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Cornell Richard P. Riney Canine Health Center

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Hyperuricosuria and hyperuricemia or urolithiasis (HUU)

Overview

Hyperuricosuria and hyperuricemia or urolithiasis (HUU) is an uncommon, inherited condition that causes a substance called uric acid to build up in the blood (hyperuricemia) and urine (hyperuricosuria). This can lead to stones (uroliths) forming in the kidneys and bladder.

Causes

Purines are common organic compounds that are part of DNA and RNA. They are either produced by a dog’s body (known as endogenous) or are consumed through diet (exogenous). Under normal circumstances, when purines are metabolized, a substance called uric acid is formed. It is then converted to allantoin, a chemically inactive substance that is passed out of the body in the urine. 

Dogs with the HUU mutation are unable to convert uric acid to allantoin. As a result, uric acid accumulates in the body and then crystallizes and can form urate stones within the kidneys and bladder.

Dalmatians are the most common breed affected, having a nearly 100% risk of having this mutation (though not all Dalmatians go on to develop stones). Bulldogs and Black Russian Terriers also have an increased risk compared to other breeds. Most dogs that form stones will do so beginning at around four years of age.

Urate stones can also be produced due to another condition known as a portosystemic shunt. With this disease process, an abnormal blood vessel (or vessels) allow blood to bypass the liver, which is responsible for removing toxins. Shunts may be congenital (present at birth) or acquired over time due to other conditions such as cirrhosis. There is likely a genetic predisposition to liver shunts in congenital cases, but there is currently no genetic test available for this condition.

Hereditary portosystemic shunts are seen in Yorkshire Terriers and Cairn Terriers, and other small and toy breed dogs may be predisposed. Numerous medium- and large-sized breeds may also be affected. They are seen equally in males and females, and affected dogs are usually diagnosed in the first year of life. 

Clinical signs

Prior to forming stones, dogs will show no clinical signs of disease.

In dogs that form urate stones, the most common signs include:

  • Straining to urinate
  • Frequent, small amounts of urination
  • Accidents in the house
  • Blood in the urine
  • Decreased appetite

The inability to urinate may occur if stones develop and cause an obstruction in the urethra, which is a medical emergency. The signs of this condition will be much more severe — including a large and firm bladder, belly pain, vomiting and lethargy. Both male and female dogs can be affected, but obstruction of urine flow is more common in males due to differences in anatomy. If left untreated, a urinary obstruction can be fatal.

Diagnosis

A test called a urinalysis will be performed to look for the presence of urate crystals, measure the pH of the urine and screen for any coexisting issues, such as a urinary tract infection. Urate crystals tend to form in acidic urine (which has a lower pH).

Specialized X-rays, ultrasounds, or other urinary imaging tests may be used to diagnose urate stones in the bladder or kidneys. 

Stones can be sent to a special lab for identification.

Treatment

Existing stones can be removed through various techniques, including surgery.

The mainstay of preventing further formation after removal of the uroliths is minimizing the urinary concentration of ammonia and uric acid, which is achieved by feeding a low-protein diet. These diets are prescription-only and can be obtained through your veterinarian.

Allopurinol, a medication that causes decreased uric acid production, can be used in conjunction with diet. Care should be taken, as treatment with allopurinol carries a risk of xanthine (a different type of bladder stone) stone formation.

Outcome

Your veterinarian will set a schedule for monitoring your dog for recurrence of urate stones by checking their urine or performing X-rays or ultrasounds to check for stones. This will allow your veterinarian to ensure that the dietary therapy is well-managed and will help them adjust your dog’s treatment if needed.

Among Dalmatians that form stones, the recurrence rate after removal is high at 33-50%.

Genetics

Urate urinary stones are typically caused by two disease processes: inherited abnormalities in the SLC2A9 gene and liver shunts.

Urate stones caused by a variant in the SLC2A9 gene are inherited in a recessive manner, meaning a dog needs two copies of the abnormal gene to be at increased risk for disease. Carriers (dogs possessing one copy of the variant) are not expected to show signs of disease due to this variant.

There is likely a genetic predisposition to liver shunts in congenital cases, but there is currently no genetic test available for this condition.

This health topic was developed as part of a collaboration between the Cornell Richard P. Riney Canine Health Center and Embark Veterinary, Inc. You can learn more about the hereditary risks of other canine health conditions by exploring our genetics articles.