Attachment: Renal Function Tests and Urinary Findings
Laboratory measurement of total body water and dehydration is not a realistic procedure in a clinical situation
however, present knowledge makes possible the clinical laboratory examination of organ function, specifically
renal function as it pertains to maintaining animal health during controlled water access studies. A basic
understanding of the mechanism of kidney function is essential to an appreciation of the significance of urinary
findings and renal function tests. With normal body function, water balance occurs routinely. The kidneys are
the chief organs regulating the internal environment of the body by maintaining a reasonable constancy of
composition of the extracellular and, to a lesser extent, the intercellular fluids. Urine is a by-product of these
regulatory activities. Changes in urine production (water loss through the kidney) occur in response to the
changes in the quantity of functional antidiuretic hormone (ADH) synthesized in the hypothalamus or released
from the posterior pituitary. The thirst center in the anterior hypothalamus is stimulated and occurs as a normal
compensatory response to maintain hydration.
The kidneys ability to maintain normal hydration is determined by its functional unit, the nephron, which
consists of two functionally distinct units:
1. the glomerulus is a vascular channel or bed that serves as a filtration unit. In passing through the glomeruli
the blood loses an essentially protein-free plasma filtrate.
2. the tubule is lined by epithelial cells which modify urine composition primarily by excretion and
reabsorption.
The kidney’s functional capabilities are in turn dependent upon the manner in which blood flows through it. The
bulk of the blood supplies the tubules but must first pass through the glomeruli. Any interference in blood flow
through the glomeruli will affect total renal function and may be followed by degenerative changes in the
tubules with resulting abnormalities in blood chemistry parameters. Identifying underlying renal disease or other
metabolic diseases which could effect the animals ability to accommodate to a wide range of water intake
amounts is essential. This is accomplished by performing routine CBC, chemistry panel and urinalysis during
initial health screening and during semi-annual health exams. It is important to recognize that a single
determination or a single renal function test indicates only the functional capacity of the kidneys at the time the
test was conducted which underscores the need for daily monitoring. The methods that are most widely used
and have the greatest value are described as follows.
Nonprotein nitrogenous substances, especially urea and creatinine, represent products of intermediary
metabolism of both tissue and ingested protein. Significantly increased values are usually the result of
accumulation of these substances in the blood because of defective kidney elimination..
Blood urea nitrogen (BUN)
A. Formation—urea is the principal end product of catabolism of protein formed by the liver. This
substance normally has no useful function in the body other than a possible mild diuretic action and
is excreted almost entirely by the kidneys.
B. Excretion of urea— The glomerulus filters urea in plasma, and under normal conditions
approximately 25 to 40 per cent of filtered urea is reabsorbed as it passes through the tubules.
Urine flow rates greater than normal diminish tubular reabsorption; conversely, low rates of urine
flow increase urea reabsorption in the tubules. Conversely, low dietary levels of protein may result a
decrease in BUN.
C. Interpretation - Anything that reduces the glomerular filtration rate (GFR) will decreases the rate of
excretion of urea nitrogen with a resulting increase in the concentration of Urea levels in the blood.
BUN is not only effected by alterations in renal function but also by non-renal physiologic factors
and diseases. Physiologically, urea nitrogen levels are increased with a dietary increase in protein.
The BUN concentration may be increased as much as 10 mg/dl if the animal is on a diet high in
protein.
1. Normal values range from 10 to 40 mg/dl
2. Low values- Protein malnutrition, Hepatic insufficiency, Technical errors in conducting the test
3. Increased values
a.
Prerenal (non-renal) causes—elevations are seldom over 100 mg/dl.
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Attachment: Renal Function Tests and Urinary Findings
(1) Reduced renal blood flow or factors that reduce net filtration in the glomerulus such
as hypotension, adrenocortical insufficiency, or alterations in fluid balance with decreased
plasma water as in severe dehydration.
(2) Increased protein in the diet causes a transient increase since protein exerts a strong
force to prevent fluid from leaving the glomerular capillaries.
(3) The status of protein metabolism within the body regardless of diet may also
influence urea nitrogen concentration. Catabolic breakdown of the tissues due to fever,
trauma, infection, or toxemia may result in a moderate increase in BUN concentration.
Similarly a rise in BUN is seen with hemorrhage into the gastrointestinal tract, and
administration of drugs that increase protein catabolism (corticosteroids, thyroid
compounds) or drugs that decrease protein anabolism (tetracyclines).
b.
Renal disease—elevation of the BUN will occur when approximately 70% of the nephrons
are nonfunctional. The correlation between the BUN level and the severity of renal disease is
usually fairly good if one considers the duration of the condition.
c.
Postrenal uremia
(1) Perforation of the urinary system allowing urine to escape
(2) Obstruction of the urinary system- Obstruction of only one ureter will not result in
uremia unless the opposite kidney is impaired.
Serum Creatinine(1). (2) (3) Creatinine production is not as easily influenced by catabolic factors affecting
urea formation. Therefore, As there are
A. Formation—creatinine is formed in the metabolism of muscle creatine and phosphocreatine and is
not affected by dietary protein, protein catabolism, age, sex, or exercise
B. Excretion—after being filtered by the glomerulus, it is excreted in the urine
1. Daily production of creatinine from muscle metabolism is relatively constant and since it is not
excreted or absorbed by the renal tubules to any degree, it can be used as a rough index of the
glomerular filtration rate (GFR).
2. Creatinine is not influenced by diet
C. Interpretation
3. Normal values for any laboratory should be established on samples from normal animals within
the area. Normal values range from 1 to 2 mg/dl.
4. Low values have no significance.
5. Increased values
a. The glomerular filtration rate is reduced when creatinine is over 2 mg/dl.
b. As with the BUN, there is a correlation between the degree of elevation and the degree of
renal impairment. There is a tendency for the creatinine to be elevated later than the BUN in
the progress of generalized renal disease.
c. In addition to primary renal disease, creatinine will be elevated in prerenal and postrenal
uremia due to impaired blood flow or obstruction of the urinary system
6. conditions such as fever, toxemia, infection, and drug administration do not as readily influence
creatinine levels. Since fewer nonrenal factors that may influence creatinine concentration, it has
had the reputation of being a more specific test for the diagnosis and prognosis of progressive
renal disease than is the determination of serum UN level.
In general, if the cause of decreased perfusion is rapidly corrected, the kidneys will return to a normal
functional status. If the condition is permitted to persist, renal ischemia may develop and result in the
destruction of organ structure. The following interpretations of the results of laboratory tests for blood urea
nitrogen can be made:
1. If BUN concentration exceeds 35 to 45 mg/dl, GFR is diminished.
2. Abnormal BUN concentration known to be caused by abnormal excretion may be due to prerenal, primary renal, or postrenal factors. Every effort should be made to determine the underlying
cause of uremia in order to establish a meaningful prognosis and select an appropriate treatment.
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Attachment: Renal Function Tests and Urinary Findings
3. Only a rough correlation can be made between the degree of elevation of BUN and the severity
of renal function impairment. This may be partly related to duration of renal disease, since
progressive diseases that destroy renal parenchyma at a relatively slow rate permit remaining
viable nephrons to undergo structural and functional compensation.
4. A single determination of BUN concentration, regardless of the value obtained, does not provide
a reliable index of the reversibility or irreversibility of the disease process. Elevated serial
determinations of BUN levels are cause for permanent exclusion from controlled water access.
Urinalysis and urine specific gravity
Urine is not only altered by diseases occurring in the kidneys, but many extrarenal conditions produce changes
that may be of diagnostic significance as to the general condition of the animal. For correct interpretation, the
urinalysis should be conducted on a somewhat selective basis and evaluated in terms of the clinical signs
observed by the attending veterinarian.
1. Gross visual examination
Although the simplest of all procedures conducted on urine, gross examination of urine is the one most
consistently overlooked. A considerable amount of information can be gained from observing and recording
volume, color, transparency, odor, and appearance of foam in a specimen.
Urine volume is dependent upon several physiologic factors, including water and other fluid intake,
environmental conditions, diet, and the size and activity of the animal. Normal urine production varies according
to animal species. In the normal animal, high urine volume is usually associated with low specific gravity and
low urine volume with high specific gravity. High urine volume and low specific gravity are often, but not
always, associated with renal disease. Urine volume will decrease with decreased fluid intake and high
environmental temperature and is commonly associated with dehydration resulting from loss of body water, as
in diarrhea and excessive vomiting, but may also occur with terminal renal disease. Renal perfusion can be
monitored by insertion of an indwelling catheter and observing the rate of urine flow. If renal perfusion is
adequate, a flow rate of 0.5 to 1.0 ml/hour/lb body weight is expected; less is an indication that renal perfusion
is decreased, and therapy should be instituted to restore it.
Increases in urine volume may be present transiently owing to increased fluid intake and following parenteral
administration of fluids or administration of corticosteroids. Pathologic increases in urine volume are associated
with metabolic diseases (diabetes mellitus), renal disease, and some liver diseases.
2. Urine color
The color of a urine specimen can be noted but to be valid, interpretation of urine color must be associated with
the physical condition of the animal, the history of drug dosage, and age of the specimen. The following color
designations can be used. The yellow color of urine depends on the concentration of urochromes. If urine is
concentrated, the amount of urochrome per volume is increased, and urine appears darker than normal;
whereas if urine volume is increased, urochromes are diluted, and the urine is pale. Dark urine, due to the
concentration of urochromes, occurs in association with dehydration, fever, decreased blood pressure,
nephrosis, renal disease, and reduced fluid intake. Pale urine, on the other hand, is seen in diabetes mellitus,
increased water intake, nephrosis, and chronic and acute generalized nephritis. Urine may also be pale following
administration of ACTH or corticosteroids or parenteral administration of fluids. In general, urine that is dark is
high in specific gravity; conversely urine that is pale is usually of low specific gravity.
Yellow-brown to greenish-yellow urine may be due to the presence of bile pigments in the specimen.
Hemoglobin produces a wine-red urine that changes to brownish as it is converted to alkaline or acid hematin
depending upon the pH. Hematuria also results in a red to brown color.
The transparency of urine can be recorded as clear, flocculent, or cloudy. Urine excreted from most species of
domestic animals is clear and may become cloudy as it cools and precipitation of crystals occurs. Precipitation is
most likely to occur in highly concentrated urine. Pathologically, cloudy urine may be observed when any of the
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Attachment: Renal Function Tests and Urinary Findings
following are present: leukocytes, erythrocytes, epithelial cells, bacteria, mucus, fat, and crystals (if present
when the urine is voided). The cause of cloudy urine can be accurately ascertained only by microscopic
examination of the specimen.
3. Urine odor
The odor of the urine is not diagnostic and is normally derived from the volatile organic acids present. An odor
of ammonia may appear if urea is being converted to ammonia by bacterial action. Ketone bodies impart a
characteristic sweetish, fruity odor and may be detected in urine in association with diabetes mellitus.
4. Specific gravity
The specific gravity of urine is a measurement of the relative amount of solids in solution and is an indication of
the degree of tubular reabsorption or concentration by the kidney. Under conditions of normal renal function
and normal metabolism, the specific gravity or urine varies inversely with the volume of urine excreted. If large
volumes of urine are excreted, the specific gravity is usually low, whereas if small quantities are being
eliminated, the specific gravity is generally high. Determination of the specific gravity of urine should be a
routine procedure in any analysis particularly if a metabolic disease is suspected or clinical signs of kidney
disease are observed. As urine specific gravity is related to urine volume, and urine volume, in turn, is related to
water intake and body metabolism, it is difficult to ascribe specific values for the normal animal. In general,
specific gravity for most animal species will be in the range of 1.015 to 1.045, but values as low as 1.001 and as
high as 1.060 to 1.080 can occur. Randomly collected urine specimens may have a specific gravity from 1.001
to 1.080 in animals with normal kidney function.
Electrolytes - alterations observed in renal disease and some of the general mechanisms involved.
It must be recognized that serum or plasma electrolyte values do not necessarily reflect total body
concentration, and deviations from the animal’s normal level must be interpreted with this fact in mind.
Electrolyte concentrations in plasma fluctuate rapidly with changes in the composition of extracellular and
intracellular fluid. These fluctuations have as their net result a redistribution of water among the fluid
compartments of the body in order to maintain osmolarity.
POTASSIUM. Potassium is removed from plasma by active reabsorption in the proximal tubules and is then
actively excreted by cells of the distal tubules. The quantity of potassium handled by the kidneys is determined
by the potassium intake. If a patient with renal disease becomes oliguric or anuric, potassium is retained and
hyperkalemia may develop. If a patient with renal disease maintains adequate urine flow, the plasma potassium
level remains normal unless acidosis develops.
SODIUM. Ability to retain sodium is frequently lost in the presence of generalized chronic renal diseases
characterized by polyuria. This functional loss is accompanied by a deficiency in total body sodium that may or
may not be reflected in plasma sodium concentration. Sodium loss through the diseased kidneys is
accompanied by water loss as the body attempts to maintain body fluid isotonicity.
PHOSPHATE. Most of the phosphate excretion by the kidney is by glomerular filtration, with a variable amount
of reabsorption by the tubules. Hyperphosphatemia typically occurs with chronic progressive and generalized
acute
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