Cystinuria

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(Redirected from Cystine urolithiasis)

Cystinuria is an autosomal-recessive genetic disease of dogs characterized by cystine urolithiasis and cystitis.

This disease is a metabolic disease caused by an inherited defect of renal reabsorption of dibasic amino acids (lysine, arginine, ornithine, and cystine)[1]. The disease is caused by a nonsense defect in the Slc3a1 gene[2].

It has been described in more than 60 dog breeds and except for Newfoundlands, cystinuria has been recognized almost exclusively in male dogs.

Identification of cystine crystals by urinalysis indicates the dog is at risk of forming cystine uroliths, but not all cystinuric dogs develop uroliths. However, the absence of uroliths does not preclude their future development, and preventive measures are indicated.

A urine cystine concentration of >75 mg/g creatinine in nonfasted dogs is predictive of susceptibility to cystine urolithiasis.

Cystine solubility depends on urine pH, with solubility increasing rapidly when urinary pH is >7.5. Dogs fed meat-based diets tend to excrete acidic urine, which leads to urine cystine supersaturation.

Cystinuria is a lifelong defect of tubular reabsorption and cannot be cured. Cystine stones tend to recur within 1 yr without management to prevent recurrence, and they often recur despite attempts at prevention.

Diagnosis is based on presenting clinical signs, detection of cystine uroliths and PCR-based molecular detection of the genetic defect[3].

Treatment involves protein-restricted alkalizing diets and administration of tiopronin N-(2-mercaptoproprionyl)-glycine (15 - 20 mg/kg orally twice daily) or penicillamine (15 mg/kg orally twice daily).

The urine should be alkalized with potassium citrate (20 - 75 mg/kg orally twice daily).

References

  1. Segal S & Their SO (1995) Cystinuria. In: The metabolic and molecular bases of inherited diseases, ed. Scriver CR, Sly WS, Beaudet AL, 7th ed., vol. 3, pp. 3581–3601. McGraw-Hill, New York, NY
  2. Henthorn PS et al (2000) Canine cystinuria: polymorphism in the canine SLC3A1 gene and identification of a nonsense mutation in cystinuric Newfoundland dogs. Hum Genet 107:295–303
  3. Matos AJ et al (2006) Efficient screening of the cystinuria-related C663T Slc3a1 nonsense mutation in Newfoundland dogs by denaturing high-performance liquid chromatography. J Vet Diagn Invest 18(1):102-105