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Frequently Asked Questions

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.

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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.

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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.

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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.

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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.

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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.

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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.

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