What do the canine and feline
E.R.D.-HealthScreen® Urine Tests measure? The canine and feline E.R.D.-HealthScreen® Urine Tests are rapid
immunoassays that detect low levels (>1.0 mg/dL) of albumin (i.e., "microalbuminuria"
["micro-" refers to small amounts of albumin, not the size of albumin]) in
canine and feline urine, respectively. The tests are specific, sensitive
and simple to use. They are intended to be used to determine whether more
comprehensive evaluation for early renal damage is indicated.
Is any amount of protein in the urine normal? Veterinarians have been taught that proteinuria is only significant once
it becomes severe (i.e., Urine Protein:Creatinine [UPC] ratio >1.0). New
information indicates that even a small amount of albumin in the urine (i.e.,
microalbuminuria) is abnormal and can be indicative of nephron damage.
Why is microalbuminuria a sensitive indicator of a dog's or cat's health
status?
The kidneys filter the entire blood volume of the dog or cat every 30 minutes.
As a result, they are continually exposed to a myriad of potentially damaging
substances, infectious agents, or conditions (e.g., antigenantibody complexes,
toxins, bacteria, hypertension). Various disease processes may damage nephrons,
resulting in leakage of albumin into the urine.
Examples of these disease processes in dogs include the following:
Inflammatory diseases (e.g., dental disease, pyoderma, immune-mediated diseases,
inflammatory bowel disease)
Infectious diseases (e.g., heartworm, ehrlichiosis, Lyme)
Metabolic diseases (e.g., diabetes mellitus, hyperadrenocorticism, hypertension)
Neoplasia
Examples of these disease processes in cats include the following:
Inflammatory diseases (e.g., dental disease, cholangiohepatitis, immune-mediated
diseases, inflammatory bowel disease)
Infectious diseases (e.g., FIV, FeLV, FIP, heartworm, ehrlichiosis)
Metabolic diseases (e.g., diabetes mellitus, hypertension, hyperthyroidism)
Neoplasia
Persistent microalbuminuria suggests the presence of either an underlying
disease process causing early renal damage or lower urinary tract disease
(LUTD). Detection of microalbuminuria during a routine health examination
provides veterinarians with a new tool to discover many common canine and
feline diseases that are subclinical.
What are the mechanisms for development of microalbuminuria in dogs and
cats? Plasma albumin is normally excluded from the glomerular filtrate primarily
because of its size. The small amount of albumin that normally escapes into
the glomerular lumen is reabsorbed or degraded by tubular epithelial cells
(Russo LM, et. al., Amer J Kidney Dis 2002;39:899-919). As a consequence,
there are two potential mechanisms by which nephron damage can lead to microalbuminuria.
First, glomerular damage can result in increased "leakage" of albumin into
the glomerular filtrate, exceeding the capacity of the tubular albumin retrieval
and degradation pathways. Second, tubular damage can result in decreased
retrieval and/or degradation of albumin from the glomerular filtrate. Therefore,
either glomerular or tubular damage can result in a continuous low level
of albumin being excreted in the urine. In addition to "renal" causes of
microalbuminuria, lower urinary tract disease (LUTD) can be a "post-renal"
cause of microalbuminuria in dogs and cats.
In a microalbuminuric dog or cat, what is the likelihood of identifying
a cause of the kidney damage?
In a retrospective study (AK Cook and LD Cowgill. J Am Anim Hosp Assoc 1996;32:313-322)
involving 137 dogs with overt proteinuria, (defined as >30 mg/dL) and
a histopathological diagnosis of glomerulopathy, significant concurrent medical
problems were identified in approximately 50% of the dogs. In a recent study,
(JC Whittemore, et. al., J Vet Int Med 2003;17:437) infectious, inflammatory,
or neoplastic diseases previously associated with proteinuria were identified
in 56% of dogs that were negative for protein on conventional urine protein
dipsticks but positive for microalbuminuria.
After identifying a dog or cat that tests positive on the E.R.D.-HealthScreen®
Urine Test, what is the next step?
As described in the "3-Step Guide: Managing Patients with Positive E.R.D.-HealthScreen®
Urine Tests," the first step is to assess the initial diagnostic work-up
(e.g., physical examination, complete urinalysis, serum chemistry panel,
complete blood count, and blood pressure measurement) for evidence of underlying
disease conditions that could be responsible for the microalbuminuria (See
Question #5).
Does increasing microalbuminuria indicate increasing disease severity?
Canine and feline E.R.D.-HealthScreen® Urine Tests normalize (i.e., standardize)
for urine specific gravity so sequential samples can be compared despite
varying urine concentrations. In humans, studies demonstrate a correlation
between increasing microalbuminuria and more rapid progression of renal disease.
In models of progressive renal disease in dogs, increasing microalbuminuria
is associated with disease progression. Long-term prospective studies are
ongoing to determine if a similar correlation exists in cats.
Therefore, more aggressive monitoring and treatment is most important for
those patients with increasing levels of microalbuminuria.
Glomerular disease is known to be common in dogs; however, tubular disease
is thought to be more common in cats. Will the E.R.D.-HealthScreen® Feline
Urine Test detect early progressive renal disease in cats?
A microalbuminuria test specific for cats has not been available until recently.
Therefore, the predictive value of microalbuminuria for detection of early
progressive renal disease from various causes in cats has not been investigated.
However, extrapolating from what is known in other species, the kidney has
a limited response to damaging elements and any disease process that results
in damage to glomeruli or proximal tubules will likely result in microalbuminuria
(See Question #5). In support of this hypothesis, new studies demonstrate
that the prevalence of microalbuminuria in cats is similar to that seen in
dogs (See Question #18).
Will all animals testing positive with the E.R.D.-HealthScreen® Urine
Test develop end-stage renal disease?
The prevalence of microalbuminuria in dogs and cats (See Question #18) exceeds
the reported occurrence of end-stage renal disease. Thus, the majority of
microalbuminuric dogs or cats will not progress to develop end-stage renal
disease. As discussed in Question #11, microalbuminuria, especially when
increasing in magnitude over time, is a risk factor for the development of
end-stage renal disease. While all persistently microalbuminuric dogs and
cats are "at risk" of developing end-stage renal disease, most will not due
to tremendous renal reserve capacity. Increased monitoring of "at risk" dogs
and cats (See Question #8: “Suggestions for Managing Microalbuminuric, Non-azotemic
Patients") will allow for earlier identification of individual animals that
progress to end-stage renal disease.
How does a positive E.R.D.-HealthScreen® Urine Test compare to abnormalities
in the urine protein to creatinine (UPC) ratio?
In all experimental models of renal disease in dogs studied to date, microalbuminuria
was detected prior to recognizing increases in the UPC ratio.
Can the presence of lower urinary tract disease, in the absence of gross
hematuria, cause a positive E.R.D.-HealthScreen® Urine Test?
Inflammation associated with lower urinary tract disease (LUTD) can result
in microalbuminuria, even in the absence of gross (i.e., visible) hematuria.
However, studies have shown that approximately 65% of dogs with pyuria were
negative for microalbuminuria. Similarly, it has been observed that not all
cats with LUTD were positive for microalbuminuria. Therefore, the dog or
cat should be re-tested for microalbuminuria after successful treatment of
the LUTD to exclude the existence of underlying kidney damage.
Do other factors (e.g., concurrent mediations) cause the E.R.D.-HealthScreen®
Urine Tests to be positive?
Preliminary results indicate that prednisone (1 mg/kg q24h) caused or increased
the severity of microalbuminuria in 50% of dogs. Studies are ongoing to determine
the effect of steroids on microalbuminuria in cats.
At what age should dogs and cats be tested for microalbuminuria?
Heska recently completed nationwide studies on the prevalence of microalbuminuria
in dogs and cats. Results demonstrate that overall approximately 25% of dogs
and cats are positive for microalbuminuria. Additionally, an age-related
increase in prevalence occurs with a significant increase in the prevalence
of microalbuminuria in middle-aged dogs and cats. Therefore, all middle-aged
and older animals should be tested. The earlier ongoing nephron damage is
detected, the earlier steps can be taken to identify a cause, and therapeutic
intervention can be initiated to halt or slow the disease progression. High-risk
breeds (e.g., breeds with congenital renal disease) or animals with additional
risk factors (e.g., systemic [inflammatory, infectious, metabolic, neoplastic]
disease) should be candidates for testing at an earlier age.
http://www.heska.com
reprinted with kind permission from Gillian Harris
Marketing Manager Woodley Equipment Co Ltd.
