Recently a colleague in private practice asked me for advice about how to treat cystine bladder stones formed by a 5.5 year-old,
spayed female Siamese cat. Although textbooks that he consulted contained information about cystine urolithiasis in dogs,
he was unable to find recommendations for this disorder in cats. How would you manage this case?
Photo 1: Photograph of multiple cystine urocystoliths removed from a 2-year-old female domestic shorthair cat.
Unlike canine cystine uroliths, which most commonly are encountered in male dogs, feline cystine uroliths occur in males and
females with equal frequency. In our experience, the mean age of cats at the time of diagnosis of cystine uroliths was 3.4
years (age range = 4 months to 12.2 years). Approximately 65 percent of cats were of the domestic shorthair breed and 20 percent
were Siamese. One was a Maine Coon, one was a Korat, and two were domestic longhair cats.
Quantitative analysis of feline cystine uroliths submitted to the Minnesota Urolith Center revealed that most are pure. Pure
cystine urocystoliths are usually ovoid and smooth (Photo 1, p. 16S). They typically have a light yellow to reddish brown
color and vary in diameter from 0.5 mm to several centimeters. All uroliths submitted to the Minnesota Urolith Center were
initially obtained from the lower urinary tract (~65 percent of samples came from the bladder, ~5 percent came from the bladder
and urethra, ~5 percent came from the urethra, and ~25 percent of samples were voided). The number of uroliths in each patient
varied from one to more than 100. Radiodense renoliths subsequently developed in two cats that initially had only urocystoliths.
Cystine is a nonessential sulfur-containing amino acid that is normally present in low concentrations in plasma. Normally
it is freely filtered by glomeruli. Most filtered cystine is then actively reabsorbed by the proximal tubules. Cystinuria
is characterized by impaired reabsorption of cystine and other amino acids by the renal tubules. Based on results of studies
in humans and dogs, it is likely that feline cystinuria is an inborn error of metabolism. Empirical observations suggest that
there may be an association between cystinuria and the Siamese breed. Evaluation of urine amino acid profiles of three affected
cats revealed increased levels of arginine, lysine, and ornithine in addition to cystine. This pattern of aminoaciduria may
be remembered with the acronym COLA (cystine, ornithine, lysine, and arginine). The major causes of morbidity and mortality
recognized in association with cystinuria are sequelae of urolith formation. Because not all cystinuric cats form crystals
or uroliths, cystinuria is a predisposing rather than a sole cause of cystine urolith formation.
The initial clinical signs of affected cats are nonspecific (e.g. hematuria, dysuria, pollakiuria and/or urethral obstruction).
They are typical of feline lower tract disease due to any cause.
The solubility of cystine in urine is pH dependent. It is relatively insoluble in acid urine, but becomes more soluble in
alkaline urine. Although cystine is less soluble in acid than alkaline urine, the urine pH of affected cats may vary from
6.0 to 8.0. Detection of flat colorless hexagonal cystine crystals is a characteristic finding in urine samples collected
from cats with cystine urocystoliths (Photo 2). The six sides of cystine crystals may or may not be equal, and the crystals
tend to aggregate and may appear layered. Caution: Cystine crystals are not constantly present in cats with cystinuria or
Photo 2: Photomicrograph of aggregates of cystine crystals in sediment of urine collected from a 1-year-old female domestic
shorthair cat. 40x = original magnification.
The radiodensity of cystine uroliths compared to soft tissue is similar to struvite, but less than calcium oxalate and calcium
phosphate. Thus, when of sufficient size, cystine uroliths can be detected by survey radiography.
Double contrast cystography is more sensitive in detecting small cystine urocystoliths than either survey radiography and
or most techniques of ultrasonography. Cystine uroliths appear radiolucent when surrounded by, but not completely submerged
in, radiopaque contrast medium. Survey radiography may be insensitive in detecting cystine urethroliths. Positive contrast
urethrography may be required to detect and localize cystine uroliths that have passed into the urethral lumen. Although uroliths
can be detected by ultrasonography, this method does not provide information about the degree of their radiodensity or shape.
Evaluation of the density and shape of uroliths by survey radiography often provides useful information in predicting their
We have had the opportunity to monitor the biological behavior of cystine urolithiasis in three cystine urolith-forming cats.
One neutered female and one neutered male with a perineal urethrostomy have been evaluated for more than 10 years since the
date of diagnosis. One neutered female cat has been monitored for seven years since the date of diagnosis. During the initial
period of evaluation of these cats, the male with a perineal urethrostomy had 14 recurrent episodes of urocystoliths over
a 4.5-year interval. One female had 68 recurrent episodes over a 7-year interval, and the other female had 28 recurrent episodes
over a 1.5-year interval. The rate of recurrence of radiographically detectable cystine urocystoliths ranged from two weeks
to approximately three months. Recurrent urocystoliths were removed by voiding urohydropropulsion. Two cats subsequently developed
nephroliths presumed to be composed of cystine. Urocystoliths stopped forming in both cats after development of nephroliths.
In one cystinuric, arginuric, ornothinuric cat, transient, but severe, hyperammonemia associated with neurologic signs was
recognized on three occasions. In this cystinuric cat, concomitant argininuria and ornithinuria likely were of sufficient
magnitude on these occasions to cause depletion of urea cycle intermediates predisposing him to hyperammonemia. Recall that
if cats do not consume adequate dietary sources of arginine to generate sufficient ornithine for conversion of ammonia and
carbon dioxide to urea via the hepatic urea cycle, life-threatening hyperammonemia may result.