Braun JP. Absence de
validation technique et biologique de la cratininmie du
chien: une des difficults de l'interprtation [Lack of technical
and biological validation of plasma creatinine in the dog: one
of the difficulties in interpretation of results]. Rev Md Vt.
1998;149:7-14.
71. Matsuzawa T, Nomura M, Unno T. Clinical pathology reference
ranges of laboratory animals. J Vet Med Sci. 1993;55:351-362.
72. Broulet V, Fayolle P, Braun JP, Thouvenot JP, Rico AG. Influence
du sexe et de l'ge sur les valeurs usuelles de l'hmatologie et
de la biochimie srique de chiens "tout-venant" [Effects of sex
and age on the usual values for hematology and serum bio-
chemistry of unselected dogs]. Prat Md Chir Anim Comp.
1986;21:221-225.
73. Passing H, Brunk R. Statistische Untersuchungen auf alters-
und geschlechtsspezifische Unterschiede von Blutparametern
an englischen Beagle-Hunden. II. Klinische Chemie [Statisti-
cal examination of age and sex-specific differences in blood
parameters of English Beagle dogs. II. Clinical chemistry]. Berl
Mnch Tierrztl Wschr. 1981;94:432-436.
74. Teske RH, Bishop SP, Righter HF, Detweiler DK. Subacute
digoxin toxicosis in the Beagle dog. Toxicol Appl Pharmacol.
1976;35:283-301.
75. Kuhl S, Mischke R, Lund C, Gnzel-Apel AR. Referenzwerte
klinisch-chemischer Blutparameter bei Hundewelpen in den
ersten acht Lebenswochen [Reference values of chemical
blood parameters for puppies during the first eight weeks of
life]. Dtsch Tierrztl Wschr. 2000;107:438-443.
76. Kraft W, Hartman K, Dereser R. Altersabhngigkeit von
Laborwerten bei Hund und Katze. Teil III. Bilirubin, Kreatinin
und Protein im Blutserum [Age dependency of laboratory val-
ues in dogs and cats. Part III. Bilirubin, creatinine and protein
in serum]. Tierztl Prax. 1996;24:610-615.
77. Nap RC, Hazewinckel HAW, Voorhout G, Brom WE van der,
Goedegebuure SA, Van 'T Klooster AT. Growth and skeletal
development in Great Dane pups fed different levels of pro-
tein intake. J Nutr. 1991;121:S107-S113.
78. Wolford ST, Schroer RA, Gohs FX, Gallo PP, Falk HB, Dente
AR. Effect of age on serum chemistry profile, electrophoresis
and thyroid hormones in Beagle dogs two weeks to one year
of age. Vet Clin Pathol. 1988;17:35-42.
79. Strasser A, Seiser M, Simunek M, Heizmann V, Niedermuller
H. Physiologische Altersvernderungen beim Hund (Longitu-
dinalstudie in einer Beagle-Kolonie) [Physiologic changes
with age in the dog (longitudinal study in a Beagle dog
colony)]. Wien Tierrztl Mschr. 1997;84:189-198.
80. Fukuda S, Kawashima N, Iida H, Aoki J, Tokita K. Age depen-
dency of hematological values and concentrations of serum
biochemical constituents in normal Beagles from 1 to 14 years
of age. Jpn J Vet Sci. 1989;51:636-641.
81. Lowseth LA, Gillett NA, Gerlach RF, Muggenburg BA. The ef-
fects of aging on hematology and serum chemistry values in
the Beagle dog. Vet Clin Pathol. 1990;19:13-19.
82. Strasser A, Hochleithner M, Bubna-Littitz H. Zur Belastung
von Gebrauchshunden bei der Suchtgiftsuche [Stress in dogs
searching for drugs]. Wien Tierztl Mschr. 1993;80:352-355.
83. Vajdovich P, Gaal T, Szilagyi A, Harnos A. Changes in some red
blood cell and clinical laboratory parameters in young and old
Beagle dogs. Vet Res Comm. 1997;21:463-470.
84. van der Brom WE, Bienwega WJ. Assessment of glomerular
filtration rate in normal dogs: analysis of the
51
Cr-EDTA clear-
ance and its relation to several endogenous parameters of
glomerular filtration rate. Res Vet Sci. 1981;30:152-157.
85. Hillp M. Some haematological and clinical-chemical para-
meters of sight hounds (Afghan hound, Saluki and Whippet).
Nord Vet Med. 1986;38:148-155.
86. Freeman WE, Couto CG, Gray TL. Serum creatinine concen-
trations in retired racing Greyhounds. Vet Clin Pathol.
2003;32:40-42.
87. Ross LA. Assessment of renal function in the dog and cat. In:
Kirk RW, ed. Current Veterinary Therapy IX Small Animal Practice.
Philadelphia, PA: WB Saunders; 1986:1103-1108.
88. Kuhn G, Hardegg W. Effects of indoor and outdoor mainte-
nance of dogs upon food intake, body weight, and different
blood parameters. Z Versuchstierkd. 1988;31:205-214.
89. Rautenbach GH, Joubert HF. A comparison of health parame-
ters in two different canine populations. Part II: chemical
pathology data. J S Afr Vet Assoc. 1988;59:135-138.
90. Strasser A, Seiser M, Heizmann V, Niedermuller H. Einfluss
des Jahreszeit auf hmatologische une klinische Parameter in
einer Beagleskohorte [The influence of season on hematolog-
ic and clinical parameters in a Beagle dog colony]. Kleintier-
praxis. 2001;46:798-804.
91. Singer U, Kraft H. Biologische Rhythmen beim Hund [Biolog-
ic rhythms in the dog]. Kleintierpraxis. 1989;36:167-174.
92. Sothern RB, Farber MS, Gruber SA. Circannual variations in
baseline values in dogs. Chronobiol Int. 1993;10:364-382.
93. Jensen AL, Wenk A, Koch J. Comparison of results of haema-
tological and clinical chemical analyses of blood samples ob-
tained from the cephalic and external jugular vein in dogs. Res
Vet Sci. 1974;56:24-29.
94. Hardy RM, Osborne CA. Water deprivation test in the dog:
maximal normal values. J Am Vet Med Assoc. 1979;174:479-483.
95. Hinchcliff KW, Olson J, Crusberg C, et al. Serum biochemical
changes in dogs competing in a long-distance sled race. J Am
Vet Med Assoc. 1993;202:401-405.
96. Chanoit G, Concordet D, Lefebvre HP, Orcel K, Braun JP. Ex-
ercise does not induce major changes in plasma muscle en-
zymes, creatinine, glucose and total proteins concentrations in
untrained Beagle dogs. J Vet Med A. 2002;49:222-224.
97. Querengaesser A, Iben C, Leibetseder J. Blood changes during
training and racing in sled dogs. J Nutr. 1994;124:2760S-2764S.
98. Hammel EP, Kronfeld DS, Ganjam VK, Dunlap HL. Metabolic
responses to exhaustive exercise in racing sled dogs fed diets
containing medium, low, or zero carbohydrate. Am J Clin Nutr.
1977;30:409-418.
99. Reynolds AJ, Reinhart GA, Carey DP, Simmerman DA, Frank
DA, Kallfelz FA. Effect of protein intake during training on
biochemical and performance variables in sled dogs. Am J Vet
Res. 1999;60:789-795.
100. Kronfeld DS, Hammel EP, Ramberg CF, Dunlap HL. Hemato-
logical and metabolic responses to training in racing sled dogs
fed diets containing medium, low, or zero carbohydrate. Am J
Clin Nutr. 1977;30:419-430.
101. Rose RJ, Bloomberg MS. Response to sprint exercise in the
Greyhound: effects on hematology, serum biochemistry and
muscle metabolites. Res Vet Sci. 1989;47:212-218.
102. Snow DH, Harris RC, Stuttard E. Changes in haematology and
plasma biochemistry during maximal exercise in Grey-
hounds. Vet Rec. 1988;123:487-489.
103. Rivers BJ, Walter PA, Letourneau JG, et al. Estimation of arcu-
ate artery resistive index as a diagnostic tool for aminoglyco-
side-induced acute renal failure in dogs. Am J Vet Res.
1996;57:1536-1544.
104. Martinez EA, Mealey KL, Wooldridge AA, et al. Pharmacoki-
netics, effects on renal function, and potentiation of atracuri-
um-induced neuromuscular blockade after administration of
a high dose of gentamicin to isoflurane-anesthetized dogs. Am
J Vet Res. 1996;57:1123-1126.
105. Brown SA, Barsanti JA, Crowell WA. Gentamicin-associated
acute renal failure in the dog. J Am Vet Med Assoc. 1985;186:686-
690.
106. Greco DS, Turnwald GH, Adams R, et al. Urinary gamma-glu-
tamyl transpeptidase in dogs with gentamicin-induced
nephrotoxicity. Am J Vet Res. 1985;46:2332-2335.
107. Rubin SI, Papich MG. Acute renal failure in dogs: a case of
gentamicin toxicity. Comp Cont Educ Pract Vet. 1987;9:510-519.
108. Lora-Michiels M, Anzola K, Amaya G, Solano M. Quantitative
and qualitative scintigraphic measurement of renal function
in dogs exposed to toxic doses of gentamicin. Vet Radiol Ultra-
sound. 2001;42:553-561.
109. Frazier DL, Aucoin DP, Rivire JE. Gentamicin pharmacoki-
netics and nephrotoxicity in naturally acquired and experi-
mentally induced disease in dogs. J Am Vet Med Assoc.
1988;192:57-63.
110. Daugaard G, Abilgaard U, Larsen S, et al. Functional and
histopathological changes in dog kidney after administration
of cisplatin. Renal Physiol. 1987;10:54-64.
111. Ogilvie GK, Straw RC, Jameson VJ, et al. Prevalence of nephro-
toxicosis associated with a four-hour saline solution diuresis
protocol for the administration of cisplatin to dogs with natu-
rally developing neoplasms. J Am Vet Med Assoc. 1993;202:1845-
1848.
112. Hardie EM, Page RL, Williams PL, Fischer WD. Effect of time
of cisplatin administration on its toxicity and pharmacokinet-
ics in dogs. Am J Vet Res. 1991;52:1821-1825.
113. Shapiro W, Fossum TW, Kitchell BE, Couto CG, Theilen GH.
Use of cisplatin for treatment of appendicular osteosarcoma in
dogs. J Am Vet Med Assoc. 1988;192:507-512.
114. Hahn KA, Rohrbach BW, Legendre AM, Frazier DL, Nolan
ML. Hematologic changes associated with weekly low-dose
cisplatin administration in dogs. Vet Clin Pathol. 1997;26:29-31.
115. Forrester SD, Fallin EA, Saunders GK, Kenny JE. Prevention of
cisplatin-induced nephrotoxicosis in dogs, using hypertonic
saline solution as the vehicle of administration. Am J Vet Res.
1993;53:2175-2178.
116. Moalli MR, Dysko RC, Rush HG, et al. Oxytetracycline-in-
duced nephrotoxicosis in dogs after intravenous administra-
tion for experimental bone labeling. Lab Anim Sci. 1996;46:497-
502.
117. Engle JE, Abt AB, Schneck DW, Schloowerth AC. Netimicine
and tobramycin. comparison of nephrotoxicity in dogs. Invest
Urol. 1979;17:98-102.
118. Randall SR, Adams LG, White MR, DeNicola DB. Nephrotox-
icity of amphotericin B administered to dogs in a fat emulsion
versus five percent dextrose solution. Am J Vet Res. 1996;
57:1054-1058.
119. Rumbeiha WK, Fitzgerald SD, Kruger JM, et al. Use of
pamidronate disodium to reduce cholecalciferol-induced tox-
icosis in dogs. Am J Vet Res. 2000;61:9-13.
120. Fooshee SK, Forrester SD. Hypercalcemia secondary to chole-
calciferol rodenticide toxicosis in two dogs. J Am Vet Med Assoc.
1990;196:1265-1268.
121. Fan TM, Simpson KW,Trasti S, Birnbaum N, Center SA,Yeager
A. Calcipotriol toxicity in a dog. J Small Anim Pract. 1998;39:581-
586.
122. Lee KW, Jang IH. Hematological effects of ivermectin by re-
peated injection in dogs. Korean J Vet Clin Med. 1996;13:26-29.
123. Lording PM, Bellamy JEC. Trimethoprim and sulfadiazine: ad-
verse effects on long-term administration in dogs. J Am Anim
Hosp Assoc. 1978;14:410-417.
124. Mathews KA, Doherty T, Dyson DH, Wilcock B, Vaillant A.
Nephrotoxicity in dogs associated with methoxyflurane anes-
thesia and flunixin meglumine analgesia. Can Vet J. 1990;31:
766-771.
125. Lobetti RG, Joubert KE. Effect of administration of non-
steroidal anti-inflammatory drugs before surgery on renal
function in clinically normal dogs. Am J Vet Res. 2000;61:1501-
1506.
126. Mathews KA, Paley DM, Foster RA, Valliant AE, Young SS. A
comparison of ketorolac with flunixin, butorphanol, and oxy-
morphone in controlling postoperative pain in dogs. Can Vet J.
1996;37:557-567.
127. Sumano H, De Vizcaya A. Tolerance and clinical evaluation of
piroxicam in dogs. Canine Pract. 1996;21:16-19.
128. Ko JCH, Miyabiyashi T, Mandsager RE, Heaton-Jones TG,
Mauragis DF. Renal effects of carprofen administered to
healthy dogs anesthetized with propofol and isoflurane. J Am
Vet Med Assoc. 2000;217:346-349.
129. Kitagawa H, Wakamiya H, Kitoh K, et al. Efficacy of monother-
apy with benazepril, an angiotensin converting enzyme in-
hibitor, in dogs with naturally acquired chronic mitral insuffi-
ciency. J Vet Med Sci. 1997;57:513-520.
130. Roudebush P, Allen TA, Kuehn NF, Magerkurth JH, Bowers TL.
The effect of combined therapy with captopril, furosemide,
and a sodium-restricted diet on serum electrolyte concentra-
tions and renal function in normal dogs and dogs with con-
gestive heart failure. J Vet Intern Med. 1994;8:337-342.
131. Atkins CE, Brown WA, Coats JR, et al. Effects of long-term ad-
ministration of enalapril on clinical indicators of renal func-
tion in dogs with compensated mitral regurgitation. J Am Vet
Med Assoc. 2002;221:654-658.
132. Grauer GF, Greco DS, Getzy DM, et al. Effects of enalapril ver-
sus placebo as a treatment of canine idiopathic glomeru-
lonephritis. J Vet Intern Med. 2000;14:526-533.
133. Holz J, Munzel T, Sommer O, Bassenge E. Converting enzyme
inhibition by enalapril in experimental heart failure. Nephron.
1990(S1);55:73-76.
134. Bagby SP, Fuchs E. Chronic CEI alters effect of low Na+ diet in
normal and coarcted pups. I. BP, renin, and GFR. Am J Physiol.
1989;256:R523-R530.
135. Gregory CR, Gourley IM, Taylor NJ, Broaddus TW, Olds RB,
Patz JD. Preliminary results of clinical renal allograft trans-
plantation in the dog and cat. J Vet Intern Med. 1987;1:53-60.
136. Guler HP, Binz K, Eigenmann E, et al. Small stature and in-
sulin-like growth factors: prolonged treatment of mini-poo-
dles with recombinant human insulin-like growth factor I.
Acta Endocrinol. 1989;121:456-464.
137. Gregory CR, Gourley IM, Taylor NJ, et al. Experience with cy-
closporin A after renal allografting in two dogs. Vet Surg.
1986;15:441-443.
138. Prahalada S, Stabinski LG, Chen HY, et al. Pharmacological
and toxicological effects of chronic porcine growth hormone
administration in dogs. Toxicol Pathol. 1998;26:185-200.
139. Ndikuwera J, Winstanley EW, Binta-Mushi G, Mushi EZ.
Haematology and serum biochemistry in the racing Grey-
hound following intraperitoneal povidone-iodine. Vet Res
Comm. 1988;12:77-86.
140. Braun JP, Guelfi JF, Thouvenot JP, Rico AG. Haematological
and biochemical effects of a single intramuscular dose of 6 al-
pha-methylprednisolone acetate in the dog. Res Vet Sci.
1981;31:236-238.
141. Lynn RC, Feldman EC. Treatment of hypoadrenocorticism
with microcrystalline desoxycorticosterone pivalate. Br Vet J.
1991;147:478-483.
142. Govendir M, Canfield PJ, Emslie DR, Watson ADJ, Church DB.
Evaluation of d,l-ethionine as a mechanism for pancreatic islet
regeneration in dogs. Aust Vet J. 2002;80:75-82.
143. Haller M, Mller W, Binder H, Estelberger W, Arnold P. Sin-
gle-injection inulin clearancea simple method for measur-
ing glomerular filtration rate in dogs. Res Vet Sci. 1998;64:151-
156.
144. Gleadhill A. Evaluation of screening tests for renal insuffi-
ciency in the dog. J Small Anim Pract. 1994;35:391-396.
145. Finco DR, Brown SA,Vaden SL, Ferguson DC. Relationship be-
tween plasma creatinine and glomerular filtration rate in
dogs. J Vet Pharmacol Ther. 1995;18:418-421.
146. Westhoff A, Meyer-Lindenberg A, Nolte I, Wohlsein P,
Trautwein G, Grneberg W. Eignung und Aussagekraft der
Jodkontrastmittel-Clearance zur Messung des glomerulren
Filtrationsrate beim Hund [Suitability of iodine contrast solu-
tion clearance for the measurement of glomerular filtration
rate in the dog]. Kleintierpraxis. 1994;39:593-606.
147. Westhoff A, Meyer-Lindenberg A, Nolte I, Wohlsein P. Mes-
sung des glomerulren Filtrationsrate (GFR) beim Hund mit-
tels nichtradioaktiver Jod-Kontrastmittel Clearance durch der
Renalyzer PRX90 [Measurement of glomerular filtration rate
(GFR) in dogs by the clearance of a nonradioactive iodine con-
trast medium with the renalyzer PRX90]. Mh Vet Med.
1993;48:573-582.
148. Biewenga WJ, van der Brom WE. Assessment of glomerular
filtration rate in dogs with renal insufficiency: analysis of the
51
Cr-EDTA clearance and its relation to the plasma concentra-
tion of urea and creatinine. Res Vet Sci. 1981;30:158-160.
149. Toutain PL, Lefebvre HP, Laroute V. New insights on effects on
kidney insufficiency on disposition of angiotensin-converting
enzyme inhibitors: case of enalapril and benazepril in dogs. J
Pharmacol Exp Ther. 2000;292:1094-1103.
150. Grauer GF, Thomas CB, Eicker SW. Estimation of quantitative
proteinuria in the dog, using the urine protein-to-creatinine
ratio from a random, voided sample. Am J Vet Res. 1985;46:2116-
2119.
151. Dzanis DA, Krook L, Harvey J, Kallfelz FA. An experimental
model of chronic renal disease in dogs by infusion of micro-
spheres into the renal arterial circulation. Am J Vet Res.
1990;51:682-687.
152. Polzin DJ, Osborne CA, Hayden DW, Stevens JB. Influence of
reduced protein diets on morbidity, mortality, and renal func-
tion in dogs with induced renal failure. Am J Vet Res.
1984;45:506-517.
153. Finco DR, Barsanti JA, Adams DD. Effects of an anabolic
steroid on acute uremia in the dog. Am J Vet Res. 1984;45:2285-
2288.
154. Lefebvre HP, Schneider M, Dupouy V, et al. Effect of experi-
mental renal impairment on disposition of marbofloxacin
and its metabolites in the dog. J Vet Pharmacol Exp Ther.
1998;21:453-461.
155. Riviere EJ, Carver MP, Coppoc GL, Carlton WW, Lantz GC,
Shy-Modjeska J. Pharmacokinetics and comparative nephro-
toxicity of fixed-dose versus fixed-interval reduction of gen-
tamicin dosage in subtotal nephrectomized dogs. Toxicol Appl
Pharmacol. 1984;75:496-509.
156. Kitagawa H, Kitoh K, Eguchi T, et al. Effects of high doses of the
angiotensin-converting enzyme inhibitor benazepril on dogs
with experimental kidney impairment. J Jpn Vet Med Assoc.
2001;54:619-624.
157. Lefebvre HP, Ferre JP, Watson ADJ, et al. Small bowel motility
and colonic transit are altered in dogs with moderate renal
failure. Am J Physiol. 2001;181:R230-R238.
158. Lefebvre HP, Laroute V,Toutain PL. Effects of renal impairment
on the disposition of orally administered enalapril, benazepril,
and their active metabolites. J Vet Intern Med. 1999;13:21-27.
159. Finco DR, Brown SA, Cromwell WA, et al. Effect of aging and
dietary protein intake on uninephrectomized geriatric dogs.
Am J Vet Res. 1994;55:1282-1290.
160. Allen TA, Jaenke RS, Fettman MJ. A technique for estimating
progression of chronic renal failure in the dog. J Am Vet Med
Assoc. 1987;190:866-868.
161. Mashita T, Yasuda J, Iijima M, Takiguchi M, Yamazaki T,
Hashimoto A. Short-term hemodialysis treatment in dogs and
cats with total uretric obstruction. Jpn J Vet Res. 1997;45:59-65.
162. Jensen AL, Aaes H. Critical difference of clinical chemical pa-
rameters in blood from dogs. Res Vet Sci. 1993;54:10-14.
163. Finco DR, Brown SA, Brown CA, Crowell WA, Cooper TA,
Barsanti JA. Progression of chronic renal failure in the dog. J
Vet Intern Med. 1999;13:516-528.
164. Finco DR, Duncan JR. Evaluation of blood urea nitrogen and
serum creatinine concentrations as indicators of renal dys-
function: a study of 111 cases and a review of related literature.
J Am Vet Med Assoc. 1976;168:593-601.
165. Ramadan P, Tadic M. Odnos ureje i kreatinina u serumu kod
bolesti bubrega u psa [Serum urea-creatinine relation during
renal disease in dogs]. Vet Arch. 1985;55:37-43.
166. Harapin I, Ramadan P, Bedrica L, Tadic M, Alegro A. Clinical
picture and blood urea nitrogen (BUN) and creatinine content
in the blood serum of piroplasmosis-affected dogs. Vet Arch.
1993;63:11-17.
167. Lefebvre HP, Laroute V, Alvinerie M, et al. The effect of exper-
imental renal failure on tolfenamic acid disposition in the dog.
Biopharm Drug Dispos. 1997;18:79-91.
168. Gabrisch K. Serumharnstoff und Serumkreatinin als Indika-
toren der Nierenfunktion beim Hund [Serum urea and serum
creatinine as indicators of renal function in the dog.]. Kleintier-
praxis. 1973;18:133-135.
169. Almy FS, Christopher MM, King DP, Brown SA. Evaluation of
cystatin C as an endogenous marker of glomerular filtration
rate in dogs. J Vet Intern Med. 2002;16:45-51.
170. Jensen AL, Bomholt M, Loe L. Preliminary evaluation of a par-
ticle-enhanced turbidimetric immunoassay (PETIA) for the
determination of serum cystatin C-like immunoreactivity in
dogs. Vet Clin Pathol. 2001;30:86-90.
171. Braun JP, Perxachs A, Pchereau D, De La Farge F. Plasma cys-
tatin C in the dog: reference values and variations with renal
failure. Comp Clin Pathol. 2002;11:44-49.
172. Reusch CE, Tomsa K, Zimmer C, et al. Ultrasonography of the
parathyroid gland as an aid in differentiation of acute and
chronic renal failure. J Am Vet Med Assoc. 2000;217:1849-1852.
173. Vaden SL. Differentiation of acute from chronic renal failure.
In: Bonagura J, ed. Kirks Current Veterinary Therapy XIII Small
Animal Practice. Philadelphia, PA: WB Saunders; 2000;856-858.
174. DiBartola SP, Tarr MJ, Parker AT, Powers JD, Pultz JA. Clinico-
pathologic findings in dogs with renal amyloidosis: 59 cases
(1976-1986). J Am Vet Med Assoc. 1989;195:358-364.
175. Oh TH, Youn HY, Han HR. Polycystic kidney disease in mon-
grel puppy. J Vet Clin Med. 2001;18:70-73.
176. Bilkei G, Blcskei A. Kurzmitteilung aus der Praxis: Praktische
Erfahrungen bei der Bekmpfung von postoperativer Urmie
[Practical experiences in the therapy of postoperative uremic
crisis]. Berl Mnch Tierrztl Wschr. 1995;108:230-232.
177. Tsukamoto H, Parker HR, Gribble DH, Mariassy A, Peoples
SA. Nephrotoxicity of sodium arsenate in dogs. Am J Vet Res.
1983;44:2324-2330.
178. Kogika MM, Hagiwara MK, Mirandola RMS. Experimental
citrinin nephrotoxicosis in dog: renal function evaluation. Vet
Hum Toxicol. 1993;35:136-140.
179. Schwalb H, Bauernfeind A, Hensel H. Die Wirkung von Natri-
umfluorid auf die renale Ausscheidung von p-Aminohip-
pursure, Kreatininn Chlorid und Harnstoff beim Hund [Ef-
fects of sodium fluoride on the renal elimination of p-amino-
hippuric acid, creatinine, chloride, and urea in the dog]. Arch
Exp Pathol Pharmakol. 1955;224:285-294.
180. Spangler WL, Gribble DH, Lee TC.Vitamin D intoxication and
the pathogenesis of vitamin D nephropathy in the dog. Am J
Vet Res. 1979;40:73-83.
181. Grig C, Brgmann M, Zentek J, Wagner F, Farlopulos S. Hy-
perkalzmie verursacht durch eine Vitamin D-Intoxikation bei
einem hllandischen Htehund. Ein Fallbericht [A case report
of hypercalcaemia/vitamin D3 toxicosis in a dog]. Tierrztl Um-
schau. 1999;54:764-682.
182. Kosaki K, Sakurai E, Uchiyama M, Matsuno N, Kosaki M, Na-
gao T. Development of hypothermic continuous perfusion
preservation machine equipped with non pulsatile pump and
its clinical application. Transplant Proc. 2000;32:5-9.
183. Homan WP, French ME, Millard P, et al. Studies on the effects
of cyclosporin A upon renal allograft rejection in the dog.
Surgery. 1980;88:168-173.
184. Finco DR, Rawlings CA, Barsanti JA, Crowell WA. Kidney graft
survival in transfused and nontransfused sibling Beagle dogs.
Am J Vet Res. 1985;46:2327-2331.
185. Finco DR, Rawlings CA, Crowell WA, Brown SA, Barsanti JA.
Effect of azathiopine versus cyclosporine on kidney graft sur-
vival in transfused and non transfused mongrel dogs. J Vet In-
tern Med. 1987;1:61-66.
186. Jin MB, Nakayama M, Ogata T, et al. A novel leflunomide de-
rivative, FK778, for immunosuppression after kidney trans-
plantation in dogs. Surgery. 2002;132:72-79.
187. Kyles AE, Gregory CR, Griffey SM, Jackson J, Bernsteen L,
Morris RE. An evaluation of combined immunosuppression
with MNA 715 and microemulsified cyclosporine on renal al-
lograft rejection in mismatched mongrel dogs. Vet Surg.
2002;31:358-366.
188. Lobetti RG, Jacobson LS. Renal involvement in dogs with
babesiosis. J Sth Afr Vet Assoc. 2001;72:23-28.
189. Jacobson LS, Lobetti RG, Becker P, Reyers F, Vaughan-Scott T.
Nitric oxide metabolites in naturally occurring canine
babesiosis. Vet Parasitol. 2002;104:27-41.
190. Palacio J, Liste F, Gascon M. Urinary protein/creatinine ratio in
the evaluation of renal failure in canine leishmaniasis. Vet Rec.
1995;129:567-568.
191. Palacio J, Liste F, Gascon M. Enzymuria as an index of renal
damage in canine leishmaniasis. Vet Rec. 1997;140:477-480.
192. Lucena R, Ginel PJ, Lopez R, Novales M, Martin E, Molleda
JM. Antinuclear antibodies in dogs with leishmaniasis. J Vet
Med A. 1996;43:255-259.
193. Lopez R, Lucena R, Novales M, Ginel PJ, Martin E, Molleda
JM. Circulating immune complexes and renal function in ca-
nine leishmaniasis. J Vet Med B. 1996;43:469-474.
194. Poli A, Abramo F, Mancianti F, Nigro M, Pieri S, Bionda A. Re-
nal involvement in canine lesihmaniasis. Nephron. 1991;57:442-
452.
195. Hartman EG, van der Ingh TS, Rothuizen J. Clinical, patholog-
ical and serological features of spontaneous canine lep-
tospirosis. An evaluation of the IgM- and IgG-specific ELISA.
Vet Immunol Immunopathol. 1986;13:261-271.
196. Kantek Navarro CE, Kociba GJ, Kowalski JJ. Serum biochemi-
cal changes in dogs with experimental Leptospira interrogans
serovar icterohaemorrhagiae infection. Am J Vet Res.
1981;42:1125-1129.
197. Venkataraman KS, Nedunchelliyan S, Ramadass P, Ramkrish-
na J. Haemato-biochemical changes in experimental lep-
tospirosis in dogs. Indian Vet J. 1992;69:1145-1146.
198. Adin CA, Cowgill LD. Treatment and outcome of dogs with
leptospirosis: 36 cases (1990-1998). J Am Vet Med Assoc. 2000;
216:371-375.
199. Azuma Y, Isogai E, Isogai H, Kawamura K. Canine Lyme dis-
ease: clinical and serological evaluations in 21 dogs in Japan.
Vet Rec. 1994;134:369-372.
200. Bouattour A, Chabchoub A, Sahli J, et al. Contribution l'-
tude de l'effet pathogne aprs inoculation exprimentale
chez le chien de 2 souches de Borrelia (Borrelia lusitaniae et Bor-
relia garinii) isoles en Tunisie [Contribution to the study of
pathogenic effects after experimental inoculation of dogs with
2 strains of Borrelia (Borrelia lusitaniae and Borrelia garinii) iso-
lated in Tunisia]. Revue Med Vet. 2001;152:291-296.
201. Omotainse SO, Anosa VO, Falaye C. Clinical and biochemical
changes in experimental Trypanosoma brucei infection of dogs.
Israel J Vet Med. 1994;49:36-39.
202. De La Rue ML, De Carli GA, Herrera HM, Silva RAMS. Bio-
chemical changes in acute infection of dogs withTrypanosoma
evansi (Steel 1885) Balbiani, 1888. J Protozool Res. 1997;7:28-35.
203. Kitagawa H, Kitoh K, Iwasaki T, Sasaki Y. Comparison of labo-
ratory data in dogs with heartworm caval syndrome surviving
and nonsurviving after surgical treatment. J Vet Med Sci.
1997;59:609-611.
204. Botha WG, Dormehl IC, Goosen DJ. Evaluation of kidney
function in dogs suffering from canine encephalitozoonosis by
standard clinical pathological techniques. J Sth Afr Vet Assoc.
1986;57:79-86.
205. Kohn B, Arnold P, Kaser-Hotz B, Hauser B, Fluckiger M, Suter
PF. Maligne Histiozytose beim Hund: 26 Flle (1989-1992)
[Malignant histiocytosis of the dog: 26 cases (1989-1992)].
Kleintierpraxis. 1993;38:409-424.
206. Stone EA, Littman MP, Robertson JL, Bove KC. Renal dys-
function in dogs with pyometra. J Am Vet Med Assoc. 1988;193:
457-464.
207. Capiau E, De Schepper J, van der Stock J. Renal failure and
serum enzymes in 127 dogs with pyometra. Vlaams Diergeneesk
Tijdschr. 1987;56:214-220.
208. Coster RD, Ieteren GD, Josse M, Jacovljevic S, Ectors F, De-
rivaux J. Aspects clinique, histologique, bactriologique et
hormonal de la mtrite chronique chez la chienne [Clinical,
histologic, bacteriologic, and hormonal aspects of chronic
metritis in the bitch]. Ann Med Vet. 1979;123:233-247.
209. Heiene R, Moe L, Molmen G. Calculation of urinary enzyme
excretion, with renal structure and function in dogs with py-
ometra. Res Vet Sci. 2001;70:129-137.
210. Mottelib AA, Misk NA. Clinical, blood picture and pathomor-
phological studies on experimental intestinal obstruction in
dogs. Zbl Vet Med A. 1976;23:600-608.
211. Wingfield WE, Cornelius LM, Young DW. Experimental acute
gastric dilation and torsion in the dog. 1. Changes in biochem-
ical and acid-base parameters. J Small Anim Pract. 1975;16:41-55.
212. Kaneko JJ, Mattheuws D, Rottiers RP, Vermuelen A. Renal
clearance, insulin secretion and glucose tolerance in sponta-
neous diabetes mellitus of dogs. Cornell Vet. 1979;69:375-383.
213. Cotton RB, Cornelius LM, Theran P. Diabetes mellitus in the
dog: a clinicopathologic study. J Am Vet Med Assoc. 1971;159:
863-870.
214. Nagode LA, Chew DJ. Nephrocalcinosis caused by hyper-
parathyroidism in progression of renal failure: treatment with
calcitriol. Semin Vet Med Surg (Small Anim). 1992;7:202-220.
215. Weller RE, Hoffman WE. Renal function in dogs with lym-
phosarcoma and associated hypercalcemia. J Small Anim Pract.
1992;33:61-66.
216. Jansen B, Thorner PS, Singh A, et al. Hereditary nephritis in
Samoyed dogs. Am J Pathol. 1984;116:175-178.
217. Jansen B, Valli VEO, Thorner P, Baumal R, Lumsden JH.
Samoyed hereditary glomerulopathy: serial, clinical and labo-
ratory (urine, serum biochemistry and hematology) studies.
Can J Vet Res. 1987;51:387-393.
218. Reusch C, Hoerauf A, Lechner J, et al. A new familial glomeru-
lonephropathy in Bernese mountain dogs. Vet Rec. 1994;134:
411-415.
219. Eriksen K, Grondalen J. Familial renal disease in soft-coated
Wheaten Terriers. J Small Anim Pract. 1984;25:489-500.
220. Nash AS, Kelly DF, Gaskell CJ. Progressive renal disease in
soft-coated Wheaten Terriers: possible familial nephropathy. J
Small Anim Pract. 1984;25:479-487.
221. Hood JC, Dowling J, Bertram JF, et al. Correlation of
histopathological features and renal impairment in autosomal
dominant Alport syndrome in Bull terriers. Nephrol Dial Trans-
plant. 2002;17:1897-1908.
222. Grodecki KM, Gains MJ, Baumal R, et al. Treatment of X-
linked hereditary nephritis in Samoyed dogs with angiotensin
converting enzyme (ACE) inhibitors. J Comp Pathol. 1997;117:
209-225.
223. Koeman JP, Biewenga WJ, Gruys E. Proteinuria associated
with glomerulosclerosis and glomerular collagen formation in
three Newfoundland dog littermates. Vet Pathol. 1994;31:188-
193.
224. Lees GE, Helman RG, Homco LD, Millichamp NJ, Hunter JF,
Frey MS. Early diagnosis of familial nephropathy in English
Cocker Spaniels. J Am Anim Hosp Assoc. 1998;34:189-195.
225. Hertzke DM, Cowan LA, Schoning P, Fenwick BW. Glomeru-
lar ultrastructural lesions of idiopathic cutaneous and renal
glomerular vasculopathy of Greyhounds. Vet Pathol. 1995;32:
451-459.
226. Krawiec DR. Renal failure in immature dogs. J Am Anim Hosp
Assoc. 1986;23:101-107.
227. Gross TL, Pascal-Tenorio A, Munn RJ, Hargis AM, Kline A. Fol-
licular lipidosis in three Rottweilers. Vet Dermatol. 1997;8:33-40.
228. Bove KC, Joyce T, Blazer-Yost B, Goldschmidt MS, Segal S.
Characterization of renal defects in dogs with a syndrome
similar to Fanconi syndrome in man. J Am Vet Med Assoc. 1979;
174:1094-1099.
229. Deppe TA, Center SA, Simpson KW, et al. Glomerular filtra-
tion rate and renal volume in dogs with congenital portosys-
temic vascular anomalies before and after surgical ligation. J
Vet Intern Med. 1999;13:465-471.
230. Schaeffer MC, Rogers QR, Buffington CA, Wolfe BM,
Strombeck DR. Long-term biochemical and physiological ef-
fects of surgically placed porto-caval shunts in dogs. Am J Vet
Res. 1986;47:346-354.
231. Yilmaz S, Kirimlioglu V, Katz D, et al. An attempt to decrease
ammonia levels after portocaval anastomosis in dogs. Hepatic
periarterial neurectomy. Dig Dis Sci. 2002;47:1943-1952.
232. Schetters TPM, Kleuskens JAGM, Scholtes NC, Pasman JW,
Goovaerts D. Vaccination of dogs against Babesia canis infec-
tion. Vet Parasitol. 1997;73:35-41.
233. Reder S, Hartmann H. Diagnostische and pathophysiologis-
che Aspekte der Nierenfunktionsbestimmuung bei Tieren
[Diagnostic and pathophysiologic aspects of the assessment of
renal function in animals]. J Vet Med A. 1994;41:253-267.
234. Heiene R, Moe L. Pharmacokinetic aspects of measurement of
glomerular filtration rate in the dog: a review. J Vet Intern Med.
1998;12:401-414.
235. Frazier LW. Plasma creatinine clearance in the dog. Physiol
Teach. 1977;6:1-3.
236. Finco DR, Coulter DB, Barsanti JA. Procedure for a simple
method of measuring glomerular filtration rate in the dog. J
Am Anim Hosp Assoc. 1982;18:804-806.
237. Finco DR, Coulter DB, Barsanti JA. Simple, accurate method
for clinical estimation of glomerular filtration rate in the dog.
Am J Vet Res. 1981;42:1874-1877.
238. Tabaru H, Finco DR, Brown SA, Cooper T. Influence of hydra-
tion state on renal functions of dogs. Am J Vet Res. 1993;54:1758-
1764.
239. Brown SA. Evaluation of a single-injection method for esti-
mating glomerular filtration rate in dogs with reduced renal
function. Am J Vet Res. 1994;55:1470-1473.
240. Krawiec DR, Twardock R, Badertscher RR, Daniel GB, Dugan
SJ. Use of 99mTc diethyleneaminepentaacetic acid for assess-
ment of renal function in dogs with suspected renal disease. J
Am Vet Med Assoc. 1988;192:1077-1080.
241. Brown SA, Finco DR, Boudinot D, Wright J, Tarver SL, Cooper
T. Evaluation of a single injection method, using iohexol, for
estimating glomerular filtration rate in cats and dogs. Am J Vet
Res. 1996;57:105-110.
242. Finco DR, Braselton WE, Cooper TA. Relationship between io-
hexol clearance and urinary creatinine clearance in dogs. J Vet
Intern Med. 2001;15:368-373.
243. Lee KE, Behrendt U, Kaczmarczyk G, Mohnhaupt R, Rein-
hardt HW. Estimation of glomerular filtration rate in con-
scious dogs following a bolus of creatinine. Comparison with
simultaneously determined inulin clearance. Pflugers Arch.
1983;396:176-178.
244. Izzat N, Rosborough JP. Renal function in conscious dogs: po-
tential effect of gender on measurement. Res Exp Med. 1989;
189:371-379.
245. Ewald BH. Renal function tests in normal Beagle dogs. Am J Vet
Res. 1967;28:741-749.
246. Houck CR. Statistical analysis of filtration rate and effective re-
nal plasma flow related to weight and surface area in dogs. Am
J Physiol. 1948;153:169-175.
247. Russo HF, Ciminera JL, Gass SR, Beyer KH. Statistical analysis
of renal clearance by the dog. Proc Soc Exp Biol Med. 1952;80:
736-740.
248. Horster M, Valtin H. Postnatal development of renal function:
micropuncture and clearance studies in the dog. J Clin Invest.
1971;50:779-795.
249. Forsyth SF, Guilford WG, Pfeiffer DU. Effect of NSAID admin-
istration on creatinine clearance in healthy dogs undergoing
anesthesia and surgery. J Small Anim Pract. 2000;41:547-550.
250. Bove KC, Joyce T. Clinical evaluation of glomerular function:
24-hour creatinine clearance in dogs. J Am Vet Med Assoc. 1979;
174:488-491.
251. Feeney DA, Osborne CA, Jessen CR. Effect of multiple excre-
tory urograms on glomerular filtration of normal dogs. Am J
Vet Res. 1980;41:960-963.
252. Finco DR. Simultaneous determination of phenolsulfonph-
thalein excretion and endogenous creatinine clearance in the
normal dog. J Am Vet Med Assoc. 1971;159:336-340.
253. Kleinman LI, Lubbe RJ. Factors affecting the maturation of
glomerular filtration rate and renal plasma flow in the new-
born dog. J Physiol. 1972;223:395-409.
254. Lane IF, Shaw DH, Buron SA, Donald AW. Quantitative uri-
nalysis in healthy Beagle puppies from 9 to 27 weeks of age.
Am J Vet Res. 2000;61:577-581.
255. Finco DR, Coooper T. Soy protein increases glomerular filtra-
tion rate in dogs with normal or reduced renal function. J Nutr.
2000;130:745-748.
256. Brown SA, Finco DR, Brown CA. Is there a role for dietary
polyunsaturated fatty acid supplementation in canine renal
disease? J Nutr. 1998;128:2765S-2767S.
257. Lulich JP, Osborne CA, Polzin DJ, Johnston SD, Parker ML.
Urine metabolite values in fed and nonfed clinically normal
Beagles. Am J Vet Res. 1991;52:1573-1578.
258. Gourley IM, Parker HR, Gribble DH, Conzelman CM, Ishizaki
G. Pathophysiological effects of renal allografts in the dog.
Arch Am Coll Vet Surg. 1975;4:22-39.
259. Emmeluth C, Bie P. Effects, release and disposal of endothelin-
1 in conscious dogs. Acta Physiol Scand. 1992;146:197-204.
260. Chetboul V, Klonjkowski B, Lefebvre HP, et al. Short-term effi-
ciency and safety of gene delivery into canine kidneys. Nephrol
Dial Transplant. 2001;16:608-614.

Creatinine Dog

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Creatinine Dog

Uploaded by

Copyright:

Available Formats

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Special Conditions Mean SD Reference

Special Conditions Mean SD Reference

You might also like