To briefly recap from the last post, cystine urolithiasis refers to the formation of urinary tract stones (uroliths) that are composed of cysteine. Cysteine is one of several amino acids that are filtered by the kidneys, and during the modification of urine prior to excretion, it is almost completely reabsorbed. Unfortunately, various disease processes can decrease reabsorption of cysteine, as well as other amino acids such as ornithine, lysine, and arginine (acronym COLA). The most common cause for failed reabsorption is a genetic mutation involving one of two genes, SLC3A1 or SLC7A9. Cysteine loss is clinically the most relevant, as it is the least soluble in urine that is either acidic or even neutral in pH. Due to this insolubility, cysteine molecules combine to form cystine crystals, which with time aggregate to form cystine uroliths.
Medical dissolution, which utilises a therapeutic diet (as previously described), and in some cases medication (2-mercaptopropionylglycine or tiopronin/'Thiola') to increase the solubility of cysteine, is generally the first line of treatment recommended. In the majority of cases this is reasonably successful in both dissolving the uroliths and also preventing recurrence. A question of interest is whether neutering should also be a standard recommendation for entire male dogs with cystine urolithiasis, and there is currently a reasonable amount of evidence to suggest that it should be.
Recent research has demonstrated that not all cases of cystine urolithiasis result from a genetic mutation involving one of the two genes mentioned above. Many cases have demonstrated an association between the presence of testosterone (also referred to as androgen-dependent) in entire/intact male dogs, and the formation of cystine uroliths. By looking at urolith submissions over a 10 year period, Florey et al. (2017) observed that there was an increased risk of cystine urolith formation in entire dogs in the United Kingdom. They also found that neuter status was significantly associated with cystine stone formation in the Staffordshire bull terrier, bulldog, Jack Russell terrier, Yorkshire terrier and West Highland white terrier, as well as in crossbreed dogs.
Similarly, Hesse et al. (2016) also looked at 1760 urolith submissions in Germany over a 35 year period, and found that more than 94% of all cystine uroliths were from entire male dogs.
In 2013, Brons et al. therefore proposed a new classification system for canine cystinuria:
The authors termed androgen-dependent cystinuria 'Type III cystinuria'; unfortunately, the underlying cause of this proposed androgen dependency is currently unknown.
Neutering/castration in these cases may prevent recurrence of cystine uroliths, removing the need for lifelong medical management. This is significant, as lifelong feeding of a commercial prescription diet or home-prepared therapeutic diet is very expensive, particularly in large-breed dogs. As mentioned above, breeds in which this has been documented include Staffordshire bull terriers, other terriers, French and English bulldogs, Mastiffs (and related crossbreeds), Scottish deerhounds, and Irish terriers. There may however, be considerably more breeds involved, with more research required – so watch this space! In the meantime, however, neutering seems advisable, and quantifying cystine loss in the urine prior to, and after, neutering may be useful to indicate whether medical management is still required, post-surgery.
Read the full paper by Brons et al. here: https://www.ncbi.nlm.nih.gov/pubmed/24001348
Disclaimer: This content is not intended to be a substitute for the professional recommendations of your pet's veterinarian. Always seek the advice of your veterinarian with any questions you may have regarding the medical condition of your pet. If you think your pet has a medical emergency, please call or visit your veterinarian or your local veterinary emergency hospital immediately.
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