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Xanthine Urolithiasis in Dogs

Xanthine is a naturally occurring by-product of purine metabolism. It is normally converted to uric acid (the waste product of proteins found in the blood) by the enzyme xanthine oxidase and passed out of the body via urine, but because xanthine is the least soluble of the purines excreted into the urine, excessive amounts of xanthines may be associated with formation of xanthine uroliths (stones). Impairment of xanthine oxidase ultimately results in xanthines in the blood (hyperxanthinemia) and xanthines spilling over into the urine (xanthinuria). It may be naturally occurring, as with enzyme deficiency, or drug-induced (allopurinol). Xanthinuria can be a congenital or an acquired disease.

In naturally occurring xanthinuria, a familial or congenital defect in xanthine oxidase activity is likely. In Cavalier King Charles spaniels, an autosomal (non-sex-linked) recessive mode of inheritance has been supposed to occur.

Acquired xanthinuria is a common complication in dogs that are being treated with the drug allopurinol for urate urinary tract stones or leishmaniasis (a parasitic infestation). Consumption of high purine diets (high protein) also increases the risk of xanthinuria in patients that are being treated with allopurinol.

Symptoms and Types

• May be asymptomatic
• Mustard colored urine
• Bladder stones:
  • Frequent urination (polyuria)
  • Difficulty urinating
  • Bloody urine (hematuria)
• Stones in the urethra:
  • Frequent urination
  • Difficulty urinating
  • Bloody urine
  • Urethra may be blocked
• Kidney stones (nephroliths):
  • Asymptomatic
  • Hydronephrosis – kidney is swollen with urine due to a blocked ureter (the tube leading to the bladder from the kidney)
  • Kidney disease

Causes

• Xanthines in the urine can lead to formation of stones
• Genetic predisposition in Cavalier King Charles spaniels
• Excessive allopurinol medication in combination with high purine diet
• Relation to urine chemistry:
  
  • Acid urine pH
  • Highly concentrated urine
  • Incomplete and infrequent urination

Diagnosis

Your veterinarian will perform a thorough physical exam on your dog, taking into account the background history of symptoms and possible prior conditions that might have led to this condition. A complete blood profile will be conducted, including a chemical blood profile, a complete blood count, a urinalysis and an electrolyte panel. The urinalysis will show xanthine crystals in the urine sediment.

These crystals cannot be distinguished by light microscopy alone. For a precise diagnosis, the urine should be sent for infrared spectroscopy, which can be used to differentiate xanthine uroliths (urinary tract stones) from other types of uroliths. Also, high-pressure liquid chromatography of urine can be done to detect xanthine, hypoxanthine, and other purine metabolites.

Ultrasonography, double-contrast cystography, and intravenous urography are some additonal diagnostic tools that can aid in detecting uroliths and the location they are originating from. Uroliths generally do not show up on normal X-rays.

Xanthine uroliths in the urethra and bladder stones near the urethra may be detected by urethrocystoscopy, which uses a small flexible tube that is equipped with a camera and can be inserted into small spaces, in this case, the urethral passage. Small uroliths may be retrieved for analysis by removing fluid using a transurethral catheter, or using a method called voiding urohydropulsion. This latter method involves filling the bladder completely while the patient is anesthetized, and then emptying the bladder, after attempting to shake stones into the urethra, so that the stones can be collected.