Canine Hyperuricosuria information

 

Hyperuricosuria (HU) is a hereditary condition in which there are higher than normal levels of uric acid in the urine. The trait can occur in any breed but is most commonly found in the Dalmatian, Bulldog, and Black Russian Terrier.

 

Other names:

Urolithiasis

Acronyms:

HU or HUU

Affected genes:

SLC2A9

Inheritance type:

Autosomal recessive

Mutation:

Point mutation

The trait can occur in any breed but is most commonly found in the:

Black Russian Terrier, English Bulldog, Dalmatian

Frequencies of the mutation in Black Russian Terriers

The allele frequency of the Cys181Phe mutation was 0.51 in BRTs. On the basis of these allele frequencies 27% of the BRT population were estimated to be hyperuricosuric

Additional breeds that were found to have a high frequency of the trait are:

American Staffordshire Terrier, Australian Shepherd, German Shepherd Dog, Giant Schnauzer, Jack Russell Terrier, Large Munsterlander, South African Boerboel, Labrador Retriever, Parson Russell Terrier, Weimaraner, Pomeranian, occurrence in other dog breed is not excluded


An autosomal-recessive condition means that a dog must inherit two copies of an abnormal gene before its health is affected. Each dog inherits one copy of a gene from its mother and one from its father. If the health status of both sire and dam are known, the likely health status of any puppies produced can be predicted. This means that any dog can be used responsibly in a breeding programme without the risk of producing clinically affected puppies, provided that the right mate is selected.

 

The following chart details the expected outcomes of matings for all possible combinations of hyperuricosuria genotypes:

 

 

FEMALE

MALE

N/N N/HU HU/HU
N/N

100% N/N

50% N/N, 50% N/HU

100% N/HU
N/HU

50% N/N, 50% N/HU

25% N/N, 50% N/HU, 25% HU/HU

50% N/HU, 50% HU/HU
HU/HU 100% N/HU

50% N/HU, 50% HU/HU

100% HU/HU


Results reported as:
 

N/N: no copies of hyperuricosuria mutation; dog is normal/clear;
N/HU: 1 copy of hyperurisosuria mutation; dog is normal but is a carrier;
HU/HU: 2 copies of hyperuricosuria mutation; dog is affected and susceptible to develop bladder/kidney stones.

 

N - normal gene

HU - hyperuricosuria mutation gene.

 

Dogs that have been tested for an autosomal-recessive condition can be described as either: clear, carrier or affected, but what do these terms mean?

The Disease


Hyperuricosuria (HU) is a hereditary condition in which there are higher than normal levels of uric acid in the urine. The trait can occur in any breed but is most commonly found in the Dalmatian, Bulldog, and Black Russian Terrier. Uric acid is a waste product that is produced by the liver as it breaks down purines that are no longer needed by the body or those that have directly come from the diet. Purines are catabolites derived from DNA and RNA. They include: adenine, guanine, hypoxanthine, xanthine, anhydrous uric acid, uric acid monohydrate, uric acid dihydrate, salts of uric acid (e.g. ammonium urate, sodium urate, calcium sodium urate) and in most mammals allantoin. Each of theses catabolites may behave differently.

In most healthy breeds of dog, if the dog has a healthy liver, the uric acid that is formed is further broken down into allantoin which is then excreted from the body via the kidney in the urine and causes no problems. However, in affected dogs, because of an abnormality in metabolic functioning caused by the inheritance of a faulty gene, most of the uric acid is not broken down, and thus high levels of uric acid appear in the blood and have to be excreted in the urine e.g. the uric acid concentration in the urine of normal dogs varies from 10-20 mg/24 hours but in for example affected Dalmatians varies between 400-600 mg/24 hours). This results in increased urate excretion in the urine, and this predisposes them to the formation of urate crystals and eventually, stones. There are a number of different urate stones. Uroliths composed of uric acid (anhydrous uric acid, uric acid dihydrate, sodium urate, ammonium urate) or xanthine form because urine is oversaturated with these substances. Ammonium urate (also known as ammonium acid urate and ammonium biurate) is the monobasic ammonium salt of uric acid. It is the most common naturally occurring purine urolith form observed in dogs affected HU. Other naturally occurring purine uroliths include sodium urate (also known as sodium acid urate or monosodium urate), sodium calcium urate, potassium urate and uric acid dihydrate. They are usually small, yellow-brown, smooth stones.

 

Common characteristics of canine purine uroliths

Chemical names formulas

Ammonium acid urate C₅H₃N₄O₃NH₄•H₂O    
Sodium acid urate C
HNONa•HO
Uric acid C
HNO•2HO
Xanthine C
HNO

Some variations in mineral composition

Ammonium urate only
Sodium calcium urate
Sodium urate only
Uric acid only
Xanthine only
Ammonium urate mixed with variable quantities of sodium urate, or sodium and calcium urate, magnesium ammonium phosphate and/or calcium oxalate
Sodium and calcium oxalate
Xanthine and uric acid

Color:

Light or dark brown, brown-green, brown-yellow

Shape:

Variable. Usually round or ovoid in urinary bladder, may assume shape of renal pelvis (funnel shaped), may assume jackstone appearance. Usually smooth, occasionally irregular or rough.

Nuclei:

Nuclei and concentric laminations are common.

Density:

Usually dense and brittle. Radiographically, purine uroliths have marginal radiodensity compared with soft tissue. Some may be radiolucent.

Number:

Single or multiple

Location: May be located in kidneys, ureters, urinary bladder (most common) and/or urethra.
Size:

Usually small (1 mm to 1 cm in diameter), occasionally large (more than 1 cm).

Prevalence Approximately 5 to 6% of all canine uroliths. Approximately 13% of canine nephroliths.
May be recurrent.
Characteristics of affected canine patients

Most common in males.
Mean age at diagnosis is four years (range <1 to >17 years).
Most commonly observed in Dalmatian, English Bulldogs, Black Russian Terriers
.

 

Urate stones that have formed in the urinary system can irritate and inflame the bladder, or, more seriously, block the urinary system leading to rapidly progressive, severe problems and even death due to kidney failure and high blood potassium levels. Blockage of the urinary system leads to a medical emergency, can cause severe pain and malaise, with rapid veterinary treatment being necessary to save life.

   

Magnification: 37.5x. Uric acid crystals form urate stones

Magnification: 122x. The image shows typical thorn-apple-shaped ammonium urate crystals

Magnification: 400x. Amorphous urate crystals

Magnification: 128x. Sodium urate crystals in the urine sediment of a dog. These needlelike crystals are often mistaken for tyrosine crystals

 

 

Hyperuricosuria itself doesn’t cause a problem, but the urate stones that commonly form as a result of it, often do. Urinary crystals in dogs form when the animal's urine becomes supersaturated with particular minerals. Once the center of the crystal has been formed, minerals will continue to adhere to it and the crystal will eventually form a stone (called a urolith). This can take anywhere from a few days to several weeks.

The intensity of the welfare impact varies depending on where the stones form and where they cause problems. It ranges from moderate, for animals with recurrent bouts of cystitis (inflammation of the bladder), which have moderate pain and discomfort, to severe for individuals with complete blockages. These animals can suffer severe pain and illness and sometimes death. They can be treated but often require major surgery which has its own welfare implications.

 

 

Photo ultrasound revealed a stone in the bladder

X-ray double contrast revealed a number of urate stones

RTG picture (You can see a lot of urate stones located in the vicinity of the penile bone, leading to complete blockage of the urethra in the male)

amonium urate stones amonium urate stones

Diagnosis of hyperuricosuria

Hyperuricosuria is inherited as a simple, autosomal, recessive trait. Individuals have pairs of genes, one of each pair having been derived from each parent. In simple, autosomal, recessive conditions, individuals that have two normal genes or one normal and one mutant gene show no signs of the disease but, in this condition, those individuals with two recessive genes show hyperuricosuria. The gene responsible for hyperuricosuria has been identified as the SLC2A9 gene. A DNA test for this specific mutation is available and can determine if dogs are normal or if they carry one or two copies of the mutation. Dogs that carry two copies of the mutation will be affected and susceptible to develop bladder/kidney stones.

Which laboratories test for this condition?

Orivet (AUS)

Genomia Genetic Laboratory (CZ)

Antagene (FR, UK, IT, BE, SP, USA & CAN, AUS)

Laboklin (DE, PL, IT, SK, AT, FIN, UK, CH)

Vet Complex (PL)

Sans Bio (RU)

My Dog DNA (RU)

Zoogen (RU)

EVG Molekularna Diagnostika (SI)

AHT Animal Health Trust (UK)

Animal DNA Diagnostics (UK)

UC Davis Veterinary Genetic Laboratory (USA)

UC of Minesota, Minnesota Urolith Center (USA)

GenSol Diagnostics LLC (USA)

Paw Print Genetics (USA)

Veterinary Diagnostics Center (DDC) (USA)

VetGen (USA)

VetNostic (USA)

Diagnosis of urolithiasis in HU predisposed dogs

HU is present in all affected (HU/HU) dogs, although not all will develop urolithiasis. The changes in the urine are generally present from birth. However it usually takes some time for crystals to form and combine into stones.

Risk factors for urate lithogenesis in dogs include:

  • genetic and indyvidual predisposition;

  • kidney function (increased renal excretion and urine concentration of uric acid or increased renal excretion or renal production of ammonium ions);

  • liver function (hepatic dysfunction);

  • the concentration of uric acid in the urine (formation of highly concentrated urine);

  • pH of the urine (aciduria - low pH urine);

  • dietary components (high-protein foods, high purine content, acidifying potential, low moisture content, ascorbic acid);

  • various comorbid diseases (neoplasia with rapid cell destruction, hyperuricemia, hyperammonuria);

  • hormonal disorders;

  • the bacterial infection (increased microbial production of ammonium ions);

  • presence of promoters or absence of inhibitors of urate urolith formation;

  • the administration of certain drugs (urine acidifiersm salicylates, chemotherapeutic agents - especially 6-mercaptopurine);

  • anatomical changes in the urinary tract that cause urine retention over obstacles, which facilitates the formation of deposits (eg stenosis of the ureter malformations, closing the urethra, bladder diverticulum, enlarged prostate, prolonged immobilization after fractures, transverse spinal cord).

Diagnosis of canine urolithiasis include:

  • determine the age, gender, condition and breed;

  • DNA testing for canine hyperuricosuria to confirm the defect in individual patients;

  • abdominal palpation, to feel stones present in the urinary bladder;

  • complete urinalysis (with microscopic examination of sediment for crystals - especially urate crystals);

  • quantitative urine culture;

  • complete blood tests (hematology and serum chemistry);

  • urinary pH;

  • determine baseline pretreatment serum uric acid concentrations and (if possible) 24-hour excretion of urine uric acid;

  • if uroliths are available, determination their mineral composition. If unavailable, determination their composition by evaluating appropriate clinical data;

  • radiographic examination (possibly with contrast media) or ultrasonographic examination to see if stones are present and their location in the urinary tract.

Symptoms

The signs you will see in your dog depend on where in the urinary tract the stones end up. They collect most commonly in the bladder in which case you may see blood in the urine, difficulty and pain in urinating, and small frequent amounts of urine. Urinary tract obstruction is a serious condition that occurs when a stone completely blocks the urethra and thus blocks the outflow of urine (more common in male dogs, who have a smaller urethra). Signs include straining to urinate, vomiting and loss of appetite, weakness and lethargy (due to toxins building up in the body). Animals can die from a blocked urinary system within 24-48 hours without appropriate treatment!

If your dog is showing the physical signs described above, you should immediately take him/her to the vet doctor. Your doctor will give him/her the necessary medical assistance. Your veterinarian will do an analysis of his/her urine (urinalysis) to look for crystals and also for a bacterial infection, which is commonly seen with this condition. Many stones can be seen with x-rays, but urate stones are radiolucent - that is, they cannot be identified in abdominal X‑rays - so their diagnosis is often made by the use of ultrasound, contrast dye X-rays, or analysis of urinary crystals or stones that were collected or removed.

Treatment

Uroliths (stones forming in the urinary system) come in various chemical types, some of which can be dissolved using special diet that for example make the urine more acidic or alkaline. Urate stones are sparingly soluble and often need to be surgically removed (particularly those of larger sizes), though sometimes if we deal only with crystals or fine sand medical treatment can help dissolve them or prevent them recurring. Medical treatment can often be difficult and is only used in dogs not showing clinical signs. The medical approach is to dissolve the stones gradually by changing the pH of the urine, ie. making it more alkaline through medication and changes in diet.

Prevention

All dogs affected with hyperuricosuria are potential urate stone-formers. Urate stones can be dissolved with a combination of a low-purine diet, urine alkalization, and control of secondary infections. Reducing purines in food is an effective way to reduce the risk of urate stones. Because most high-protein foods are also high in purines, veterinarians often recommend switching urate-forming dogs to a low-protein diet. Special diets also result in a larger volume of more dilute urine, making it easier for a dog to pass the crystals, sand or small stones. In all cases of urolithiasis, in addition to paying careful attention to your dog's diet, you can help to reduce the formation of stones by providing lots of fresh water and regular opportunities to urinate, so that urine doesn't accumulate in the bladder allowing time for stones to form. You can increase your dog's water consumption by feeding a canned diet with a high water content, or mixing dry food with water. Some HU affected dogs owners believe that giving their dogs who are prone to forming urate stone only mineral-free distilled water has helped prevent more stones from forming, but no scientific evidence for this exists.

it is important to watch the corresponding pH of urine. The target range of urine pH during dissolution is 7.0 to 7.5. Care must be taken not to alkalize too much, making the urine pH higher than 7.5, because that can lead to the formation of calcium phosphate stones or shells around urate stones, making them difficult or impossible to dissolve. Urinary pH can be monitored using test strips with the goal of maintaining a neutral (7.0) pH in dogs prone to urate stones.

The veterinarian may decide to administration of allopurinol. Allopurinol (Zyloprim, and generics) reduces the production of uric acid in the body. Allopurinol helps prevent the formation of bladder stones in dogs that are caused by high levels of uric acid.

Your veterinarian should monitor your dog's progress through periodic radiographs and ultrasound examination and analysis of the urine and blood.

Breeding for Health

Dog breeders today have a number of different considerations to make when choosing which dogs to use for breeding, these include:

  • Temperament;

  • Breed type and characteristics;

  • Health test results;

  • Genetic diversity;

  • General health of the sire and dam.

Responsible breeders will consider the health of their puppies to be a priority, increasing the probability that healthy puppies will go on to live long and happy lives. Most DNA tested dogs can be used responsibly in a breeding programme, but the decisions you make when choosing which dogs to mate must be informed and carefully planned.

 

 

Producing all clear puppies N/N X N/N RECOMMENDED

All puppies from this mating will be clear from the specific condition you have tested for and have none of the abnormal genes associated with the condition. If you wish to use these puppies for future matings, then clear puppies can be mated to carrier and affected dogs without risk of producing affected puppies.

 

 

Producing clear and carries puppies N/N X N/HU ACCEPTED

 

This mating may produce both clear and carrier puppies. Once the puppies are born, it is important to test all of the puppies before they themselves are bred from or are passed on to new homes. Clear puppies will have none of the abnormal genes associated with the condition you have tested for. If you wish to use these puppies for future matings, then clear puppies can be mated to carrier or affected dogs without risk of producing affected puppies. Carrier puppies will carry a single copy of the abnormal gene and could pass this on if they themselves are bred from. When used responsibly, carriers are an important part of any breeding plan and should not be overlooked when making mating choices. By using carriers, you can keep good, healthy dogs in the breeding population. Just be sure that if you breed a carrier dog, you know the health status of the other dog.

 

 

Producing all carries puppies N/N X HU/HU ACCEPTED

 

This mating will produce all carrier puppies that will not be affected by the condition you have tested for. Once the puppies are born, it is important to test all of the puppies before they themselves are bred from or are passed on to new homes. Carrier puppies will carry a single copy of the abnormal gene and could pass this on if they themselves are bred from. When used responsibly, carriers can be an important part of any breeding plan and should not be overlooked when making breeding plans. By using carriers, you can keep good, healthy dogs in the breeding population. Just be sure that if you mate a carrier dog, you know the health status of the other dog. Carriers should never be used to produce affected dogs.

 

 

Producing clear, carries and affected puppies N/HU X N/HU UNACCEPTABLE

 

This mating may produce clear, carrier and affected puppies. Producing affected puppies that will develop the condition you tested for is taking a risk on canine health and welfare.  A mating which may produce affected puppies should never knowingly be carried out. If this mating accidentally occurs, it is important to test all of the puppies before they themselves are bred from or are passed on to new homes. Veterinary advice should be sought as to the clinical management of any affected puppies. If you wish to use affected puppies for future matings, then affected puppies (without any symptoms of these disease) can be conditionally mated in future only to clear dogs without risk of producing affected puppies. Clear puppies will have none of the abnormal genes associated with the condition you have tested for. If you wish to use these puppies for future matings, then clear puppies can be mated to carrier or affected dogs without risk of producing affected puppies. Carrier puppies will carry a single copy of the abnormal gene and could pass this on if they themselves are bred from. When used responsibly, carriers are an important part of any breeding plan and should not be overlooked when making mating choices. By using carriers, you can keep good, healthy dogs in the breeding population. Just be sure that if you breed a carrier dog, you know the health status of the other dog. Please remember that carrier and affected dogs should never be used to produce other affected dogs!.

 

 

Producing carries and affected puppies N/HU X HU/HU UNACCEPTABLE

 

This mating may produce carrier and affected puppies. Producing affected puppies that will develop the condition you tested for is taking a risk on canine health and welfare. A mating which may produce affected puppies should never knowingly be carried out. If this mating accidentally occurs, it is important to test all of the puppies before they themselves are bred from or are passed on to new homes. Veterinary advice should be sought as to the clinical management of any affected puppies. If you wish to use affected puppies for future matings, then affected puppies (without any symptoms of these disease) can be conditionally mated only to clear dogs without risk of producing affected puppies. Carrier puppies will carry a single copy of the abnormal gene and could pass this on if they themselves are bred from. When used responsibly, carriers are an important part of any breeding plan and should not be overlooked when making mating choices. By using carriers, you can keep good, healthy dogs in the breeding population. Just be sure that if you breed a carrier dog, you know the health status of the other dog. Please remember that carrier and affected dogs should never be used to produce other affected dogs!.

 

 

Producing all affected puppies HU/HU X HU/HU UNACCEPTABLE

 

This mating will produce all affected puppies. Producing affected puppies that will develop the condition you tested for is taking a risk on canine health and welfare. A mating which may produce all affected puppies should never knowingly be carried out. If this mating accidentally occurs, it is important to inform new owners about these disease before each puppy passed on to new home. Veterinary advice should be sought as to the clinical management of any affected puppies. If you wish to use these affected puppies for future matings, then affected puppies should be official tested and can be conditionally mated (if they do not show any symptoms of the disease) only to clear dogs without risk of producing affected puppies. Please remember that affected dogs should never be used to produce other affected dogs!.

 

 


 

References:

Bannasch D, N Safra, A Young, N Karmi, RS Schaible and GV Ling (2008) Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog. PLoS Genetics 4(11): e1000246. doi:10.1371/journal.pgen.1000246


Karmi N, EA Brown, SS Hughes, B McLaughlin, CS Mellersh, V Biourge, and DL Bannasch (2010) Estimated Frequency of the Canine Hyperuricosuria Mutation in Different Dog Breeds. Journal of Veterinary and Internal Medicine 2010;24:1337–1342.

 

Treatment and Prevention of Kidney and Bladder Stones. The Whole Dog Journal. June 2010 Issue.

 

Small Animal Clinical Nutrition, 5th Edition. Chapter 39: Canine Purine Urolithiasis: Causes, Detection, Management and Prevention References. Carl A. Osborne Joseph W. Bartges, Jody P. Lulich, Hasan Albasan, Carroll Weiss.

 

Breeding for Health. The Kennel Club Information Guide.

 


 

BRT International Hyperuricosuria Database

This database is still open and any additional information is welcome. If you would like to add test result of your dog please send information to us by e-mail.

 

Disclaimer: These hyperuricosuria database are not official hyperuricosuria database branded by any kennel club or veterinary health organization. The database was established for the purpose of the our web site and is for educational information only. Data is compiled from personal records or publicly available sources and no warranty as to accuracy is stated or implied - users should verify all data with the owners or breeders in question. If you spot any incorrect results please accept our apologies and please send us correct result by e-mail. We rely on the goodwill of volunteers to provide us with results and mistakes are corrected as soon as we receive them.

 

LAST UPDATED 27.12.2016

 


 

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