Case of the month: cystinuria in a 9-month-old female cat

Here's an unusual and interesting case that was recently referred to us for a nutrition consult. A 9-month-old female spayed domestic medium-haired cat presented to the referring veterinarian with a two week history of painful urination. Analysis of the urine revealed large numbers of cystine crystals in the urine. An ultrasound also demonstrated mild bilateral renal mineralisation and marked crystalluria. The cat was subsequently referred to us for a nutrition plan and recipes for a homemade diet, given that, unfortunately, there were no ideal commercial therapeutic diets suitable for a growing cat.

Cystine crystals in urine (credit: http://www.swissnephro.org)

Cystinuria is characterized by a selective proximal renal tubular defect affecting reabsorption of the amino acids, cystine, ornithine, lysine, and arginine. In healthy animals, these amino acids are almost completely reabsorbed by the proximal tubules of the kidneys. Animals that have defects in the amino acid transport system excrete high concentrations of these substances in their urine. Cysteine, a nonessential amino acid containing sulfur, can precipitate into crystals and uroliths (stones) that can cause crystalluria, stranguria, dysuria, haematuria, urinary tract obstructions, and renal failure.

Cysteine vs cystine - what's the difference? Cystine is the oxidized dimer form of the amino acid cysteine; it is only slightly soluble in water. High concentrations of the amino acid cysteine in the urine can lead to the formation of cystine stones.

Cystinuria occurs in many species, and in humans, dogs and cats, it is caused by variants in two genes, either SLC3A1 or SLC7A9. Cystinuria can be inherited in humans as an autosomal recessive and dominant trait, due to SLC3A1 (IA and IIA) and SLC7A9 (IB and IIB) variants, respectively. In dogs, a similar pattern of inheritance has been observed. Feline cystinuria was first documented in a single case report in 1991. It is very uncommon, with cystine calculi representing only 0.1% of all feline uroliths in the United States and Canada, compared with 0.3–1% of all canine uroliths.

Cystine uroliths (credit: http://www.swissnephro.org)

So what were the nutritional goals for this cat with cystinuria? Essentially, our aim was to create a high moisture diet appropriate for growth, with low total protein, restricted methionine and cysteine, and increased arginine and taurine. Protein is restricted in order to avoid causing aciduria, which can significantly decrease the solubility of cystine in urine.

Increasing dietary moisture will help to produce more dilute urine; increasing urine volume can decrease the concentration of sulfur-containing amino acids in the urine, helping to prevent the formation of cystine uroliths. Prevention of cystine uroliths also involves inducing undersaturation of urine with the sulfur-containing amino acids, methionine and cysteine, mainly by avoiding ingredients that are a rich source of methionine, like most meats, wheat and peanuts.

We also recommended monitoring urine pH carefully, as the effects of diet on urine pH can be difficult to calculate with any degree of certainty. This is important, as the solubility of cystine in urine is pH dependent and a substantial increase in solubility occurs at a urinary pH above 7.5. Finally, we also ensured that the diet was enriched with arginine, because cystinuric cats with impaired intestinal absorption and renal reabsorption of arginine can become arginine deficient; this can then lead to hyperammonaemia and neurological signs.

Not surprisingly, it can be a challenge to formulate low protein, high moisture recipes for cats that are very palatable. For this cat, we formulated two recipes - one using chicken, rice, zucchini and egg as the base, and one using tuna, cottage cheese and rice. Hopefully at least one of these recipes will appeal to this cat.

As with any new diet, a gradual transition will be essential in this case - cats can take a long time (often a month or more) to slowly and sneakily transition from one diet to another. Patience is essential! Unfortunately, the prognosis for cats with cystinuria doesn't appear to be very good, although only a small number of cases have been described, and (as far as we know), none have used an arginine-supplemented home-prepared diet as part of management. We will be following this case with great interest, and really hope to hear good news.

If you have a dog or cats with urinary stones, and you would like advice or recipes for a home-prepared therapeutic diet, please email us: info@vngpets.com