Hyperuricosuria

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(Redirected from Urate uroliths)

Hyperuricosuria is an autosomal recessive genetic urinary disease characterized by urate urolithiasis and cystitis.

The disease is caused by a missense mutation in the SLC2A9 gene, which results in inefficient transport of uric acid in both the liver and renal proximal tubules[2]. Normally, the canine kidney utilizes bidirectional transport of urate along the nephron, which results in net reabsorption of urate from the glomerular filtrate. In hyperuricosuria, hepatic failure of transforming uric acid into allantoin results in uricosemia which exceeds glomerular filtration rate, leading to excretion of uric acid rather than allantoin in the urine[3]. Affected dogs are consequently predisposed to form urinary calculi composed of urate[4].

Hyperuricosuria has been reported in a number of dog breeds including the American Staffordshire Terrier, Australian Shepherd, Dalmatian, Bulldog, Large Munsterlander, Black Russian Terrier, German Shepherd, Giant Schnauzer, Jack Russell Terrier, Weimeraner and South African Boerboel. Up to 3% of Bulldogs and 25% of the Black Russian Terriers are carriers.

Clinically affected dogs present with early-onset hematuria and dysuria.

Ultrasonography of the kidneys and bladder is required to establish the location of urolithiasis, as both organs can be affected. Blood tests are usually unrewarding but may reveal uricosemia.

Urinalysis may show increased uric acid:creatinine ratio levels[5] and when cooled, the urine forms a crystallized precipitate. In Dalmatians, stone-forming dogs have significantly lower urinary excretion of Tamm-Horsfall protein and and glycosaminoglycans[6].

Diagnosis is achieved by establishing the presence of glucosuria and definitive diagnosis requires PCR-based DNA molecular testing[7].

A differential diagnosis would include portosystemic shunts, where urate uroliths are associated with secondary liver disease such as congenital hepatic fibrosis[8].

Treatment is difficult but may be alleviated by cystotomy and physical removal of uroliths.

Dietary modifications through administration of dietary allopurinol and palliative treatment of secondary cystitis will assist recovery[9].

References

  1. ASAP Labs
  2. Bannasch D et al (2008) Mutations in the SLC2A9 gene cause hyperuricosuria and hyperuricemia in the dog. PLoS Genet 4(11):e1000246
  3. Safra N et al (2005) Exclusion of urate oxidase as a candidate gene for hyperuricosuria in the Dalmatian dog using an interbreed backcross. J Hered 96(7):750-754
  4. Friedman MS (1948) Observations concerning the casues of the excess excretion of uric acid in the Dalmatian Dog. J Biol Chem 175:727–735
  5. Karmi N et al (2010) Estimated frequency of the canine hyperuricosuria mutation in different dog breeds. J Vet Intern Med 24(6):1337-1342
  6. Carvalho M et al (2003) Role of urinary inhibitors of crystallization in uric acid nephrolithiasis: Dalmatian dog model. Urology 62(3):566-700
  7. Safra N et al (2006) Linkage analysis with an interbreed backcross maps Dalmatian hyperuricosuria to CFA03. Mamm Genome 17(4):340-345
  8. McCue J et al (2009) Urate urolithiasis. Compend Contin Educ Vet 31(10):468-475
  9. Bartges JW et al (1999) Canine urate urolithiasis. Etiopathogenesis, diagnosis, and management. Vet Clin North Am Small Anim Pract 29(1):161-191