Dietetic diet: decreasing risk of cystine stones (uroliths)

Pathophysiology

These uroliths are composed of the amino acid cystine. The global prevalence of cystine urolithiasis in dogs is approximately 1%, although this varies considerably from country to country.
They occur in dogs and cats with cystinuria, which is an inborn error of metabolism characterized by abnormal transport of cystine, a nonessential sulfur-containing amino acid by the renal tubules. Cystine is normally present in low concentrations in plasma. It is freely filtered at the glomerulus and most is actively reabsorbed in proximal tubules. Unlike normal dogs, cystinuric dogs reabsorb a much smaller proportion of cystine from glomerular filtrate and may even have net cystine secretion.
Cystine is relatively insoluble in acid urine but becomes more soluble in alkaline urine (above pH 7.2), so urolith formation enhanced by acid urine pH, highly concentrated urine, and incomplete and infrequent micturition. Unless protein intake is severely restricted; cystinuric dogs have no detectable clinical or serum chemistry abnormalities associated with amino acid loss, with the exception of formation of cystine uroliths.
The exact mechanism of cystine urolith formation is unknown. Because not all cystinuric dogs form stones, cystinuria is a predisposing factor rather than a primary cause of urolith formation. Urine amino acid profile reveals abnormal quantities of cystine, and in some dogs and cats lysine, arginine and ornithine.
Cystine stones are radiolucent to slightly radiopaque and have a smooth to slightly irregular surface .
Breeds significantly affected by cystine urolithiasis are the:
- Bulldog Bulldog.
- Bassett Hound Basset Hound.
- Bull Mastiff Bullmastiff.
- Deerhound Deerhound.
- Irish Terrier Irish Terrier.
- Mastiff Mastiff.
- Newfoundland Newfoundland.
- Rottweiler Rottweiler.
- Staffordshire Bull Terrier Staffordshire Bull Terrier.
- Whippet Whippet.
Males are significantly over-represented with few cases occurring in females.
The average age at which cystine urolithiasis occurs is 73 months, with 63% of cases occurring between 37-96 months. In cats, primarily adults are affected (mean age 4 yrs). It is most commonly recognized (although uncommon) in domestic shorthaired cats and Siamese cats.
Medical dissolution in dogs involves a combination of N-(2-mercaptopropionly)-glycine (2 MPG) and low protein alkalinizing wet diet to reduce urinary excretion of cystine, promote formation of alkaline urine, and reduce urine concentration.
This diet is used in conjunction with 2 MPG for stone dissolution; diet alone is often effective in preventing recurrence. High protein dry diets, especially those rich in methionine, a precursor of cysteine increase the risk of cysteine uroliths. Reduction of dietary protein has the potential of minimizing formation of cystine uroliths. Increased dietary sodium may enhance cystinuria, therefore potassium citrate is better than sodium bicarbonate to maintain alkaline urine (eg pH of 7.5).