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Diagnostic Options for Proteinuria and Renal Disease
Recently, proteinuria has been shown to be a valuable prognostic
indicator of morbidity and death in dogs and cats with kidney disease.
Identification of persistent renal proteinuria is a hallmark of
glomerular disease. Diagnosing and addressing renal disease before an
animal becomes azotemic can allow for early treatment and improvement
in patient quality of life.
There are several ways to evaluate urine protein. Urine dipsticks
and the microalbuminuria assay lack specificity and sensitivity, and
are prone to false-positive and/or false-negative results. Because
these tests lack specificity, they should always be followed up by a
confirmatory test.
"Any positive on the microalbuminuria test should be
followed up by a urine protein:creatinine ratio." Dr. Jonathon Elliott1
The sulfosalicylic acid (SSA) precipitation test provides an
excellent semi-quantitative analysis of urine protein. Unfortunately,
this test is inconvenient for in-house use. At IDEXX Reference
Laboratories, a confirmatory SSA test is automatically performed on
all urinalyses when the dipstick assays are positive for protein.
The urine protein:creatinine (UPC) ratio offers a technique to
fully assess proteinuria in dogs and cats, and is available through
IDEXX Reference Laboratories, as well as in-house on the IDEXX VetTest® Chemistry Analyzer. The UPC ratio
can be used to screen for early renal disease, confirm other screening
tests (dipstick and microalbuminuria), quantify protein loss, monitor
disease progression and evaluate therapeutic response.
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| Q: |
What is the difference between proteinuria and
microalbuminuria? |
| A: |
Proteinuria refers to an excessive amount of protein detected in
the urine. Urine protein can be a complex combination of components
that may include albumin, globulins, immunoglobulin light chains and
low molecular-weight proteins. Microalbuminuria refers to the
measurement of small quantities of albumin in the urine. In other
words, microalbuminuria alludes to a small urine albumin
concentration, typically <30 mg/dL, that is undetectable by
semi-quantitative dipstick tests.
The IDEXX
Urine P:C Ratio measures all fractions of urine protein,
including albumin. Different methodologies used for the urine
protein measurement will have variable sensitivities to different
protein fractions, especially the globulin fractions. However,
almost all methodologies will detect the albumin fraction.
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| Q: |
Is it important to detect the other proteins in addition
to the albumin? |
| A: |
Yes, it is important to detect the other proteins in addition to
the albumin. In renal diseases, albumin can be the predominant
protein; however, other urine protein fractions may also be present,
and these concentrations can vary, depending on the underlying
condition. Immunoglobulins and other proteins can have an impact on
the urine protein results, depending on the nature of the underlying
disease. |
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| Q: |
For years, veterinarians have used the dipstick for
detecting proteinuria. Isn't the dipstick good enough? |
| A: |
Unfortunately, many veterinarians today are depending on the
urine protein dipstick dye test to determine proteinuria. This test
is neither sensitive nor specific, and can often yield erroneous
results.
"If you're interested in detecting a low level of
protein in the urine, the dipstick is not sensitive enough. We're
going to get a lot of false-positives, but we may also see some
false-negatives with a low proteinuria level. The sulfosalicylic
acid, urine microalbumin, and urine protein:creatinine ratio tests
are much more sensitive than the dipstick at detecting these lower
concentrations of protein in the urine." Dr. Gregory F. Grauer1
Because of poor specificity of the dipstick as a screening tool,
IDEXX Reference
Laboratories routinely performs a confirmatory SSA with any
urinalysis when a dipstick assay is positive for protein. The SSA
test result is included in the urinalysis report.
"The standard dipstick tests for protein are of little
help when screening cat urine because there are so many
false-positives. There are two possible approaches: 1.) run a urine
protein:creatinine ratio initially and forget the screening test, or
2.) screen with the microalbuminuria test." Dr. Jonathon Elliott1
Regardless of the screening test used, initial discovery of
proteinuria requires localization, proof of persistence and tracking
of trends via the UPC ratio.
"We mainly use serial urine protein:creatinine ratios to
evaluate proteinuria magnitude because they are useful for measuring
any level of proteinuria." Dr. George E. Lees1
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| Q: |
How is proteinuria determined to be persistent? |
| A: |
Proteinuria can be transient and not associated with renal
disease, therefore, it must be determined to be persistent.
Persistent renal proteinuria in nonazotemic animals is a sign of
early renal disease. After the urine protein is localized to the
kidney and evidence of lower urinary tract disease is not
identified, it must be determined to be persistent. Persistence in
nonazotemic animals is determined by identifying proteinuria on
three or more occasions at least two weeks apart. By detecting the
damage to the kidneys before azotemia is present and the patient's
urine concentration ability is impaired, the veterinarian can
minimize disease progression and improve the patient's prognosis. If
the animal is azotemic and proteinuric, and lower urinary tract
disease is excluded, the proteinuria can be attributed to renal
disease.
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