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What does the IDEXX Urine P:C Ratio measure?
The IDEXX Urine P:C Ratio measures urinary protein loss. It can
detect very low levels of protein (5 mg/dL) in canine and feline
urine samples. By also measuring urine creatinine levels and forming a
ratio of urine protein to urine creatinine, the IDEXX Urine P:C Ratio
measures urinary protein loss while automatically correcting for
variations in urine volume and concentration.
Does an elevated Urine P:C Ratio indicate renal disease?
An elevated Urine P:C Ratio indicates that there is a clinically
significant amount of protein in the urine. In order to determine if
renal disease is responsible for this urinary protein loss, you must
first localize the protein loss to the kidneys by ruling out prerenal
and postrenal causes (via a history, PE, CBC, biochemical profile and a
complete urinalysis). And because the test is so sensitive, you must
rule out transient proteinuria (which can be caused by fever, exercise
and changes in temperature) to determine that the proteinuria is
persistent.
What are the reference ranges for the individual urine
chemistriesurine protein and urine creatinine?
We do not have reference ranges for urine protein and urine
creatinine. The individual urine protein and urine creatinine results
should not be evaluated on their own since the individual measurements
(UPRO and UCRE) can change significantly within a short time frame, and
are sensitive to urine volume and concentration. The benefit of the
urine protein:creatinine ratio is that it automatically corrects for
variations in urine volume and concentration.
Is a negative result for protein on a urine dipstick
insignificant?
Urine protein dipsticks are semi-quantitative and are influenced by
urine pH, volume, concentration and color. While it is very easy to
perform, the urine dipstick is neither a sensitive nor specific
indicator of urinary protein loss. The lower limit of detection for
urine protein on a dipstick is 30 mg/dL. The IDEXX Urine P:C Ratio has
a lower limit for urine protein of 5 mg/dL, and is highly specific for
dog and cat proteinuria. Furthermore, the IDEXX Urine P:C Ratio
corrects for variations in urine concentration and volume. You should
perform a Urine P:C Ratio on all suspect renal disease patients
regardless of a negative urine protein dipstick result.
At what age should dogs and cats be tested for early renal
disease with an IDEXX Urine P:C Ratio?
Given the high prevalence of renal disease in geriatric dogs and
cats, IDEXX recommends adding the Urine P:C Ratio to your senior care
diagnostic protocol. We also recommend performing a Urine P:C Ratio on
all animals suspected of having renal disease, regardless of age.
Special attention should be given to breeds
predisposed to renal disease, as well as all patients with diseases
associated with secondary renal complications.
After identifying a dog or cat that tests positive on the
IDEXX Urine P:C Ratio, what is the next step?
As described in the diagnostic
protocol, the first step is to localize the protein to the kidney
by ruling out prerenal and postrenal causes of proteinuria. This is
done by assessing the physical examination, complete urinalysis
(including sediment exam), serum chemistry panel and complete blood
count for evidence of underlying disease conditions that could be
responsible for the proteinuria. The next step outlined in the
diagnostic protocol is to rule out transient proteinuria by repeating
the IDEXX Urine P:C Ratio. After both of these steps are completed, the
diagnostic
protocol aids in the evaluation of urinary protein loss.
Why do I have to determine persistence?
Because the urine protein:creatinine ratio is so sensitive, it can
detect very small amounts of protein in the urine that are of a
transient nature. You have to rule out this transient, or functional
proteinuria, which can be associated with increases in blood pressure
as well as stress, exercise and fever, in order to determine that the
protein is significant.
Does the Urine P:C Ratio result correlate to patient
prognosis?
Several studies have indicated a strong correlation between the UPC
result and patient prognosis. The higher the urine protein:creatinine
ratio, the worse the prognosis. Since the IDEXX Urine P:C Ratio is
fully quantitative, the veterinarian can use this test not only to
diagnose renal disease, but also as a prognostic indicator. Sequential
Urine P:C Ratios can be used to monitor patient response to treatment
and disease progression.
Why do some dogs and cats with end-stage renal disease test
negative for protein on the Urine P:C Ratio or have a result that
actually decreases over time?
Dogs and cats with end-stage renal disease can potentially have a
negative result with the Urine P:C Ratio. As the number of functional
nephrons (the functional units of the kidney) decline, proteinuria may
decrease or become negative. It is not uncommon to find a decreasing
trend in the magnitude of Urine P:C Ratio as renal disease progresses
to a terminal state.
Is kidney disease reversible?
At this time, it has not been proven that medical intervention can
physiologically reverse nephron damage. However, by catching the
disease in an early stage, the veterinarian has the ability to prevent
further damage and arrest disease progression.
Can I use the Urine P:C Ratio to monitor therapeutic
response?
Yes. Because the Urine P:C Ratio is fully quantitative, it can be
used to monitor therapy. In fact, recent studies have shown that
persistently high urine protein:creatinine ratios are significantly
correlated to a poor prognosis.
Is the Urine P:C Ratio of benefit in dogs and cats that have
evidence of a urinary tract infection?
In the majority of cases of postrenal disease, a urine
protein:creatinine ratio offers little diagnostic benefit and may be
misinterpreted as a false-positive result. The protein in postrenal
disease is of cellular origin (RBC, WBC, bacteria, tumor cells, etc.),
and is not indicative of glomerular disease. In this case, a high urine
protein:creatinine ratio may result due to a high protein level without
a corresponding high creatinine level. Glomerular function cannot be
evaluated until the underlying postrenal disease is resolved. It is
important to mention that pyelonephritis (bacterial infection of the
kidneys) will also have bacteria in the urine and should be suspected
in complicated UTI cases or whenever there is a UTI in a clinically ill
patient.
What is the difference between proteinuria and
microalbuminuria?
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.
Is it important to detect the other proteins in addition to
the albumin?
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.
For years, veterinarians have used the dipstick for
detecting proteinuria. Isn't the dipstick good enough?
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
How is proteinuria determined to be persistent?
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.
| Advanstar Communications. Proteinuria and Renal Disease: A
Round-Table Discussion. Lenexa, Ka: Advanstar Healthcare
Veterinary Communications. 2005. |
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