Cystinuria

Cystinuria is a hereditary metabolic disorder that may lead to the formation of urinary stones or possible obstruction. It has been described in many breeds of dog, as well as occurring naturally in species of wild animals and additionally in humans too (such as cats, and a variety of other captive and wild species, such as otters, maned wolves, dolphins and ferrets to name but a few).

Cystinuria, some of the dog breeds referenced, (in alphabetical order) that can be affected- Airedale, American Pit Bull, Australian Cattle Dog, Austalian Shepherd, Azawakh, Basenji, Basset Hound, Beagle, Bichon Frise, Boxer, Bulldog, Bullmastiff, Cairn Terrier, Cardigan Welsh Corgi, Cavalier King Charles Spaniel, Chesapeake Bay Retriever, Chihuahua, Chinese Crested, Collie, Dachshund, Drever, French Bulldog, GSD, Great Pyrenees, Iris Terrier, Labrador Retriever, Mastiff, Minature Pinscher, Minature Schnauzer, Musterlander, Newfoundland, Pekingese, Pembroke Welsh Corgi, Poodle, Rhodesian Ridgeback, Rottweiller, Scottish Deerhound, Scottish Terrier, Shetland Sheepdog, Shih Tzu, Silky Terrier, Staffordshire Bull Terrier, Swedish Lapphund, Tibetan Spaniel, Tosa Inu, Vorster, Welsh Corgi, Whippet, Yorkshire Terrier.

*This is not an exhaustive list as there has been records of over 70 breeds that have been affected by this condition.

There are several sub-types of cystinuria, each having a different mode of inheritance and genetic mutation within different breeds of dog. To-date three types of cystinuria have been identified (so far) Type I, Type II, and Type III with differing degrees of symptoms and treatments.

Type III which can affect Male Mastiffs only, is sex and scientific research suggests hormonally linked. (type III sex-limited/androgen-dependent inheritance) although if condition expressed, environmental factors may exasperate it (i.e diet, certain medication or lack of hydration levels).

How is it diagnosed when its symptomatic (showing symptoms)?

Is your male Mastiff (or other breed of dog within the household) exhibiting any of these signs:

* Bloody urine

* Straining to urinate

* Frequent urination

* Painful when urinating

* Re-occuring urinary tract infections UTIs

Immediate veterinary consultation is imperative for a swift diagnosis and treatment.

We are in a positive position with our breed the Mastiff, as luckily its one of the breeds that can be screened by a simple DNA test that comprises of a cheek (buccal) swab test that can be posted to a laboratory to find out their individual test results, which can be clear, carrier or affected. (1.1, 1.2, 2.2 - N/N, N/cy, Cy/Cy) Males with two copies of the condition 2.2 - Cy/Cy may become affected as the most at risk, if they are intact (un-neutered) male dogs. Treatment can be relatively simple, only if detected early before an amount of crystals develop (an annual nitroprusside urine test can help with detection) castration should completely alleviate symptoms, once testosterone hormone levels have abated. Bitches do not have symptoms or illness but may pass on the mutation to their offspring.

Simple (cheek/buccal swab) targeted testing within the breed gene pool, means that dogs within the breeding programme can be carefully bred with some degree of confidence without losing important dogs and their genetic diversity (loss of diversity could cause long lasting and catastrophic health consequences for the breeds long term future) without producing 2.2 - Cy/Cy affected male dogs. Prevention through DNA and nitroprusside testing is the best form of treatment, as late onset surgery involves surgical removal of the crystals/stones (Cystotomy) or a more permanent surgery is a complicated operation (perineal urethrostomy) with a slow and difficult recovery rate.

* The DNA cheek swab test kits are available to members through the Mastiff Association.

Many Mastiffs who test positive (2.2, Cy/Cy) for cystinuria do not go on to form stones, but may still have the potential to form cystine stones into the future, it is recommended to neuter these male dogs as soon as possible. Research shows that randomly some male Mastiffs will go on to show clinical signs and others do not. With this in mind it is imperative (as we are lucky enough to have scientists and researchers showing an interest in our breeds health and welfare) that we help and support this with funding, providing samples, specimens and information for the great work this organisation is doing to further our understanding, and utilise this important tool for our breed, with much gratitude for all the hard work and research into cystinuria by The University of Pennsylvania USA LINK- Test Details Cystinuria

(With grateful thanks to the Mastiff Association for their support & financial donations to Pennsylvania University for ongoing research into Cystinuria)

This DNA test is also available at Laboklin laboratories UK LINK- LABOKLIN (UK)| Genetic Diseases | Dogs| Cystinuria

Questions and Answers

My dog has been diagnosed with cystinuria. What treatment is there for this condition?

Preventative treatment for type III Cystinuria in Mastiffs entails testicular castration, if your male dog has been found to have the DNA test positive (2.2, Cy/Cy) for cystinuria. Unfortunately without removing high testosterone levels (male castration) It can be an incurable genetic defect of the kidneys. However, just because your dog has cystinuria does not mean he will form stones. It appears that many, perhaps even the majority, of dogs with cystinuria do not form stones. It is not clear what the difference is between stone-formers and non-stone-formers, but at this time the difference is not believed to be solely one of diet or other environmental factors, but of hormonal levels, and there are plausably genetic factors at play.

If your dog has cystinuria, you must watch him carefully for any signs of urinary obstruction: Frequent urination, blood in the urine, frequent urinary tract infections, difficult urination, scanty urination, dribbling urination, evidence of pain when urinating, a reluctance to urinate, or anything at all about their urinary habits that doesn't seem totally normal.

You then have to make sure that you obtain veterinary care from a veterinarian who knows that cystine stones are not always able to be seen in an x-ray (although they might be seen), or on an ultrasound. Sometimes it's necessary to do a procedure called a contrast study to be sure that no stones are present. For more information, read the section on the Diagnosis of Canine Cystinuria.

My dog has formed stones. Is there a treatment for that?

YES! And it's not optional. You have to get those stones out of there and treat or prevent any urinary obstruction. This can be a life-threatening condition.

The most urgent need is to unblock the urinary tract if it's obstructed. This can be done with a technique known as retrograde hydropulsion, which will attempt to push any stones blocking the urethra back into the bladder. This will relieve the immediate obstruction, however, the stones in the bladder still need to be treated. This is usually done with a procedure known as a cystotomy, where the stones are removed from the bladder surgically.

If the hydropulsion does not work, an alternative urinary tract will have to be created. The preferred surgery is known as a scrotal urethrostomy, where a new opening for urination is created between the dog's penis and scrotum. This is difficult, complicated surgery and should be done by a board certified surgeon. It is expensive and the recovery period can be bloody, although in recent years new techniques have been developed that have reduced the bleeding. A cystotomy will also be performed to remove the stones in the bladder. There is a complete description of both cystotomy and retrograde hydropulsion here.

If the hydropulsion is successful and surgery is not an option or needs to be delayed, it is possible to dissolve the stones with the drug Thiola (tiopronin). Although thiola is usually well-tolerated by dogs, it is very expensive in the dosages needed for larger dogs.

Another drug, much less expensive, is penicillamine. Although it can cause more side effects than thiola, if your dog tolerates it, it may be a better choice. However, both these drugs have the potential to cause serious side effects.

Can I dissolve cystine stones with diet?

No, they cannot be dissolved with diet.

Once my dog's stones are treated, can I prevent more from forming in the future?

In Mastiffs (type III cystinuria) the most effective and reliable way to stop stone/crystal formation is to castrate male dogs. In some other breeds veterinarians, including many well-known kidney specialists, feel strongly that cystine stones can be prevented, or the incidence greatly reduced, by feeding ultra-low-protein diets (such as Hills u/d) and alkalinizing the urine with drugs or supplements. Other veterinarians believe that diet is of minimal or no use in controlling the formation of stones, and that only the drug Thiola is effective for this purpose. You can read some intriguing research on this subject here.

On the Canine Cystinuria email list, most of us have found that diet and urinary alkalinization have failed to prevent our dogs from forming stones, and have sometimes caused other problems, including other types of stones that form in alkaline urine. Some of us are also concerned about feeding ultra-low-protein diets to dogs, particularly giant breed dogs, and dogs of breeds prone to cardiomyopathy.

Unfortunately, thiola is very expensive, prohibitively so for most owners of large dogs. For this reason, many owners of dogs with cystinuria who form stones opt for a scrotal urethrostomy even if their dog is not obstructed, because with this procedure, male dogs will tend to pass stones the way female dogs do, and the risk of obstruction is reduced, or even eliminated. (Female dogs with cystinuria rarely get a urinary obstruction from stones.) There is a description of this procedure toward the end of the page here.

All of us with dogs with cystinuria who form stones wish there was a simple way to treat or prevent these stones with diet or an accessible, affordable drug, but as of today that is not the case.