Urinalysis Interpretation: How to Squeeze Out

the Maximum Information from a Small Sample

Nyssa J. Reine, DVM, Dipl. ACVIM (Internal Medicine), and
Cathy E. Langston, DVM, Dipl. ACVIM (Internal Medicine)
The urinalysis is an essential part of the diagnostic evaluation for all urinary and many
metabolic diseases. Its assessment includes evaluation of physical characteristics (color,
clarity, and volume), biochemical parameters (urine pH, blood, glucose, ketones, bilirubin,
urobilinogen, and protein) and microscopic sediment evaluation (RBC, WBC, organisms,
epithelial cells, crystals, and casts). Many of these parameters are inuenced by collection
method and therefore, it is essential to interpret accordingly. Knowledge of factors that can
interfere with the accuracy of some test results can decrease improper interpretation.
When all of these parameters are evaluated in combination with clinical signs, physical
examination, thorough history and other laboratory tests, a diagnosis will often be attained.
Clin Tech Small Anim Pract 20:2-10 2005 Elsevier Inc. All rights reserved.
KEYWORDS urinalysis, urine sediment, urine collection, fractional excretion of electrolytes
I
nterpretation of a urinalysis can yield a great deal of infor-
mationsome beyond the connes of the urinary system.
Through coordination of biochemical testing, urinalysis nd-
ings, history, and physical examination, many common dis-
orders can be included in or excluded from the differential
diagnoses (ie, diabetes mellitus, chronic renal failure, etc.).
Urine sediment evaluation can alert the clinician to important
problems while the patient is still asymptomatic (ie, ammo-
nium biurate crystals, pyuria in a diabetic patient). Also,
there are some diseases for which early detection may lead to
better survival (ie, protein losing nephropathy). This article
will review the basics of urinalysis interpretation and how to
glean the maximum amount of information from it.
Urine Collection
The method of collecting the urine sample may affect the
results of analysis. A standardized volume of urine should be
obtained each time, to allow comparison of urine sediment
examination with subsequent samples.
Free-Catch Urine Sampling
When collecting a free-catch urine sample, a mid-stream
sample is preferred. The initial urine that is voided will con-
tain cells, bacteria, and debris from the urethra and vulva or
prepuce, and may not be a representative sample. Because
female dogs are usually positioned with the vulva close to the
ground when urinating, a shallow container (such as a pie
pan) may be helpful. The sample container should be clean
and free of detergent to avoid interference with the biochem-
ical analysis. Samples collected from midstream into a sterile
container may have false positive urine culture results from
external contaminants (ie, hair on prepuce or hindquarters).
Urine samples brought in by owners are rarely suitable for
urine culture. Quantitative analysis should be performed on
all free-catch samples submitted for bacterial culture.
Obtaining a free-catch midstream urine sample from a cat
can be a difcult task. Removing the litter from the litter box
or replacing it with nonabsorbent material [NoSorb beads
(Catco, Inc. Cape Coral, FL), plastic packing material, un-
popped popcorn, etc.] may allow collection of a suitable
sample. Plastic wrap can be loosely placed over the litter to
collect urine fromdeclawed cats. Although these samples will
not be appropriate for culture, many other parameters will
still be valid.
Manual expression of the bladder to facilitate obtaining a
free-catch sample is rarely successful in awake animals and
may induce vesiculoureteral reux at pressures necessary to
induce voiding. If the urine is infected, this introduces the
risk of causing ascending pyelonephritis.
Urinary Catheterization
Male dogs are placed in lateral recumbency for catheteriza-
tion. The penis is extruded from the prepuce, and the tip
cleaned with dilute chlorhexiderm solution to remove any
debris or discharge. Sterile lubricant is placed on the tip of
the urinary catheter, which is then placed in the urethral
Animal Medical Center, New York, NY.
Address reprint requests to Nyssa J. Reine, DVM, Dipl. ACVIM (Internal
Medicine), Animal Medical Center, 510 E. 62
nd
Street, New York, NY
10021. E-mail: nyssa.reine@amcny.org
2 1096-2867/05/$-see front matter 2005 Elsevier Inc. All rights reserved.
doi:10.1053/j.ctsap.2004.12.002
orice and the catheter advanced into the bladder. It is help-
ful to create a sleeve from the catheter packaging to maintain
sterility while passing the catheter (Fig 1). Some resistance
may be met at the pelvic exure region, which can usually be
overcome by gentle pressure. While performing catheteriza-
tion it is important to observe the ease with which the cath-
eter is passed as this may be helpful information for dogs
having difculty urinating.
Most female dogs need chemical restraint to allow urinary
catheterization. Lidocaine gel can be placed in the vaginal
vault by syringe (without needle) to facilitate catheter place-
ment without chemical restraint in some dogs. Some clini-
cians are able to place catheters with the dog in lateral or
dorsal recumbency, but most clinicians prefer sternal recum-
bency. The dog is placed with the hind legs off the table.
Keeping the dog straight will make catheter placement easier.
Placing a sandbag or pillow beneath the pelvis may aid in
positioning and stabilization. Some clinicians prefer to visu-
alize the urethral papilla using a vaginal speculum or ano-
scope. Blind, manually guided placement is also readily
achievable. Wearing sterile gloves, the urethral papilla is pal-
pated. The urethral papilla is located on the oor of the
vagina canal, and is recognizable as a subtle deviation on the
oor. In my experience, it can usually be palpated just before
encountering the vestibulovaginal stenosis present in many
dogs. It is also typically located behind the caudal aspect of
the pubis, which can be palpated. The lubricated urinary
catheter is passed just under the nger on the urethral pa-
pilla, which helps direct the catheter down and into the ure-
thra (Fig 2). The catheter should pass very smoothly in nor-
mal dogs and urine should ow out of the catheter. If the
catheter passes easily and no urine ows, the catheter may
have been passed into the vagina. As with male dogs, easy of
catheterization should be recorded.
Both male and female cats usually need chemical restraint
to allow urinary catheterization. A male cat should be posi-
tioned on his back with his hind legs drawn forward. The
penis is exteriorized from the prepuce. Because the penile
urethra is normally directed downward, the penis should be
retracted and lifted dorsally, to align the urethra parallel to
the spine, eliminating the natural curve (Fig 3). A 3.5 to 5
French catheter can then be placed into the bladder. The
technique for catheterizing female cats is similar to the tech-
nique for female dogs, except that visualization is rarely pos-
sible because of size. A 3.5 to 6 French catheter can be used
in most female cats.
After passing a urinary catheter to obtain a urine sample,
the rst few milliliters of urine should be discarded, as that is
the portion most likely to have debris from the urethra. A
second aliquot can then be obtained for urinalysis and quan-
titative culture if desired. The risk of creating a urinary tract
infection from catheterization is higher in female dogs com-
pared with males.
1
Cystocentesis
Cystocentesis is the best method for obtaining urine samples
for bacterial culture and can be performed on awake animals.
With both cystocentesis and urinary catheterization, there is
a risk of iatrogenic hematuria. The patient is usually posi-
tioned in dorsal recumbency. Palpating the bladder with one
hand helps immobilize it while acquiring the sample. The
needle should be angled caudally, toward the pelvic inlet so
that as the bladder empties, the needle is still in the lumen of
Figure 1 Using urinary catheter to obtain urine sample from male
dog. Sleeve of catheter wrapping is being used to maintain sterility
of catheter during placement.
Figure 2 Blind placement of urinary catheter in female dog. Placing
the tip of the nger just past the urethral opening helps guide the
urinary catheter down and into the urethra.
Figure 3 Contrast urethrogram of male cat showing normal urethral
position. Retraction of the penis dorsally and caudally will
straighten urethra for placement of urinary catheter.
Urinalysis interpretation 3
the bladder. It is also possible to use a lateral or standing
approach when the bladder is palpable. A 1 inch, 22-gauge
needle is preferred, and for very large or obese dogs, a 1.5 to
2-inch needle may be required.
Iatrogenic hematuria can occur if the need is in contact
with the opposite bladder wall. If the UA is being performed
to monitor hematuria, a free catch sample may be preferable
to cystocentesis or catheterization. Other complications in-
clude puncture of the colon, laceration of the bladder, and
laceration of the major blood vessels dorsal to the bladder.
Inadvertent puncture of the colon can cause bacterial con-
tamination of the urine sample, and a mixed population of
bacteria on the urine culture may result.
Urinalysis Procedure
Multiple parameters are assessed when performing a urinal-
ysis (Fig 4). Results are most accurate if a fresh urine sample
is evaluated. If the sample will not be analyzed within 1 to 2
hours of collection, it should be refrigerated.
Physical Characteristics
Urine Color
Normal urine is typically transparent and yellow on visual in-
spection. Concentrated urine samples may appear amber col-
ored and dilute urine may be a lighter yellow color. However,
urine color should NEVER be used to replace USG assessment.
There are many exogenous and endogenous pigments that
can cause abnormal coloration. When a patient has abnormal
urine color, a thorough investigation into diet, medications,
and environment should be undertaken. The most com-
monly observed abnormal urine colors in dogs and cats are
red, brown, and black with hematuria, hemoglobinuria,
myoglobinuria, and bilirubinuria being the most common
causes. Centrifugation of a discolored urine sample should
discern between true hematuria versus myoglobinuria or he-
moglobinuria as intact red blood cells should settle into the
bottom of the sample, leaving a clear supernatant.
The serum color may provide information about the cause
of alterations in the urine color. Patients with bilirubinuria
will typically have hyperbilirubinemia, although bilirubin-
uria without hyperbilirubinemia can occur in normal male
dogs. Cats with bilirubinuria in absence of hyperbiliru-
binemia should have serial urine and biochemical assessment
to monitor for the development of icterus. Patients that have
hemoglobinuria are expected to have pink tinged, hemolyzed
serum. If normal serum color is present, an ammonium sul-
fate test should be performed for myoglobin.
2
Urine Clarity
Like color, clarity of urine can be affected by urine concen-
tration. A well-concentrated urine sample is more likely to be
turbid than a dilute sample. Other things that can increase
turbidity include white blood cells (WBC), red blood cells
(RBC), crystals, bacteria, mucus, lipid, and contaminating
materials. Evaluation of the urine sediment should help to
elucidate the cause of increased turbidity. It is best to assess
urine clarity immediately after collection as crystals can pre-
cipitate during storage, thus inuencing turbidity.
3
Urine Volume
The daily volume of urination reported by an owner is an
important determinant of which portion of the urinary tract
should be investigated. A patient that has disease limited to
the lower urinary tract will present with signs of stranguria
(difcult urination) or pollakiuria (abnormally frequent uri-
nation) that could easily be mistaken for polyuria (excessive
volume of urine) by an owner. Diseases of the urinary bladder
or urethra alone do not cause polyuria. The presence of poly-
uria would imply that either the upper urinary tract is the
source of the problem (ie, kidneys) or there is another met-
abolic problem causing the excessive urination (ie, diabetes
mellitus, Cushings disease, etc.). It is often difcult for own-
ers to discern between pollakiuria and polyuria. The easiest
way to get around this would be to have the owner quantitate
water consumption for a few days. A normal dog should
drink 1 oz per pound per day.
Urine Specic Gravity (USG)
Specic gravity is dened as the ratio of the weight of a
volume of liquid to the weight of an equal volume of distilled
water. Specic gravity is dependent on particle number, size
and weight. This differs from urine osmolality, which is de-
pendent only on the number of particles in the solution.
Because determination of urine osmolality requires special-
ized equipment and urine specic gravity (USG) can be de-
termined with a simple refractometer, specic gravity is used
Figure 4 Step-by step guide to performing a urinalysis.
4 N.J. Reine and C.E. Langston
much more commonly in clinical practice to reect the con-
centration of a patients urine. Either of these values reects
the kidneys ability to concentrate and dilute urine.
4-7
Recent
studies have documented that specic gravity is not affected
by storage.
3
Normal USG
Healthy animals can have a wide range of USG(1.001-1.065)
as water consumption and thus urine concentration can vary
based on activity, diet, etc. More commonly, it is accepted
that a dog with normal renal function will have a USG
1.030 and a cat 1.035.
Hyposthenuria
Hyposthenuria is dened as a USG 1.008 and reects that
the osmolality of the urine is lower than that of plasma. For
dilution of urine, the renal distal convoluted tubule must be
intact. The presence of hyposthenuria does very little to dis-
tinguish between causes of polyuria (PU) and polydipsia
(PD) as it can be caused by central diabetes insipidus, neph-
rogenic diabetes insipidus (the cause of PU/PD in Cushings
disease, hypercalcemia, pyometra, prostatitis), medullary
washout, and psychogenic polydipsia. Patients with renal
failure are not able to dilute urine below 1.008.
Isosthenuria
Isosthenuria is dened as a USG 1.007 to 1.012 and reects
that the osmolality of urine is equal to that of plasma. The
presence of isosthenuria may be suggestive of primary renal
failure, though patients with other causes of PU/PD(ie, Cush-
ings disease, diabetes mellitus, hypercalcemia) may also have
a urine specic gravity in this range.
8
With renal disease,
isosthenuria occurs with greater than 66% damage to the
kidney (renal insufciency), whereas azotemia does not oc-
cur until greater than 75% damage has been sustained (renal
failure).
USG Interpretation
It is important to interpret USG in relation to hydration sta-
tus. The presence of a concentrated USG in the face of dehy-
dration virtually eliminates the possibility of renal failure as
the cause of dehydration. It is never appropriate for a dehy-
drated patient to have a lowUSG. In addition to renal failure,
other diseases (ie, ketoacidotic diabetes mellitus, Addisons
disease) may cause impaired urine concentrating ability with
concurrent dehydration. USG in azotemic patients can dif-
ferentiate prerenal causes from renal causes. USG must be
evaluated before intravenous uid therapy. Also, patients
that are normal can have a urine specic gravity that is isos-
thenuria or hyposthenuric. A patient who has unexpected
isosthenuria or hyposthenuria should have its water con-
sumption quantied to assess for polydipsia that has gone
unrecognized.
Biochemical Analysis
Urine dipstick analysis is a convenient method of assessing
several biochemical aspects of urine. Visibly bloody or turbid
urine samples should be centrifuged and the supernatant
used for dipstick analysis.
Urine pH
Urine pH can give an indication about renal disease (ie, tu-
bular acidosis) or systemic acid-base status, and urine pH
affects the solubility of several types of urinary crystals. Urine
dipsticks containing methyl red, bromthymol blue, and phe-
nolphthalein can detect pH in the range of 5 to 9. Results of
urine dipstick pHmeasurements may vary substantially from
pH meter measurements.
9
pH paper is not accurate enough
for clinical decision making. Portable pHmeters are the most
accurate compared with laboratory methods, although regu-
lar electrode maintenance and daily calibration is recom-
mended to ensure accuracy.
10
Blood, Hemoglobin, and Myoglobin
The heme portion of hemoglobin and myoglobin acts as a per-
oxidase and can cause a color change on a reagent test strip. The
hemoglobin in intact RBC will react to the reagent strip. Small
number of intact RBCs will cause spotting of the test pad,
whereas hemoglobin, myoglobin, or large numbers of intact
RBCs will cause a homogenous color change. Most test strips can
detect 5 to 20 RBC/mL or 0.015 to 0.062 mg/dL of free hemo-
globin (equivalent to 5-20 RBC/mL). About 0.5 mL blood per
liter of urine (approx. 2500 RBC/mL) is necessary for visual
detection of hematuria. Up to 5 RBC/mL of urine is considered
normal in people. False positive reactions may occur if the sam-
ple is contaminated with oxidizing agents in disinfectants. False
negative reactions may occur if RBCs have settled to the bottom
of the sample, leading to a disparity between the dipstick and
sediment evaluation. RBCs will lyse in dilute (USG 1.008) or
alkaline urine.
Hematuria with intact RBC can indicate disease of the
lower urinary or genital tract (urethra, prostate, vagina, pe-
nis, bladder) including infection, neoplasia, idiopathic or in-
ammatory disease, and upper urinary (kidney, ureter) in-
cluding pyelonephritis, protein-losing nephropathy, or
neoplasia.
Hemoglobinuria can occur if intact RBCs hemolyze in the
urine (dilute or alkaline urine), or if hemoglobin levels in the
blood are elevated fromhemolysis (ie, immune-mediated he-
molytic anemia, toxins, genetic disorders, infectious agents,
hypophosphatemia, or physical damage). Myoglobinuria oc-
curs fromtrauma, toxic, or ischemic injury or necrosis (rhab-
domyolysis). To help distinguish hematuria from hemoglo-
binuria or myoglobinuria, inspect the supernatant after
centrifuging the urine sample. If it clears, hematuria is
present. Dipstick methods cannot differentiate myoglobin-
uria from hemoglobinuria, but the presence of icteric or dis-
colored plasma suggests hemoglobinuria. An elevated myo-
globin level in the blood does not cause a color change in
plasma.
Glucose
Glucosuria is detected by a glucose oxidase enzymatic reac-
tion that is specic for glucose. Most urine dipstick methods
have a practical lower limit of sensitivity for urine glucose
concentrations from about 40 to 80 mg/dL, but they are
semiquantitative above that level, with more intense color
change reactions indicating higher glucose concentrations up
to 2,000 mg/dL. The reagent pads have a limited shelf life and
should be protected from sunlight. Refrigerated urine sam-
Urinalysis interpretation 5
ples should be warmed to room temperature to avoid false
negative results. Ascorbic acid (vitamin C) interferes with the
test, leading to false negative results if a high concentration of
ascorbic acid and a low concentration of glucose are present
in the urine. Formaldehyde (a metabolite of the urinary an-
tiseptic methenamine) can also cause false negative results.
False positive results may be obtained if the sample is con-
taminated with hydrogen peroxide, chlorine, or hypochlorite
(bleach).
Glucosuria may be caused by hyperglycemia or renal prox-
imal tubular damage. The proximal tubule normally reab-
sorbs almost all of the ltered glucose. When the blood con-
centration and thus the ultraltrate concentration exceeds
the capacity of the proximal tubule for reabsorption (about
180 mg/dL for dogs and 300 mg/dL for cats), glucose appears
in the urine. Hyperglycemia can occur from diabetes melli-
tus, stress or excitement in cats, or dextrose administration.
Proximal tubular disorders, such as acute tubular necrosis,
pyelonephritis, Fanconis syndrome, or primary renal glucos-
uria, can lead to normoglycemic glucosuria.
Ketones
The primary ketones encountered in small animals are ace-
toacetic acid, acetone, and -hydroxybutyric acid. Ketone
reagent strips containing sodium nitroprusside react with
acetoacetic acid and acetone to cause a purple color change.
They are more sensitive to acetoacetic acid compared with
acetone (lower limit of detection 5-10 mg/dL vs. 70 mg/dL,
respectively). They do not detect -hydroxybutyric acid. The
reagents are sensitive to the effects of moisture, heat, and
light, so the container should be kept closed when not in use.
Large amounts of bilirubin or other substances that discolor
urine can cause a false positive reaction.
Ketones are produced from fatty acid metabolism. Poorly
controlled diabetes mellitus is the most common reason for
their development, but starvation, a high protein and low
carbohydrate diet, and some drugs can also cause ketonuria.
Bilirubin
When hemoglobin is degraded, the heme portion is con-
verted to bilirubin, which is conjugated in the liver and ex-
creted in the bile. Some conjugated bilirubin escapes to the
circulation and is ltered by the glomerulus and appears in
the urine. The kidney can metabolize hemoglobin to biliru-
bin and secrete it in dogs but not in cats. Male dogs have a
higher secretory ability compared with female dogs. Dipstick
reagent pads use diazoniumsalts to create a color change and
are more sensitive to conjugated bilirubin than free bilirubin.
False negative reactions may occur with large amounts of
ascorbic acid or nitrites. False positive reactions can occur if
a large dose of a phenothiazine drug has been administered.
The practical sensitivity of bilirubin reagent sticks is re-
ported to be 0.4 to 0.8 mg/dL. Small amounts of bilirubin are
normal in dogs, but bilirubinuria is never normal in cats.
Because conjugated bilirubin is freely ltered, bilirubinuria
may precede bilirubinemia. Bilirubinuria tends to be higher
with extrahepatic biliary obstruction compared with intrahe-
patic disease.
Urobilinogen
Conjugated bilirubin is excreted into bile then degraded by
intestinal bacteria into urobilinogen. Most of the urobilino-
gen is then oxidized to urobilin, but a small amount is reab-
sorbed and excreted in the urine. Urobilinogen is unstable
and stored urine samples yield inaccurate results. Urobilino-
gen is a normal nding. Urobilinogen concentration is poorly
correlated to hepatobiliary disease and this test has question-
able clinical usefulness.
Nitrite
Some bacteria are able to convert nitrate to nitrite. Although
nitrite test pads are available on some dipsticks, nitrite is not
a reliable marker of bacteriuria in small animals.
Leukocytes
The leukocyte esterase reaction detects esterases found in
granules of granulocytes (neutrophils, basophils, and eosin-
ophils). In dogs, the test is specic, but not sensitive, mean-
ing the test fails to detect many cases of pyuria, but a positive
test is indicative of pyuria. WBCs may be present from infec-
tion or inammation. Because of the high false positive rate in
cats, this test is not useful in this species.
Protein
Urine dipsticks can give a semiquantitative estimate of pro-
teinuria. The color indicator (tetrabromophenol blue) is
more sensitive to albumin than to globulins, and most urine
protein is albumin. Results are reported as trace (10 mg/dL),
1 (30 mg/dL), 2 (100 mg/dL), 3 (300 mg/dL), or 4
(1000 mg/dL). Very alkaline or highly concentrated urine
may cause false positive results. The sulfosalicylic acid turbi-
dimetric test precipitates protein and can be used to conrm
positive dipstick results. A semiquantitative microalbumin-
uria dipstick is available to detect 1 to 30 mg/dL of urinary
albumin (ERD-HealthScreen, Heska Corp., Fort Collins,
CO). It uses ELISA technology specic for canine or feline
albumin. Because of minor species differences in albumin,
there are different kits for dogs and cats. The microalbumin-
uria test can detect lower concentrations of albumin than
would be detected with a standard dipstick. Hematuria must
be macroscopic to increase the microalbuminuria (or urine
protein:creatinine) measurements, although pyuria is vari-
ably associated with increased values.
11
A positive dipstick reading for protein may occur in con-
centrated urine and still represent normal urine protein ex-
cretion. In people, the gold standard is the 24-hour protein
excretion, calculated by analyzing an aliquot of all urine pro-
duced over a 24-hour period. Collecting a complete 24-hour
urine sample is cumbersome in animals. The urine protein:
creatinine ratio (UPC) accounts for the variations in urine
volume throughout the day by means of the creatinine con-
centration. UPC values correlate well to 24 hour urine pro-
tein excretion in dogs and cats.
12,13
Values below 0.5 are
considered normal in nonazotemic dogs and cats, and values
above 0.5 in azotemic dogs and 0.4 in azotemic cats should
prompt intervention.
14
Proteinuria can be preglomerular, glomerular, or postglo-
merular in origin. Preglomerular causes include fever, stren-
uous exercise, seizures, extremes of heat of cold, venous con-
6 N.J. Reine and C.E. Langston
gestion, or hyperproteinemia (ie, multiple myeloma).
Glomerular proteinuria is caused by damage to the glomer-
ular ltration barrier and is the most common and most
serious type of proteinuria. Postglomerular proteinuria can
be caused by inammation of the bladder or genital tract or
by tubular disease (inammation in the tubules or failure to
reabsorb the normal small amount of ltered protein). In the
presence of pyuria or hematuria, differentiating between glo-
merular and postglomerular proteinuria can be difcult.
Sediment Evaluation
Low speed centrifugation (1,000-1,500 revolutions per
minute for 3-5 minutes) minimizes disruption of cellular
elements of the urine sediment. After centrifugation, the su-
pernatant should be removed and the sediment then resus-
pended in the small remaining volume of urine. Ideally, a
consistent volume of urine should be utilized for re-suspen-
sion of each sample. Once suspended, a drop should be
placed on a microscope slide with a coverslip. It is best to
examine unstained samples with the condenser low, the mi-
croscope light dimmed and the iris diaphragm closed. This
will maximize contrast. Alternatively, sediment stains (ie, Se-
diStain, Becton-Dickinson, Sparks, MD) can be used to
enhance contrast. The sediment should be evaluated under
low and high power (Fig 5).
15
RBC
Normal urine should contain very few red blood cells. Own-
ers may observe macroscopic hematuria but microscopic he-
maturia will go undetected without sediment evaluation. He-
maturia can result from infection, inammation, neoplasia,
bleeding disorders, or trauma (Table 1). Iatrogenic hematuria
may result from cystocentesis. If blood contamination is ob-
served, particularly as the needle is being withdrawn fromthe
Figure 5 Common urine sediment ndings (400magnication). (A) Struvite crystals; (B) Oxalate dihydrate crystals;
(C) Unstained urine sediment with RBCs and WBCs; (D) Granular cast; (E) Mixed bacterial infection, Wrights stain.
Table 1 Causes of Hematuria by Location
Kidney/Ureter Bladder Urethra Genital Tract Extra-Urinary
Pyelonephritis Infection Stones Prostatic disease Coagulopathy
Nephrolithiasis Stones Infection Vaginal disease Trauma
Ureterolithiasis Neoplasia Inammation Vulvar disease Strenuous exercise
Neoplasia Drugs (Cytoxan) Neoplasia Uterine disease
Benign renal hematuria Idiopathic cystitis Granulomatous urethritis Preputial disease
Infarct Parasite Normal estrus
Urinalysis interpretation 7
bladder and skin, this should be noted and the results inter-
preted accordingly. If it is unclear if hematuria is iatrogenic, a
free catch sample performed a few days later can be sub-
mitted.
WBC
The presence of increased WBC indicates the presence of
urinary tract inammation. Typically, greater than 5 WBC/
high power eld (HPF) is excessive though individual labo-
ratory ranges may vary slightly. The presence of pyuria cer-
tainly raises concern of the presence of bacterial urinary tract
infection. Sterile inammation associated with urolithiasis
and neoplasia can also cause pyuria. Pyuria in a sample ob-
tained via cystocentesis may indicate infection or inamma-
tion of the kidneys, ureters, urinary bladder, or prostate. For
free catch samples, the vaginal cavity or skin may contribute
as well.
1
Any patient with pyuria, particularly those with
signs referable to the urinary tract (ie, stranguria, pollakiuria,
hematuria, polyuria) should have a urine culture and sensi-
tivity performed. Patients with diabetes mellitus are predis-
posed to urinary tract infection and many times do not have
signicant pyuria.
16
Organisms
Bacteria
Normal urine is sterile. Because bacteria can be found in the
distal urethra and genital tract, samples obtained via free-
catch or catheterization may have some degree of contami-
nation. Cystocentesis is the method of choice for obtaining
the urine sample when bacterial urinary tract infection is
suspected. Although bacteria can be visualized on micro-
scopic examination, it is sometimes difcult to distinguish
bacteria from debris. The presence of pyuria in the same
sample would support the nding of bacteriuria. Microscopic
examination of modied Wrights stained urine samples have
been shown to be superior to traditional wet-mounts when
attempting to identify bacterial urinary infections in dogs.
17
A
bacterial culture and sensitivity should be performed on
urine samples with microscopic evidence of bacteriuria.
Bacterial urinary tract infections are quite common in
dogs. Dogs with recurrent or persistent urinary tract infec-
tions will frequently have either a metabolic or structural
reason for recurrent infection. It has been documented that
dogs with diabetes mellitus and Cushings disease can have
urinary tract infections without the presence of stranguria,
pollakiuria, or abnormal urine color. In one study, pyuria
was found in 60%of dogs with hyperadrenocorticismand/or
diabetes mellitus.
18
Based on this information, it is essential
that patients with either of these diseases have frequent uri-
nalysis and urine cultures performed, regardless of clinical
signs. Recurrent bacterial urinary tract infection is also well
documented in dogs with recessed or juvenile vulvar confor-
mation. Surgical correction has been shown to minimize re-
currence.
19
Another patient group to consider frequent uri-
nalysis and urine culture testing would be patients with
chronic kidney failure.
In contrast to dogs, the incidence of bacterial urinary tract
infection in cats is quite low, relative to the incidence of lower
urinary tract signs (5%).
20
Older cats (10 years) are more
likely than younger cats to have urinary tract infection asso-
ciated with lower urinary tract signs.
21
As in dogs, cats with
diabetes mellitus and kidney failure should have frequent
testing of their urine for evidence of infection (pyuria, bacte-
ruria, positive urine culture) regardless of clinical signs.
Yeast
Occasionally, yeast or fungal hyphae may be seen in a urine
sample and often represent contamination. In cats, true fun-
gal urinary tract infections are most commonly seen associ-
ated with prolonged antibiotic and/or glucocorticoid ther-
apy, aciduria, and the use of indwelling transurethral
catheters.
22
Fungal organisms can also be identied in the
urinary bladder of patients with systemic mycoses (ie, blas-
tomycosis).
Epithelial/Transitional Cells
Transitional cells are the epithelial cells lining the mucosa of
the renal pelvis, ureter, urinary bladder, and urethra. There
are also epithelial cells associated with the prostate, vagina,
and uterus. It is normal to have occasional small epithelial
cells in a urine sample. The size of the epithelial cells seen
may aid in determining where in the urinary tract they come
from as cells from the kidney are the smallest; the ureter,
bladder and proximal urethra have cells larger than the kid-
ney cells; and the cells from the distal urethra, vagina, and
prepuce are the largest. Increased numbers of epithelial cells
can be seen in association with infection, inammation, irri-
tation, and neoplasia.
Transitional cells are very reactive cells. It is very difcult
to distinguish neoplastic transitional cells from metaplastic
changes in transitional cells associated with inammation,
infection or mechanical (ie, calculus) or chemical (ie, cyclo-
phosphamide) irritation. This explains why urine cytology
evaluation is not the ideal method of diagnosing transitional
cell carcinoma.
23
Urinary Casts
Casts form in the renal tubular lumen and are composed of
matrix mucoprotein and varying cell types and numbers.
There can be 1 to 2 casts per lowpower eld in normal urine.
Tamm-Horsfall mucoprotein (THM) is likely the matrix for
cast formation in dogs and cats. Secretion or precipitation of
THM is increased in acidic, highly concentrated urine and
during times of low tubular ow rate (ie, when there is a
decrease in GFR). Increased THM favors increased cast for-
mation. Cylindruria (increased number of casts) indicates
that there is disease in the kidney, though not necessarily
kidney failure. It does not mean that the kidney is the primary
organ involved in the disease process. For example, hypoxia
associated with hypovolemic shock can result in cylindruria.
The presence of casts does not discriminate between glomer-
ular, interstitial, and tubular disease. The different types of
casts seen are hyaline, cellular, epithelial (white cell, red cell,
or granular), waxy, and broad casts.
Hyaline Casts
There are pure protein precipitates (THM and albumin).
They are transparent and can be easily missed in an unstained
sample. Using Sedi-Stain will make them pink and more
visible. Hyaline casts will be increased in disease processes
that favor proteinuria (ie, protein-losing nephropathy, fever,
8 N.J. Reine and C.E. Langston
exercise, acute tubular necrosis) but their presence doesnt
indicate the source of the protein.
Cellular Casts
Samples of urine from normal dogs and cats should never
have cellular casts. The most common cellular casts are epi-
thelial cell casts, white cell casts and red cell casts.
Epithelial Cell Casts
These contain renal epithelial cells. They form in situations
where there is sloughing of the renal tubular epithelium (ie,
renal tubular necrosis). These are most commonly associated
with acute renal tubular injury (ie, nephrotoxicity or isch-
emia).
White Cell Casts. It can be difcult to distinguish renal ep-
ithelial cells from white blood cells when there has been
signicant degeneration. Examination of a fresh sample
should minimize the likelihood of degeneration. White cell
casts most commonly contain neutrophils. They are seen
most commonly in patients with acute bacterial pyelonephri-
tis but can be seen with other forms of interstitial nephritis.
Red Cell Casts. Red cell casts are rare. They form when red
cells aggregate associated with tubular bleeding. Fresh sedi-
ment should be evaluated as these casts degenerate easily.
Granular Casts. These casts contain debris associated with
tubular cell necrosis and degeneration. They are typically
coarse initially after damage then progress to ne granular
casts. These casts usually indicate tubulointerstitial disease.
Waxy Casts. These represent the latest stage of degeneration
of granular casts and are more stable than their precursors.
They are usually associated with chronic renal disease.
Broad Casts. These are wide casts of any type. They are
usually formed in the collecting duct or other portions of the
distal tubule that are abnormally dilated. These casts can be
seen with chronic renal disease or during recovery from an
oliguric state.
1
Crystals
The presence of crystalluria is inuenced by urine pH, urine
specic gravity, urine saturation with precursors, and the
presence of crystal promoters or inhibitors. Patients with
highly concentrated urine samples, high concentrations of
crystallogenic substances in their urine, and low urine ow
rates are predisposed to crystal formation.
Unfortunately, crystals found in stored samples may have
formed after sampling. A recent studies investigating crystal-
luria in dogs and cats documented that interpretation of 28%
of stored samples positive for crystalluria were false positives.
In fact, crystals formed in vitro less frequently in nonrefrig-
erated samples compared with those stored in a refrigerator.
3
Urine samples should be analyzed with an hour to increase
the likelihood that it is truly representative of what is going
on in the patient. Ideally, all samples, particularly serial sam-
ples in the same patient, should be interpreted in a timely
manner.
Crystals (struvite, amorphous phosphates, oxalates) may
be seen in samples obtained from patients without signs of
lower urinary tract disease. A recent investigation found that
92% of cats without urinary tract signs fed a mixture of wet
and dry food had crystalluria on stored urine samples.
24
This
may lead to inappropriate use of diets formulated for crystal
prevention and potential increased incidence of other crystal
types. If fresh urine samples were utilized, only 24% of the
cats had crystalluria. Remembering that none of these cats
had lower urinary tract signs, the presence of crystalluria
found in urine samples from cats should be interpreted with
caution, particularly in those fed some amount of dry food.
Miscellaneous Urine Tests
Fractional excretion is the fraction of a ltered substance that
appears in the urine as a result of tubular reabsorption and
secretion. It is calculated from the formula: FE (U
x
/S
x
) *
(S
Cr
/U
Cr
) * 100, where U is the urine concentration, S is the
serumconcentration, x is the electrolyte being measured, and
Cr is creatinine. Diurnal variation, diet, and hormonal inu-
ences affect fractional excretion, which does not correlate
well with 24-hour electrolyte excretion.
25,26
Results should
be interpreted in light of the entire clinical picture (Table 2).
Veterinary bladder tumor antigen test [VBTA, Alidex Inc.
(subsidiary of Polymedco Inc.), Redmond, WA] can be used
as a screening test for transitional cell carcinoma. Unfortu-
nately, this test is not specic for transitional cell carcinoma,
in that dogs with nonneoplastic bladder disease (eg, UTI,
polypoid cystitis) frequently have positive test results. On the
other hand, a negative test almost rules out neoplasia.
27
This
test might be considered for routine screening of dogs pre-
disposed to bladder cancer (ie, Scottish Terriers
28
) who do
not have signs of lower urinary tract disease.
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