Photo 1: Multiple xanthine urocystoliths were removed from a 2-year-old domestic shorthaired cat.
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Recently a colleague in private practice asked me for advice about how to treat xanthine bladder stones formed by an 11-month-old,
spayed female domestic shorthaired cat.
The sources of information she consulted indicated that in dogs the most common cause of xanthine uroliths was an adverse
event during treatment with the drug allopurinol. However, she was unable to find information about xanthine uroliths in cats.
This cat was not being treated with allopurinol. How would you manage this case?
Epidemiology
Review of samples submitted to the Minnesota Urolith Center revealed that xanthine uroliths were detected in the urinary tracts
of 64 cats. None of the cats had been treated with allopurinol. In our series, 60 percent of these cats were males (80 percent
of males were neutered and 20 percent were not neutered) and 40 percent were neutered females. The mean age of cats at the
time of diagnosis was 2.8 years (range = 4 months to 10 years).
Eight of the 64 cats were less than 1-year old at the time of xanthine urolith detection. Forty-four affected cats were of
the domestic short hair breed, 12 were domestic long hair, four were domestic medium hair, one was Siamese, one was designated
as British short hair and one was designated as European short hair. The breed of one cat was not identified.
Photo 2: Photomicrograph of xanthine crystals in urine sediment collected from the cat described in Photo 1.
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Xanthine uroliths were obtained from the lower urinary tract of 95 percent of these cats, and the upper urinary tract of 5
percent of them.
Quantitative analysis revealed that almost all of these stones were pure xanthine. A few contained small quantities of uric
acid. Uroliths composed primarily of xanthine were often multiple in number, ranged in size from 1 to 5 mm, and were radiolucent.
The physical appearance of xanthine uroliths resembled ammonium urate in that they typically had a smooth surface contour,
and were yellow, tan or light brown in color. On cross section, they commonly had numerous concentric laminations that readily
separated from each other (Photo 1, p. 14S).
Etiopathogenesis
Xanthine, a normal degradation product of purine metabolism, is converted to uric acid by the enzyme xanthine oxidase (Table
1, p.14S). However, because xanthine is the least soluble of the purines excreted in urine, abnormal quantities of xanthine
in urine may result in formation of xanthine uroliths. Acid urine pH, highly concentrated urine, and incomplete and infrequent
micturition enhance the risk of xanthine urolith formation.
Naturally occurring (xanthine oxidase deficiency) or drug-induced (allopurinol) impairment of xanthine oxidase ultimately
results in hyperxanthinemia and xanthinuria.
We have observed naturally occurring xanthinuria more commonly in cats than dogs. Although the precise underlying abnormality
in cats has not been determined, a familial or congenital defect in xanthine oxidase activity is likely. To date, we have
not identified a breed predisposition.
Table 1.
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In dogs, acquired xanthinuria is a common complication of treatment of urate urolithiasis or Leishmaniasis with allopurinol.
Allopurinol is a xanthine oxidase inhibitor, and thus impairs conversion of xanthine to uric acid (Table 1). Consumption of
high purine diets increases the risk of xanthinuria in patients treated with allopurinol.
Clinical findings
The initial clinical signs of affected cats were nonspecific (e.g. hematuria, dysuria, pollakiuria and/or urethral obstruction).
They were typical of feline lower tract disease due to any cause.
The urine color of some cats with xanthine uroliths was mustard yellow. (Xanthine is the Greek word for "yellow.") Xanthine
crystals (which are indistinguishable from amorphous urate or uric acid crystals) were observed in urine samples collected
from some cats (Photo 2). Their urine pH was variable, ranging from 6.0 to 8.0. Hematuria was common in cats without concomitant
bacterial urinary tract infection. Changes typical of inflammation (pyuria, hematuria and proteinuria) were observed in urine
of cats with concomitant urinary tract infections.
The radiodensity of xanthine uroliths is similar to soft tissue. Thus, xanthine uroliths cannot be reliably detected by survey
radiography. Double contrast cystography is more sensitive in detecting xanthine urocystoliths than either survey radiography
and/or most techniques of ultrasonography. Xanthine uroliths appear radiolucent when surrounded by appropriate concentrations
of radiopaque contrast medium. Positive contrast urethrography may be required to detect and localize xanthine uroliths that
have passed into the urethral lumen.
Evaluation of hemograms and serum biochemical profiles of a limited number of unobstructed cats revealed no abnormalities.
In male cats with urethral obstruction caused by xanthine uroliths, hematological and serum biochemical findings were characteristic
of post-renal azotemia. Evaluation of a urine sample of a cat by high-pressure liquid chromatography revealed xanthinuria
and a low concentration of uric acid. Further studies are in progress to determine if hyperxanthinemia and hyperxanthinuria
associated with reduced serum and urine concentrations of uric acid are a consistent abnormality in cats with xanthine uroliths.
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