Igenity Canine Wellness testing identifies increased risk for urate urinary crystals and stones based on a specific genetic mutation linked to hyperuricosuria.1 The mutation is fixed in Dalmatians, but also affects other breeds. Risk status is useful for diet recommendations and educating clients about early signs of urinary crystals or stones, enabling prompt treatment. The phenotypic result of the mutation may vary between individuals and breeds due to differences in urate transport within the liver and kidney. Presence of the mutation increases risk but does not diagnose the presence or type of crystalluria or stones.
What is Hyperuricosuria?
Hyperuricosuria is an increased amount of uric acid in the urine. When most mammals metabolize a substance in high-protein foods called purine, it is excreted in a form called allatonin. However, for humans and dogs with the SLC2A9 gene mutation, they instead excrete purines as uric acid. This can cause increased concentrations of uric acid in the blood (hyperuricemia) or urine (hyperuricosuria).
Where do purines come from?
Purine concentration is higher in meat products, especially organs such as liver and kidney. Avoid or minimize these foods with dogs carrying the SLC2A9 gene mutation.
Breeds Affected
This risk allele is typically fixed in Dalmatians – nearly all Dalmatians will be at increased risk for urate stones.
The risk allele has also been found in other breeds:
Monitoring & Clinical Signs
Early identification of clinical signs associated with crystalluria or bladder stones may help prevent advanced conditions such as urinary obstruction and renal failure.
Signs for owners to look for:
- Straining to urinate
- Blood in urine
Vet hospital visits:
- Urinalysis every 3 to 6 months:
- Check urine sediment for crystals:
- Aim to establish the following:
- pH ≥7
- Urine specific gravity ≤1.020
- Ultrasound every 6 to 12 months to detect stones early and enable intervention without surgery.
- Ammonium biurate stones are relatively radiolucent – typically they aren’t visible on x-ray.
Dietary Considerations
Consider diets with reduced protein (and therefore reduced purines)
- Avoid organ meats such as liver and kidney, which have the highest concentration of purines.
- Stick to diets with egg, rice and whey (dairy casein).
Increase water consumption by feeding canned food or adding water to dry kibble.
Consider allopurinol to decrease uric acid concentration.
Test Limitations
- The test does not indicate risk for other types of crystals or stones such as calcium oxalate, struvite or cystine.
- Does not screen for all genetic causes of urinary crystals and stones.
- Not all dogs with hyperuricosuria will form uroliths, or even crystals in the urine, due to variations of urate transport within the liver and kidney.
- The test does not account for other causes of hyperuricosuria, such as liver dysfunction or portosystemic shunts.
Science and Genetics
In 2008, Bannasch, et al., discovered a G to T missense mutation in the SLC2A9 gene on chromosome 3, which resulted in a defect in urate transport in the liver and kidney.1
Mode of Inheritance:
Hyperuricosuria is inherited as an autosomal recessive trait. Only dogs who are homozygous affected for the genetic mutation will be an increased risk for hyperuricosuria. Carriers of the condition are not at increased genetic risk for Hyperuricosuria but could pass on the risk allele to their offspring.Potential Test Outcomes
| Genotype | Phenotype |
|---|---|
| No variant detected | No increased risk based on the variant tested |
| CARRIER: 1 copy of the risk allele in the SLC2A9 gene | No increased risk based on the variant tested |
| AFFECTED: 2 copies of the risk allele detected in the SLC2A9 gene | Increased risk for urate urinary crystals and stones |
About the SLC2A9 gene:
The SLC2A9 gene encodes protein necessary for urate transport. As a result, uric acid from the serum does not get efficiently transported into hepatocytes where it is typically degraded into allantoin. In human populations, variants in the SLC2A9 gene have been associated with gout as well as uric acid levels.2,3
References
- Bannasch, D., Safra, N., Young, A., Karmi, N., Schaible, R. S., & Ling, G. V. (2008). Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genetics, 4(11). https://doi.org/10.1371/journal.pgen.1000246
- Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, et al. (2008) SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet 40: 437–442.
- Brandstatter A, Kiechl S, Kollerits B, Hunt SC, Heid IM, et al. (2008) Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes Care 31: 1662–1667.
https://www.vetmed.umn.edu/sites/vetmed.umn.edu/files/canine_urate_uroliths.pdf