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Basics ⬇

Basics

Overview

  • Xanthine, a degradation product of purine metabolism, is converted to uric acid by the enzyme xanthine oxidase. Naturally occurring (enzyme deficiency) or drug-induced (allopurinol) impairment of xanthine oxidase ultimately results in hyperxanthinemia and xanthinuria.
  • In naturally occurring xanthinuria, a familial or congenital defect in xanthine oxidase activity is likely. A breed predisposition has not been identified in cats (number = 392 submitted to the Minnesota Urolith Center (MUC) 1981–2014). In Cavalier King Charles spaniels, an autosomal recessive mode of inheritance has been postulated to occur. Xanthine nephrolithiasis in a dachshund associated with renal failure has been reported.
  • Acquired xanthinuria is a common complication of treatment of urate urolithiasis or leishmaniasis with allopurinol. High purine diets increase the risk of xanthinuria in patients treated with allopurinol.
  • Xanthine is the least soluble of the purines excreted in urine.

Signalment

  • Dog and cat. Naturally occurring xanthinuria is more common in cats than in dogs.
  • In dogs, allopurinol-induced xanthinuria may affect any breed, age, or gender. Naturally occurring xanthinuria and xanthine uroliths have been observed in young Cavalier King Charles spaniels.
  • In cats, xanthine uroliths affect adult males (66%) and females (33%) (mean age at diagnosis 3.3 years; range 2 months–13 years). Most common in the domestic shorthair and domestic longhair breeds.

Signs

  • Dependent on location, size, and number of uroliths.
  • Pollakiuria, dysuria, hematuria and voiding of small, smooth, yellow uroliths. Complete outflow obstruction may result in azotemia.
  • May be asymptomatic. Nephroliths may be associated with hydronephrosis and renal insufficiency.

Causes & Risk Factors

  • Xanthinuria
  • Canine breed predisposition include Cavalier King Charles spaniels and dachshunds.
  • Cats: uroliths often recur unless prophylactic therapy is initiated.
  • Retrospective data from the MUC shows that approximately 11% of cats had >1 occurrence of xanthine uroliths. Urolith formation enhanced by acid urine pH, highly concentrated urine, and incomplete and infrequent micturition.
  • In animals given excessive allopurinol, xanthinuria is enhanced by failure to appropriately restrict dietary purine precursors.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Uroliths mimic other causes of pollakiuria, dysuria, hematuria, and/or outflow obstruction.
  • Differentiate from other types of uroliths, especially ammonium urate, by urinalysis, radiography, and quantitative analysis of retrieved uroliths.

CBC/Biochemistry/Urinalysis

Xanthine crystals cannot be distinguished from ammonium urate or amorphous urates by light microscopy. All these crystals are usually brown or yellow-brown and may form spherules of varying size.

Other Laboratory Tests

  • Infrared spectroscopy, X-ray diffraction, or other quantitative techniques are required to differentiate xanthine from ammonium urate, sodium urate, and uric acid.
  • High-pressure liquid chromatography of urine to detect xanthine, hypoxanthine, and other purine metabolites.

Imaging

  • Radiography-Similar to that of soft tissue. Cannot be reliably detected by survey radiography.

  • Ultrasonography, double contrast cystography, and intravenous urography aid in detecting uroliths and their location.

Other Diagnostic Procedures

  • May be detected by urethrocystoscopy.
  • Uroliths for analysis may be retrieved by aspiration via a transurethral catheter or voiding urohydropulsion.

Treatment

  • Medical protocols that consistently promote dissolution of xanthine uroliths have not been developed.
  • Remove small urocystoliths by voiding urohydropropulsion.
  • Surgery remains the most reliable method to remove larger active uroliths from the lower urinary tract.
  • Minimize further growth of existing uroliths by reducing dietary risk factors. Discontinue or reduce allopurinol medication dosages.
  • Pending further studies in cats with naturally occurring xanthine uroliths, consider canned renal-failure diets to increase urine volume, minimize purine precursors, and minimize formation of acid urine.
  • Consider perineal urethrostomies for recurrent urethral obstruction in male cats.

Medications ⬆ ⬇

Medications

Drug(s)

Urine Alkalinizers

  • Consider in patients that have acid urine despite dietary therapy.
  • A sufficient quantity of potassium citrate or sodium bicarbonate should be given to sustain a urine pH of 7.0–7.5.

Allopurinol

  • When treating urate urolithiasis in dogs, adjust dosage of allopurinol in context of magnitude of concentration of urine, uric acid, and quantity of dietary purines (see Urolithiasis, Urate).
  • In dogs, allopurinol-induced uroliths may dissolve by discontinuing allopurinol therapy but continuing a low purine diet.

Contraindications/Possible Interactions

Do not give allopurinol to cats or dogs with naturally occurring xanthine uroliths.

Follow-Up

  • Monitor dissolution at 30-day intervals by urinalysis, contrast radiography or ultrasonography.
  • Recurrence does not occur in all xanthinuric cats and dogs.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

  • Urate urolithiasis
  • Nephrolithiasis

Suggested Reading

Bartges JW, Osborne CA, Felice LJ. Canine xanthine uroliths: Risk factor management. In: Kirk RW, Bonagura JD, eds., Current Veterinary Therapy XI. Philadelphia: Saunders, 1992, pp. 900–905.

Kucera J, Bulkova T, Rychlat R, Jahn P. Bilateral xanthine nephrolithiasis in a dog. J Small Anim Pract 1997, 38(7):302–305.

Osborne CA, Lulich JP, Lekcharoensuk C, et al. Feline xanthine urolithiasis: A newly recognized cause of feline lower urinary tract disease. In: Proceedings 21st Annual ACVIM Forum, Charlotte, North Carolina, 2003, pp. 781–782.

Tsuchida S, Kagi A, Koyama H. Xanthine urolithiasis in a cat: A case report and evaluation of a candidate gene for xanthine dehydrogenase. J Feline Med Surg 2007, 9:505–508.

Authors Carl A. Osborne and Joseph W. Bartges

Consulting Editor Carl A. Osborne