What tests are required for the diagnosis of kidney disease?
Generally, the following screening tests are recommended: a complete blood count (CBC), a serum biochemical profile, and a urinalysis.
What might these tests indicate if my pet has kidney disease?
A) A complete blood count (CBC) involves the evaluation of the red blood cells, the white blood cells and the platelet components of a single blood sample. A hematology (blood) analyzer will provide your veterinarian with the total numbers of these cells, and evaluation of a blood smear will allow a look at the physical characteristics of these cells.
The kidneys produce a substance called erythropoietin that is necessary for proper red blood cell production within the bone marrow. With kidney disease, the amount of erythropoietin produced may be decreased, causing a decrease in red blood cell production. This shows up in the CBC as anemia.
The white blood cell numbers may be increased if the underlying cause of the kidney disease is due to an infection or inflammation.
Rarely, platelet numbers may be reduced if a clotting problem has occurred as a result of the underlying kidney disease.
B) The serum biochemistry profile requires a separate blood sample from which the serum (the liquid portion of blood) is separated from the cellular portion of blood. Serum contains many substances including enzymes, proteins, lipids (fats), glucose (sugar) and metabolic waste products.
Of most importance in the diagnosis of kidney disease are the determination of the levels of two substances, namely blood urea nitrogen (BUN) and creatinine.
BUN is a waste product of protein catabolism (breakdown) and creatinine is produced as a consequence of normal muscle metabolism. These two substances are normally cleared from the bloodstream by the kidneys and therefore are indicators of how well the kidneys are functioning.
Increases in BUN and creatinine may be seen with kidney disease, as well as with dehydration and other causes of reduced blood flow to the kidneys.
The magnitude of increase in BUN and creatinine reflects the degree of kidney disease. Unfortunately, the serum concentration of these substances does not increase significantly until approximately 75% of kidney function is already lost.
An additional blood test for kidney function called symmetrical dimethylarginine (SDMA) is also available from some laboratories. This particular parameter becomes elevated in kidney disease before BUN and creatinine, and so is better able to detect kidney disease sooner.
"Severe increases in potassium may cause cardiac arrhythmias."
The biochemistry profile will also measure other substances whose blood concentrations are normally regulated by the kidneys. These substances include electrolytes such as sodium, potassium, chloride, bicarbonate, phosphorus, and calcium. It is important to document the concentrations of these substances because marked increases or decreases due to kidney disease can lead to other complications. For example, severe increases in potassium may cause cardiac arrhythmias (electrical disturbances in the beating of the heart).
C) A complete urinalysis is essential for the proper interpretation of the urea and creatinine values in a serum biochemistry profile. A urinalysis may also provide important clues with respect to the possible underlying cause of kidney disease.
In addition to its many other functions, the kidneys are responsible for regulation of body water by either concentrating or diluting urine. Normally, the degree of urine concentration depends upon the amount of fluid consumed by your pet and how well hydrated they are. For example, drinking a large amount of fluid will result in a dilute urine whereas drinking a limited volume will result in very concentrated urine.
"The specific gravity is important because with kidney disease, the kidneys lose their ability to effectively concentrate or dilute urine."
The degree of urine concentration is determined by measurement of the specific gravity of the urine. This is done using a special instrument called a refractometer. The specific gravity is important because, with kidney disease, the kidneys lose their ability to effectively concentrate or dilute urine.
The specific gravity is vital in determining the significance of any elevations in the serum BUN and creatinine.
In addition to kidney disease, dehydration or any other cause of decreased blood flow to the kidneys may result in an increase in serum BUN and creatinine. Healthy kidneys will respond to dehydration or reduced blood flow by producing concentrated urine. If kidney disease exists, the urine will not be concentrated, even in the face of elevated serum BUN and creatinine.
Other components of urine (such as the pH and the amount of protein or blood present in a sample) can be measured by using urinary dipsticks. Urine dipsticks are simply small plastic strips that have special pads attached to them. These pads contain different chemicals that react with the different urinary components, allowing their measurement through color changes. The presence of blood or increased protein in a urine sample will alert your veterinarian to the possibility of urinary tract infection as a cause of kidney disease. Some kidney diseases are characterized by a large loss of protein in the urine. Such clues derived from the dipstick measurements may help your veterinarian to determine what factors are contributing to your pet's kidney disease.
The final component of the complete urinalysis is the evaluation of the urine sediment. This involves spinning a urine sample in a special instrument called a centrifuge so that any cellular elements within it are concentrated in the bottom of the container. This sediment can then be transferred to a slide and examined under a microscope.
The presence of certain elements in the sediment may provide clues as to the underlying cause of kidney disease. These include the presence of red blood cells, white blood cells, bacteria, crystalline material, and cellular casts.
Elevated numbers of red blood cells, white blood cells and bacteria indicate that an infection may be partially or wholly responsible for the kidney disease.
The presence of different types of crystals may suggest that urinary tract stones, or perhaps even the ingestion of toxins (for example, ethylene glycol or antifreeze), has resulted in kidney disease.
Casts are formed when damaged or destroyed cells are molded into the shape of the damaged internal kidney structures. Their presence may indicate that there is recent damage to the kidney cells.
Will these screening tests determine exactly what the underlying cause of the kidney disease is?
Occasionally, specific changes in these screening tests will point to an infectious, inflammatory, or toxic cause for the kidney disease.
However, because there are many underlying causes of kidney disease, and because the kidneys are able to compensate for damage so well, testing may not tell your veterinarian the exact reasons why the kidneys are malfunctioning. A reduction in kidney function characterized by either a decreased urinary concentrating ability, or an increase in serum BUN and creatinine, is not measurable until two thirds to three quarters of the kidney function is already lost. By this time, many kidney diseases have progressed to a chronic phase and the original cause can no longer be determined. This is one reason why the SDMA test described earlier is important, as it is able to detect subtle kidney disease much sooner.
Nevertheless, it is still important to evaluate your pet using these tests. Not only will they allow your veterinarian to confirm that the cause of your pet's clinical symptoms is kidney disease, but they will also allow your veterinarian to choose the most appropriate course of treatment and may indicate if further testing is required.
What other testing might be required?
Depending upon your pet's clinical signs, and the results of the initial screening tests, further testing for kidney disease may include any of the following:
A urinary protein/creatinine ratio is recommended if the urine dipstick evaluation suggests that an excessive amount of protein is being lost in the urine. A urine sample is sent to a veterinary referral laboratory, and the ratio of protein to creatinine in that sample is calculated. An increased protein/creatinine ratio can indicate kidney damage.
Urine culture may be performed if the urinalysis findings are suggestive of a bacterial infection as the cause of the kidney disease.
Leptospirosis titers may be recommended if this organism is suspected of causing the kidney disease. See handout “Antibody Titers” for more information.
Occasionally ultrasound examination and/or kidney biopsy may be recommended to evaluate the kidneys.