DIAGNOSTIC TESTS USED IN RENAL DISEASE

Table Of Content
Introduction
Sample collection and handling
Urinalysis
Blood Chemistry
Renal Function Tests
Renal biopsy and prostate fluid cytology
Diagnostic Imaging
Conclusion
References

Introduction
Renal disease is any morphological or biochemical lesion in the kidney. Strictly speaking, it is
differentiated from renal failure which is loss of renal function for several reasons. Usually, clinical
signs and laboratory abnormalities are not apparent until renal disease is considerably advanced
because of renal compensation. Several renal functions are also closely related to each other. Hence
it is not easy to evaluate the actual renal state.
Renal functions which can be detected by laboratory methods list as:
1. the excretion of nitrogenous wastes (e.g. urea and creatinine)
2. acid-base balance
3. body fluid and electrolyte homeostasis
4. the decomposition of certain substances (e.g. amylase and lipase)
5. the secretion of a certain hormones (e.g. erythropoietin).
Renal diagnostic aids can provide valuable data for detecting or supporting a clinical diagnosis of
renal disorders and information related to other organ systems such as the liver, pancreas and blood.
They should be done repeatedly to prevent potential interpretation errors due to delayed response
and interpreted with clinical signs and other diagnostic results. To deliver a more rational and
accurate diagnosis, practitioners should have a better understanding of normal renal physiology and
anatomy and several renal diagnostic methods.
In this essay, sample collection and handling and diagnostic aids used in renal disease and their
interpretation will be discussed.

Sample collection and handling

Urine collection techniques
If a meaningful result is to be obtained, proper collection of a urine sample is extremely important.
Although several methods for urine collection are available, cystocentesis followed by catheterization
is preferred.

1. Voided sample

A voided urine sample is the simplest method of collecting urine from an animal and can be
obtained by the owner. Since contamination is a major problem, this method is not suitable for
urinary culture. Washing the external genitalia and collecting a mid stream sample can
decrease the contamination. Because dogs tend to stop urinating when approached,
attaching a paper cup to a long pole is one way to overcome this problem. In cats this method
is not successful. They are induced to urinate in a clean, empty litter tray.

2. Catheterization

A catheterised urine sample is more diagnostic than a voided sample but is not suitable for
bacterial culture. Catheterization can potentially cause urinary tract trauma or lead to urinary
tract infection.

3. Cystocentesis
 This method is the best for collecting urine for urinalysis and culture. However, iatrogenic
haematuria or leakage of urine into the abdominal cavity are potential problems.

Handling and preservation of urine sample

Correct handling and preservation of urine samples are essential if an accurate result is to be
obtained.

1. Handling

Samples should be examined within 30 minutes of collection to prevent microbial growth and
chemical degradation. Because cell cytology can rapidly change, urine should be centrifuged
immediately and 1-2 drops of the patient’s serum or bovine albumin should be added to
preserve cell morphology. Refrigeration at 5ÙY in a dark environment is the most desirable
method of preservation if samples can not be examined within 30 minutes. However
refrigeration tends to increase the number of crystals in urine. The sample should be warmed
before chemical analysis, because enzyme-based tests may be affected at low temperature
and specific gravity of cold urine is higher than warm urine.

2. Container

There are many kinds of disposable and reusable commercial container used in practice.
Urine containers should be clean, readily available, inexpensive and sterile and have tight-
fitting lids. Opaque containers are more preferable to transparent containers if urinalysis can
not be performed within 30 minutes after collection, because bright light can degrade urine
constituents. Common household containers are often contaminated so as interfere with test
results.

3. Preservatives

Several types of preservatives can be used if analysis is delayed, although none are ideal.
There are two groups of preservative in practice. One group is used to prevent microbial
growth while the other group is used to prevent chemical changes.

Preservative for preventing microbial growth

 Formaldehyde

It prevents microbial growth and preserves casts and cellular elements. Usually
one drop of 40% formalin is added to 30 ml of urine. It is the best for examining
formed elements in urine. However it interferes with the detection of glucose.

 Thymol

It is added to urine as a 10%(w/v) solution in isopropanol. 5 to 10 ml is

sufficient to preserve a 24-hr urine collection. It will cause a false positive
reaction for protein when either sulfosalicylic acid or Exton's reagent is used.

 Toluene
 It prevents microbial proliferation when added in a sufficient volume to form a
thin film over the urine. It may reduce the quantity of acetone in urine, because
acetone is soluble in toluene.

 Boric acid

It is superior to other preservatives in preventing bacterial growth. One gram of

boric acid is adequate to preserve a 24-hr urine sample (10ml). It does not
interfere with analysis of some hormones such as aldosterone and pituitary
gonadotropins.

Preservative for preventing chemical changes

 Hydrochloric acid (HCl)

One ml HCl per 100ml Urine; It is used for analysis of estrogens
and catecholamines
Acidification of urine is recommended for preserving casts or
cellular elements, because these components can dissolve in
alkaline urine. However some crystals found in alkaline urine can be
dissolve.

 Sodium fluoride

Ten mg sodium fluoride and 1 mg thymol per 1 ml of urine. It can affect the
dipstick tests including glucose test.

 Metaphosphoric acid (HPO3)

Metaphophoric acid (10%) is added to urine in a ratio of 1:5.

Urinalysis
Physical Examination

1. Colour

Normal colour of urine is yellow or amber. While concentrated urine is a darker yellow or
yellow-brown, diluted urine is light yellow or colourless. Main causes of dark urine are
dehydration, reduced water intake and fever. Colourless urine can be observed in advanced
renal failure, diabetes insipidus, hyperadrenocorticism, pyometra and psychogenic polydipsia.
Yellowish brown or greenish brown urine indicates bilirubinuria. Pinkish brown or reddish
brown urine indicates porphyrinuria. Haematuria is opaque and the supernatant is clear after
centrifugation, if haemolysis has not occurred. Certain drugs can change the colour of urine.

2. Transparency (turbidity) and foam

 Urine is normally clear in dogs and cats. Cloudy urine implies the presence of suspended
material such as cells, crystals, lipids or mucus.

Normal urine produces a white foam when shaken. Haemoglobin, myoglobin and bilirubin will
concentrate in foam.

3. Specific gravity (SG)

Specific gravity, unlike osmolarity, is the ratio of the weight of water to the weight of solutes.
The urine osmolarity can be determined by multiplying the last two digit by 36 (SG is 1.012,
the urine osmolarity is 12 ÙO 36). Urine SG is a measure of the renal ability to concentrate or
dilute urine. Urine SG in dogs can range from 1.001 to 1.065, but is usually 1015 to 1.045. In
cats the range is 1.001 to 1.080, but is normally 1.035 to 1.060 (Osborne et al 1995).

Specific gravity should be related to the state of hydration, presence or absence of azotaemia
and urine solutes such as glucose and protein (table 1.1). If an animal is 3% dehydrated, its
urine SG increases due to renal concentration and ADH secretion. However if its SG is low
with azotaemia, it indicates renal disease. Specific gravity is a useful diagnostic aid to
differentiate the causes of azotaemia. If SG is increased with azotaemia, it indicates prerenal
azotaemia, while if SG is decreased with azotaemia, it indicates renal or postrenal azotaemia.

Urine SG is measured by using a refractometer. Urine reagent sticks are not accurate. It is
affected by abnormal substances. The SG increases by 0.001 for every 4g of protein or for
every 2.7g of glucose per litre. Cells, crystals and mucus can also increase the SG value.
Decreased specific gravity Increased specific gravity

- Temporary - Pathological  Dehydration

 Overabsorption of water
 Late renal disease
 Administration of diuretics
 Acute nephritis
 Parenteral fluid therapy
 Severe renal amyloidosis
 Corticosteroid and ACTH Diabetes
insipidus
 Oestrus and sex hormone
 Pyometra
 Renal cortical hypoplasia
 Hyperadrenocorticism
 Chronic generalised pyelonephritis
 Fever
 Oedema by circulatory disturbance
 Burns (rare)
 Acute nephritis (early)
 Diabetes melitus
 Shock
 Abnormal contents in urine
 Glucosuria or proteinuria
 Inflammatory exudate (rare)

Table 1.1 Conditions which can alter urine SG

Chemical Examination

1. pH

Urine pH is affected by the type of diet. Generally herbivores produce alkaline urine
following to the high carbohydrate content in the diet. In carnivores and omnivores, urine pH
is more acidic but is variable depending on the proportion of protein in the diet. Although
several methods are available to measure urine pH, pH- meter and pH-paper are commonly
 used in practice. Urine pH can be changed by physiological and pathological causes (table
1.2).
Alkaliuria Aciduria
 Highly vegetable contained diets  Highly protein contained diets
 Cystitis  Starvation by anabolism of protein
 Stasis of urine  Fever
 Fast absorption of transudates  Acidosis (e.g. uraemia, diabetes
 Alkalosis mellitus)
 Administration alkali salts  Administration of acid salts
 Continuous muscle exercise
Table 1.2. The conditions associated with Urine pH change
2. Protein

A trace to 1+ proteinuria is not significant in concentrated urine, while a trace in diluted urine
is significant. Therefore protein loss in the urine should be related to urine SG and volume.
The urine protein/urine creatinine (UP/UC) ratio is more accurate indicator of protein loss.

Globulin can not normally pass through the glomerulus owing to its large molecular weight.
Hence the protein observed in urine is mostly albumin even though light chained globulin or
Bence-Jones protein can be detected in some conditions. Because urine stick detects only
albumin, an acid precipitation method or electrophoresis should be considered if Bence-Jones
proteinuria is suspected.

Physiological proteinuria can occur with muscular exercise, high protein diets, and oestrus.
Pathological proteinuria is mainly caused by haemorrhage into the urinary tract or glomerular
disease (table 1.3). Proteinuria due to urinary tract inflammation or haemorrhage can be
differentiated by occult blood test and urine sediment test. A 3+to 4+ proteinuria is typical of
primary glomerular diseases, especially glomerulonephritis and renal amyloidosis. In primary
renal tubular disease, proteinuria is less than 2+. Absence of proteinuria should not exclude
renal disease, because non-glomerular diseases can occur without proteinuria.

Protein can be measured in urine by using the Robert's test, sulfosalicylic acid test and urine
stick. Urine stick gives a false positive reaction in alkaline urine, which can be corrected by
adding a drop of 40% hydrochloric acid. Because proteinuria is related to urine SG and urine
sediments, it should be interpreted with these parameters.
Physiological Prerenal causes Post renal causes Renal causes
causes
1. Severe muscle 1. Multiple 1. Lower urinary 1. Severe
exercise myeloma tract  Haematuria by
2. Stress (Bence-Jones obstruction/infe cancer
3. Protein Protein) ction  Acute nephritis
overtake 2. Haemolytic 2. Urolithiasis  Glomerulonephritit
4. Seizure diseases s
3. Myoglobinuria  Nephrosis by drug
4. Cardiac poisoning
diseases  Amyloidosis
5. Dehydration 2. Moderate
6. Genital infection  Pyelonephritis
or inflammation
 Polycystic kidney
disease
3. Mild
 Late renal
disease

Table 1.3. The causes of proteinuria

 3. Glucose

Glucose is reabsorbed by the proximal renal tubular cells and is not normally detected in urine
using urine dip sticks. Commonly used methods for detecting glucose in urine are the
Benedict method and an enzymatic method. Urine samples containing vitamin C can give a
false negative reaction. Enzymatic methods can also produce a false positive reaction in cats
with cystitis.

The most common cause of glucosuria is hyperglycaemia. However, glucosuria can occur with
normoglycaemia and so it should be interpreted with blood sugar levels (table 1.4).
Glucosuria with hyperglycaemia Glucosuria without hyperglycaemia
 Diabetes mellitus  Primary renal glycosuria
 Acute pancreatic necrosis  Proximal tubular dysfunction (Falconi
 Hyperadrenocorticism syndrome)
 Administration of glucose fluid  Drugs: Streptomycin, chloramphenicol,
 Carbohydrate overloading terramycin, aureomycin, Vit C.
 Hyperthyroidism morphine, salicylate, chloral hydrate,
phlorizine
Table 1.4. The interpretation of glucosuria with or without hyperglycaemia.
4. Ketones

Ketones are not normally present in urine and occur with abnormal fatty acid metabolism
associated with carbohydrate deficiency or abnormal glucose metabolism. Three types of
ketones (acetone, acetoacetate and -hydroxybutylate) are found in animals. Acetone gives a
sweet odour to urine. Starvation can result in a mild ketonuria in animals, though rare in dogs
and cats. The Ross test, Hart-Lange method and urine stick method are commonly available
in practice. Although -hydoxybutyrate is the most sensitive indicator of ketosis, it is not
detected by urine sticks which detect only acetone and acetatoacetate.

The common causes of ketonuria are ketosis, diabetes mellitus, lactic acidosis, excessive
lipid intake, starvation and hepatic failure. Of the above, only ketoacidotic diabetes is usually
associated with significant ketonaemia. The renal threshold for ketones is low so ketonuria
tends to precede detectable ketonaemia.

5. Bilirubin/Urobilinogen

Bilirubin is derived from the degradation of haemoglobin by the mononuclear phagocytic

system. Bilirubin is conjugated in the liver to direct bilirubin. It is excreted mainly by the
intestine and partly by the kidney. Because indirect bilirubin is combined with albumin, it can
not filtered by renal glomerulus. Therefore the origin of bilirubin in urine is direct bilirubine.

It is a useful test for detecting hepatic diseases, biliary system problems and haemolytic
diseases. Trace to 1+ bilirubinuria is normal in dogs, because dogs have a low threshold for
bilirubin and occurs before bilirubinaemia is clinically detected. while any kind of bilirubinuria
is abnormal in cats.

Because bilirubinuria implies the obstruction of bile flow and regurgitation of direct bilirubin
into the circulation, it occurs in obstructive biliary diseases and hepatocellular diseases.
However, intravascular haemolysis and haemoglobinuria can also induce bilirubinuria due to
renal tubular conjugation of indirect bilirubin. Bilirubinuria alone is not reliable and should be
interpreted with other hepatic function tests and haematology. Foam test, Harrison method
and urine stick method are available in practice for detecting bilirubinuria.

Urobilinogen is formed by the bacterial action on direct bilirubin in the duodenum. It is used to
differentiate between haemolytic and obstructive jaundice. As the correlation between urine
urobilinogen and hepatobiliary in dogs and cats is so poor, the usefulness of this test is
minimal. The Ehrlich aldehyde method and the urine stick method are available in practice.
 Generally urobilinogenuria may occur in hepatic and haemolytic diseases, but not in
obstructive biliary diseases. Table 1.5 shows laboratory findings for three types of jaundice.
Bilirubin Urobilinogen Bilirubin Urobilinogen
Prehepatic ++ (Mostly indirect) ++ - ++
Hepatic ++ (Both) ++ ++ ++
Posthepatic ++ (Mostly direct) - ++ -
Table 1.5 The differentiation of aetiology of jaundice
6. Occult blood

This test detects the presence of blood, haemoglobin and myoglobin in urine. The benzidine
method and urine stick are used in veterinary practice. Urine stick is more sensitive for
detecting haemoglobin and myoglobin than erythrocytes. Haematuria and haemoglobinuria
may be differentiated by centrifugation. Haemoglobin and myoglobin may be differentiated by
using the ammonium sulphate solution method or the Caboney haemoglobin spectrometer
method. High SG, severe proteinuria and vitamin C give a false negative or reduce colour
development. The causes of haematuria, haemoglobinuria and myoglobinuria are summarised
in table 1.6.
Haematuria Haemoglobinuria Myoglobinuria
 Urinary diseases  Neonatal haemolytic  Muscular inflammation
 Urolithiasis disease or necrosis
 Oestrus or after  Severe Burns  Severe muscular
parturition  Photosensitization exercise
 Severe infectious  Improper blood
disease transfusion
(Leptospirosis, ICH)  Infectious diseases
 Poisonings (Copper, (Leptospirosis,
mercury, sulphas, babesiosis)
phenol)  Chemical poisoning
 Parasite
(Dioctophyma,
Dirofilaria)
 Congestive heart
failure/ vegetative
endocarditis
 Thrombocytopenia
Table 1.6 The causes of haematuria, haemoglobinuria and myoglobinuria
7. Nitrite

Nitrite is not normally found in urine and is produced by the bacterial reduction of nitrate to
nitrite. However, it is not a reliable test in canine and feline urine. Griess's test and urine stick
method are used for detecting nitrite in urine.

Urine Sediment Examination

Urine sediment examination is one of the most important parts of urinalysis. Generally urine samples
collected by cystocentesis are ideal. Although a stained urine sample makes identification of cell type
or cast types easier, a non-stained urine sample is more desirable because artifacts are less likely to
occur. Usually centrifugation is used to concentrate the urine sediments and the slide is examined
under light microscopy with the condenser fully extended.

Organised Sediments

1. Erythrocytes

Normally, there are less than 5 RBC per high power field (hpf). The normal number and
shape of RBC in urine are affected by sampling methods, SG and pH. It is normal 0-3
cells/hpf in cystocentesis, 0-5/hpf in catheterised sample and 0-7/hpf in varied samples. The
shape of RBC is round in normal urine, crenated or distorted in concentrated urine, and
swollen or globular in diluted urine. Erythrocytolysis may occur in very dilute urine (less than
SG 1.008).

An increased number of RBC in the urine implies haemorrhage or inflammation in the urinary
system. If RBC are found in casts, it indicates renal haemorrhage. Haematuria commonly
occurs with urolithiasis, urinary tumours, bacterial infection, trauma, sterile cystitis, renal
diseases, renal parasite infestation and thrombocytopenia. In free catched samples, it is also
associated with genital haemorrhage or inflammation.

2. Leukocytes

Normally, there are less than 5 leukocytes (WBC) per hpf. Like RBC in urine, they are also
affected by the same factors. The normal number of WBC in urine is the same as that of RBC.
More than 5 WBC in the urine indicate urinary tract inflammation. The practitioner should
submit the sample for bacterial culture, even though bacteriuria is not obvious.

3. Epithelial cells

The types of epithelial cells found in urine are tubular cell, transitional cells and squamous
cells. Normally, urine contains low numbers of squamous and transitional epithelial cells.
Squamous epithelial cells are large, angular and irregular shaped cells with small nuclei
derived from urethra, vagina or prepuce. Transitional epithelial cells vary in size and shape
and are derived from the renal pelvis, ureter, bladder and proximal urethra. They are more
common in catheterised samples. Renal epithelial cells are small round in shape and are
derived from the renal tubules. However they are difficult to distinguish from WBC due to
cellular degeneration. Malignant cells in urine are difficult to distinguish from early
degeneration of epithelial cells. Hence urinary bladder wash and biopsy are more desirable.
The number of epithelial cells can be increased with cystitis, tumours or inflammation.

4. Micro-organisms

Normal urine is sterile, but can be contaminated during collection. If bacteria are present, a
bacterial culture should be performed. Eggs of Capilaria plica or Dictophyma renale and
microfilaria of Dirofilaria immitis can be observed in urine samples.

5. Casts

Cast are elongate, parallel structures or moulds that form in an acidic environment in the
distal renal tubules. Certain types and number present may indicate renal disease but they do
not correlate well with the severity of renal damage and their absence does not exclude renal
disease. Casts can be disrupted by fast centrifugation and dissolved in alkaline urine.

One or two hyaline and granular casts per low power field (lpf) is normal. Large numbers of
casts implies active generalised renal disease.

Hyaline casts are composed mainly of mucoprotein and are not significant when present in
low numbers. Granular casts are hyaline casts combined with degenerated cells. They are the
most common cast type observed and are commonly seen in many renal diseases. Epithelial
casts are observed in severe renal tubular disease such as heavy metal intoxication or
ischaemic tubular injury. Waxy casts represent older degenerate granular casts and imply
chronic tubular pathology. Leukocyte casts occur in renal inflammation, urinary tract
inflammation or non-septic nephritis. Erythrocyte casts indicate renal tubular haemorrhage,
severe glomerular inflammation or renal ischaemia.

Fatty casts are very common in cats due to high lipid content in the tubular cells. It can
indicate non-specific tubular cell degeneration or protein-losing glomerulopathies.

6. Spermatozoa
They can be observed in normal entire male animals and in recently coital female animals.

Unorganised Sediments

1. Lipiduria

Lipid in urine sample appears as floating black, refractile spheres of variable size which can
be stained by Sudan III or Oil red O stain. Lipiduria is common in cats and is influenced by
diet. It can be also observed in animals with lipiaemia and renal disease.

2. Crystals

Several crystals can be found in urine samples. Some crystals form normally, while others
indicate pathological changes.

A. Bilirubin

Bilirubin crystals can be found in highly concentrated urine and in urine associated
with disturbances of bilirubin metabolism.

B. Calcium oxalate

Regardless of urine pH, these crystals are normally found in dog and cat urine but can
occur with oxalate urolithiasis or ethylene glycol poisoning.

C. Calcium phosphate

Calcium phosphate crystal occur in normal dogs, especially in alkaline urine. They can
be also found in dogs with infection-induced struvite crystalluria.

D. Cystine

Cystine crystals are not found in normal urine. They are often seen in acidic urine of
dogs with cystine urolithiasis.

E. Drug-associated crystalluria

Various drugs can form crystals in urine. The shape and pH preference is also
variable, depending on the drug. Sulphonamide crystals are the most common drug
crystals seen in urine.

F. Magnesium ammonium phosphate (Struvite)

Struvite crystals are the most common crystal found in dog and cat urine. They can
form in any urine pH, especially alkaline urine and are commonly seen in urinary tract
infections and urolithiasis.

G. Ammonium biurate

Ammonium biurate crystals may form spherulites or spheric bodies with long irregular
protrusions especially in neutral and alkaline urine. They are commonly found in
dalmatians and English bulldogs (Osborne et al 1995). They are also more often
observed in dogs with portal vascular anomalies.

H. Uric acid

Uric acid crystals are normally found in dogs and cats especially dalmatians but may
indicate urolithiasis.
 Blood Chemistry
Azotaemia
Azotaemia means an increased concentration of urea and/or creatinine in the blood and should be
differentiated from uraemia which is azotaemia accompanied by clinical and biochemical signs of
renal failure. Azotaemia usually reflects decreased glomerular filtration. Despite a significant
decrease in glomerular filtration, plasma urea (PU) and creatinine can be mildly elevated. Renal
azotaemia reflects structural renal damage. Azotaemia should be interpreted with SG and other
laboratory results (fig 1.1)
Prerenal azotaemia is more common than renal azotaemia. It results from any causes which lead to
reduced renal perfusion which activates ADH secretion and increases urine concentration. High SG
occurs in urine. Azotaemia with isosthenuric or minimally concentrated urine indicates renal disease.
Loss of renal concentrating ability usually equates with loss of function of at least 3/4 of the
nephrons. Postrenal azotaemia occurs with urinary obstruction or post renal urinary tract rupture and
can be diagnosed with other results such as urolithiasis or signs of uroperitoneum.

1. Plasma Urea

Most PU is synthesised by the hepatic urea cycle enzymes from ammonia and is excreted
mainly by the kidneys. Because it is freely filtered by the glomerulus, any decrease in
glomerular filtration can induce a rise of PU. Unlike creatinine, it is reabsorbed passively by
renal tubules and then returns to the circulation. At high flow rates, only about 40% of luminal
urea will be resorbed into blood, while at low flow rates, up to 70% will be resorbed. Because
tubular creatinine resorption does not occur, it can be used to distinguish between renal and
prerenal azotaemia (fig 1.1).

The main causes of increased PU are either increased breakdown of tissue or dietary
proteins or impaired excretion. The main causes of decreased PU levels are reduced
synthesis due to hepatic dysfunction or malnutrition. Important physiological and pathological
causes that affect PU levels are summarized in table 1.8.

PU is not very sensitive, because 75% renal function needs to be lost before it significantly
rises above normal. It is also affected by diet, bacterial contamination of sample, exercise or
lipidaemia (wet chemistry, only). Best results are obtained if fasted blood sample are collected
and examined within a few hours of collection or refrigerated.

There are many methods to measure PU. The urease reagent strip (Azo Stick ) is commonly
used, but is not accurate. Colorimetric methods are the most reliable and sensitive method for
measuring urea.
Causes of increased urea levels Causes of decreased urea levels
1. Renal disease 1. Low protein diet
2. Disease which reduces GFR 2. Anabolic steroids
3. Dehydration 3. Hepatic failure
4. Heart disease 4. Portosystemic shunt
5. High protein diet 5. Diabetes insipidus
6. Urinary obstruction 6. Primary hyperammonemia(rare)
Normal PU level (Bush 1991) Dog: 2.5-7 mmol/l. Cat: 5-11 mmol/l.
Table 1.8. Causes that affect plasma urea.
Fig. 1.1 Algorithm for the diagnosis of renal failure (PU= plasma urea, CR= creatinine, RF= renal
failure, UTO = urinary tract obstruction; Osborne 1995)

2. Creatinine

Creatinine in most animals is mainly excreted by glomerular filtration. Therefore it is better

than PU in evaluating glomerular filtration rate (Duncun et al 1994). The factors that affect
plasma creatinine level are muscle mass, muscular disease, exercise, renal perfusion and
 muscle contained in diets. Unlike urea, it is less affected by the catabolism of tissue or dietary
protein (Bush 1991). Due to its slow and progressive loss in plasma samples with time, the
practitioner should perform the test within 24 hr after collection. High levels of plasma bilirubin
may reduce the level of creatinine measured with the Jaffe method (Bush 1991) and high
levels of ketone may increase its level. Drugs such as cephalosporins, salicylates,
trimethoprim and cimetidine can also increase its level.

Elevated plasma creatinine levels indicate reduced renal function which may be due to renal,
prerenal or postrenal causes (table 1.9). Plasma urea/creatinine ratio is based on the differences
between urea and creatinine in terms of diffusion rates, tubular reabsorption, effects of protein
catabolism and diet and is advocated for differentiating prerenal and renal azotaemia. If the
value is larger than 50:1, it may indicate prerenal azotaemia, and if the value is less than 37:1,
it may imply renal azotaemia (Duncun et al 1994). However it is affected by too many variable
factors and so is not valid in veterinary practice.
Causes of increased creatinine levels
1. Decreased renal perfusion (Dehydration or cardiac disease)
2. Primary renal failure
3. Chronic renal failure
4. Obstruction of urinary flow
5. Urinary bladder rupture
6. Severe exercise
7. Presence of ketones or drugs (Error)
Normal creatinine level (Bush 1991) Dog: 40-130 umol/l. Cat: 40-130 umol/l.
Table 1.9. Causes that affect plasma creatinine.(based on Bush 1991)
3. Electrolytes

One of the main functions of the kidney is maintenance of electrolyte homeostasis. However,
several factors such as total body electrolyte stores, diet, intestinal disorders and hydration
can significantly affect plasma levels. Hence each electrolyte value alone is of limited value
for diagnosing kidney disease. Fractional clearance of electrolyte (FE) is superior to the
evaluation of electrolytes in diagnosis of kidney disease or renal dysfunction.

In animals with renal diseases, the concentration of potassium may be increased due to
reduced renal excretion, while that of sodium will be initially decreased due to sodium pump
deficits and later increased due to dehydration. Plasma chloride levels vary and are inversely
proportional to the bicarbonate concentration. In advanced renal disease, the chloride
concentration will be increased while that of bicarbonate will be decreased. In dogs and cats
with reduced renal function, the plasma phosphorus concentration will be increased, while in
the horse it will be decreased. Plasma calcium concentration is not consistent in renal disease,
however it is usually increased in advanced chronic renal failure and decreased in acute renal
disease.
Type Renal changes Result
Sodium Increased excretion Hyponatraemia
Potassium Decreased excretion Hyperkalaemia
Bicarbonate Reduced preservation Acidaemia
Phosphorus Decreased excretion Hyperphosphataemia
Calcium Increased excretion Hypocalcaemia
Blood pH Reduced removal of H+ Acidaemia
Lipid Increased synthesis Hypercholesterolemia
Protein Persistent proteinuria Hypoalbuminaemia
Table 1.10. Biochemical changes in renal disease (Meyer et al 1993) Rare, but occurs in man. Others
There are many other biochemical profiles which can be informative and support a diagnosis,
even if they are usually less valuable and informative than those mentioned. In this section,
some biochemical profiles such as blood pH, triglyceride and total protein will be discussed.
 1. Blood pH

Changes in acid-base balance is observed frequently in renal failure especially when

advanced.

2. Lipid

Hyperlipidaemia can occur in animals with renal disease, such as nephrotic syndrome.
Increased hepatic lipoprotein synthesis and hypoalbuminaemia is proposed in the
pathogenesis. (Meyer et al 1993).

3. Plasma protein

Generally the concentration of plasma protein is elevated due to dehydration but can
be reduced in primary glomerular diseases such as glomerulonephritis and renal
amyloidosis.

4. Amylase and lipase

Elevated plasma lipase and amylase levels can be observed in dogs with renal
disease, because these two enzymes are eliminated by the kidneys (fig 1.2).

5. Total Red blood cell

In chronic renal disease, non-regenerative anaemia is commonly observed. It is

mainly due to a reduced erythropoietin level secondary to the loss of renal
parenchyma. Other causes of anaemia in renal disease include haemorrhage, shorter
the life span of erythrocytes and bone marrow depression.

Fig 1.2 Algorithm in the diagnosis of increased serum amylase and lipase (Meyer et al 1993).

Renal Function Tests

Renal function tests are usually indicated in an animal suspected of renal dysfunction such as
azotaemia, generalised oedema, hypoproteinaemia and urinary disturbances. They may also be
indicated prior to major surgery and monitoring renal function after therapeutic implementation.
There are many tests available for assessing renal function. A proper application and careful
interpretation should be considered. Hence in this section, general principles associated with renal
function tests and their advantages and disadvantages will be discussed.
Renal Clearance Tests
An ideal substance used for measuring glomerular filtration rate (GFR) must be freely filtered without
renal tubular involvement.

1. Sodium sulfanilate & PSP clearance

These tests are no longer used in veterinary practice.

2. Measurement of Glomerular filtration rate (GFR) and renal blood flow (RBF)

Several radioisotopes such as 125I-iothalamate (GFR) or 131I-iodohippurate (RBF) are

mainly used in research.

3. Endogenous creatinine clearance

Since creatinine in most species is primarily excreted by glomerular filtration, it can be used
for measuring glomerular filtration rate. Because this test requires urine to be collected in a
metabolism cage and overnight hospitalisation in practice, many modified tests have been
 developed to overcome these difficulties. A brief procedure of endogenous creatinine
clearance test is summarized in table 1.11.

Prerenal renal failure due to hypotension or hypovolaemia and postrenal renal failure due to
urolithiasis, trauma or neoplasia are more common causes of reduced creatinine clearance.
Reduced creatinine clearance due to acute renal failure is less common than chronic renal
failure. Non-creatinine chromogens can interfere with creatinine assay.

Normal endogenous creatinine clearance is 2.4-5.0 ml/min/kg in dogs and 1.9-5.0 ml/min/kg
in cats. Values less than 1.0-1.5 ml/min/kg are considered abnormal in both species (Charles
1996).
Endogenous creatinine clearance
1. Obtain a blood sample for creatinine analysis.
2. Catheterise the bladder and rinse the bladder several times with sterile saline
Discard the rinse. Empty the bladder.
3. Begin timing immediately and collect all urine for a 20-minute or 24-hour period
(the latter is more precise).
4. At the end of this period (20 minutes or 24 hours), empty the bladder.
Measure the total urine volume collected. Rinse the bladder thoroughly with
Sterile saline. Empty the bladder and save the rinses. Submit an aliquot of urine
rinse saline for creatinine analysis.
5. Calculate creatinine clearance with the equation:
Creatinine clearance = (Uv X Uc) / Pc
Uv = urine volume; Uc = urine creatinine concentration; Pc = plasma creatinine
6. Normal clearance in dogs is 2.8 +/- 0.96 ml/min/kg.

Table 1.11. Protocol for endogenous creatinine clearance (Felderman and de Gopegui 1997).
4. Fractional clearance of electrolytes

Fractional electrolyte clearance (FE) can be used to differentiate between prerenal and renal
causes. Generally renal parenchymal damage can result in an increase in fractional
electrolyte clearance of one or more electrolytes, while in prerenal causes such as
dehydration or circulatory disturbances, no change occurs.

Fractional clearance of electrolytes can be calculated as follows.

Pcreatinine X Ucreatinine
FEx = -------------------------------------
Pelectrolyte X Uelectrolyte
U= Urine P= Plasma (Finco 1995)
Na K Cl P
0 - 0.7 0 - 20 0 - 0.8 3 - 39
0.24 - 0.1 6.7 - 23.9 0.41 - 1.3 17 - 73
*** Dog, Cat
Table 1.15. Normal range of fractional clearance (Fc) of major electrolytes (Meyer et al 1993)
Because fractional clearance may be influenced by dietary intake, overnight fasting should be
done and a standard diet should be given for several days before testing. The FE value can
reflect normal renal tubular function in response to an abnormal external hormonal stimulus
and can reflect compensatory homeostatic responses and tubular dysfunction.

The FE(Na) is the most reliable for assessing renal function. FE(Na) is decreased (<1%) in
prerenal azotaemia due to sodium retention. FE(Na) is increased in tubular failure (1%) but
can be normal or low in acute to subacute glomerular disease. FE(P) is usually increased in
both acute and chronic renal failure due to decreased glomerular filtration rate. It is less
sensitive and specific for assessing renal function. However it is a very sensitive indicator of
 renal secondary hyperparathyroidism.

Urine Concentration tests

An increase in plasma osmolarity stimulates ADH secretion by the posterior pituitary gland. ADH
stimulates renal water resorption and increases urine SG. These tests are designed to identify
concentrating defects in the kidney. They are indicated in animals that show polydipsia/polyuria
(PD/PU) without azotaemia and dehydration and are contraindicated in dehydrated animals, pregnant
animals or azotaemic animals with diluted urine.

1. Water deprivation test

The water deprivation test is used to differentiate between neurogenic and nephrogenic
diabetes insipidus and psychogenic polydipsia.

There are two types of water deprivation tests; acute water deprivation and graded water
deprivation. Although the former method is more applicable in practice because it is less time
consuming, it is less accurate as medullary washout may have occurred. This test is used to
diagnose psychogenic polydipsia. Table 1.12 shows a brief procedure of this test and its
interpretation will be discussed later.
Water Deprivation Test
Preparation
1. 72 hours before the test, limit water intake to 120 m~day in small portions.
2. 48 hours before the test, limit water intake to 90 ml/kg/day.
3. 24 hours before the test, limit water intake to 60-80 m~day.

Before the test:

1. Withdraw food and all water.
2. Empty the bladder completely.
3. Determine the exact body weight.
4. Check the urine osmolarity/specific gravity.
5. Obtain a BUN determination to check for azotaemia.
6. Check hydration and CNS status.

During the Test

1. Empty the bladder and determine the exact body weight every 30-60 minutes.
2. Check the urine specific gravity and osmolarity at each interval.
3. Check hydration and CNS status at each interval.
4. Recheck the BUN and serum osmolarity values.
5. Weigh the patient at each interval.

After the Test

 If the dog is dehydrated, appears ill, or has lost about 5% of its body weight:
1. Obtain a blood sample for determination of the vasopressin concentration.
2. Empty the bladder.
3. Collect a final urine sample and check specific gravity and osmolarity.

Table 1.12. Protocol for the modified water-deprivation test in dogs (Felderman and de Gopegui
1997).
2. Desmopressin concentration (Vasopressin response) test

The desmopressin concentration test is used to differentiate neurogenic diabetes insipidus

from nephrogenic diabetes insipidus and is commonly done after the water deprivation test.

In practice, the aqueous desmopressin concentration test is more commonly preferred due to
the shorter testing time. It is usually indicated if a water deprivation test has failed.

The procedure and interpretation of test results is summarized in table 1.13.

Desmopressin Concentration Test

1. Withhold food and water before testing, empty bladder & measure SG.
2. Give 2,5 unit desmopressin if body weight is less than 7.5Kg, give 5 unit, if
more
than 7.5Kg
3. After 3-6 hr, empty bladder and measure SG
4. Collect urine after 9, 12 and 24hr, respectively and check SG.

Test Results
 Normal
If SG is higher than 1.020, 9hr after injection, it is normal.
 Diabetes insipidus
SG is higher than 1.020, 9- 24 hr after injection
 Renal insufficiency
SG is lower than 1.020, 24hr after injection.
 Medullary washout
SG is higher than 1.025, if 5 unit vasopressin is administered daily for 2-4 days

Table 1.13. Protocol for Desmopressin response test in dogs (based on Sodikoff 1997).
3. Interpretation of urine concentration tests

In psychogenic polyuria, urine concentration will be restored following gradual water

deprivation. While neurogenic diabetes insipidus will respond to exogenous desmopressin
administration, nephrogenic diabetes insipidus will not respond due to lack of ability of the
tubule to respond to ADH. However other renal function tests are normal in nephrogenic
 diabetes insipidus (Duncan et al 1994).

Loss of about 2/3 of the functioning nephrons will result in reduced urine concentration tests
before azotaemia occurs. More detailed information is present in fig 1.3

Fig 1.3 Algorithm for the diagnosis of polydipsia (Osborne 1995)

4. Hickey-Hare test

This is a hypertonic saline test for distinguishing neurogenic diabetes insipidus and
psychogenic polydipsia complicated by renal medullary washout from nephrogenic diabetes
insipidus. It can be used after animals have failed the water deprivation and desmopressin
test. Animals with psychogenic polydipsia will respond to the injection of hypertonic saline due
to plasma hyperosmolarity stimulating endogenous ADH release. However animals with
nephrogenic diabetes insipidus will not respond due to lack of ADH response. Nephrogenic
and neurogenic diabetes insipidus can be differentiated by exogenous ADH injection.
Neurogenic diabetes insipidus may respond.

Other renal function tests

1. Urine Protein/creatinine ratio

Urine protein/creatinine ratio (UP/UCr) is used to calculate urine protein loss into the urine
without a need for 24 hour urine collection. Compared to conventional 24 hour- urinary protein
value, UP/UCr is less time consuming and less accurate.

The UP/UCr is normally less than 1.0 in dogs and less than 0.7 in cats. Generally in dogs with
proteinuria, UP/UCr is greater than 1.0.
Uprotein(mg/dl)
UP/UCr =
-----------------------
Ucreatinine(mg/dl)

U= Urine

Step 1. Collection of 5 to 10 ml urine between 10 AM to 2 PM by the cystocentesis

Step 2. Centrifuge urine sample as general urine sediment test

Step 3. Protein determination by using the trichloroacetic acid-ponceau S method

(mg/dl)

Step 4. Creatinine determination by using the alkaline picric method or The semi-
automated chemistry method (mg/dl)

Step 5. Calculate UP/UCr ratio by using above mentioned equation.

Table 1.14. The procedure for calculating Urine Protein/creatinine ratio (UP/UCr)

In animals with haematuria and urinary tract inflammation, UP/UCr will be increased, but will
return to normal when the haemorrhage or inflammation is resolved. An elevated UP/UCr in
the absence of urinary tract inflammation or haemorrhage indicates prerenal or renal
proteinuria. Glomerular disease usually produce a higher UP/UCr than renal tubular disease,
 because the defective glomerulus allows heavier protein (albumin) to be filtered. Although
UP/Ur alone can not be reliable for diagnosing glomerular diseases, the highest ratios have
been reported with renal amyloidosis (Finco 1995).
Renal biopsy and prostate fluid cytology
Renal biopsy
Renal biopsy is invaluable in practice despite several potential side effects, because morphological
diagnosis may often provide a rapid diagnosis. Generally core biopsy and aspiration biopsy are used
to collect samples from the kidneys. Several kinds of special needles are designed and developed for
renal biopsy. Before performing a renal biopsy, the animal should be checked by physical
examination and laboratory tests to reduce risk. After biopsy, the animal should be monitored
carefully and regularly. Renal biopsy can be performed percutaneously or by laparoscopy or
laparotomy with or without general anaesthesia. Percutaneous fine needle biopsy generally can be
done using heavy sedation and local anaesthesia.
Biopsies are used to confirm and support a diagnosis, formulate effective therapy and establish a
meaningful prognosis. Serial biopsies can be used to monitor progression of the renal disease.
A serious complication of renal biopsy is excessive haemorrhage. The severity of the renal damage
depends on the technique used. Hence, it is contraindicated in animals with blood dyscrasias,
haemorrhagic diathesis and renal abscess. In anuric animals, a more careful consideration should be
given, because blood clot can be formed in the renal pelvis and obstruct renal outflow (Bartges and
Osbornel 1995b).
Prostate fluid cytology
Prostate cytology is an essential test when clinical signs indicate prostate disease. Prostate fluid or
tissue can be collected by fine needle aspiration, biopsy with/without ultrasound guide, ejaculation,
guarded urethral brush and prostatic wash (Ling 1995).
The cytology of normal prostatic fluid may vary depending on sampling technique. The differences
are in cellular components, number and types of contaminating cells. Normal prostatic fluid contains
occasional red and white blood cells and epithelial cells. Epithelial cells have centrally located nuclei
and acidophilic and granular cytoplasm (Barsanti 1995). In prostatic inflammation and neoplasia
increased neutrophils and malignant prostatic cells may be observed and if present, are diagnostic. If
inflammation is present, bacterial culture should be performed.
Diagnostic Imaging
Survey radiograph of kidney
The kidneys can be evaluated radiographically and the findings may be specific for some diseases.
Renal radiographs are taken as for normal abdominal radiograph with the beam centred over the
caudal aspect of the 13th rib in dogs and 3-5cm caudal to the 13th rib in cats. Normal kidney length is
2.5-3.5 ÙO L2 in dogs and 2.5-3.0 ÙO L2 in cats. Normally, the right kidney is located at T13-L2 and
the left kidney is at L2-L4 in dogs, while in cats the right kidney is located at L1-L3 and left kidney at
L2-L5.
Radiographic criteria for kidney examination are size, shape, position and/or density.

1. Size and shape change

Several kidney diseases can alter the normal size and/or shape of the kidneys. Table 1.16
indicates differential diagnoses for these changes.

Type
Bilateral, Large, Regular
Bilateral, Large, irregular
Bilateral, Small, Regular
Bilateral, Small, irregular
Unilateral, Large, Regular
Interpretation
Bilateral ureteral obstruction, bilateral pyelonephritis and
tumour, lymphosarcoma, polycystic kidney, Lipidosis due
to diabetes melitus, ethylene glycol toxicity, myeloma, FIP
FIP, lymphosarcoma, bilateral tumours, acute
pyelonephritits
Chronic interstitial nephritis, renal hypoplasia, renal
dysplasia
Chronic interstitial nephritis, chronic pyelonephritis, renal
infarcts, renal dysplasia
Compensatory hyperplasia, ureteral obstruction, acute
 pyelonephritis, lymphosarcoma, FIP, renal tumour,
pyonephrosis, perirenal cyst, renal vein thrombosis,
myeloma
Unilateral, Large, irregular FIP, renal tumour, lymphosarcoma, renal cyst, renal
abscess, adenocarcinoma
Unilateral, Small, Regular Congenital hypoplasia, chronic interstitial nephritis
Unilateral, Small, irregular Chronic interstitial nephritis, chronic pyelonephritis,
multiple renal infarcts
Normal size and shape Acute tubular nephrosis, renal calculi, kidney rupture,
acute pyelonephtitis, neoplasia
Table 1.16. Differential diagnoses of kidney diseases depending on the change of size and shape
(Based on Burk and Ackerman 1997)
2. Density changes

The deposition of calcium salts on the renal papillae and renal calculi can cause an increase
in density of the kidney. These changes may occur as a result of metastatic or dystrophic
calcification (Burk and Ackerman 1997).

3. Position changes

Most positional changes of the kidney seen in radiographs are due to inappropriate
positioning. However congenital anomalies, traumatic avulsion and neoplasia may result in
the displacement of one or both kidneys.

Contrast studies
Contrast studies of the urinary system are helpful in evaluating the kidneys. Urography and
cystography are inexpensive techniques that can be used in practice. They may be indicated in
animals with haematuria, crystalluria, isostheuria, or dysuria (Allan 1996).

1. Excretory urography

Excretory urography is divided into two phases, nephrogram and pyelogram. The diffuse
opacification of the renal parenchyma is characteristic of the nephrogram phase. The vascular
supply, the presence of renal functional tissue and renal perfusion can be evaluated in this
phase. When the renal pelvis and recesses are opacified by contrast medium, this is the
pyelogram phase and is seen in radiographs taken 5 and 10 minutes post injection. The
Renal pelvis and collecting structures can be seen in this phase. Table 1.7 shows more
detailed information about excretory urography such as preparation and procedure.

Table 1.17. Animal preparation and procedure of excretory urography (Lavin 1994)
Potential problems that may occur with excretory urography include poor visualization due to
reduced renal function and systemic reactions to the contrast injected(Johnston et al 1995).

Ultrasonography
Ultrasonography is a non-invasive method which is an alternative for conventional survey and
contrast radiography. Generally it is indicated if survey radiograph reveals some abnormalities in the
kidney, or if abnormal findings related to renal function are noticed in physiological examination and
laboratory assessments. It can provide crucial information such as extent and location of renal lesion,
tissue composition (solid/cystic)and presence of metastases.
Endoscopy
Endoscopy is indicated in lower urinary tract disease such as dysuria, urinary tract infection,
haematuria and urinary incontinence. Rigid and flexible endoscopy are used. Rigid endoscopy
provides a better and wider view than flexible endoscopy (Senior1995).

Conclusion
The use, limitations and interpretation of diagnostic tests used in renal disease and renal failure were
discussed. Several methods were not discussed in this essay, because they are no longer used in
veterinary practice. An accurate diagnosis requires proper handlings of sample, proper indications for
the use of a particular diagnostic tests and careful interpretation.

TUMOURS OF THE URINARY BLADDER

I. EPlTHELIAL TUMOURS
 Tumori epiteliali Papilloma
 Adenoma
 Transitional cell carcinoma
 Carcinoma delle cellule di transizione
 Variants of transitional cell carcinoma
 Varianti del carcinoma delle cellule di transizione With squamous metaplasia con metaplasia
squamosa
 With glandular metaplasia con metaplasia ghiandolare
 With squamous and glandular metaplasia con metaplasia squamosa e ghiandolare
 Squamous cell carcinoma
 Carcinoma squamoso
 Adenocarcinoma
 Undifferentiated carcinoma
 Carcinoma indifferenziato

II. NONEPITHELIAL TUMOURS

Tumori non epiteliali Muscle tumours
Tumori della componente muscolare

Vascular tumours
Tumori della componente vascolare

Flbroblastic tumours
Tumori della componente connettivale

Other nonepithelial tumours

Altri tumori non epiteliali

III. TUMOURS WITH COEXISTING EPITHELIAL AND MESENCHYMAL ELEMENTS

Tumori con coesistenti elementi epiteliali e mesenchimali

IV. SECONDARY TUMOURS

Tumori secondarii 8000/6

V. UNCLASSIFIED TUMOURS
Tumori non classificati 8000/

VI. PROLIFERATIVE CHANGES

Lesioni proliferative

Tumours of the urinary bladder are uncommon in all domestic animals except cattle in certain
regions. Where cattle eat bracken (Pteridium aquilinum) there is a high incidence of these tumours.
Epithelial tumours are the most frequently encountered neoplasms in cattle and in dogs -the two
species most studied. They are described under the following names: papilloma, adenoma,
transitional cell carcinoma (with variants), squamous cell carcinoma, adencarcinoma and
undifferentiated carcinoma.

An important reason for studying the occurrence and nature of tumours of the urinary bladder in
animals other than man is that the information obtained may help to clarify the etiology of the human
disease. Unfortunately, careful studies of the subject are rarely made and most reviews of the
epidemiology of cancer in animals provide little information about these tumours. One explanation for
this may be that the only lesions reported are large masses plainly visible at autopsy. Small mucosal
lesions in a viscus, such as the urinary bladder, may not be noticed if the organ is not distended,
bisected, and carefully examined.
Urinary bladder tumours have been studied in cattle more than in other domestic animals and reports
indicate that these tumours are common in certain parts of the world, reaching a prevalence as high
as 25% in slaughtered cattle over 2 years of age. These neoplasms are associated with a syndrome
known as chronic enzootic haematuria. All breeds of cattle between the ages of 4 and 12 years may
be affected; the disease is rarely seen in younger animals. The tumours occur also in the domestic
water buflfalo in Turkey, Formosa, and Indonesia. They are found in the male as frequently as in the
female in both species.
The occurrence of bovine urinary bladder tumours in different parts of the world has often been linked
with the geographical distribution of bracken (Pteridium aquilinum). Studies have demonstrated
clearly that such tumours are related to the ingestion of this fern. When the plant was fed in small
quantities to cattle for a long period (mean: 550 days), the animals developed urinary bladder
tumours (including carcinomas) indistinguishable from those that occur naturally in areas of the world
where bracken abounds.
The tumours are rare in cattle living outside areas of endemicity and relatively infrequent when
bracken is not eaten. Thus a prevalence of 0.1% has been reported in cattle in Kenya and 0.01% in
the USA.
Primary tumours of the urinary bladder are seldom reported in sheep, but this does not necessarily
mean that they are rare. These animals are mostly killed for food at an early age, before they have
had a chance to develop such tumours. Recently carcinoma of the urinary bladder was described in a
flock of aged merino wethers in Australia that had had access to bracken for at least 18 months. The
high incidence of tumours in the sheep examined, and the number showing clinical haematuria,
suggested that 5-8 % of the flokc probably had bladder tumours. No information is available on the
incidence of primary vesical tumours in goats. Primary tumours of the urinary bladder occur
infrequently in dogs, comprising less than 1% of all canine neoplasms. The average age of the dogs
with these tumours was 9-10 years at the time of diagnosis. The frequency of the tumours does not
seem to be related to the sex or breed. Although little is known of the etiology of naturally occurring
canine bladder tumours, a variety of chemicals can produce urinary bladder neoplasia
experimentally.
Cats apparently have a very low incidence of bladder tumours -only 14 cases have been reported in
this species: 8 primary carcinomas of the bladder, 2 papillomas, 2 Iymphosarcomas, 1 myxoma, and
1 leiomyoma. Vesical tumours are not usually found in cats under 8 years of age. These animals
seem to be more resistant to the development of much tumours than are other domestic species that
permitted to live most of their life span. This istance may be due to differences in metabolic pathways
between species rather than to differences in tissue susceptibility. For example, it has been shown
that cats metabolize tryptophane -an essential aminoacid‹by a process that does not involve the
production of large quantities of orthoaminophenol metabolites. Consequently, unlike the dog, and
man, the cat has an extremely low level of such tryptophane metabolites in the urine. Certain of these
metabolites have been implicated as etiologic agents in the genesis of human bladder cancer.
Primary neoplasms of the urinary bladder are frequent in horses. So far, only 37 cases have been
reported, nearly all of them in horses over 10 years age. The tumours were more common in males
than in females. Urinary bladder tumours are exceedingly rare in swine. One papilloma was found in
the bladder of animal 6 months old.
Because of the small number of such tumours reported in cats, sheep, horses, and swine, this
histological classification will be based mainly on the findings in cattle and dogs. However, reference
will also be made to other species in the explanatory notes.
A wide variety of benign and malignant tumours occur in the urinary bladder. Epithelial tumours are
the most common, accounting for approximately 80% (145 of 177 cases) and 77% (123 of 160
cases) of all primary bladder tumours in cattle and dogs, respectively. Malignant epithelial tumours
are more frequently found than benign ones. Tumours of the urinary bladder may be of primary or
secondary origin. Primary tumours are the most common in cattle and dogs, and most primary
malignant tumours are of epithelial origin.
Grading of carcinomas is of particular importance from the standpoint of prognosis. It is based solely
on the degree of anaplasia of the cells and not on the pattern of tumours, the cell type, or the extent
of invasion into the bladder wall. All carcinomas may be graded according to the following histological
indications of cellular anaplasia: (l) increased cellularity; (2) nuclear crowding; (3) disturbance of
cellular polarity; (4) failure of differentiation from base to surface; (5) polymorphism; (6) irregularity in
the size of cells; (7) variation in the shape of nuclei and in chromatin pattern; (8) presence of giant
cells; and (9) displaced or abnormal mitotic figures. The presence of one or more of these criteria is
acceptable as evidence of anaplasia. Care must be taken to exclude reactive or regenerative
conditions in which some of these features may be present.
Tumours that demonstrate slight anaplasia are designated as Grade I carcinoma (Fig. 3, 4). At the
opposite extreme are tumours showing severe anaplasia, which should be classified as Grade III
carcinoma (Fig. 6, 7). Any tumour that does not fit readily into Grade I or Grade III is assigned to the
intermediate grade, i.e., Grade II (Fig. 5). Sections used for grading should be of adequate size:
usually a piece of tissue measuring about 1.5 x 2.0 cm will show the full range of the tumour pattern.
Occasionally a definite variation in grade, as distinct from mere variation in structural pattern, may be
seen in the same histological section. The grading should then be that of the most malignant part of
the growth. Consistency of grading can be acquired only after considerable experience.